case study fetal alcohol syndrome

Fetal Alcohol Spectrum Disorders: A Case Study

Affiliation.

• 1 Center for Behavioral Teratology and Department of Psychology, San Diego State University, San Diego, CA 92120.
• PMID: 28948136
• PMCID: PMC5609722
• DOI: 10.1007/s40817-016-0027-7

This grand rounds manuscript reviews important considerations in developing case conceptualizations for individuals with a history of prenatal alcohol exposure. This case study provides an introduction to fetal alcohol spectrum disorders, diagnostic issues, a detailed description of the individual's history, presenting symptoms, neuropsychological test results, and an integrated summary. We describe a 9-year old girl diagnosed with a fetal alcohol spectrum disorder (FASD): Neurobehavioral Disorder Associated with Prenatal Alcohol Exposure (ND-PAE). This patient is a composite of a prototypical child who participated as part of a research project at the Center for Behavioral Teratology who was subsequently seen at an outpatient child psychiatry facility.

Keywords: Prenatal alcohol exposure; fetal alcohol spectrum disorder (FASD); fetal alcohol syndrome (FAS); neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE); neuropsychological assessment.

Grants and funding

• F31 AA022261/AA/NIAAA NIH HHS/United States
• U01 AA014834/AA/NIAAA NIH HHS/United States

• Case report
• Open access
• Published: 19 December 2019

Two case reports of fetal alcohol syndrome: broadening into the spectrum of cardiac disease to personalize and to improve clinical assessment

• R. Onesimo 1 ,
• C. De Rose 1 ,
• A. B. Delogu 2 , 3 ,
• A. Battista 2 ,
• C. Leoni 1 ,
• S. Veltri 1 ,
• G. De Rosa 2 , 3 &
• G. Zampino 1 , 3  

Italian Journal of Pediatrics volume  45 , Article number:  167 ( 2019 ) Cite this article

5464 Accesses

3 Citations

Metrics details

Fetal alcohol spectrum disorder (FASD) refers to a broad spectrum of disabilities, in infants and children, resulting from moderate to excessive prenatal alcohol exposure.

Significant associations with alcohol exposure were already reported with congenital structural heart defects: i.e. ventricular septal defects, atrial septal defects, conotruncal defects.

Cases presentation

We describe two cases of children with FASD, both admitted to the Center for Rare Diseases and Birth Defects of Policlinico Universitario Agostino Gemelli, in whom asymptomatic cardiac rhythm alterations were detected in absence of structural cardiovascular system anomalies or cardiac channelopathies.

Conclusions

No other reports about cardiac rhythm anomalies in individuals affected by FASD are actually available from the literature.

We would like to make an alert for clinician, given the possibility of finding anomalies of heart conduction and rhythm in children affected by FASD even without structural congenital heart disease.

Introduction

The term fetal alcohol spectrum disorder (FASD) refers to a broad spectrum of disabilities, in infants and children, resulting from moderate to excessive prenatal alcohol exposure [ 1 ]. It includes fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), Alcohol Related Birth Defects (ARBD) and Alcohol Related Neurodevelopmental Disorders (ARND) [ 2 ].

FAS is characterized by the presence of all of the following criteria: two of the three typical facial features (short palpebral fissures, thin vermillion border and a smooth philtrum), growth retardation and central nervous system (CNS) anomalies. FAS diagnosis does not require documentation of prenatal alcohol exposure. pFAS is defined by two of the previously reported facial features plus other structural defects. ARBD has physical defects secondary to known fetal alcohol exposure, without neurobehavioral disorders. ARND refers to neuropsychiatric impairment caused by prenatal alcohol exposure in the absence of physical defects [ 3 , 4 ].

According to recent US data, the prevalence of FASD vary considerably from 24 to 48 per 1000 children; however, if we consider particular subpopulation groups, FASD rates might be considerably higher. FASD incidence in Europe is estimated to be 1–3:10000; in the US 2–7:1000 and 2–5% respectively for FAS and FASD [ 5 ].

In Lazio (Italy) prevalence of FAS is 3.7–7.4 per 1000 children, the rate of FASD is 20.3 to 40.5 per 1000 and estimated between 2.3 and 4.1% of all children [ 6 ].

FASD is the most common cause of mental retardation acquired during childhood; however, structural involvement of other systems (cardiovascular, renal, musculoskeletal, ocular and auditory systems) has already been associated with this condition [ 7 ].

Significant associations with alcohol exposure were reported with ventricular septal defects and atrial septal defects. Furthermore, mothers who drink alcohol during pregnancy have 1.64 fold times increased risk to have a newborn affected by conotruncal defects (CTDs) subtypes such as transposition of the Great Arteries (dTGA) [ 7 ]. This evidence suggests both prenatal heavy drinking and binge drinking are strongly associated with an overall increased risk to present babies with congenital heart defects [ 7 ].

We know that alcohol consumption during pregnancy can have negative effect on the fetus cardiovascular system; however only congenital structural heart defects have been reported to date [ 7 ]. No reports about cardiac rhythm anomalies in individuals affected by FASD are actually available from the literature.

Herein we report the cases of two children with FASD, both admitted to the Center for Rare Diseases and Birth Defects of our Institution, in whom asymptomatic cardiac rhythm alterations were detected in absence of structural cardiovascular system anomalies during routine follow-up.

The proband was admitted for the first time at 7 year old, to confirm the hypothesis of FASD. The child was born in Russia and he was adopted at the age of four. Few data were available from his perinatal history: he was born at term, with detected microcephaly. His mother was an alcoholic; however, no further information were available about the alcohol rate during pregnancy.

At the time of the adoption, the child had psychomotor delay with poor language development; retinal angiopathy; the echocardiography evaluation showed a normal heart anatomy.

In Italy, he underwent neuropsychological tests confirming a mild intellectual disability. Genetic consult was performed and chromosomal rearrangements were absent at arrayCGH.

In the presence of neurological impairment, growth delay and typical facial features (short palpebral fissures, thin vermillion border, and a smooth philtrum), after multidisciplinary evaluations, diagnosis of FAS was confirmed by exclusion of the other conditions.

At the last clinical evaluation, performed at the age of 8 years, he showed a global good clinical setting. According to the CDC growth charts, height and weight were within the normal limits, cranial circumference was − 1.8 SD. Child neurologist confirmed behavioral disorders and mild intellectual disability.

On physical examination, the heart rate, blood pressure and respiratory rate were normal, but cardiac auscultation revealed an irregular rhythm, so that an ECG with a long rhythm strip was required. On ECG, premature ventricular contractions (PVCs) were identified; repeated echo study excluded structural heart disease (except for a patent foramen ovale) or functional abnormalities.

On 24-h Holter monitoring, PVCs were frequent (14,567/24 h) and appeared uniform and isolated with ventricular bigeminy and trigeminy; no couplets, triplets or ventricular tachycardia were detected.

On exercise stress testing, rare monomorphic PVCs were present, without symptoms at rest or during exercise. PVCs demonstrated a right bundle branch block morphology with a right axis deviation, suggesting a fascicular origin.

Laboratory studies including full blood count (for anemia), electrolytes, blood glucose, and thyroid function testing were performed and were normal.

Since, the patient was asymptomatic - without underlying heart disease - and he had uniform and isolated PVCs - without induction or exacerbation of arrhythmia with exercise - further extensive investigation or treatment was not considered to be required and cardiac follow up with ECG, 24-h Holter monitoring and exercise stress testing was scheduled.

A 8 year old male was admitted to our Center to confirm a diagnosis of FASD.

The child lived in Poland until he was 6 years and a history of maternal alcohol abuse during pregnancy was recorded from past medical history reports. He had no history of growth delay, microcephaly or cardiac abnormalities. Adopted parents reported generic emotional and behavioral problems.

Clinical evaluation showed the typical phenotype of FASD: telecantus, jaw hypoplasia, nasal saddle hypoplasia and thin vermillion border.

A neuropsychiatric evaluation and a cognitive assessment (Leiter scale) were performed, with no evidence of major problems with the exception for low attention level. Array CGH did not reveal anomalies and genetic consultation confirmed FASD.

Six months after the first physical examination, the child reported complaints of palpitations, with sudden start and stop of rapid heartbeats, without other signs or symptoms. Then a complete cardiac check was performed.

An echocardiographic evaluation detected a structurally normal heart (except for a small patent foramen ovale) without functional abnormalities. Routine ECG during office visit revealed sinus rhythm with frequent premature atrial contractions (PACs). On 24-h Holter monitoring, sinus rhythm was interrupted by frequent PACs and short runs of ectopic atrial tachycardia (maximal heart rate 146 beats/minute, 6 beats).

On exercise stress testing, many isolated premature atrial contractions were present, with occasional couplets and triplets and frequent runs of atrial ectopic tachycardia (the longer supraventricular tachycardia (SVT) with 12 beats at maximal heart rate 160 beats/minute); at high workload, isolated and monomorphic ectopic ventricular beats appeared, with a left bundle branch block QRS morphology; no ventricular repolarization abnormalities were detected.

To rule out other medical conditions suspected as a cause of supraventricular tachycardia, laboratory studies including full blood count (for anemia), electrolytes, blood glucose, and thyroid function testing were performed and were normal.

Since, no heart disease was found and the patient tolerated very well this kind of SVT - due to short runs of tachycardia at low heart rate, without any hemodynamic significance - specific treatment was not indicated and cardiac follow up with ECG, 24-h Holter monitoring and exercise stress testing was scheduled.

A different alcohol rate abuse during pregnancy causes a broad spectrum of disorders known as FASD, in which FAS who includes the presence of peculiar facial features, growth delay and CNS anomalies represent the worst condition [ 3 ].

Due to the lack of genetic or biochemical diagnostic tests, the decisive step to identify a patient with FASD is to ascertain maternal alcohol consumption during pregnancy. The absence of this data, however, does not exclude the diagnosis that must be formalized following the recent guidelines [Hoyme HE, 2016] which are based on the multidisciplinary approach to the mother-child dyad and are aimed at analyzing three essential aspects of the syndrome: - the morphological anonymities of the newborn; − the child’s neuropsychological, intellectual and social development; − maternal risk factors [ 3 ].

Structural defects in cardiovascular, renal, musculoskeletal, ocular, and auditory systems have already been described in FASD [ 8 ]. Interestingly no data about cardiac rhythm disturbances in patients with FASD have never been reported to date.

In the neonatal period, FASD may be suspected by the presence of small infant for gestational age (SGA), microcephaly and typical dysmorphic features (middle-facial hypoplasia, short palpebral fissures, elongated and flat nasolabial filter, thin upper lip, telecantus, jaw hypoplasia, the anomalies of the ears, the poorly modeled pavilions).

The evidence of alcohol abuse during pregnancy helps clinicians in the differential diagnosis with other syndromic disorders.

By passing time, neuropsychiatric issues may progressively appear such as psychomotor delay, behavioral disorders and attention deficit, scholastic and social problems.

Our patients were both diagnosed as having FASD during scholar age, no cardiac concerns were reported in the previous years.

In Case 1 the ECG was performed to confirm extrasystoles detected during routine cardiac auscultation whereas in Case 2 was performed because of reported episodes of palpitations.

The cardiac evaluation showed a sinus rhythm with isolated but frequent junctional and monomorphous ventricular extrasystoles in case 1, in absence of any other cardiac symptom. The second child (case 2) showed a sinus rhythm with rare ectopic ventricular beats, frequent ectopic supraventricular beats and episodes of supraventricular tachycardia associated to palpitations.

In both cases, in the absence of clinical history of sincope and ECG findings of QT prolongation, repolarization anomalies and/or complex ventricular arrhythmias, molecular investigations for cardiac channelopathies were not performed.

Generally, premature ventricular contractions (PVCs) may appear in otherwise healthy children and are benign, particularly if they are uniform and disappear or become less frequent with exercise. PVCs are more significant if they are associated with underlying heart disease as preoperative or postoperative status or cardiomyopathy, if there is a history of syncope or a family history of sudden death, if they are precipitated by activity, if they are multiform, particularly couplets, if there are runs of PVCs with symptoms and if there are incessant or frequent episodes of paroxysmal ventricular tachycardia. In patients without structural heart disease, ventricular ectopic beats are usually monomorphic, isolated, they manifest at low heart rates and disappear during exercise; this benign condition usually does not require any treatment. On the other hand, the presence of symptomatic extrasystoles, polymorphic ectopic beats, usually organized in pairs or triplets, which appear or increase with stress must be investigated in depth [ 9 , 10 ].

Generally, premature atrial contractions (PACs) may appears in healthy children, including newborns, without any hemodynamic significance, and usually no treatment is needed. Supraventricular isolated extrasystoles can be found in many healthy children and no therapy is required. These type of extrasystoles can be followed by a normal or abnormal QRS (LBBB or RBBB shape); in some cases the input can be stopped at the level of the AV node, resulting in the absence of the following QRS (apparent pause). In newborns, atrial extrasystoles are quite frequent and usually regress within the first few weeks of life; atrial extrasystoles are a benign condition and there is no risk of degeneration in more severe arrhythmias. In older children, frequent supraventricular extrasystoles may anticipate the development of a breast node dysfunction (see sick sinus syndrome) especially following cardiac surgery or in association with cardiomyopathy [ 9 , 10 ].

Supraventricular tachycardia (SVT) is the most common arrhythmia in infancy and usually affects subjects with structural normal heart. SVT is idiopathic in over 50% of cases, especially in infants. Ectopic atrial tachycardia is a type of supraventricular tachycardia (SVT) believed to be secondary to increased automaticity of nonsinus atrial focus or foci and most patients have a structurally normal heart (idiopathic). Patients with congenital heart diseases, both during natural history or after surgery, have an higher risk of developing SVT; it is estimated that the 9–32% of these patients present at list one episode of SVT. Most of the idiopathic SVTs remain asymptomatic [ 11 ]. However, in children with negative history for cardiac conditions, episodes of palpitations or tachycardia usually do not have a cardiac origin but occur as a physiological response to external or internal factors (e.g. anxiety, fever, hypovolemia, orthostatic hypotension). Moreover, these episodes might be related to extra cardiac conditions: pheochromocytoma, arteriovenous fistula, intake of stimulant drugs, anemia, hyperthyroidism, electrolyte imbalances and gastrointestinal problems (especially gastro-esophageal reflux) [ 12 , 13 , 14 ]. In chronic cases of ectopic atrial tachycardia, cardiac heart failure may occur, and there is a high association with tachycardia-induced cardiomyopathy, refractory to medical therapy and cardioversion. In these cases, the goal may be to slow the ventricular rate rather than to try to convert the arrhythmia to sinus rhythm [9,10].

Direct effects of alcohol dependence on the cardiovascular system and cardiac rhythm in the general population have already been reported; however the pathogenetic mechanisms related to the pro-arrhythmic effects of alcohol are still unclear. The risk of arrhythmias is dose-dependent, not influenced by preexisting cardiovascular diseases or heart failure and can affect otherwise healthy subjects. Acute alcohol toxicity can lead to cardiac contraction impairment with rhythm disturbances (holiday heart syndrome), transient ischemic attacks and, in rare cases, sudden cardiac death. Cardiac effects of chronic high alcohol consumption include ventricular dysfunction, chronic rhythm disturbances, alcoholic cardiomyopathy and coronary artery disease [ 15 , 16 ].

The exact teratogenic mechanism of alcohol on fetal development is still unclear. Several factors such as the onset of alcohol abuse during pregnancy, daily dose and maternal comorbidities may influence the severity of FASD. Toxic effect on autonomic nervous system may not be excluded and could explain the presence of arrhythmic abnormalities in the absence of structural cardiac defects in our patients.

We do not know if the presence of arrhythmic abnormalities of our patients is a casual association or a feature that could enlarge the FASD spectrum. Our report is an alert for clinicians.

To define the prevalence of this event it is necessary to study systematically a wider cohort of patients with FASD.

Given the possibility of finding anomalies of heart conduction and rhythm in children affected by FASD even without congenital structural defect, we would suggest to clinicians to include periodic ECGs monitoring in the follow-up of these children, even without the presence of suggestive cardiac symptoms.

FASD is not a genetic but rather a multisystem disorder, hence multidisciplinary team should perform FASD follow up. Since there is no treatment to reverse alcohol-induced damages, primary and secondary preventions are the only chances to detect and if necessary to treat heart abnormalities. Finally, on the light of the described clinical experience and related findings, a screening for arrhythmias by using ECG even in children affected by FASD without structural congenital heart disease has to be performed.

Abbreviations

Alcohol related birth defects

Alcohol related neurodevelopmental disorders

Central nervous system

ConoTruncal defects

Transposition of the great arteries

• Fetal alcohol syndrome

Fetal alcohol spectrum disorder

Premature atrial contractions

partial Fetal Alcohol Syndrome

Premature ventricular contractions

Small for gestational age

Supraventricular tachycardia

Cook JL, Green CR, Lilley CM, et al. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. CMAJ. 2016;188:191–7.

Article   Google Scholar  

Koren G, Nulman I, Chudley AE, et al. Fetal Alchol spectrum disorder. CMAJ. 2003;169(11):1181–5.

PubMed   PubMed Central   Google Scholar  

Hoyme HE, Kalberg W, Elliot AJ, et al. Updated clinical guidelines for diagnosis of fetal alcohol spectrum disorders. Pediatr. 2016;138:e20154256.

Young JK, Giesbrecht HE, Eskin MN, Aliani M, Suh M. Nutrition implications for fetal alcohol spectrum disorder. Adv Nutr Int Rev J. 2014;5:675–92.

Article   CAS   Google Scholar  

Roozen S, Peters G-JY, Kok G, Townend D, Nijhuis J, Curfs L. Worldwide prevalence of fetal alcohol spectrum disorders: a systematic literature review including meta-analysis. Alcohol Clin Exp Res. 2016;40:18–32.

May PA 1 , Fiorentino D, Phillip Gossage J, Kalberg WO, Eugene Hoyme H, Robinson LK, Coriale G, Jones KL, del Campo M, Tarani L, Romeo M, Kodituwakku PW, Deiana L, Buckley D, Ceccanti M. Epidemiology of FASD in a province in Italy: Prevalence and characteristics of children in a random sample of schools. Alcohol Clin Exp Res. 2006;30(9):1562–1575.

Yang J, Qiu H, Qu P, Zhang R, Zeng L, Yan H. Prenatal alcohol exposure and congenital heart defects: a meta-analysis. PLoS One. 2015;10:e0130681.

Caputo C, Wood E, Jabbour L. Impact of fetal alcohol exposure on body systems: a systematic review. Birth Defects Res C Embryo Today. 2016;108(2):174–80.

Allen HD. What is our future? Congenit Heart Dis. 2018;13(3):347–8.

Dominic J. Abrams. Invasive electrophysiology in paediatric and congenital heart disease. Heart. 2007;93(3):383–91.

Bronzetti G, Mariucci E, Cervi E, D'Angelo C, Corzani A, Brighenti M, Bonvicini M. [Supraventricular tachycardia in children]. G Ital Cardiol (Rome). 2013;14(9):597–612. doi: https://doi.org/10.1714/1311.14485

Aman R, Qureshi AU, Sadiq M. Yield of 48-hour Holter monitoring in children with unexplained palpitations and significance of associated symptoms. J Pak Med Assoc. 2017;67(7):975–9.

PubMed   Google Scholar  

Hou Y, Scherlag BJ, Lin J, Zhang Y, Lu Z, Truong K, Patterson E, Lazzara R, Jackman WM, Po SS. Ganglionated plexi modulate extrinsic cardiac autonomic nerve input: effects on sinus rate, atrioventricular conduction, refractoriness, and inducibility of atrial fibrillation. J Am Coll Cardiol. 2007;50:61–8.

Roman C, Bruley des Varannes S, Muresan L, Picos A, Dumitrascu DL. Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review. World J Gastroenterol. 2014;20(28):9592–9.

Pankuweit S. Alcohol consumption in women and the elderly : When does it induce heart failure? Herz. 2016;41(6):494–7.

Pfeiffer D, Jurisch D, Neef M, Hagendorff A. Alcohol and arrhythmias. Herz. 2016;41(6):498–502.

Download references

Acknowledgements

Not applicable.

Ethical approval and consent to participate

Availability of supporting data, author information, authors and affiliations.

Center for Rare Diseases and Birth Defects, Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito 8, 00168, Rome, IT, Italy

R. Onesimo, C. De Rose, C. Leoni, S. Veltri & G. Zampino

Pediatric Cardiologic Unit, Department of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

A. B. Delogu, A. Battista & G. De Rosa

Università Cattolica del Sacro Cuore, Institute of Pediatrics, Rome, Italy

A. B. Delogu, G. De Rosa & G. Zampino

You can also search for this author in PubMed   Google Scholar

Contributions

All authors have participated in the diagnostic pathways, all authors have read and approved he final manuscript.

Corresponding author

Correspondence to R. Onesimo .

Ethics declarations

Consent for publication.

For the publication, the authors have obtained consent from the parents of both children.

Competing interests

The authors declare that they have no competing interests.

Conflict of Interest: All authors have no conflicts of interest to disclose.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Cite this article.

Onesimo, R., De Rose, C., Delogu, A.B. et al. Two case reports of fetal alcohol syndrome: broadening into the spectrum of cardiac disease to personalize and to improve clinical assessment. Ital J Pediatr 45 , 167 (2019). https://doi.org/10.1186/s13052-019-0759-y

Download citation

Received : 29 June 2019

Accepted : 06 December 2019

Published : 19 December 2019

DOI : https://doi.org/10.1186/s13052-019-0759-y

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Cardiac defect

Italian Journal of Pediatrics

ISSN: 1824-7288

• Submission enquiries: Access here and click Contact Us
• General enquiries: [email protected]

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Published: 23 February 2023

Fetal alcohol spectrum disorders

• Svetlana Popova   ORCID: orcid.org/0000-0002-6308-1157 1 ,
• Michael E. Charness 2 , 3 , 4 , 5 ,
• Larry Burd 6 ,
• Andi Crawford 7 ,
• H. Eugene Hoyme 8 ,
• Raja A. S. Mukherjee 9 ,
• Edward P. Riley   ORCID: orcid.org/0000-0001-8747-891X 10 &
• Elizabeth J. Elliott 11 , 12  

Nature Reviews Disease Primers volume  9 , Article number:  11 ( 2023 ) Cite this article

30k Accesses

41 Citations

115 Altmetric

Metrics details

• Human behaviour
• Neonatal brain damage

Alcohol readily crosses the placenta and may disrupt fetal development. Harm from prenatal alcohol exposure (PAE) is determined by the dose, pattern, timing and duration of exposure, fetal and maternal genetics, maternal nutrition, concurrent substance use, and epigenetic responses. A safe dose of alcohol use during pregnancy has not been established. PAE can cause fetal alcohol spectrum disorders (FASD), which are characterized by neurodevelopmental impairment with or without facial dysmorphology, congenital anomalies and poor growth. FASD are a leading preventable cause of birth defects and developmental disability. The prevalence of FASD in 76 countries is >1% and is high in individuals living in out-of-home care or engaged in justice and mental health systems. The social and economic effects of FASD are profound, but the diagnosis is often missed or delayed and receives little public recognition. Future research should be informed by people living with FASD and be guided by cultural context, seek consensus on diagnostic criteria and evidence-based treatments, and describe the pathophysiology and lifelong effects of FASD. Imperatives include reducing stigma, equitable access to services, improved quality of life for people with FASD and FASD prevention in future generations.

Similar content being viewed by others

Hospitalizations and mortality among patients with fetal alcohol spectrum disorders: a prospective study

Sarah Soyeon Oh, Young Ju Kim, … Eun-Cheol Park

Maternal alcohol consumption and risk of offspring with congenital malformation: the Japan Environment and Children’s Study

Hiroshi Kurita, Noriko Motoki, … the Japan Environment and Children’s Study (JECS) Group

A data driven approach to identify trajectories of prenatal alcohol consumption in an Australian population-based cohort of pregnant women

Evelyne Muggli, Stephen Hearps, … Peter J. Anderson

Introduction

Alcohol consumption has occurred for centuries, with harms from prenatal alcohol exposure (PAE) being mentioned in Greek and biblical verses and depicted in the art and literature of the eighteenth and nineteenth centuries 1 , 2 . A French-language publication from 1968, which received little attention at the time, described perinatal death, prematurity, growth retardation, facial features and malformations in the offspring of women who consumed alcohol during pregnancy 3 . Unaware of the French publication, Jones et al. described a similar pattern of altered morphogenesis and function in 11 children of mothers with ‘alcoholism’ in the Lancet in 1973 (ref. 4 ). They reported specific facial features (thin upper lip, smooth philtrum (the vertical groove between the base of the nose and the border of the upper lip) and short palpebral fissures) and coined the term fetal alcohol syndrome (FAS) 5 . By 1977, the US government had issued a warning about the health risks of alcohol use during pregnancy, which was endorsed by professional organizations in the USA 6 , 7 . In 1981, the US Surgeon General issued stronger advice that “women who are pregnant (or considering pregnancy) not drink alcoholic beverages” 8 and other countries subsequently issued similar advice. The teratogenic effects of alcohol were subsequently confirmed in animal studies 9 .

Later studies found that, in addition to FAS, PAE could cause behavioural, cognitive and learning problems, such as attention deficit hyperactivity disorder (ADHD) and speech and language delay, in the absence of facial and other physical features 10 . Recognition of the disconnect between the neurodevelopmental and physical effects (which relate to first-trimester exposure) of PAE and the wide range of outcomes caused by PAE led to the introduction of the term fetal alcohol spectrum disorders (FASD) 11 . Subsequent research identified groups at increased risk of FASD 12 and associations between FASD and metabolic, immunological and cardiovascular diseases in adults 13 , 14 .

FASD occur in all socioeconomic and ethnic groups 15 and are complex, chronic conditions that affect health and family functioning 16 . Individuals with FASD usually require lifelong health care as well as social and vocational support. Some require remedial education and others interact with the justice system. Early diagnosis and a strength-based management approach will optimize health outcomes.

FASD are the most common of the potentially preventable conditions associated with birth anomalies and neurodevelopmental problems 13 , and their global effects, including huge social and economic costs, are substantial 17 . For example, in Canada, the annual cost associated with FASD is an estimated ~CAD$ 1.8 billion (CAD$ 1.3 billion to CAD$ 2.3 billion) 17 , which is attributable in part to productivity loss (41%), correction services (29%) and health care (10%). In North America, the lifetime cost of supporting an individual with FASD is estimated at >CAD$ 1 million 18 . Addressing and preventing alcohol use in pregnancy is a public-health imperative.

This Primer presents the epidemiology of FASD and the latest understanding of its pathophysiology as well as approaches to diagnosis, screening and prevention. The Primer also describes outcomes across the lifespan, management and quality of life (QOL) of people living with FASD, and highlights important areas for future research and clinical practice.

Epidemiology

Alcohol use during pregnancy.

No safe level of PAE has been established 19 , and international guidelines advise against any amount or type of alcohol use during pregnancy 20 , 21 , 22 , 23 . Nevertheless, ~10% of pregnant women worldwide consume alcohol 24 , 25 . The highest prevalence of alcohol use during pregnancy is in the WHO European Region (25.2% 24 ; Fig.  1 ), consistent with the prevalence of heavy alcohol use, heavy episodic drinking and alcohol use disorders in this region 26 .

The highest pooled prevalence (%) of alcohol use during pregnancy in the general population is estimated in the WHO European Region (25.2%, 95% CI 21.6–29.6), followed by the Region of the Americas (11.2%, 95% CI 9.4–12.6), the African Region (10.0%, 95% CI 8.5–11.8), the Western Pacific Region (8.6%, 95% CI 4.5–11.6) and the South-East Asia Region (1.8%, 95% CI 0.9–5.1), and the lowest prevalence is estimated in the Eastern Mediterranean Region (0.2%, 95% CI 0.1–0.9), where most of the population is of Muslim faith and the rates of abstinence from alcohol are very high. The pooled global prevalence of alcohol use during pregnancy in the general population is estimated at 9.8% (95% CI 8.9–11.1). Data from ref. 24 .

In 40% of the 162 countries evaluated, >25% of women who consumed any alcohol during pregnancy drank at ‘binge’ levels (defined as ≥4 US standard drinks containing 14 g of pure alcohol per drink on a single occasion). Binge drinking, which increases the risk of FASD, is common in early pregnancy and before pregnancy recognition 25 , 27 . Many fetuses are inadvertently exposed to alcohol because binge drinking is prevalent in young women, millions of women who consume alcohol report having unprotected sex and approximately half of all pregnancies are unplanned 28 , 29 , 30 , 31 . Alcohol use during pregnancy is higher in certain subpopulations, including some Indigenous populations in Australia (55%) 32 , South Africa (37%) 33 and Canada (60%) 34 , often in the context of disadvantage, violence and ongoing traumatic effects of colonization 35 .

Risk factors for maternal alcohol consumption

Various risk factors have been identified for maternal alcohol use in pregnancy, including higher gravidity and parity 36 , delayed pregnancy recognition, inadequate prenatal care or reluctance of health professionals to address alcohol use 37 , 38 , a history of FASD in previous children 38 , alcohol use disorder and other substance use (including tobacco) 39 , mental health disorders (such as depression) 39 , a history of physical or sexual abuse, social isolation (including living in a rural area during pregnancy), intimate partner violence 38 , 40 , alcohol and/or drug use during pregnancy by the mother’s partner 38 , 41 or other family members 38 , 41 , and poverty 42 .

Risk factors for alcohol use during pregnancy vary across countries and throughout the course of pregnancy. For example, in Australia, first-trimester alcohol use was associated with unplanned pregnancy 43 , age <18 years at first intoxication 30 , frequent and binge drinking in adolescence 44 , and current drinking and a tolerant attitude to alcohol use in pregnancy 45 . Women who continued to drink alcohol throughout pregnancy were more likely to be older, have higher socioeconomic status, salary and educational levels, smoke, have a partner who consumes alcohol, and have an unintended pregnancy than those who abstained, and were less likely to agree with guidelines that recommend avoiding alcohol use in pregnancy 30 , 31 , 46 , 47 .

FASD prevalence

The estimated global prevalence of FASD among the general population is 7.7 cases per 1,000 individuals 25 , 48 . Consistent with rates of alcohol use during pregnancy, FASD prevalence (Fig.  2 ) is highest in the WHO European Region (19.8 per 1,000) and lowest in the WHO Eastern Mediterranean Region (0.1 per 1,000) 25 , 48 . In terms of individual countries, South Africa (111.1 per 1,000), Croatia (53.3 per 1,000), Ireland (47.5 per 1,000), Italy (45.0 per 1,000) and Belarus (36.6 per 1,000) have the highest FASD prevalence, whereas Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates have no recorded cases of FASD 25 , 48 . Furthermore, 76 countries have a prevalence of FASD of >1% 25 , 48 , which exceeds the prevalence of neurodevelopmental conditions, including Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), spina bifida and anencephaly in the USA 49 , and is similar to the prevalence of autism spectrum disorders (1.1–2.5%) 50 .

In line with the prevalence of alcohol use during pregnancy, the highest pooled prevalence (per 1,000) of fetal alcohol spectrum disorders (FASD) was in the WHO European Region (19.8 per 1,000 population, 95% CI 14.1–28.0), followed by the Region of the Americas (8.8 per 1,000 population, 95% CI 6.4–13.2), the African Region (7.8 per 1,000 population, 95% CI 5.4–10.7), the Western Pacific Region (6.7 per 1,000 population, 95% CI 4.5–11.7) and the South-East Asia Region (1.4 per 1,000 population, 95% CI 0.6–5.3), and the lowest prevalence was estimated in the Eastern Mediterranean Region (0.1 per 1,000 population, 95% CI 0.1–0.5). The pooled global prevalence of FASD was estimated to be 7.7 (95% CI 4.9–11.7) per 1,000 in the general population. Data from refs. 25 , 48 .

Based on global epidemiological data, an estimated 1 in 13 women who consume alcohol while pregnant will deliver a child with FASD, resulting in the birth of ~630,000 children with FASD globally every year 48 . FASD confers lifelong disability, and an estimated >11 million individuals aged 0–18 years and 25 million aged 0–40 years have FASD 51 .

A systematic review and meta-analysis revealed that FASD prevalence is 10–40 times higher in some subpopulations than in the general population, including in children in out-of-home care and correctional, special education, and specialized clinical settings 12 (Fig.  3 ). The pooled prevalence of FASD among children in out-of-home or foster care is 25.2% in the USA and 31.2% in Chile (32-fold and 40-fold higher than the global prevalence, respectively) 12 . FASD prevalence among adults in the Canadian correctional system (14.7%) is 19-fold higher than in the general population, and the prevalence among special education populations in Chile (8.4%) is over 10-fold higher than in the general population 12 . Moreover, the prevalence of FASD is 62% among children with intellectual disabilities in care in Chile 52 , >50% in adoptees from Eastern Europe 53 , 54 and ~40% among children in Lithuanian orphanages 55 . The prevalence of FASD is 36% in one Australian youth correctional service 56 , >23% in Canadian youth correctional services 57 , >14% among USA populations in psychiatric care 58 and 19% in some remote Australian Indigenous communities 59 . The highest prevalence estimates for FAS (46–68%) are in children with developmental abnormalities in Russian orphanages 60 . The high prevalence of FASD in some subpopulations has prompted calls for targeted screening in these groups.

The pooled prevalence (per 1,000) of fetal alcohol spectrum disorders (FASD) is markedly higher in some subpopulations than in the general global population. Subpopulations with a high prevalence of FASD include children in out-of-home care, individuals involved with correctional services and those receiving special education. FAS, fetal alcohol syndrome.

Mechanisms/pathophysiology

Alcohol rapidly equilibrates between the maternal and fetal compartments and is eliminated primarily through maternal metabolism 61 . As previously mentioned, no safe level of PAE has been established 19 . Several developmentally important molecular targets of alcohol, including the L1 neural cell adhesion molecule and GABA A receptors, are disrupted at blood alcohol concentrations attained after one or two US standard drinks 62 , 63 , 64 , 65 , 66 . Hence, repeated exposure to low levels of alcohol or a single exposure at critical periods in gestation could affect development. Indeed, drinking ≤20 g of alcohol per occasion (≤1.5 US standard drinks) or ≤70 g alcohol per week (≤5 US standard drinks) was associated with mild facial dysmorphology (determined via 3D facial imaging) 67 , microstructural brain abnormalities, and externalizing behaviours such as aggression and violation of social norms 68 . The Adolescent Brain Cognitive Development (ABCD) Study, a large, prospective, longitudinal study of child and adolescent development, reported a dose-dependent association between low-level drinking during pregnancy, increased cerebral volume and regional cortical surface area, and a range of adverse cognitive, psychiatric and behavioural outcomes in children aged 9–10 years 69 . There was no inflexion point in the dose–response curves to suggest a cut-off for PAE effects, and significant effects were observed with as little as 1.1 US standard drinks per week throughout pregnancy. Increased brain volume was attributed to impairment of synaptic pruning in the preadolescent brain, consistent with research demonstrating the effect of PAE on trajectories of brain development 70 , 71 .

Genes associated with PAE

Several gene variants confer heightened risk or resilience to PAE 72 , 73 , 74 , and there is higher concordance for FAS among monozygotic than among dizygotic twins 74 . Genetic effects may be exerted through the mother and/or the fetus 72 . ADH1 (encoding alcohol dehydrogenase 1) polymorphisms, such as ADH1B*2 and ADH1B*3 , which increase alcohol metabolism and decrease blood alcohol levels, are associated with reduced risk of FASD 72 . Moreover, zebrafish with pdgfra (encoding platelet-derived growth factor receptor-α) haploinsufficiency have increased susceptibility to craniofacial malformations caused by PAE, which is mirrored in individuals with PDGFRA polymorphisms 75 . Similarly, haploinsufficiency of either Shh or Gli2 (a downstream effector of Shh ) is clinically silent in mice; however, PAE in these mice results in midline craniofacial malformations 76 . Interestingly, hypermethylation of GLI2 (which decreases GLI2 expression) was identified in genome-wide DNA methylation profiling of children with FASD 77 . Prenatal or postnatal choline supplementation improves cognition in animal models and clinical studies 78 and the effect of choline supplementation is modified by polymorphisms in SLC44A1 (encoding choline transporter-like protein 1) 79 .

Timing and quantity of PAE during gestation

The effects of PAE vary according to the quantity, frequency, duration, pattern and timing of exposure 80 . Periconceptional alcohol exposure can adversely affect fetal development and predispose to disease in later life 81 , 82 . PAE at different stages of organogenesis has distinct developmental consequences. PAE during first-trimester organogenesis may cause brain, craniofacial, skeletal and internal organ dysmorphology 80 . In mice, PAE during gastrulation (equivalent to the third week post-fertilization in humans, when an embryo transforms from a bilaminar disc to a multilayered structure comprising the three primary germ layers: ectoderm, mesoderm and endoderm) reproduces the sentinel craniofacial abnormalities of FAS: thin upper lip, smooth philtrum and short palpebral fissures 9 (Fig.  4 ). By contrast, alcohol exposure during neurulation (starting in gestational week three in humans, resulting in the folding of the neural plate to form the neural tube) produces a facial phenotype that resembles DiGeorge syndrome, a chromosomal disorder (22q11.2 deletion) associated with facial anomalies, immune dysfunction, cardiac defects and neurodevelopmental abnormalities 83 .

a , b , The facial phenotype of fetal alcohol spectrum disorders can be reproduced in a preclinical model. Comparable to the facial features of the child with fetal alcohol syndrome (FAS) (part a ), the mouse fetus exposed prenatally to alcohol shows a thin upper lip with a smooth philtrum, short palpebral fissures and a small midface (part b ). c , The normal features in a control mouse fetus (not prenatally exposed to alcohol). Part a courtesy of Sterling Clarren. Parts b and c adapted with permission from ref. 9 , AAAS.

The brain is vulnerable to PAE throughout pregnancy 84 , 85 . PAE after 8 weeks of gestation affects neurogenesis, differentiation of neural precursor cells, neuronal migration, pathfinding, synaptogenesis and axon myelination 72 , 85 , 86 but does not cause sentinel craniofacial dysmorphology or major organ defects. Thus, PAE after major organogenesis may result in a FASD phenotype with neurodevelopmental disorder but without physical alterations, making diagnosis difficult 80 . Nutritional deficiency during pregnancy may potentiate the effects of PAE on developmental outcomes, and maternal alcohol intake may further reduce the availability of developmentally important nutrients 87 .

Effects of PAE on the embryo and fetus

Brain development.

As previously mentioned, PAE can affect brain development 88 , 89 . Retrospective examination of 149 brains from individuals with PAE who died between birth and adulthood identified gross abnormalities in brain development causing microcephaly (a smaller than normal head for age and sex using population-based normative data, often associated with a smaller than normal brain (micrencephaly)) in 20.8%. This study found isolated hydrocephalus in 4.0% of individuals with PAE, corpus callosum defects in 4.0%, prenatal ischaemic lesions in 3.4%, minor subarachnoid heterotopias (the presence of normal tissue at an abnormal location, such as an ectopic cluster of neurons within the white matter, often due to abnormal neuronal migration during early brain development) in 2.7%, holoprosencephaly (whereby the embryonic forebrain fails to develop into two discrete hemispheres, often affecting midline brain and craniofacial structures) in 0.7% and lissencephaly (smoothness of the brain surface due to impaired development of cerebral gyri) in 0.7% 88 . Hence, because macroscopic neuropathology is not present in most individuals with FASD, microscopic neuropathology likely underlies many of the associated cognitive and behavioural abnormalities of this disorder. Studies in non-human primates show that first-trimester-equivalent alcohol exposure reduces brainstem and cerebellar volume and disrupts various white matter tracts, including one connecting the putamen and primary sensory cortex 90 . Third-trimester-equivalent alcohol exposure reduced hippocampal neuronal numbers in infant and juvenile Vervet monkeys 86 .

Brain structure

Relatively few macroscopic brain lesions have been identified in clinical neuroimaging studies of children with FASD 80 , 91 . Blind evaluation of clinical MRI studies by neuroradiologists identified clinically significant abnormalities in 3% of individuals with PAE or FASD and in 1% of typically developing controls 91 . Four of 61 patients with FAS had heterotopias 92 . By contrast, quantitative research imaging studies in groups of children with PAE and FASD have revealed region-specific increases or decreases in grey matter thickness, microstructural white matter abnormalities, and neuronal and glial migration defects 69 , 93 , 94 . Volume reduction is disproportionate in the cerebrum, cerebellum, caudate, putamen, basal ganglia, thalamus and hippocampus after accounting for overall reductions in brain volume 94 . Age-dependent decreases in cortical gyrification are also observed 94 , 95 , 96 and the corpus callosum can be hypoplastic, posteriorly displaced or, in rare cases, absent 94 , 97 , 98 , 99 , 100 . Moreover, studies using diffusion tensor imaging reveal reduced integrity of large white matter tracts, including in the corpus callosum, cerebellar peduncles, cingulum and longitudinal fasciculi 101 . Hypoplasia of the corpus callosum in children with FASD is associated with impaired interhemispheric transfer of information 102 .

Imaging studies have also demonstrated the effect of PAE on postnatal grey matter development 99 , 103 . Typical brain development is associated with a large increase in cortical grey matter during early childhood followed by loss of cortical grey matter during late childhood and adolescence via synaptic pruning, a process that reflects cortical plasticity 70 . By contrast, children with FASD show region-specific loss of grey matter and decreased gyrification from early childhood through adolescence 70 , 99 , 102 . This change may partly explain contradictory findings of increased or decreased grey matter volume in various studies, which sampled different brain regions during distinct developmental periods or evaluated populations with different levels of PAE 69 . A relatively small sample size is another source of variation in results among brain imaging studies 104 .

One frequently observed effect of PAE is the disruption of brain plasticity 105 . Animal models and human studies have demonstrated enduring deficits in learning and memory following PAE, associated with abnormal plasticity in hippocampal, thalamic, cortical and cerebellar circuits 105 , 106 , 107 . These deficits are associated with changes in alpha oscillations on magnetoencephalography, fractional anisotropy (a measure of white matter integrity) on diffusion tensor imaging, and functional and resting-state MRI in children with PAE 68 , 94 , 108 , 109 .

Craniofacial development

Brain and craniofacial development are mechanistically linked; therefore, brain and craniofacial abnormalities frequently co-occur 98 , 110 . For example, abnormalities of midline brain structures, such as the corpus callosum, diencephalon and septum, are associated with midline craniofacial abnormalities 98 , 103 , 110 . Craniofacial development relies on the highly choreographed migration of cranial neural crest cells and is most sensitive to PAE during the third week of gestation. Alcohol induces apoptosis of neural crest cells through oxidative injury and disruption of Sonic hedgehog (Shh) signalling 111 . Shh regulates embryonic morphogenesis and organogenesis, including the organization of cells of the central nervous system (CNS), limbs and other body parts. In animal models, diverse antioxidants and inhibitors of apoptosis mitigate the effects of alcohol on neural crest cells 112 , 113 .

Mechanisms of alcohol teratogenesis

Multiple mechanisms of alcohol-induced teratogenesis have been elucidated 9 , 80 , 114 , 115 (Fig.  5 ). Alcohol has protean effects on brain and craniofacial development in part because it is a weak drug that requires millimolar concentrations to produce even mild euphoria 116 . For example, in the USA, legal intoxication is defined as 17.4 mM or 0.08 g/dl; at these high concentrations, alcohol interacts with diverse molecules and signalling pathways that regulate development 117 .

Alcohol (ethanol) metabolism to acetaldehyde and acetic acid generates reactive oxygen species (ROS) that induce programmed cell death. During gastrulation, acetaldehyde competes with retinaldehyde for metabolism by retinaldehyde dehydrogenase 2 (RALDH2), reducing the biosynthesis of retinoic acid, a critical morphogen. Acetyl-CoA, a metabolite of acetic acid, acetylates histones and, therefore, modifies gene expression. Alcohol also alters epigenetic gene regulation through changes in DNA methylation. Moreover, alcohol disrupts neuronal–glial interactions, induces inflammatory changes in the developing brain and causes microencephaly partly by depletion of neural stem cells. Other effects of alcohol include the disruption of Shh signalling (an effect that is potentiated by cannabinoids) and disrupted neuronal migration. The effects of alcohol on the placenta contribute to intrauterine growth retardation and adverse neurodevelopmental outcomes. Modification of gut microbiota by alcohol may influence brain development through the action of circulating microbial by-products. Collectively, these actions of alcohol result in altered neural circuits and decreased neuronal plasticity. ADH, alcohol dehydrogenase; ALDH2, aldehyde dehydrogenase.

Epigenetic changes and disrupted development

Epigenetic changes are chemical modifications (methylation or acetylation) to DNA and surrounding histones that influence gene expression and often occur in response to environmental exposures 118 , 119 . Normal development depends on numerous epigenetic changes in embryonic stem cells that facilitate their transition to fully differentiated and functional cell lineages such as neurons, muscle and fat cells 120 . Alcohol can disrupt development by inducing DNA methylation and histone acetylation in gene clusters and altering gene expression 121 . Epigenetic alterations resulting from PAE have been observed in animal models and humans, and these changes may be lifelong and inherited by future generations 118 , 122 , 123 , 124 . A pattern of DNA methylation in buccal epithelial cells was reasonably accurate (positive predictive value 90%; negative predictive value 78.6%) in discriminating children with FASD from typically developing controls or children with autism spectrum disorders 125 . Large replication studies in different populations are required before this approach might be considered for diagnostic purposes.

Brain injury

Exposure of astrocytes to alcohol and metabolism of alcohol by cytochrome P450 2E1 result in the production of damaging reactive oxygen species 84 , 126 . Alcohol is metabolized to acetaldehyde, a toxin that causes DNA damage, epigenetic gene regulation, mitochondrial and proteosome dysfunction, and altered cellular metabolism 127 , 128 , 129 . Metabolism of acetaldehyde to acetate and then to acetyl-CoA modifies gene expression in the brain via increased histone acetylation 121 (Fig.  5 ).

Disruption of morphogens and growth factors

Retinoic acid is a critical morphogen (a signalling molecule that alters cellular responses to modulate patterns of tissue development), and its deficiency causes craniofacial defects similar to those of FASD 127 , 130 . Retinol is oxidized to retinaldehyde, which is subsequently oxidized by retinaldehyde dehydrogenase 2 (RALDH2) to retinoic acid (Fig.  5 ). During gastrulation, RALDH2 is the predominant enzyme for acetaldehyde metabolism. Therefore, acetaldehyde and retinaldehyde compete for RALDH2, reducing the synthesis of retinoic acid and inducing a state of retinoic acid deficiency, thereby promoting craniofacial defects associated with PAE 127 , 130 .

Another critical morphogen, Shh, is a downstream target of retinoic acid 72 , 130 . Genetic abnormalities of the Shh pathway cause holoprosencephaly syndrome, which is associated with abnormal midline craniofacial and brain development similar to that of FASD 72 , 76 . Alcohol exposure in chick embryos decreases Shh expression and induces craniofacial dysmorphology and cranial neural crest cell death; viral vector-mediated expression of Shh rescues these effects 111 . Alcohol exposure during neurulation of the mouse rostroventral neural tube disrupts the function of cilia, which transduce Shh signals by modulating the expression of genes that regulate ciliogenesis, protein trafficking and stabilization of primary cilia 131 , 132 . The associated dysmorphology in zebrafish can be mitigated by activating downstream elements in the Shh signalling pathway 133 . Alcohol also decreases cellular stores of cholesterol, thereby reducing the covalent binding of cholesterol to Shh (which is necessary for Shh secretion and function) 72 , 134 . These findings suggest that alcohol causes a transient ciliopathy, secondarily disrupting Shh signalling within cilia and producing craniofacial and brain dysmorphology 131 .

Disruption of neuronal and glial migration

PAE is associated with macroscopic and microscopic evidence of impaired neuronal and glial migration, including heterotopias (collections of aberrantly migrated neurons). Heterotopias are associated with seizures, and seizures or abnormal EEG results are reported in up to 25% of individuals with FASD 135 . The L1 neural cell adhesion molecule regulates neuronal migration, axon fasciculation and pathfinding in the developing brain 136 . Mutations in L1CAM (which encodes L1) cause neurodevelopmental abnormalities such as those observed in FASD, including hydrocephalus, hypoplasia or agenesis of the corpus callosum, and dysplasia of the anterior cerebellar vermis 64 . Alcohol inhibits L1-mediated cell adhesion by binding to specific amino acids at a functionally important domain in the extracellular portion of L1 (ref. 137 ). The sensitivity of L1 to alcohol is regulated by phosphorylation, which promotes L1 association with the cytoskeleton 62 , 138 . Importantly, molecules that block alcohol inhibition of L1 adhesion prevent the teratogenic effects of alcohol in mouse embryos 62 , 139 .

GABAergic interneurons comprise the principal inhibitory network of the brain. Alcohol enhances GABA A receptor-mediated depolarization of migrating GABAergic interneurons through activation of L-type voltage-gated calcium channels, thereby accelerating tangential migration 63 . Dysfunction of GABAergic interneurons may impair inhibitory control of brain networks. In mice, PAE during corticogenesis also disrupts radial migration and pyramidal cell development in the somatosensory cortex, which could be linked to decreased tactile sensitivity during adolescence 140 .

Effects on neural stem cells

Effects of PAE on neural stem cells (NSCs) may contribute to reduced brain volume in individuals with FASD. Alcohol causes cell death in differentiated neural cells but not in NSCs; rather, PAE depletes NSCs by blocking their self-renewal and accelerating their transition into more mature neural progenitors and differentiation into astroglial lineages 141 . PAE also selectively upregulates gene expression for the calcium-activated potassium channel Kcnn2 in neural progenitor cells from the motor cortex, and Kcnn2 blockers in adult mice reduced motor learning deficits 142 . Alcohol may trigger the maturation of NSCs by increasing the release of selected microRNAs (miRNAs) from extracellular vesicles in NSCs and activating certain pseudogenes that encode non-protein-coding RNAs 141 , 143 . Proteomic analysis revealed selective enrichment of extracellular vesicles for RNA-binding and chaperone proteins in alcohol-exposed NSCs 144 .

Disruption of neuronal–glial interactions

Brain growth and development are dependent on neuronal–glial interactions 84 , 85 . PAE decreases the proliferation of radial glial cells partly by decreasing Notch1 and fibroblast growth factor 2 receptor signalling 145 . This altered signalling reduces the density and fasciculation of radial glial fibres, which serve as a scaffold for migrating neurons 85 , 145 . PAE perturbs the maturation of oligodendroglia in human fetal brains, increasing the expression of markers of early oligodendroglia progenitors (Oct4 and Nanog) and decreasing the expression of markers of mature oligodendroglia (Olig1, Olig2 and myelin basic protein) 146 . Alcohol also increases apoptosis to a greater extent in oligodendroglia than in neurons 146 , 147 . As myelination is mediated by oligodendroglia, apoptosis of these cells might partly account for the effects of PAE on white matter integrity. The associated upregulation of oligodendroglia-derived chemokines (CXCL1/GRO, IL-8, GCP2/CXCL6, ENA78 and MCP1) could also affect neuronal survival 146 . Astroglial apoptosis is mediated by acetaldehyde toxicity, reactive oxygen species, reductions in the antioxidant glutathione and inflammatory signalling 85 .

Neuroinflammation

PAE activates an inflammatory response in the developing nervous system. Alcohol stimulates the production of reactive oxygen species in microglia and astrocytes, leading to neuronal apoptosis 84 . Moreover, alcohol stimulates the production of pro-inflammatory cytokines (such as IL-1β and TNF) and chemokines (such as CCL2 and CXCL1) through enduring epigenetic modifications that sustain a chronic neuroinflammatory response 119 (Fig.  5 ). Unique networks of pro-inflammatory cytokines in serum from women in the second trimester of pregnancy are markers of PAE and adverse neurodevelopmental outcomes 148 . The persistence of pro-inflammatory cytokines in childhood could predispose to autoimmune and inflammatory conditions later in life 149 . Similarly, PAE may hypersensitize microglia to increased inflammatory signalling, leading to an enduring, heightened neuroinflammatory response 84 .

Gut microbiota alterations

PAE may cause enduring changes in the gut microbiota 150 , and there is increasing recognition of the interplay between gut microbes and nervous system development and function. In a mouse model of PAE, gut microbial metabolites were detected in maternal plasma, fetal liver and fetal brain 151 . Further research is required to determine how effects of PAE on the gut microbiota influence development and later health.

Placental effects

Not all developmental effects of PAE result from the direct actions of alcohol on the developing nervous system. A retrospective autopsy study reported placental abnormalities in 68% of individuals with PAE or FASD 88 . PAE in humans decreases placental weight, epigenetic marks, vasculature and metabolism 81 . PAE during the first 60 of 168 days of gestation in rhesus macaques caused diminished placental perfusion and ischaemic placental injury from middle to late gestation 152 . RNA sequencing analysis revealed activation of inflammatory and extracellular matrix responses. Rats with PAE demonstrate reduced nitric oxide-mediated uterine artery relaxation, potentially contributing to dysregulation of uterine blood flow and intrauterine growth retardation 153 . miRNA act by silencing RNA and modifying post-transcriptional regulation of gene expression. A cluster of 11 extracellular miRNA from serum of women in the second trimester of pregnancy was a marker of PAE and predicted adverse neurodevelopmental outcomes in Ukrainian and South African populations 154 , 155 . Injection of the same 11 miRNAs into pregnant mice decreased placental and fetal growth, suggesting that they mediate the adverse outcomes of PAE 156 .

Synergistic effects of alcohol and other substances

PAE is often associated with prenatal exposure to other drugs. Among 174 individuals with PAE, almost all had prenatal nicotine exposure 88 . Nicotine and alcohol synergistically decrease birthweight and increase the risk of sudden infant death syndrome 157 . The legalization of cannabis has led to increases in the combined use of cannabinoids and alcohol during pregnancy 158 . Alcohol and cannabinoids synergistically increase the frequency of ocular defects in mice by disrupting separate elements in the Shh signalling pathway 132 . PAE and opioids each affect neurodevelopment, raising the possibility of additive or synergistic effects 159 . Alcohol also disrupts the developing blood–brain barrier, exposing the developing CNS to drugs and toxins that are normally excluded 160 .

Diagnosis, screening and prevention

Diagnosis of fasd, principles of diagnosis.

Diagnosis of FASD requires assessment of PAE, neurodevelopmental function and physical features, including facial features (Fig.  6 ). Timely, accurate diagnosis of FASD is crucial to enable early intervention and improve outcomes 161 , but there is no diagnostic test, biomarker or specific neurodevelopmental phenotype for FASD. Ideally, assessment and diagnosis should be conducted by a multidisciplinary team (MDT) comprising paediatricians, neuropsychologists, speech pathologists, occupational therapists, physiotherapists and social workers, with access to psychiatrists and geneticists/dysmorphologists. However, this approach is expensive, time consuming and unavailable to many children worldwide. Often, children present first to family physicians, paediatricians and psychologists who lack sufficient expertise to confidently diagnose FASD. Thus, education and training are urgently needed to increase the capacity for recognition of FASD outside specialist FASD assessment services 51 , 162 and to address its underdiagnosis and misdiagnosis 163 , 164 .

Fetal alcohol syndrome has three characteristic (sentinel) facial features: thin upper lip (with absent cupid bow), smooth philtrum (with absence of the normal midline vertical groove and lateral ridges extending from the base of the nose to the vermilion border of the upper lip) and short palpebral fissures (the space between the medial and lateral canthus of the open eye). Image created by Ria Chockalingam using an image from Generated Photos and modified with Adobe Photoshop.

Approaches to the diagnosis of FASD

The most commonly used diagnostic systems for FASD are the Collaboration on FASD Prevalence (CoFASP) Clinical Diagnostic Guidelines 10 , the University of Washington 4-Digit Diagnostic Code 165 , 166 and the Canadian Guidelines 167 (Table  1 ). The Canadian Guidelines have been adapted for use in Australia 168 and the UK 169 and are also used in New Zealand 170 . Guidelines have also been recommended by the US Centers for Disease Control and Prevention 171 , the State Agency for Prevention of Alcohol-Related Problems (PARPA) in Poland 172 , and The German Federal Ministry of Health 173 .

All diagnostic systems recommend evaluating PAE, facial and non-facial dysmorphology, and CNS structure and function using an MDT approach. Although all these systems recommend assessing otherwise unexplained prenatal and postnatal growth restriction, the Canadian and derivative guidelines exclude growth as a diagnostic criterion. The diagnostic systems differ in their definitions of PAE, thresholds for individual diagnostic elements, required combination of elements to confirm an FASD diagnosis and diagnostic classifications.

Diagnosis of FASD can be challenging. Confirmation of PAE by biological mothers during a diagnostic assessment of children with suspected FASD is often difficult: the topic is sensitive and recall bias is possible 174 . Additionally, many children live in foster or adoptive care, and obstetric records often lack details about PAE 80 . In these situations, clinicians should seek firsthand witness reports and child protection, justice and medical records. A standardized tool 175 , 176 , 177 should be used, when possible, to record the pattern of alcohol intake, either at an interview with the biological mother or using witness reports or records. A challenge in evaluating facial dysmorphology is the unavailability of suitable lip-philtrum guides and standards for palpebral fissure length (PFL) for many racial and ethnic groups, including Indigenous Australians 178 . PFL is the distance between the endocanthion and exocanthion of the eye (the inner (nasal) and outer points, respectively, where the upper and lower eyelids meet) and may be shortened following PAE. Because some domains of cognitive function cannot be evaluated in infants and young children, confirmation of brain dysfunction in this population may be based on global developmental delay, established using a validated tool 10 , 167 . FASD are diagnosed with increasing confidence in children aged 6 years and older, who are more cooperative in physical examinations, and in whom facial dysmorphology and neurocognitive function can be assessed with greater reliability using digital photography and standardized psychometric tests.

In the absence of a ‘gold standard’ for diagnosis of FASD, no diagnostic system may be considered superior. Each system has advantages and disadvantages, including its use in clinical and community settings and the sensitivity and specificity of diagnostic criteria. Diagnosis using these systems shows incomplete agreement 179 , 180 , 181 , confirming the need for a unified approach internationally (Table  1 and Supplementary Boxes  1 and 2 ).

A clinical diagnosis of FASD requires recognition of neurodevelopmental disabilities and a reproducible pattern of minor malformations (dysmorphic features), none of which are pathognomonic, and many of which overlap with other teratogenic or genetic disorders (phenocopies). Thus, a diagnosis of FASD is a diagnosis of exclusion that is made after considering and excluding other causes for the phenotype 10 , 167 . For example, prenatal exposure to teratogens, such as toluene, anticonvulsants or phenylalanine (when the mother has phenylketonuria), can result in dysmorphic features also observed in FASD 10 , 182 , 183 . Additionally, postnatal exposures (such as adverse childhood experiences (ACE)) can contribute to neurodevelopmental impairment, comorbidities (Box  1 ) and adverse ‘secondary’ outcomes (Box  2 ). Genetic conditions with dysmorphic features similar to FASD include Aarskog syndrome, blepharophimosis, ptosis, epicanthus inversus syndrome, CHARGE syndrome, de Lange syndrome, 22q11.2 deletion, Dubowitz syndrome, inverted duplication 15q, Noonan syndrome, Smith–Lemli–Opitz syndrome and Williams syndrome. Patients with intellectual disability without a recognizable pattern of anomalies may also share some dysmorphic features with FASD 10 , 182 . Thus, before establishing a diagnosis of FASD, it is important to ask whether the family history suggests a genetic disorder, whether other teratogenic exposures occurred during pregnancy and whether the patient has features not previously described in FASD. If so, referral to a clinical geneticist/dysmorphologist for evaluation is recommended. When indicated, genetic testing should include chromosome microarray analysis 184 , 185 and exclusion of Fragile X syndrome 186 as a minimum, and whole-exome sequencing should be performed if other genetic pathologies due to point mutations are suspected 10 , 187 . When PAE is confirmed and/or the physical and neurodevelopmental examinations are supportive, the diagnosis can be made by a paediatrician or other health professional familiar with FASD.

Neurobehavioural impairment accounts for the major functional disabilities associated with FASD. Although the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) 188 criteria for intellectual disability are not always met in patients with FASD, cognitive impairment is often identified and can affect multiple domains, including executive function, memory, mathematical and other academic skills, attention and visuospatial processing 80 , 189 . Poor social skills, inattention and impaired impulse control can adversely affect school and work performance and independent living.

Although no specific constellation of neurobehavioural deficits have been identified in FASD, some groups have attempted to characterize clusters of impairment associated with PAE 190 , 191 . One set of criteria, Neurodevelopmental Disorder associated with PAE, has been proposed as a condition for further study in the DSM-5 (ref. 188 ); it requires deficits in cognition, behaviour and social adaptation. The ICD-11, published in 2022, lists several ‘toxic or drug-related embryofetopathies’ (code LD2F.0) including ‘fetal alcohol syndrome’ (code LD2F.00) 192 . The confounding or potentiating influence of ACE presents a major challenge in identifying a specific neurobehavioural profile 193 .

Box 1 Common comorbidities in patients with fetal alcohol spectrum disorders

More than 400 comorbid conditions have been identified in individuals with fetal alcohol spectrum disorders, which span 18 of the 22 chapters of the ICD-10 (ref. 13 ), the most prevalent coming from the groups of:

Congenital malformations, deformations and chromosomal abnormalities (Chapter XVII) and Mental and behavioural disorders (Chapter V). Shown below are selected comorbid conditions (with codes) from Chapters V and XVII and diseases of the eye (Chapter VII) and ear (Chapter VIII). For more detailed information, see ref. 13 .

Chapter XVII. Congenital malformations, deformations and chromosomal abnormalities

Q02 Microcephaly

Q03 Congenital hydrocephalus

Q04.0 Congenital malformations of corpus callosum

Q04.3 Other reduction deformities of brain

Q04.6 Congenital cerebral cysts

Q04.8 Other specified congenital malformations of brain

Q04.9 Congenital malformation of brain, unspecified

Q05 Spina bifida

Q06.8 Other specified congenital malformations of spinal cord

Chapter V. Mental and behavioural disorders

F10.2 Mental and behavioural disorders due to use of alcohol, dependence syndrome

F19.2 Mental and behavioural disorders due to the use of multiple drugs and use of other psychoactive substances, dependence syndrome

F41.1/F33.8 Anxiety/depression

F80.1 Expressive language disorder

F80.2 Receptive language disorder

F81.9 Developmental disorder of scholastic skills, unspecified

F89 Unspecified disorder of psychological development

F90.0 Disturbance of activity and attention

F91 Conduct disorder

G40 Epilepsy/seizure disorder

Chapter VII. Diseases of the eye

H47.0 Disorders of optic nerve

H52.6 Refractive errors

H54 Visual impairment

Q10.0 Congenital ptosis

Q10.3 Other congenital malformations of eyelid

Q10.6 Other congenital malformations of lacrimal apparatus

Q11.2 Microphthalmos

Q12.0 Congenital cataract

Chapter VIII. Diseases of the ear

H65.0 Acute serous otitis media

H65.2 Chronic serous otitis media

H90.8 Mixed conductive and sensorineural hearing loss, unspecified

Box 2 Challenges for adolescents and adults with fetal alcohol spectrum disorders

Involvement in child welfare services (75%) 309

Disrupted school experiences due to learning and/or behavioural problems (61%) 267

Interaction with the justice system (30% 309 to 60% 267 )

Confinement (detention, prison, or psychiatric or alcohol/drug inpatient setting; 50%) 267

Substance use disorder: alcohol and other drugs (50%) 309

Inappropriate sexual behaviour (49%) 236 , 310

Increased risk of metabolic abnormalities (includes type 2 diabetes, low high-density lipoprotein, high triglycerides, and female-specific overweight and obesity) 311

Difficulties with independent living and trouble gaining and retaining employment (80%) 267

Mean life expectancy (34 years; 95% CI 31–37 years) is considerably lower than in the general population 275 ; leading causes of death are ‘external causes’ (44%), including suicide (15%), accidents (14%), poisoning by illegal drugs or alcohol (7%) and other external causes (7%)

Screening for alcohol use in pregnancy

Early detection of alcohol use during pregnancy can lead to decreased consumption, abstinence or decreased risk of alcohol use in subsequent pregnancies 22 , 194 . The early identification of alcohol use facilitates education about the harms of PAE, delivery of timely, office-based brief interventions, and referral to substance use treatment services if required. Reducing the high prevalence of FASD requires large-scale, population-based screening programmes to ensure that every pregnant woman is asked about alcohol use, with special attention to populations at high risk 22 , 195 , 196 (Table  2 ).

Screening for alcohol use during pregnancy is underused globally 197 , 198 . Barriers to screening include lack of public-health guidelines 199 or screening mandates, insufficient clinician training 200 , 201 , 202 , 203 , competing demands on clinician time, the cost of completing validated alcohol use screening questionnaires 204 , 205 , 206 , and the unavailability of clinically reliable biological markers for PAE. Even a single, clinician-directed question about alcohol use may reduce PAE 207 , 208 ; however, successful screening requires that practitioners understand the importance of preventing PAE and providing non-judgmental screening and brief interventions 196 . Preliminary evidence suggests that web-based or app-based mobile health interventions may mitigate patient stigma and reluctance to report alcohol use and might circumvent barriers related to clinician time constraints, training and motivation 209 . Similarly, mobile health approaches may reduce alcohol and substance use in the preconception, prenatal, and postnatal periods 209 and improve access to interventions for families in rural and remote settings. Empathic, compassionate support of abstinence during pregnancy may improve opportunities for treatment of substance use disorders 22 , 47 , 196 , 202 . Screening for alcohol and substance use should be repeated throughout pregnancy and equally across populations to avoid stigmatizing marginalized populations with selective screening 22 , 196 , 210 , 211 . People who screen positive should be directed to a well-developed management pathway for clinical care.

Prevention (Fig.  7 ) and treatment of alcohol and substance use disorders in pregnancy are central to the 2015 United Nations Sustainable Development Goals (SDG 3.5) 212 . The WHO recommends universal screening and intervention for alcohol use in pregnancy as a primary prevention strategy for FASD 22 , 213 . Prevention programmes should be evidence based and evaluated following implementation. A wide range of approaches has been deployed, including public awareness strategies, preconception interventions (such as preconception clinics and school-based FASD education), holistic support of women with substance use disorders, and postpartum support for new mothers and babies 214 , 215 . These approaches show promise in increasing awareness of FASD and decreasing alcohol use during pregnancy 216 ; however, the quality of supporting evidence is highly variable. Any primary prevention strategy must be underpinned by evidence-based policy and legislation intended to minimize harms from alcohol, including increased alcohol pricing and taxation, restrictions on advertising and promotion of alcohol, and restricted access to alcohol such as by limiting opening hours and the density of liquor outlets 217 . Public-health authorities agree that the alcohol industry should have no involvement in the development of public-health policies owing to their inherent conflict of interest 218 , 219 . The framework in Fig.  7 illustrates one approach that could be linked to national policy to address diverse aspects of population-based prevention of FASD.

A hierarchy of strategies can be used to prevent fetal alcohol spectrum disorder (FASD), ranging from awareness campaigns for the whole population to health, educational and social support for women and children. The strategies are placed in the context of cultural, political and environmental factors that influence access to, use of and attitudes towards alcohol use in pregnant women. SES, socioeconomic status.

Level 1: raising public awareness through campaigns and other broad strategies

Public-health initiatives that promote and support women’s health, in general, may raise awareness about PAE/FASD. More specific measures include warning signs on alcohol products, pamphlets and public education programmes that encourage healthy, alcohol-free pregnancies 220 , 221 . However, evidence in support of these campaigns is preliminary 216 . Moreover, campaigns that use triggering imagery or blaming/shaming language (such as ‘FASD is 100% preventable’) can stigmatize and isolate pregnant women who use alcohol, particularly when paired with judgmental interventions 196 . Reframing alcohol use in pregnancy as a shared responsibility of women, partners, prenatal health-care providers, treatment programmes for substance use disorder, families, community and government may be helpful 222 .

Level 2: brief counselling with women and girls of reproductive age

Discussing alcohol use and its associated risks with women of childbearing age during preconception conversations about reproductive health is effective in preventing PAE and FASD 215 , primarily by improving contraception use 207 . Screening, Brief Intervention and Referral to Treatment (S-BIRT) for non-pregnant adolescent and adult women reduces the risk of PAE 207 , particularly following multi-session interventions 223 . Preliminary studies suggest that such interventions are also beneficial for Indigenous communities 224 , 225 .

Level 3: specialized prenatal support

Treatment for alcohol use during pregnancy may prevent ongoing PAE and decrease adverse infant outcomes 226 . The combination of case management by a social worker or nurse (including problem identification and preparation, implementation and monitoring of a health-care plan) and motivational interviewing (an evidence-based approach to facilitating behaviour change) reduce drinking by pregnant women at high risk 194 . Moreover, specialized, intensive home-visiting interventions for pregnant women at high risk improve maternal and child outcomes and are cost-effective in preventing new cases of FASD 227 , 228 . Improving maternal nutrition and reducing smoking and family violence may also improve child outcomes in current and future pregnancies 227 , 229 , 230 .

Level 4: specialized postnatal support

In the postpartum period, home-visiting of women at high risk by health professionals or lay supporters improves child outcomes and reduces the risk of PAE in future pregnancies 227 , 231 , 232 . Application of a FASD prevention framework requires consideration of local policy and practices. Best practice programmes support the needs of both the mother and child, recognizing the connections between women’s alcohol use, parenting, family influences and child development. Central to the effective implementation of prevention strategies is the establishment of strong cross-cultural and community partnerships and the embrace of cultural knowledge systems and leadership 233 . Mitigating stigma is vital while addressing the structural and systemic factors that promote prenatal alcohol consumption 35 .

Principles of management of FASD

The complex pathophysiology of FASD (Boxes  1 and  2 ) emphasizes the need for thorough, individualized assessment and treatment. Treatment plans should be culturally appropriate, consider the family and community context, and be developed in partnership with families and individuals with lived experience of FASD 234 , 235 .

Therapeutic approaches must be tailored to individual strengths and needs. For example, an individual who has experienced trauma but has normal intelligence and social and emotional skills requires a trauma-informed, emotion-focused approach. By contrast, an individual with cognitive deficits and poor social and emotional skills may require a more directed, psycho-educational approach or environmental modifications to support and prevent secondary outcomes of FASD such as poor academic performance or inability to obtain/maintain employment 236 .

Management involves multiple service providers and changing interventions across the lifespan. Treatment comprises interventions to anticipate the delivery of a newborn with PAE, prevention of exposure to ACE, home-visiting by a public-health nurse, referral to infant developmental services, vision and hearing screening, preschool speech and language therapy, school-based support for learning disorders, occupational and physical therapy, behavioural and psychological interventions, pharmacotherapy, vocational support, and support for independent living in adolescence and adulthood. Specialized medical or surgical interventions may be required for congenital anomalies and accompanying comorbidities. There remains limited evidence from high-quality trials to support specific interventions for FASD 237 , 238 .

Behaviour support

Several large-scale randomized controlled trials (RCTs) support specific developmental and psychological interventions for FASD in children but few high-quality studies have been conducted in adolescents and adults 237 .

Positive behaviour support 239 is supported by positive results from RCTs and underpins three interventions for FASD: GoFAR 240 , the Math Interactive Learning Experience (MILE) 241 and the Families Moving Forward programme 242 . Positive behaviour support strengthens skills that enhance success and satisfaction in social, academic, work and community settings while proactively preventing problem behaviours; maintaining family involvement is an important element 16 . Where available, these specialized programmes oblige therapists to prioritize treatment for individuals most likely to benefit. The GoFAR intervention (FAR is an acronym for Focus and plan, Act, and Reflect) promotes self-regulation and adaptive function using direct instruction, practice and feedback, and strategies for emotional and behavioural self-regulation 243 . Interventions such as GoFAR, which involve the child and parents in the context of real-life adaptive behavioural problems, improve daily living skills and attention 243 . The MILE intervention provides individualized mathematical instruction through interactive learning and environmental modifications and improves math knowledge and parent report of child behaviour problems 241 , 244 , 245 . Families Moving Forward helps parents reframe their child’s behaviour within a neurodevelopmental paradigm. Adaptation of this approach to an app-based platform may reduce barriers to care 242 .

Self-regulation and executive function

Most children with FASD have significant problems with executive function and self-regulation 189 . The ALERT programme, a 12-week manualized approach using sensory integration and cognitive behavioural strategies, aims to help children regulate their behaviour and address sensory challenges 246 in a home environment 247 , 248 but is less effective when delivered in schools 249 . ALERT programme training is available online but requires adaptation to the family and community context 249 .

Social skills

Interventions to improve social connections in children with FASD include the Children’s Friendship Training (CFT) 250 and the Families on Track programme 251 . CFT involves 12 weeks of social and friendship skill training for children with FASD and their parents; it improves social skills and decreases problem behaviours in children with FASD 250 . Similarly, the Families on Track programme increases emotional regulation and self-esteem and decreases anxiety and disruptive behaviour 251 . However, interventions such as CFT and Families on Track are not widely available, and barriers to their use include the need to adapt to cultural context 252 . International partnerships and sharing of expertise may increase accessibility to these interventions 252 .

Pharmacological interventions

Pharmacological interventions for FASD are widely used and include medications, such as cognitive enhancers, to treat core impairments and medications to treat comorbidities, including ADHD, anxiety, and arousal or sleep disorders 253 . Large RCTs evaluating their effectiveness in FASD are urgently needed.

Children with FASD and ADHD have a different pattern of neurocognitive and behavioural abnormalities than children with ADHD alone 254 , suggesting the need for a tailored therapeutic approach. Expert consensus approaches for the management of ADHD in FASD have been developed. Recommendations in the UK suggest the use of a dexamphetamine-based medication (rather than a methylphenidate-based medicine) for first-line treatment of ADHD in children and adults with FASD; however, research is needed to understand the basis of treatment responses 255 . Guanfacine XL or similar medications can be used in individuals with comorbidities such as autism spectrum disorders 255 . Algorithms have also been developed in Canada for the use of psychotropic medications in FASD 256 . Although based on clinical consensus, these strategies form the basis for future research 256 .

Preclinical trials suggest that choline supplements improve cognitive deficits following PAE but clinical data are limited 257 . A small, placebo-controlled RCT demonstrated that children who received choline supplementation had higher non-verbal intelligence and visual-spatial skills, better working memory and verbal memory, and fewer behavioural symptoms of ADHD at 4-year follow-up than children who received placebo 258 . Despite these positive results, choline supplementation is not routinely recommended for children with FASD due to a lack of strong evidence for its effectiveness.

The role of exposure to adversity

A relationship between PAE and ACE is well established, and both may influence the life course in FASD 193 . Comprehensive neuropsychological assessment and MRI show that PAE accounts for the largest proportion of the variance in regional brain size and brain function in children with both exposures 259 . Furthermore, PAE imparts more risk for adverse outcomes than ACE in individuals with PAE in adoptive care 260 . However, adversity does affect the developmental trajectory and ACE are associated with maladaptive problems in children with FASD 261 . For example, school-age children with FASD and ACE are particularly vulnerable to language and social communication deficits 262 , which are hypothesized to result from the additive effect of prenatal and postnatal environmental exposures. This emphasizes the need for an individualized approach to treatment for individuals with life trauma and FASD.

Attempts have been made to understand the individual and combined effects of PAE and postnatal events on individual behaviours in FASD 263 . One model of complex trauma (Supplementary Fig.  1 ) displays neurodevelopmental variation as a complex interplay between prenatal and postnatal events and improves understanding of their interactions and association with outcomes. Child maltreatment viewed through a neurodevelopmental lens highlights the benefit of a sequential model of therapeutics rather than a focus on specific therapeutic techniques 264 .

Supplementary Fig.  1 highlights how vulnerabilities may present, whereas Supplementary Fig.  2 identifies methods to manage the same vulnerabilities based on understanding the individual and using anticipatory interventions to support development. Box  3 contains some useful resources on FASD for professionals and parents.

Box 3 Resources on alcohol use in pregnancy and fetal alcohol spectrum disorders

Australian guidelines to reduce health risks from drinking alcohol

Canada No. 245 — Alcohol Use and Pregnancy Consensus Clinical Guidelines 312

Centers for Disease Control and Prevention

Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD)

Fetal Alcohol Spectrum Disorders (FASD) — American Academy of Pediatrics

FASD Hub Australia

FASD United

FASD — Care Action Network

Learning with FASD

National Organization for FASD Australia (NOFASD)

National Institute for Health and Care Excellence UK. Quality Standard QS204. FASD

National Institute on Alcohol Abuse and Alcoholism. Fetal Alcohol Exposure

Pan American Health Organization. Assessment of Fetal Alcohol Spectrum Disorders (2020) 313

The European FASD Alliance

WHO. Guidelines for identification and management of substance use and substance use disorders in pregnancy (2014) 22

Quality of life

Few published studies address QOL in individuals with FASD. One systematic review and meta-analysis identified more than 400 comorbid conditions among individuals with FASD, spanning 18 of 22 chapters of the ICD-10 (ref. 13 ). The most prevalent conditions were within the chapters of “Congenital malformations, deformations, and chromosomal abnormalities” (Chapters Q00–Q99; 43%) and “Mental and behavioural disorders” (Chapters F00–F99; 18%). Comorbid conditions with the highest pooled prevalence (50–91%) included abnormal functional studies of the peripheral nervous system and special senses, conduct disorder, receptive and expressive language disorders, and chronic serous otitis media 13 . Other studies report a high prevalence of vision and hearing problems among people with FASD 265 , 266 . All of these comorbid conditions affect the function and QOL of individuals with FASD and their families (Box  1 ).

Neurodevelopmental impairments may lead to lifelong ‘secondary’ disabilities, including academic failure, substance abuse, mental health problems, contact with law enforcement and inability to live independently or obtain/maintain employment 267 (Box  2 ). These conditions adversely affect QOL and require health, remedial education and correctional, mental health, social, child protection, developmental, vocational and disability services across the lifespan 17 , 268 , 269 . Lack of societal understanding of FASD is a barrier to addressing these secondary disabilities 16 , 270 .

A shift from a deficit-based to a strength-based management approach emphasizes the need to harness the abilities of individuals with FASD to improve their QOL and well-being. A review of 19 studies exploring the lived experience of people with FASD highlighted their strengths, including self-awareness, receptiveness to support, capacity for human connection, perseverance and hope for the future 271 . The lack of accessible, FASD-informed services perpetuates a deficit-based model.

Longitudinal cohort studies of FASD consistently show that adverse outcomes are more likely where support services are lacking. These studies are limited by selection bias and are based on cohorts with severe deficits rather than population-based cohorts receiving adequate support 267 , 270 . Nevertheless, they suggest the potential to modify developmental trajectories by addressing postnatal environmental exposures and opportunities. To address QOL, future studies should better articulate outcomes of interest for individuals and families living with FASD 272 .

FASD is associated with an increased risk of premature death of affected individuals, their siblings and mothers 273 , 274 . One study reported a mean age at death of 34 years for individuals with FASD 275 . Individuals with FASD have nearly fivefold higher mortality risk than people of the same age and year of death, and nearly half of all deaths occur in young adults 276 . In childhood, the leading causes of death in FASD are congenital malformations of the CNS, heart or kidney, sepsis, cancer, and sudden infant death syndrome, and more than half of deaths (54%) occur in the first year of life 277 . In the USA, >29% of adolescent males with FASD reported a serious suicide attempt, which is >19-fold higher than the national average 236 , 278 .

Among children and adolescents with FASD, the mortality rate of siblings with and without FASD is 114 per 1,000, which is approximately sixfold higher than among age-matched controls 273 . Furthermore, mothers of children with FASD have a 44.8-fold increased mortality risk compared with mothers of children without FASD 274 .

Caregiver burden

The complexity of parenting a child with FASD increases across adolescence and young adulthood. Caregivers of children with FASD experience increased burden, levels of stress and feelings of isolation 279 , 280 . The lifelong challenges and unmet needs of caregivers negatively affect family functioning and QOL 281 .

Early recognition of FASD and early emphasis on the prevention of secondary disabilities may decrease demands on families. Moreover, a diagnosis of FASD may indicate the need for specific interventions and parenting supports such as respite care, peer-support groups, treatment for parental alcohol misuse and education of other professionals who care for people with FASD.

FASD are the most common preventable cause of neurodevelopmental impairment and congenital anomalies 164 . These disorders are the legacy of readily available alcohol and societal tolerance to its widespread use, including during pregnancy. FASD affect all strata of society, with enormous personal, social and economic effects across the lifespan.

Diagnostic challenges

The greatest global challenges in the clinical management of FASD are the paucity of resources for diagnosis and treatment and the large number of affected individuals 163 . A substantial increase in resources is required, both for centres of expertise with MDTs and to build diagnostic capacity among non-specialist health services. However, this alone will not bridge the gap in services for children and adults, and a paradigm shift is needed. This might include recognition of the important role of primary care providers and use of new technologies such as app-based screening, diagnostic and treatment tools. Telehealth services will reduce the need for face-to-face care 282 and tele-education could build clinician awareness and skills, especially in rural and remote areas 283 . However, in many low-income and middle-income countries, this technology is not widely available.

Without a definitive diagnostic test, a clinical diagnosis of FASD must be made. Diagnosis is facilitated by identification of PAE in association with neurodevelopmental impairment, with or without specific craniofacial dysmorphology, and exclusion of alternative diagnoses. Many clinicians fail to document alcohol use in pregnancy or PAE in children, highlighting the need for enhanced training, standardized tools to document PAE and, especially, routine screening for alcohol use before and during pregnancy. Biomarkers for PAE are urgently needed because many children with FASD live in out-of-home care and reliable PAE histories are frequently unavailable. Although biomarkers for PAE (such as fatty acid ethyl esters, ethyl glucuronide and phosphatidylethanol) are identifiable in maternal hair, blood and meconium, their clinical use is limited, and testing may be costly or unavailable 284 . Identification of miRNAs from women in the second trimester and epigenetic signatures in placental and infant tissue hold promise as biomarkers for PAE and hence for risk of abnormal neurodevelopment 154 , 155 , 156 , 187 ; however, further research is required before their use becomes routine in clinical practice 81 , 125 .

Accessible e-health technologies to facilitate the diagnosis of FASD are under development. For example, 3D facial imaging may facilitate diagnosis by automatically quantifying the three sentinel facial features of FASD and identifying more subtle facial dysmorphology that reflects PAE after gastrulation 67 , 285 . The use and availability of 3D imaging will increase as more sophisticated and cheaper 3D cameras evolve and image capture on smartphones combined with cloud-based image analysis become available. Similarly, web-based tools are in development for identification of neurocognitive impairments associated with FASD. BRAIN-online enables screening for cognitive and behavioural features of PAE or FASD 286 . Decision trees simplify neurocognitive testing by including only tests that contribute most to the diagnosis of FASD 287 . Porting this software to tablets or online websites will broaden access to relevant neurocognitive testing. For example, the FASD-Tree 288 provides a dichotomous indication and a risk score for FASD, considering both neurobehaviour and dysmorphology, and successfully discriminates between children with and without PAE with a high predictive value 289 .

The lack of internationally agreed diagnostic criteria for FASD is challenging and hinders the comparison of prevalence and clinical outcomes between studies. In response, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has convened an international consensus committee to analyse data derived from existing diagnostic systems and develop a consensus research classification for FASD 290 . The field would also benefit from improved, population-based, normative data for growth and PFL as well as internationally accepted definitions of a standard drink and of the ‘low, moderate and high’ levels of risk of PAE. Additionally, the range and aetiology of adult outcomes require clarification to inform assessment and prognosis in FASD 291 . A research initiative for elderly people with FASD is urgently needed as there is virtually no information about the diagnostic criteria or neuropsychological outcomes of FASD in this age group.

Understanding pathophysiology

Functional MRI can be used to elucidate brain growth trajectories and disruptions to neuronal pathways after PAE (including low-level PAE), thereby assisting our understanding of CNS dysfunction in FASD 68 . Advances in our understanding of the genetics of rare neurodevelopmental disorders may identify genes that govern susceptibility or resilience to PAE and provide additional insights into the pathogenesis of FASD 187 . Advances in neuroscience research, including novel preclinical studies, may help elucidate the relationship between PAE-induced brain dysfunction and the FASD phenotype and inform therapeutics and prevention 292 .

Prevention and management

Preclinical studies suggest that epigenetic changes induced by PAE underpin metabolic, immunological, renal and cardiac disorders in FASD 13 , but further studies in patients are required to confirm this. The paucity of high-quality evidence to inform the treatment of neurodevelopmental impairments and comorbidities associated with FASD across the lifespan requires urgent redress 237 , 238 . Behavioural, family-based, school-based and pharmacological treatments require evaluation through multicentre RCTs. Moreover, little attention has been paid to preventing and managing the secondary outcomes of FASD in adults: substance use, mental health disorders, contact with the justice system, and issues with sleep, sexuality and violence. These must be prioritized to improve the QOL of individuals and reduce the societal and economic effects of FASD.

The COVID-19 pandemic demonstrated the use of telemedicine for virtual neuropsychiatric assessment and delivery of therapy 282 . Telemedicine approaches may also partly fill the need to increase health professionals’ capacity for FASD-informed care and to help education, child protection and justice professionals to recognize and understand FASD 283 .

Improving the primary prevention of alcohol use in pregnancy and hence FASD is also warranted 237 , 238 . Alcohol consumption and binge drinking are increasing among women of childbearing age in many countries, particularly in the most populous countries such as China and India 26 . This rise reflects increased availability of alcohol, societal acceptance of drinking among women, shifting gender roles, increasing income of women, and targeted marketing of alcohol to women and predicts a future global increase in FASD prevalence. Alcohol use in adolescence predicts subsequent use during pregnancy, and family physicians can play a role in identifying young women at risk 293 .

Another concern is that a large proportion of pregnancies globally are unplanned 29 , which can result in unintentional exposure of the embryo to PAE in the earliest stages of pregnancy. Accordingly, effective and cost-effective population-based preventive strategies should be adapted such as those promoted by the WHO in their Global Action Plan for the Prevention and Control of NCDs 294 and their Global Strategy to Reduce the Harmful Use of Alcohol 295 .

Although the role of national guidelines, community education and family support is important, these efforts must be underpinned by strategies proven to drive behavioural change and reduce alcohol harm, including legislated restrictions on the advertising and promotion of alcohol, appropriate taxation and pricing, and limited access to alcohol through restricted liquor outlets and opening hours and community-initiated alcohol restrictions 26 , 295 .

In pregnant women with ongoing alcohol consumption, food supplementation with folic acid, selenium, DHA, L-glutamine, boric acid or choline may reduce the effects of PAE 87 , 296 . However, research is required to define optimal levels of nutritional supplementation for pregnancy. Women who consume large amounts of alcohol often have iron deficiency, which increases the risk of FASD, and iron supplementation may be valuable 297 . Although novel in utero therapies with potential to prevent harm from PAE have been explored in preclinical models, none have been proven safe or effective in human RCTs 298 , 299 , 300 , 301 , 302 , 303 , 304 , 305 , 306 , 307 . Candidate therapies include agents that reduce ethanol-induced oxidative stress, cerebral neuronal apoptosis, growth deficits and structural anomalies caused by PAE 308 .

Future research should be collaborative and informed by people living with FASD and their families. FASD is a lifelong condition and information must be sought about adult patients, including the elderly. Further understanding of the pathophysiology underpinning the teratogenic and neurotoxic effects of PAE is required to inform prevention and management. Moreover, novel diagnostic tools and treatments must be rigorously tested, and new approaches are needed to reduce stigma, improve the QOL of people with FASD and prevent FASD in future generations.

Gellius, A. & Beloe, W. The Attic Nights of Aulus Gellius (Johnson, J., 1795).

Goodwin, W. W. (ed.) Plutarch’s Morals (Little & Brown, 1871).

Lemoine, P., Harousseau, H., Borteyru, J. P. & Menuet, J. C. Children of alcoholic parents: observed anomalies: discussion of 127 cases. Ouest Med. 8 , 476–482 (1968). This article describes FAS, beginning the modern era of understanding of the impact of PAE on development.

Google Scholar  

Jones, K., Smith, D., Ulleland, C. & Streissguth, A. Pattern of malformation in offspring of chronic alcoholic mothers. Lancet 301 , 1267–1271 (1973). This article describes FAS, beginning the modern era of understanding of the impact of PAE on development.

Article   Google Scholar  

Jones, K. & Smith, D. Recognition of the fetal alcohol syndrome in early infancy. Lancet 302 , 999–1001 (1973). This article describes FAS, beginning the modern era of understanding of the impact of PAE on development.

Article   CAS   PubMed   Google Scholar  

Warren, K. R. & Hewitt, B. G. Fetal alcohol spectrum disorders: when science, medicine, public policy, and laws collide. Dev. Disabil. Res. Rev. 15 , 174 (2009).

Brown, J. M., Bland, R., Jonsson, E. & Greenshaw, A. J. A brief history of awareness of the link between alcohol and fetal alcohol spectrum disorder. Can. J. Psychiatr. 64 , 164–168 (2019).

Armstrong, E. M. & Abel, E. L. Fetal alcohol syndrome: the origins of a moral panic. Alcohol Alcohol. 35 , 276–282 (2000).

Sulik, K. K., Johnston, M. C. & Webb, M. A. Fetal alcohol syndrome: embryogenesis in a mouse model. Science 214 , 936–938 (1981). This article demonstrates the replicability of the sentinel facial characteristics of FASD in a mouse model of PAE and the importance of the timing of PAE in determining dysmorphology.

Hoyme, H. E. et al. Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics 138 , e20154256 (2016).

Article   PubMed   PubMed Central   Google Scholar  

Bertrand, J. et al. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Report by National Task Force on FAS & FAE (Centers for Disease Control and Prevention, 2004).

Popova, S., Lange, S., Shield, K., Burd, L. & Rehm, J. Prevalence of fetal alcohol spectrum disorder among special subpopulations: a systematic review and meta‐analysis. Addiction 114 , 1150–1172 (2019).

Popova, S. et al. Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. Lancet 387 , 978–987 (2016).

Article   PubMed   Google Scholar  

Cook, J. C., Lynch, M. E. & Coles, C. D. Association analysis: fetal alcohol spectrum disorder and hypertension status in children and adolescents. Alcohol Clin. Exp. Res. 43 , 1727–1733 (2019).

Popova, S. et al. Population-based prevalence of fetal alcohol spectrum disorder in Canada. BMC Public Health https://doi.org/10.1186/s12889-019-7213-3 (2019).

Phillips, N. L. et al. Impact of fetal alcohol spectrum disorder on families. Arch. Dis. Child. 107 , 755–757 (2022).

Popova, S., Lange, S., Burd, L. & Rehm, J. The economic burden of fetal alcohol spectrum disorder in Canada in 2013. Alcohol Alcohol. 51 , 367–375 (2016).

Popova, S., Stade, B., Bekmuradov, D., Lange, S. & Rehm, J. What do we know about the economic impact of fetal alcohol spectrum disorder? A systematic literature review. Alcohol Alcohol. 46 , 490–497 (2011).

Charness, M. E., Riley, E. P. & Sowell, E. R. Drinking during pregnancy and the developing brain: Is any amount safe? Trends Cogn. Sci. 20 , 80–82 (2016).

Centers for Disease Control and Prevention. Advisory on Alcohol Use During Pregnancy. A 2005 Message to women from the US Surgeon General (CDC, 2005).

Graves, L. et al. Guideline no. 405: Screening and counselling for alcohol consumption during pregnancy. J. Obstet. Gynaecol. Can. 42 , 1158–1173.e1 (2020).

World Health Organization. Guidelines for the Identification and Management of Substance Use and Substance Use Disorders in Pregnancy (World Health Organization, 2014).

National Health and Medical Research Council. Australian Guidelines to Reduce Health Risks from Drinking Alcohol (Australian Research Council and Universities Australia, Commonwealth of Australia, 2020).

Popova, S., Lange, S., Probst, C., Gmel, G. & Rehm, J. Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis. Lancet Glob. Health 5 , e290–e299 (2017). Presents the epidemiology of PAE and FAS.

Popova, S., Lange, S., Probst, C., Gmel, G. & Rehm, J. Global prevalence of alcohol use and binge drinking during pregnancy, and fetal alcohol spectrum disorder. Biochem. Cell Biol. 96 , 237–240 (2018).

World Health Organization. Global Status Report on Alcohol and Health, 2018 (World Health Organization, 2018).

Lange, S., Probst, C., Rehm, J. & Popova, S. Prevalence of binge drinking during pregnancy by country and World Health Organization region: systematic review and meta-analysis. Reprod. Toxicol. 73 , 214–221 (2017).

Green, P. P., McKnight-Eily, L. R., Tan, C. H., Mejia, R. & Denny, C. H. Vital signs: alcohol-exposed pregnancies — United States, 2011-2013. MMWR Morb. Mortal. Wkly Rep. 65 , 91–97 (2016).

Sedgh, G., Singh, S. & Hussain, R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud. Fam. Plann. 45 , 301–314 (2014).

Muggli, E. et al. “Did you ever drink more?” A detailed description of pregnant women’s drinking patterns. BMC Public Health 16 , 683 (2016).

McCormack, C. et al. Prenatal alcohol consumption between conception and recognition of pregnancy. Alcohol Clin. Exp. Res. 41 , 369–378 (2017).

Fitzpatrick, J. P. et al. Prevalence and patterns of alcohol use in pregnancy in remote western Australian communities: the Lililwan project. Drug Alcohol Rev. 34 , 329–339 (2015).

Petersen Williams, P., Jordaan, E., Mathews, C., Lombard, C. & Parry, C. D. Alcohol and other drug use during pregnancy among women attending midwife obstetric units in the cape metropole, South Africa. Adv. Prev. Med. 2014 , 871427 (2014).

Allen, L. et al. Pregnant and early parenting Indigenous women who use substances in Canada: a scoping review of health and social issues, supports, and strategies. J. Ethn. Subst. Abus. https://doi.org/10.1080/15332640.2022.2043799 (2022).

Gonzales, K. L. et al. An indigenous framework of the cycle of fetal alcohol spectrum disorder risk and prevention across the generations: historical trauma, harm and healing. Ethn. Health 26 , 280–298 (2021).

Mulat, B., Alemnew, W. & Shitu, K. Alcohol use during pregnancy and associated factors among pregnant women in sub-Saharan Africa: further analysis of the recent demographic and health survey data. BMC Pregnancy Childbirth 22 , 361 (2022).

Singal, D. et al. Prenatal care of women who give birth to children with fetal alcohol spectrum disorder in a universal health care system: a case–control study using linked administrative data. CMAJ Open 7 , E63 (2019).

Esper, L. H. & Furtado, E. F. Identifying maternal risk factors associated with fetal alcohol spectrum disorders: a systematic review. Eur. Child Adolesc. Psychiatry 23 , 877–889 (2014).

Popova, S., Dozet, D., O’Hanlon, G., Temple, V. & Rehm, J. Maternal alcohol use, adverse neonatal outcomes and pregnancy complications in British Columbia, Canada: a population-based study. BMC Pregnancy Childbirth 21 , 74 (2021).

Poole, N. in Fetal Alcohol Spectrum Disorder: Management and Policy Perspectives of FASD Ch. 9 (eds Riley, E. P., Clarren, S., Weinberg, J. & Jonsson, E.) 161–173 (Weily, 2010).

May, P. A. et al. Prevalence and characteristics of fetal alcohol spectrum disorders. Pediatrics 134 , 855–866 (2014).

Skagerstróm, J., Chang, G. & Nilsen, P. Predictors of drinking during pregnancy: a systematic review. J. Womens Health 20 , 91–913 (2011).

Colvin, L., Payne, J., Parsons, D., Kurinczuk, J. J. & Bower, C. Alcohol consumption during pregnancy in nonindigenous west Australian women. Alcohol Clin. Exp. Res. 31 , 276–284 (2007).

Hutchinson, D. et al. Longitudinal prediction of periconception alcohol use: a 20-year prospective cohort study across adolescence, young adulthood and pregnancy. Addiction 117 , 343–353 (2022).

Peadon, E. et al. Attitudes and behaviour predict women’s intention to drink alcohol during pregnancy: the challenge for health professionals. BMC Public Health 11 , 584 (2011).

Australian Institute of Health and Welfare. National Drug Strategy Household Survey 2016: Detailed Findings (Australian Institute of Health and Welfare, 2017).

Tsang, T. W. et al. Predictors of alcohol use during pregnancy in Australian women. Drug Alcohol Rev. 41 , 171–181 (2022).

Lange, S. et al. Global prevalence of fetal alcohol spectrum disorder among children and youth: a systematic review and meta-analysis. JAMA Pediatr. 171 , 948–956 (2017). Presents the epidemiology of FASD.

Parker, S. E. et al. Updated national birth prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res. A Clin. Mol. Teratol. 88 , 1008–1016 (2010).

Zablotsky, B. et al. Prevalence and trends of developmental disabilities among children in the United States: 2009-2017. Pediatrics https://doi.org/10.1542/peds.2019-0811 (2019).

Popova, S., Dozet, D. & Burd, L. Fetal alcohol spectrum disorder: can we change the future? Alcohol Clin. Exp. Res. 44 , 815–819 (2020).

Mena, M., Navarrete, P., Avila, P., Bedregal, P. & Berríos, X. Alcohol drinking in parents and its relation with intellectual score of their children. Rev. Med. Chile 121 , 98–105 (1993).

CAS   PubMed   Google Scholar  

Landgren, M., Svensson, L., Strömland, K. & Grönlund, M. A. Prenatal alcohol exposure and neurodevelopmental disorders in children adopted from eastern Europe. Pediatrics 125 , e1178–e1185 (2010).

Colom, J. et al. Prevalence of fetal alcohol spectrum disorders (FASD) among children adopted from eastern European countries: Russia and Ukraine. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph18041388 (2021).

Kuzmenkovienė, E., Prasauskienė, A. & Endzinienė, M. The prevalence of fetal alcohol spectrum disorders and concomitant disorders among orphanage children in Lithuania. J. Popul. Ther. Clin. Pharmacol. 19 , e423 (2012).

Bower, C. et al. Fetal alcohol spectrum disorder and youth justice: a prevalence study among young people sentenced to detention in Western Australia. BMJ Open 8 , e019605 (2018).

Fast, D. K., Conry, J. & Loock, C. A. Identifying fetal alcohol syndrome among youth in the criminal justice system. J. Dev. Behav. Pediatr. 20 , 370–372 (1999).

Bell, C. & Chimata, R. Prevalence of neurodevelopmental disorders among low-income African Americans at a clinic on Chicago’s south side. Psychiatr. Serv. 66 , 539–542 (2015).

Fitzpatrick, J. P. et al. Prevalence and profile of neurodevelopment and fetal alcohol spectrum disorder (FASD) amongst Australian aboriginal children living in remote communities. Res. Dev. Disabil. 65 , 114–126 (2017).

Legonkova, S. V. Clinical and Functional Characteristics of Fetal Alcohol Syndrome in Early Childhood [Russian] Thesis, St. Peterburg’s State Paediatric Medical Academy (2011).

Heller, M. & Burd, L. Review of ethanol dispersion, distribution, and elimination from the fetal compartment. Birth Defects Res. A Clin. Mol. Teratol. 100 , 277–283 (2014).

Dou, X., Lee, J. Y. & Charness, M. E. Neuroprotective peptide NAPVSIPQ antagonizes ethanol inhibition of L1 adhesion by promoting the dissociation of L1 and Ankyrin-G. Biol. Psychiatry 87 , 656–665 (2020).

Lee, S. M., Yeh, P. W. L. & Yeh, H. H. L-type calcium channels contribute to ethanol-induced aberrant tangential migration of primordial cortical GABAergic interneurons in the embryonic medial prefrontal cortex. eNeuro https://doi.org/10.1523/eneuro.0359-21.2021 (2022).

Ramanathan, R., Wilkemeyer, M. F., Mittal, B., Perides, G. & Charness, M. E. Alcohol inhibits cell-cell adhesion mediated by human L1. J. Cell Biol. 133 , 381–390 (1996).

Kalinowski, A. & Humphreys, K. Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries. Addiction 111 , 1293–1298 (2016).

Cuzon, V. C., Yeh, P. W., Yanagawa, Y., Obata, K. & Yeh, H. H. Ethanol consumption during early pregnancy alters the disposition of tangentially migrating GABAergic interneurons in the fetal cortex. J. Neurosci. 28 , 1854–1864 (2008).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Muggli, E. et al. Association between prenatal alcohol exposure and craniofacial shape of children at 12 months of age. JAMA Pediatr. 171 , 771–780 (2017). Shows the potential of 3D imaging in identifying individuals with FASD and PAE.

Long, X. & Lebel, C. Evaluation of brain alterations and behavior in children with low levels of prenatal alcohol exposure. JAMA Netw. Open 5 , e225972 (2022).

Lees, B. et al. Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the adolescent brain cognitive development study. Am. J. Psychiatry 177 , 1060–1072 (2020).

Lebel, C. et al. A longitudinal study of the long-term consequences of drinking during pregnancy: heavy in utero alcohol exposure disrupts the normal processes of brain development. J. Neurosci. 32 , 15243–15251 (2012).

Kar, P. et al. Trajectories of brain white matter development in young children with prenatal alcohol exposure. Hum. Brain Mapp. https://doi.org/10.1002/hbm.25944 (2022).

Eberhart, J. K. & Parnell, S. E. The genetics of fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 40 , 1154–1165 (2016).

Kaminen-Ahola, N. Fetal alcohol spectrum disorders: genetic and epigenetic mechanisms. Prenat. Diagn. 40 , 1185–1192 (2020).

Astley Hemingway, S. J. et al. Twin study confirms virtually identical prenatal alcohol exposures can lead to markedly different fetal alcohol spectrum disorder outcomes-fetal genetics influences fetal vulnerability. Adv. Pediatr. Res. https://doi.org/10.24105/apr.2019.5.23 (2018).

McCarthy, N. et al. Pdgfra protects against ethanol-induced craniofacial defects in a zebrafish model of FASD. Development 140 , 3254–3265 (2013).

Kietzman, H. W., Everson, J. L., Sulik, K. K. & Lipinski, R. J. The teratogenic effects of prenatal ethanol exposure are exacerbated by sonic hedgehog or GLI2 haploinsufficiency in the mouse. PLoS ONE   9 , e89448 (2014).

Cobben, J. M. et al. DNA methylation abundantly associates with fetal alcohol spectrum disorder and its subphenotypes. Epigenomics 11 , 767–785 (2019).

Ernst, A. M. et al. Prenatal and postnatal choline supplementation in fetal alcohol spectrum disorder. Nutrients https://doi.org/10.3390/nu14030688 (2022).

Smith, S. M. et al. Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: an exploratory study of oral choline supplementation. Am. J. Clin. Nutr. 114 , 617–627 (2021).

Wozniak, J. R., Riley, E. P. & Charness, M. E. Clinical presentation, diagnosis, and management of fetal alcohol spectrum disorder. Lancet Neurol. 18 , 760–770 (2019). Outlines the key neurodevelopmental characteristics in children with PAE and FASD.

Steane, S. E. et al. Prenatal alcohol consumption and placental outcomes: a systematic review and meta-analysis of clinical studies. Am. J. Obstet. Gynecol. 225 , 607.e1–607.e22 (2021).

Gårdebjer, E. M. et al. Effects of periconceptional maternal alcohol intake and a postnatal high-fat diet on obesity and liver disease in male and female rat offspring. Am. J. Physiol. Endocrinol. Metab. 315 , E694–E704 (2018).

Lipinski, R. J. et al. Ethanol-induced face-brain dysmorphology patterns are correlative and exposure-stage dependent. PLoS ONE   7 , e43067 (2012).

Kane, C. J. M. & Drew, P. D. Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders. J. Neurosci. Res. 99 , 1973–1985 (2021).

Wilhelm, C. J. & Guizzetti, M. Fetal alcohol spectrum disorders: an overview from the glia perspective. Front. Integr. Neurosci. 9 , 65 (2015).

PubMed   Google Scholar  

Burke, M. W., Ptito, M., Ervin, F. R. & Palmour, R. M. Hippocampal neuron populations are reduced in vervet monkeys with fetal alcohol exposure. Dev. Psychobiol. 57 , 470–485 (2015).

Young, J. K., Giesbrecht, H. E., Eskin, M. N., Aliani, M. & Suh, M. Nutrition implications for fetal alcohol spectrum disorder. Adv. Nutr. 5 , 675–692 (2014).

Jarmasz, J. S., Basalah, D. A., Chudley, A. E. & Del Bigio, M. R. Human brain abnormalities associated with prenatal alcohol exposure and fetal alcohol spectrum disorder. J. Neuropathol. Exp. Neurol. 76 , 813–833 (2017).

Marguet, F. et al. Prenatal alcohol exposure is a leading cause of interneuronopathy in humans. Acta Neuropathol. Commun. 8 , 208 (2020).

Wang, X. et al. In utero MRI identifies consequences of early-gestation alcohol drinking on fetal brain development in rhesus macaques. Proc. Natl Acad. Sci. USA 117 , 10035–10044 (2020).

Treit, S., Jeffery, D., Beaulieu, C. & Emery, D. Radiological findings on structural magnetic resonance imaging in fetal alcohol spectrum disorders and healthy controls. Alcohol Clin. Exp. Res. 44 , 455–462 (2020).

Sullivan, E. V. et al. Graded cerebellar lobular volume deficits in adolescents and young adults with fetal alcohol spectrum disorders (FASD). Cereb. Cortex 30 , 4729–4746 (2020).

Lebel, C., Roussotte, F. & Sowell, E. R. Imaging the impact of prenatal alcohol exposure on the structure of the developing human brain. Neuropsychol. Rev. 21 , 102–118 (2011).

Nguyen, V. T. et al. Radiological studies of fetal alcohol spectrum disorders in humans and animal models: an updated comprehensive review. Magn. Reson. Imaging 43 , 10–26 (2017).

De Guio, F. et al. A study of cortical morphology in children with fetal alcohol spectrum disorders. Hum. Brain Mapp. 35 , 2285–2296 (2014).

Infante, M. A. et al. Atypical cortical gyrification in adolescents with histories of heavy prenatal alcohol exposure. Brain Res. 1624 , 446–454 (2015).

Boronat, S. et al. Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders. Eur. J. Med. Genet. 60 , 65–71 (2017).

Yang, Y. et al. Callosal thickness reductions relate to facial dysmorphology in fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 36 , 798–806 (2012).

Yang, Y. et al. Abnormal cortical thickness alterations in fetal alcohol spectrum disorders and their relationships with facial dysmorphology. Cereb. Cortex 22 , 1170–1179 (2012).

Donald, K. A. et al. Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review. Acta Neuropsychiatr. 27 , 251–269 (2015).

Ghazi Sherbaf, F., Aarabi, M. H., Hosein Yazdi, M. & Haghshomar, M. White matter microstructure in fetal alcohol spectrum disorders: a systematic review of diffusion tensor imaging studies. Hum. Brain Mapp. 40 , 1017–1036 (2019).

Biffen, S. C. et al. Compromised interhemispheric transfer of information partially mediates cognitive function deficits in adolescents with fetal alcohol syndrome. Alcohol Clin. Exp. Res. 46 , 517–529 (2022).

Roussotte, F. F. et al. Regional brain volume reductions relate to facial dysmorphology and neurocognitive function in fetal alcohol spectrum disorders. Hum. Brain Mapp. 33 , 920–937 (2012).

Marek, S. et al. Reproducible brain-wide association studies require thousands of individuals. Nature 603 , 654–660 (2022).

Medina, A. E. Fetal alcohol spectrum disorders and abnormal neuronal plasticity. Neuroscientist 17 , 274–287 (2011).

Marquardt, K. & Brigman, J. L. The impact of prenatal alcohol exposure on social, cognitive and affective behavioral domains: insights from rodent models. Alcohol 51 , 1–15 (2016).

Harvey, R. E., Berkowitz, L. E., Hamilton, D. A. & Clark, B. J. The effects of developmental alcohol exposure on the neurobiology of spatial processing. Neurosci. Biobehav. Rev. 107 , 775–794 (2019).

Stephen, J. M., Hill, D. E. & Candelaria-Cook, F. T. Examining the effects of prenatal alcohol exposure on corticothalamic connectivity: a multimodal neuroimaging study in children. Dev. Cogn. Neurosci. 52 , 101019 (2021).

Candelaria-Cook, F. T., Schendel, M. E., Flynn, L., Hill, D. E. & Stephen, J. M. Altered resting-state neural oscillations and spectral power in children with fetal alcohol spectrum disorder. Alcohol Clin. Exp. Res. 45 , 117–130 (2021).

Suttie, M. et al. Combined face-brain morphology and associated neurocognitive correlates in fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 42 , 1769–1782 (2018). Shows the potential of 3D imaging in identifying individuals with FASD and PAE.

Ahlgren, S. C., Thakur, V. & Bronner-Fraser, M. Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. Proc. Natl Acad. Sci. USA 99 , 10476–10481 (2002).

Li, Y. et al. Sulforaphane protects against ethanol-induced apoptosis in human neural crest cells through diminishing ethanol-induced hypermethylation at the promoters of the genes encoding the inhibitor of apoptosis proteins. Front. Cell Dev. Biol. 9 , 622152 (2021).

Chen, S.-Y. & Sulik, K. K. Free radicals and ethanol-induced cytotoxicity in neural crest cells. Alcohol Clin. Exp. Res. 20 , 1071–1076 (1996).

Chung, D. D. et al. Toxic and teratogenic effects of prenatal alcohol exposure on fetal development, adolescence, and adulthood. Int. J. Mol. Sci. 22 , 8785 (2021).

Mitoma, H., Manto, M. & Shaikh, A. G. Mechanisms of ethanol-induced cerebellar ataxia: underpinnings of neuronal death in the cerebellum. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph18168678 (2021).

Charness, M. E., Simon, R. P. & Greenberg, D. A. Ethanol and the nervous system. N. Engl. J. Med. 321 , 442–454 (1989).

Harris, R. A., Trudell, J. R. & Mihic, S. J. Ethanol’s molecular targets. Sci. Signal. 1 , re7 (2008).

Gutherz, O. R. et al. Potential roles of imprinted genes in the teratogenic effects of alcohol on the placenta, somatic growth, and the developing brain. Exp. Neurol. 347 , 113919 (2022).

Lussier, A. A., Bodnar, T. S. & Weinberg, J. Intersection of epigenetic and immune alterations: implications for fetal alcohol spectrum disorder and mental health. Front. Neurosci. 15 , 788630 (2021).

Cheedipudi, S., Genolet, O. & Dobreva, G. Epigenetic inheritance of cell fates during embryonic development. Front. Genet. https://doi.org/10.3389/fgene.2014.00019 (2014).

Mews, P. et al. Alcohol metabolism contributes to brain histone acetylation. Nature 574 , 717–721 (2019).

Cantacorps, L., Alfonso-Loeches, S., Guerri, C. & Valverde, O. Long-term epigenetic changes in offspring mice exposed to alcohol during gestation and lactation. J. Psychopharmacol. 33 , 1562–1572 (2019).

Gangisetty, O., Chaudhary, S., Palagani, A. & Sarkar, D. K. Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: evidence for male germline transmission. PLoS ONE   17 , e0263340 (2022).

Jarmasz, J. S. et al. Global DNA Methylation and histone posttranslational modifications in human and nonhuman primate brain in association with prenatal alcohol exposure. Alcohol Clin. Exp. Res. 43 , 1145–1162 (2019).

CAS   PubMed   PubMed Central   Google Scholar  

Lussier, A. A. et al. DNA methylation as a predictor of fetal alcohol spectrum disorder. Clin. Epigenetics 10 , 5 (2018).

Ehrhart, F. et al. Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders. Mol. Psychiatry 24 , 10–17 (2019).

Shabtai, Y., Bendelac, L., Jubran, H., Hirschberg, J. & Fainsod, A. Acetaldehyde inhibits retinoic acid biosynthesis to mediate alcohol teratogenicity. Sci. Rep. 8 , 347 (2018).

Yan, T., Zhao, Y., Jiang, Z. & Chen, J. Acetaldehyde induces cytotoxicity via triggering mitochondrial dysfunction and overactive mitophagy. Mol. Neurobiol. 59 , 3933–3946 (2022).

Weeks, O. et al. Embryonic alcohol exposure disrupts the ubiquitin-proteasome system. JCI Insight https://doi.org/10.1172/jci.insight.156914 (2022).

Petrelli, B., Bendelac, L., Hicks, G. G. & Fainsod, A. Insights into retinoic acid deficiency and the induction of craniofacial malformations and microcephaly in fetal alcohol spectrum disorder. Genesis 57 , e23278 (2019).

Boschen, K. E., Fish, E. W. & Parnell, S. E. Prenatal alcohol exposure disrupts sonic hedgehog pathway and primary cilia genes in the mouse neural tube. Reprod. Toxicol. 105 , 136–147 (2021).

Fish, E. W. et al. Cannabinoids exacerbate alcohol teratogenesis by a CB1-hedgehog interaction. Sci. Rep. 9 , 16057 (2019).

Burton, D. F. et al. Pharmacological activation of the sonic hedgehog pathway with a Smoothened small molecule agonist ameliorates the severity of alcohol-induced morphological and behavioral birth defects in a zebrafish model of fetal alcohol spectrum disorder. J. Neurosci. Res. 100 , 1585–1601 (2022).

Li, Y. X. et al. Fetal alcohol exposure impairs hedgehog cholesterol modification and signaling. Lab. Invest. 87 , 231–240 (2007).

Boronat, S. et al. Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders. Eur. J. Med. Genet. 60 , 72–78 (2017).

Maness, P. F. & Schachner, M. Neural recognition molecules of the immunoglobulin superfamily: signaling transducers of axon guidance and neuronal migration. Nat. Neurosci. 10 , 19–26 (2007).

Arevalo, E. et al. An alcohol binding site on the neural cell adhesion molecule L1. Proc. Natl Acad. Sci. USA 105 , 371–375 (2008).

Dou, X. et al. L1 coupling to ankyrin and the spectrin-actin cytoskeleton modulates ethanol inhibition of L1 adhesion and ethanol teratogenesis. FASEB J. 32 , 1364–1374 (2018).

Wilkemeyer, M. F. et al. Differential effects of ethanol antagonism and neuroprotection in peptide fragment NAPVSIPQ prevention of ethanol-induced developmental toxicity. Proc. Natl Acad. Sci. USA 100 , 8543–8548 (2003).

Delatour, L. C., Yeh, P. W. & Yeh, H. H. Ethanol exposure in utero disrupts radial migration and pyramidal cell development in the somatosensory cortex. Cereb. Cortex 29 , 2125–2139 (2019).

Salem, N. A. et al. A novel Oct4/Pou5f1-like non-coding RNA controls neural maturation and mediates developmental effects of ethanol. Neurotoxicol. Teratol. 83 , 106943 (2021).

Mohammad, S. et al. Kcnn2 blockade reverses learning deficits in a mouse model of fetal alcohol spectrum disorders. Nat. Neurosci. 23 , 533–543 (2020).

Tseng, A. M. et al. Ethanol exposure increases miR-140 in extracellular vesicles: implications for fetal neural stem cell proliferation and maturation. Alcohol Clin. Exp. Res. 43 , 1414–1426 (2019).

Chung, D. D. et al. Dose-related shifts in proteome and function of extracellular vesicles secreted by fetal neural stem cells following chronic alcohol exposure. Heliyon 8 , e11348 (2022).

Rubert, G., Miñana, R., Pascual, M. & Guerri, C. Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytes. J. Neurosci. Res. 84 , 483–496 (2006).

Darbinian, N. et al. Ethanol-mediated alterations in oligodendrocyte differentiation in the developing brain. Neurobiol. Dis. 148 , 105181 (2021).

Creeley, C. E., Dikranian, K. T., Johnson, S. A., Farber, N. B. & Olney, J. W. Alcohol-induced apoptosis of oligodendrocytes in the fetal macaque brain. Acta Neuropathol. Commun. 1 , 23 (2013).

Bodnar, T. S. et al. Immune network dysregulation associated with child neurodevelopmental delay: modulatory role of prenatal alcohol exposure. J. Neuroinflammation 17 , 39 (2020).

Bodnar, T. S. et al. Modulatory role of prenatal alcohol exposure and adolescent stress on the response to arthritis challenge in adult female rats. EBioMedicine 77 , 103876 (2022).

Bodnar, T. S. et al. Evidence for long-lasting alterations in the fecal microbiota following prenatal alcohol exposure. Alcohol Clin. Exp. Res. 46 , 542–555 (2022).

Virdee, M. S. et al. An enriched biosignature of gut microbiota-dependent metabolites characterizes maternal plasma in a mouse model of fetal alcohol spectrum disorder. Sci. Rep. 11 , 248 (2021).

Lo, J. O. et al. Effects of early daily alcohol exposure on placental function and fetal growth in a rhesus macaque model. Am. J. Obstet. Gynecol. 226 , 130.e1–130.e11 (2022).

Naik, V. D. et al. Mechanisms underlying chronic binge alcohol exposure-induced uterine artery dysfunction in pregnant rat. Alcohol Clin. Exp. Res. 42 , 682–690 (2018).

Balaraman, S. et al. Plasma miRNA profiles in pregnant women predict infant outcomes following prenatal alcohol exposure. PLoS ONE   11 , e0165081 (2016).

Mahnke, A. H. et al. Infant circulating microRNAs as biomarkers of effect in fetal alcohol spectrum disorders. Sci. Rep. 11 , 1429 (2021).

Tseng, A. M. et al. Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation. Life Sci. Alliance https://doi.org/10.26508/lsa.201800252 (2019).

Elliott, A. J. et al. Concurrent prenatal drinking and smoking increases risk for SIDS: safe passage study report. EClinicalMedicine 19 , 100247–100247 (2020).

Page, K. et al. Prevalence of marijuana use in pregnant women with concurrent opioid use disorder or alcohol use in pregnancy. Addict. Sci. Clin. Pract. 17 , 3 (2022).

Lowe, J. R. et al. Early developmental trajectory of children with prenatal alcohol and opioid exposure. Pediatr. Res. https://doi.org/10.1038/s41390-022-02252-z (2022).

Siqueira, M. & Stipursky, J. Blood brain barrier as an interface for alcohol induced neurotoxicity during development. Neurotoxicology 90 , 145–157 (2022).

Chudley, A. E. & Longstaffe, S. E. in Management of Genetic Syndromes Ch. 25 (eds Cassidy, S. B. & Allanson, J. E.) 363–380 (Wiley, 2010).

Clarren, S. K., Lutke, J. & Sherbuck, M. The Canadian guidelines and the interdisciplinary clinical capacity of Canada to diagnose fetal alcohol spectrum disorder. J. Popul. Ther. Clin. Pharmacol. 18 , e494–e499 (2011).

Chasnoff, I. J., Wells, A. M. & King, L. Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure. Pediatrics 135 , 264–270 (2015).

May, P. A. et al. Prevalence of fetal alcohol spectrum disorders in 4 US communities. JAMA 319 , 474–482 (2018).

Astley, S. J. Validation of the fetal alcohol spectrum disorder (FASD) 4-digit diagnostic code. J. Popul. Ther. Clin. Pharmacol. 20 , e416–e467 (2013).

Astley, S. J. Diagnostic Guide for Fetal Alcohol Spectrum Disorders: The 4-Digit Diagnostic Code (Univ. Washington, 2004).

Cook, J. L. et al. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. CMAJ Open 188 , 191–197 (2016).

Bower, C. & Elliott, E. J. Australian Guide to the Diagnosis of FASD (Australian Government Department of Health, 2020).

Scottish Intercollegiate Guidelines Network. Children and Young People Exposed Prenatally to Alcohol (SIGN publication no. 156) (SIGN, 2019).

Gibbs, A. & Sherwood, K. Putting fetal alcohol spectrum disorder (FASD) on the map in New Zealand: a review of health, social, political, justice and cultural developments. Psychiatr. Psychol. Law 24 , 825–842 (2017).

Centres for Disease Control. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis (US Department of Health and Human Services, 2004).

Okulicz-Kozaryn, K., Maryniak, A., Borkowska, M., Śmigiel, R. & Dylag, K. A. Diagnosis of fetal alcohol spectrum disorders (FASDs): guidelines of interdisciplinary group of Polish professionals. Int. J. Environ. Res. Public Health 18 , 7526 (2021).

Landgraf, M. N., Nothacker, M. & Heinen, F. Diagnosis of fetal alcohol syndrome (FAS): German guideline version 2013. Eur. J. Paediatr. Neurol. 17 , 437–446 (2013).

Chudley, A. E. et al. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Can. Med. Assoc. J. 172 (Suppl. 5), S1–S21 (2005).

Bush, K., Kivlahan, D. R., McDonell, M. B., Fihn, S. D. & Bradley, K. A. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Arch. Intern. Med. 158 , 1789–1795 (1998).

Sokol, R. J., Martier, S. S. & Ager, J. W. The T-ACE questions: practical prenatal detection of risk-drinking. Am. J. Obstet. Gynecol. 160 , 863–870 (1989).

Chiodo, L. M. et al. Increased cut-point of the TACER-3 screen reduces false positives without losing sensitivity in predicting risk alcohol drinking in pregnancy. Alcohol Clin. Exp. Res. 38 , 1401–1408 (2014).

Tsang, T. W. et al. Digital assessment of the fetal alcohol syndrome facial phenotype: reliability and agreement study. BMJ Paediatr. 1 , e000137 (2017).

Hemingway, S. J. A. et al. Comparison of the 4-digit code, Canadian 2015, Australian 2016 and Hoyme 2016 fetal alcohol spectrum disorder diagnostic guidelines. Adv. Pediatr. Res. https://doi.org/10.35248/2385-4529.19.6.31 (2019).

Coles, C. D. et al. A comparison among 5 methods for the clinical diagnosis of fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 40 , 1000–1009 (2016).

Coles, C. D. et al. Comparison of three systems for the diagnosis of fetal alcohol spectrum disorders in a community sample. Alcohol Clin. Exp. Res. https://doi.org/10.1111/acer.14999 (2022).

Leibson, T., Neuman, G., Chudley, A. E. & Koren, G. The differential diagnosis of fetal alcohol spectrum disorder. J. Popul. Ther. Clin. Pharmacol. 21 , e1–e30 (2014).

Pearson, M. A., Hoyme, H. E., Seaver, L. H. & Rimsza, M. E. Toluene embryopathy: delineation of the phenotype and comparison with fetal alcohol syndrome. Pediatrics 93 , 211–215 (1994).

Abdelmalik, N. et al. Diagnostic outcomes of 27 children referred by pediatricians to a genetics clinic in the Netherlands with suspicion of fetal alcohol spectrum disorders. Am. J. Med. Genet. A 161A , 254–260 (2013).

Douzgou, S. et al. Diagnosing fetal alcohol syndrome: new insights from newer genetic technologies. Arch. Dis. Child. 97 , 812 (2012).

Malinowski, J. et al. Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability. Genet. Med. 22 , 986–1004 (2020).

McKay, L., Petrelli, B., Chudley, A. E. & Hicks, G. G. In Fetal Alcohol Spectrum Disorder: Advances in Research and Practice Vol. 188 (eds Chudley, A. E. & Hicks, G. G.) 77–117 (Springer USA, 2022).

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5 5th edn (American Psychiatric Association, 2013).

Mattson, S. N., Bernes, G. A. & Doyle, L. R. Fetal alcohol spectrum disorders: a review of the neurobehavioral deficits associated with prenatal alcohol exposure. Alcohol Clin. Exp. Res. 43 , 1046–1062 (2019). This article outlines the key neurodevelopmental characteristics in children with PAE and FASD.

PubMed   PubMed Central   Google Scholar  

Klug, M. G., O’Connell, A. M., Palme, A., Kobrinsky, N. & Burd, L. A validation study of the alcohol related neurodevelopmental disorders behavioral checklist. Alcohol Clin. Exp. Res. 45 , 765–772 (2021).

Kable, J. A. et al. Characteristics of the symptoms of the proposed ND-PAE disorder in first grade children in a community sample. Child Psychiatry Hum. Dev. https://doi.org/10.1007/s10578-022-01414-8 (2022).

World Health Organization. International Classification of Diseases, Eleventh Revision (ICD-11), for mortality and morbidity statistics. WHO https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/362980699-11 (2022).

Kambeitz, C., Klug, M. G., Greenmyer, J., Popova, S. & Burd, L. Association of adverse childhood experiences and neurodevelopmental disorders in people with fetal alcohol spectrum disorders (FASD) and non-FASD controls. BMC Pediatrics 19 , 498 (2019).

May, P. A. et al. Case management reduces drinking during pregnancy among high risk women. Int. J. Alcohol Drug Res. 2 , 61–70 (2013).

Poole, N., Schmidt, R. A., Bocking, A., Bergeron, J. & Fortier, I. The potential for fetal alcohol spectrum disorder prevention of a harmonized approach to data collection about alcohol use in pregnancy cohort studies. Int. J. Environ. Res. Public Health 16 , 2019 (2019).

Dozet, D., Burd, L. & Popova, S. Screening for alcohol use in pregnancy: a review of current practices and perspectives. Int. J. Ment. Health Addict. https://doi.org/10.1007/s11469-021-00655-3 (2021).

Arnold, K. et al. Fetal alcohol spectrum disorders: knowledge and screening practices of university hospital medical students and residents. J. Popul. Ther. Clin. Pharmacol. 20 , e18–e25 (2013).

Payne, J. et al. Health professionals’ knowledge, practice and opinions about fetal alcohol syndrome and alcohol consumption in pregnancy. Aust. NZ J. Public Health 29 , 558–564 (2005).

Furtwængler, N. A. F. F. & de Visser, R. O. Lack of international consensus in low-risk drinking guidelines. Drug Alcohol Rev. 32 , 11–18 (2013).

Wangberg, S. C. Norwegian midwives’ use of screening for and brief interventions on alcohol use in pregnancy. Sex. Reprod. Healthc. 6 , 186–190 (2015).

France, K. et al. Health professionals addressing alcohol use with pregnant women in western Australia: Barriers and strategies for communication. Subst. Use Misuse 45 , 1474–1490 (2010).

Doi, L., Cheyne, H. & Jepson, R. Alcohol brief interventions in Scottish antenatal care: a qualitative study of midwives’ attitudes and practices. BMC Pregnancy Childbirth 14 , 170 (2014).

Doi, L., Jepson, R. & Cheyne, H. A realist evaluation of an antenatal programme to change drinking behaviour of pregnant women. Midwifery 31 , 965–972 (2015).

Oni, H. T. et al. Barriers and facilitators in antenatal settings to screening and referral of pregnant women who use alcohol or other drugs: a qualitative study of midwives’ experience. Midwifery 81 , 102595 (2020).

Lange, S., Shield, K., Koren, G., Rehm, J. & Popova, S. A comparison of the prevalence of prenatal alcohol exposure obtained via maternal self-reports versus meconium testing: a systematic literature review and meta-analysis. BMC Pregnancy Childbirth 14 , 127 (2014).

Szewczyk, Z. et al. Cost, cost-consequence and cost-effectiveness evaluation of a practice change intervention to increase routine provision of antenatal care addressing maternal alcohol consumption. Implement. Sci. 17 , 14 (2022).

Floyd, R. L. et al. Preventing alcohol-exposed pregnancies: a randomized controlled trial. Am. J. Prev. Med. 32 , 1–10 (2007).

Tzilos, G. K., Sokol, R. J. & Ondersma, S. J. A randomized phase I trial of a brief computer-delivered intervention for alcohol use during pregnancy. J. Womens Health 20 , 1517–1524 (2011).

Wouldes, T. A., Crawford, A., Stevens, S. & Stasiak, K. Evidence for the effectiveness and acceptability of e-SBI or e-SBIRT in the management of alcohol and illicit substance use in pregnant and post-partum women. Front. Psychiatr. 12 , 634805 (2021).

Coons, K. D., Watson, S. L., Yantzi, N. M., Lightfoot, N. E. & Larocque, S. Health care students’ attitudes about alcohol consumption during pregnancy: responses to narrative vignettes. Glob. Qual. Nurs. Res. 4 , 2333393617740463 (2017).

Greenmyer, J. R. et al. Pregnancy status is associated with screening for alcohol and other substance use in the emergency department. J. Addict. Med. 14 , e64–e69 (2020).

United Nations. The UN Sustainable Development Goals (United Nations, 2015).

Schölin, L. Prevention of Harm Caused by Alcohol Exposure in Pregnancy: Rapid Review and Case Studies from Member States (World Health Organization, Regional Office for Europe, 2016).

Poole, N., Schmidt, R. A., Green, C. & Hemsing, N. Prevention of fetal alcohol spectrum disorder: current Canadian efforts and analysis of gaps. J. Subst. Abus. Treat. 2016 , 1–11 (2016).

Poole, N. Fetal alcohol spectrum disorder (FASD) prevention: Canadian perspectives. Public Health Agency of Canada https://www.phac-aspc.gc.ca/hp-ps/dca-dea/prog-ini/fasd-etcaf/publications/cp-pc/pdf/cp-pc-eng.pdf (2008).

Jacobsen, B., Lindemann, C., Petzina, R. & Verthein, U. The universal and primary prevention of foetal alcohol spectrum disorders (FASD): a systematic review. J. Prev. 43 , 297–316 (2022).

Centers for Disease Control and Prevention. Alcohol & public health — preventing excessive alcohol use . CDC https://www.cdc.gov/alcohol/fact-sheets/prevention.htm (2022).

Jernigan, D. H. & Trangenstein, P. J. What’s next for WHO’s global strategy to reduce the harmful use of alcohol? Bull. World Health Organ. 98 , 222–223 (2020).

Babor, T. et al. Who is responsible for the public’s health? The role of the alcohol industry in the WHO global strategy to reduce the harmful use of alcohol. Addiction 108 , 2045–2047 (2013).

Driscoll, D. L., Barnes, V. R., Johnston, J. M., Windsor, R. & Ray, R. A formative evaluation of two FASD prevention communication strategies. Alcohol Alcohol. 53 , 461–469 (2018).

Thomas, G., Gonneau, G., Poole, N. & Cook, J. The effectiveness of alcohol warning labels in the prevention of fetal alcohol spectrum disorder: a brief review. Int. J. Alcohol Drug Res. 3 , 91–103 (2014).

Choate, P., Badry, D., MacLaurin, B., Ariyo, K. & Sobhani, D. Fetal alcohol spectrum disorder: what does public awareness tell us about prevention programming? Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph16214229 (2019).

Reid, N. et al. Preconception interventions to reduce the risk of alcohol‐exposed pregnancies: a systematic review. Alcohol Clin. Exp. Res. 45 , 2414–2429 (2021).

Symons, M., Pedruzzi, R. A., Bruce, K. & Milne, E. A systematic review of prevention interventions to reduce prenatal alcohol exposure and fetal alcohol spectrum disorder in indigenous communities. BMC Public Health 18 , 1227 (2018).

Montag, A., Clapp, J. D., Calac, D., Gorman, J. & Chambers, C. A review of evidence-based approaches for reduction of alcohol consumption in Native women who are pregnant or of reproductive age. Am. J. Drug Alcohol Abuse 38 , 436–443 (2012).

O’Connor, E. A. et al. Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: updated evidence report and systematic review for the US preventive services task force. JAMA 320 , 1910–1928 (2018).

Erng, M. N., Smirnov, A. & Reid, N. Prevention of alcohol‐exposed pregnancies and fetal alcohol spectrum disorder among pregnant and postpartum women: a systematic review. Alcohol Clin. Exp. Res. 44 , 2431–2448 (2020).

Thanh, N. X. et al. An economic evaluation of the parent–child assistance program for preventing fetal alcohol spectrum disorder in Alberta, Canada. Adm. Policy Ment. Health 42 , 10–18 (2015).

Keen, C. L. et al. The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example. BioFactors 36 , 125–135 (2010).

McQuire, C., Daniel, R., Hurt, L., Kemp, A. & Paranjothy, S. The causal web of foetal alcohol spectrum disorders: a review and causal diagram. Eur. Child Adolesc. Psychiatr. 29 , 575–594 (2020).

Samawi, L., Williams, P. P., Myers, B. & Fuhr, D. C. Effectiveness of psychological interventions to reduce alcohol consumption among pregnant and postpartum women: a systematic review. Arch. Womens Ment. Health 24 , 557–568 (2021).

Greenmyer, J. R., Popova, S., Klug, M. G. & Burd, L. Fetal alcohol spectrum disorder: a systematic review of the cost of and savings from prevention in the United States and Canada. Addiction 115 , 409–417 (2020).

Wolfson, L. et al. Collaborative action on fetal alcohol spectrum disorder prevention: Principles for enacting the truth and reconciliation commission call to action #33. Int. J. Environ. Res. Public Health https://doi.org/10.3390/ijerph16091589 (2019).

Reid, N., Crawford, A., Petrenko, C., Kable, J. & Olson, H. C. A family-directed approach for supporting individuals with fetal alcohol spectrum disorders. Curr. Dev. Disord. Rep. 9 , 9–18 (2022).

Bertrand, J. Interventions for children with fetal alcohol spectrum disorders (FASDs): overview of findings for five innovative research projects. Res. Dev. Disabil. 30 , 986–1006 (2009).

Streissguth, A. P., Barr, H. M., Kogan, J. & Bookstein, F. L. Understanding the Occurrence of Secondary Disabilities in Clients with Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE). Final Report to the Centers for Disease Control and Prevention (CDC). Report No. 96-06 (Univ. Washington, Fetal Alcohol & Drug Unit, 1996).

Reid, N. et al. Systematic review of fetal alcohol spectrum disorder interventions across the life span. Alcohol Clin. Exp. Res. 39 , 2283–2295 (2015).

Ordenewitz, L. K. et al. Evidence-based interventions for children and adolescents with fetal alcohol spectrum disorders — a systematic review. Eur. J. Paediatr. Neurol. 33 , 50–60 (2021).

Carr, E. G. et al. Positive behavior support: evolution of an applied science. J. Posit. Behav. Inter. 4 , 4–16 (2002).

Kable, J. A., Taddeo, E., Strickland, D. & Coles, C. D. Improving FASD children’s self-regulation: piloting phase 1 of the GoFAR intervention. Child Fam. Behav. Ther. 38 , 124–141 (2016).

Kable, J. A., Coles, C. D. & Taddeo, E. Socio-cognitive habilitation using the math interactive learning experience program for alcohol-affected children. Alcohol Clin. Exp. Res. 31 , 1425–1434 (2007).

Petrenko, C. L., Parr, J., Kautz, C., Tapparello, C. & Olson, H. C. A mobile health intervention for fetal alcohol spectrum disorders (families moving forward connect): development and qualitative evaluation of design and functionalities. JMIR mHealth uHealth 8 , e14721 (2020).

Coles, C. D., Kable, J. A., Taddeo, E. & Strickland, D. GoFAR: improving attention, behavior and adaptive functioning in children with fetal alcohol spectrum disorders: brief report. Dev. Neurorehabil. 21 , 345–349 (2018).

Coles, C. D., Kable, J. A. & Taddeo, E. Math performance and behavior problems in children affected by prenatal alcohol exposure: intervention and follow-up. J. Dev. Behav. Pediatr. 30 , 7–15 (2009).

Kully-Martens, K. et al. Mathematics intervention for children with fetal alcohol spectrum disorder: a replication and extension of the math interactive learning experience (MILE) program. Res. Dev. Disabil. 78 , 55–65 (2018).

Williams, M. S. & Shellenberger, S. How Does Your Engine Run?: A Leader’s Guide to the Alert Program for Self-Regulation (TherapyWorks, Inc., 1996).

Soh, D. W. et al. Self-regulation therapy increases frontal gray matter in children with fetal alcohol spectrum disorder: evaluation by voxel-based morphometry. Front. Hum. Neurosci. 9 , 108 (2015).

Wells, A. M., Chasnoff, I. J., Schmidt, C. A., Telford, E. & Schwartz, L. D. Neurocognitive habilitation therapy for children with fetal alcohol spectrum disorders: an adaptation of the Alert Program ® . Am. J. Occup. Ther. 66 , 24–34 (2012).

Wagner, B. et al. School-based intervention to address self-regulation and executive functioning in children attending primary schools in remote Australian Aboriginal communities. PLoS ONE 15 , e0234895 (2020).

Frankel, F. D. & Myatt, R. J. Children’s Friendship Training (Routledge, 2013).

Petrenko, C. L. M., Pandolfino, M. E. & Robinson, L. K. Findings from the families on track intervention pilot trial for children with fetal alcohol spectrum disorders and their families. Alcohol Clin. Exp. Res. 41 , 1340–1351 (2017).

Petrenko, C. L. M. & Alto, M. E. Interventions in fetal alcohol spectrum disorders: an international perspective. Eur. J. Med. Genet. 60 , 79–91 (2017).

Ritfeld, G. J., Kable, J. A., Holton, J. E. & Coles, C. D. Psychopharmacological treatments in children with fetal alcohol spectrum disorders: a review. Child Psychiatry Hum. Dev. 53 , 268–277 (2022).

Coles, C. D. et al. A comparison of children affected by prenatal alcohol exposure and attention deficit, hyperactivity disorder. Alcohol Clin. Exp. Res. 21 , 150–161 (1997).

Young, S. et al. Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus. BMC Psychiatry 16 , 324 (2016).

Mela, M. et al. Treatment algorithm for the use of psychopharmacological agents in individuals prenatally exposed to alcohol and/or with diagnosis of fetal alcohol spectrum disorder (FASD). J. Popul. Ther. Clin. Pharmacol. 27 , e1–e13 (2020).

Akison, L. K., Kuo, J., Reid, N., Boyd, R. N. & Moritz, K. M. Effect of choline supplementation on neurological, cognitive, and behavioral outcomes in offspring arising from alcohol exposure during development: a quantitative systematic review of clinical and preclinical studies. Alcohol Clin. Exp. Res. 42 , 1591–1611 (2018).

Wozniak, J. R. et al. Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder. J. Neurodev. Disord. 12 , 9 (2020).

Hemingway, S. J. A., Davies, J. K., Jirikowic, T. & Olson, E. M. What proportion of the brain structural and functional abnormalities observed among children with fetal alcohol spectrum disorder is explained by their prenatal alcohol exposure and their other prenatal and postnatal risks? Adv. Pediatr. Res. 7 , 41 (2020).

McSherry, D. & McAnee, G. Exploring the relationship between adoption and psychological trauma for children who are adopted from care: a longitudinal case study perspective. Child Abus. Negl. 130 , 105623 (2022).

Koponen, A. M., Kalland, M. & Autti-Rämö, I. Caregiving environment and socio-emotional development of foster-placed FASD-children. Child. Youth Serv. Rev. 31 , 1049–1056 (2009).

Coggins, T. E., Timler, G. R. & Olswang, L. B. A state of double jeopardy: impact of prenatal alcohol exposure and adverse environments on the social communicative abilities of school-age children with fetal alcohol spectrum disorder. Lang. Speech Hear. Serv. Sch. 38 , 117–127 (2007).

Joseph, J. J., Mela, M. & Pei, J. Aggressive behaviour and violence in children and adolescents with FASD: a synthesizing review. Clin. Psychol. Rev. 94 , 102155 (2022).

Perry, B. D. Examining child maltreatment through a neurodevelopmental lens: clinical applications of the neurosequential model of therapeutics. J. Loss Trauma 14 , 240–255 (2009).

Cheung, M. M. Y. et al. Ear abnormalities among children with fetal alcohol spectrum disorder: a systematic review and meta-analysis. J. Pediatr. 242 , 113–120.e16 (2022).

Tsang, T. W. et al. Eye abnormalities in children with fetal alcohol spectrum disorders: a systematic review. Ophthalmic Epidemiol. https://doi.org/10.1080/09286586.2022.2123004 (2022).

Streissguth, A. P. et al. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J. Dev. Behav. Pediatr. 25 , 228–238 (2004).

Oh, S. S. et al. Hospitalizations and mortality among patients with fetal alcohol spectrum disorders: a prospective study. Sci. Rep. 10 , 19512 (2020).

Greenmyer, J. R., Klug, M. G., Kambeitz, C., Popova, S. & Burd, L. A multicountry updated assessment of the economic impact of fetal alcohol spectrum disorder: costs for children and adults. J. Addict. Med. 12 , 466–473 (2018).

Petrenko, C., Tahir, N., Mahoney, E. & Chin, N. Prevention of secondary conditions in fetal alcohol spectrum disorders: identification of systems-level barriers. Matern. Child Health J. 18 , 1496–1505 (2014).

Flannigan, K. et al. Balancing the story of fetal alcohol spectrum disorder: a narrative review of the literature on strengths. Alcohol Clin. Exp. Res. 45 , 2448–2464 (2021).

Mukherjee, R., Wray, E., Commers, M., Hollins, S. & Curfs, L. The impact of raising a child with FASD upon carers: findings from a mixed methodology study in the UK. Adopt. Foster. 37 , 43–56 (2013).

Burd, L., Klug, M. & Martsolf, J. Increased sibling mortality in children with fetal alcohol syndrome. Addict. Biol. 9 , 179–186 (2004).

Li, Q., Fisher, W. W., Peng, C.-Z., Williams, A. D. & Burd, L. Fetal alcohol spectrum disorders: a population based study of premature mortality rates in the mothers. Matern. Child Health J. 16 , 1332–1337 (2012).

Thanh, N. X. & Jonsson, E. Life expectancy of people with fetal alcohol syndrome. J. Popul. Ther. Clin. Pharmacol. 23 , e53–e59 (2016).

Burd, L. et al. Mortality rates in subjects with fetal alcohol spectrum disorders and their siblings. Birth Defects Res. Part. A Clin. Mol. Teratol. 82 , 217–223 (2008).

Article   CAS   Google Scholar  

Thompson, A., Hackman, D. & Burd, L. Mortality in fetal alcohol spectrum disorders. Open J. Pediatr. 4 , 21–33 (2014).

O’Connor, M. J., Portnoff, L. C., Lebsack-Coleman, M. & Dipple, K. M. Suicide risk in adolescents with fetal alcohol spectrum disorders. Birth Defects Res. 111 , 822–828 (2019).

Bobbitt, S. A. et al. Caregiver needs and stress in caring for individuals with fetal alcohol spectrum disorder. Res. Dev. Disabil. 55 , 100–113 (2016).

Domeij, H. et al. Experiences of living with fetal alcohol spectrum disorders: a systematic review and synthesis of qualitative data. Dev. Med. Child Neurol. 60 , 741–752 (2018).

Reid, N. & Moritz, K. M. Caregiver and family quality of life for children with fetal alcohol spectrum disorder. Res. Dev. Disabil. 94 , 103478 (2019).

Connolly, S. L., Miller, C. J., Gifford, A. L. & Charness, M. E. Perceptions and use of telehealth among mental health, primary, and specialty care clinicians during the COVID-19 pandemic. JAMA Netw. Open https://doi.org/10.1001/jamanetworkopen.2022.16401 (2022).

Petrenko, C. L. A review of intervention programs to prevent and treat behavioral problems in young children with developmental disabilities. J. Dev. Phys. Disabil. https://doi.org/10.1007/s10882-013-9336-2 (2013).

Bager, H., Christensen, L. P., Husby, S. & Bjerregaard, L. Biomarkers for the detection of prenatal alcohol exposure: a review. Alcohol Clin. Exp. Res. 41 , 251–261 (2017).

Suttie, M. et al. Facial dysmorphism across the fetal alcohol spectrum. Pediatrics 131 , e779–e788 (2013).

Indiana Alliance on Prenatal Substance Exposure. BRAIN-online. Indiana Alliance on Prenatal Substance Exposure https://inalliancepse.org/brain-online/ (2023).

Goh, P. K. et al. A decision tree to identify children affected by prenatal alcohol exposure. J. Pediatr. 177 , 121–127.e1 (2016).

Mattson, S. N. et al. Validation of the FASD-Tree as a screening tool for fetal alcohol spectrum disorders. Alcohol Clin. Exp. Res. 1-10 https://doi.org/10.1111/acer.14987 the CIFASD (2022).

Bernes, G. A. et al. Development and validation of a postnatal risk score that identifies children with prenatal alcohol exposure. Alcohol Clin. Exp. Res. 46 , 52–65 (2022).

Mooney, S. M., Petrenko, C. L. M., Hamre, K. M. & Brigman, J. Proceedings of the 2021 annual meeting of the fetal alcohol spectrum disorders study group. Alcohol 102 , 23–33 (2022).

Himmelreich, M., Lutke, C., Hargrove, E., Begun, A. & Murray, M. in The Routledge Handbook of Social Work and Addictive Behaviors (eds Begun, A. L. & Murray, M. M.) (Routledge, 2020).

Altimus, C. M. et al. The next 50 years of neuroscience. J. Neurosci. 40 , 101–106 (2020).

Brown, S. A. & Tapert, S. F. Adolescence and the trajectory of alcohol use: basic to clinical studies. Ann. NY Acad. Sci. 1021 , 234–244 (2004).

World Health Organization. Global Action Plan for the Prevention and Control of NCDs 2013–2020 (World Health Organization, 2013).

World Health Organization. Global Strategy to Reduce the Harmful Use of Alcohol (World Health Organization, 2010).

Yanaguita, M. Y. et al. Pregnancy outcome in ethanol-treated mice with folic acid supplementation in saccharose. Childs Nerv. Syst. 24 , 99–104 (2008).

Helfrich, K. K., Saini, N., Kling, P. J. & Smith, S. M. Maternal iron nutriture as a critical modulator of fetal alcohol spectrum disorder risk in alcohol-exposed pregnancies. Biochem. Cell Biol. 96 , 204–212 (2018).

Joya, X., Garcia-Algar, O., Salat-Batlle, J., Pujades, C. & Vall, O. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. Birth Defects Res. A Clin. Mol. Teratol. 103 , 163–177 (2015).

Zhang, Y., Wang, H., Li, Y. & Peng, Y. A review of interventions against fetal alcohol spectrum disorder targeting oxidative stress. Int. J. Dev. Neurosci. 71 , 140–145 (2018).

Zheng, D. et al. The protective effect of astaxanthin on fetal alcohol spectrum disorder in mice. Neuropharmacology 84 , 13–18 (2014).

Peng, Y. et al. Ascorbic acid inhibits ROS production, NF-κB activation and prevents ethanol-induced growth retardation and microencephaly. Neuropharmacology 48 , 426–434 (2005).

Shirpoor, A., Nemati, S., Ansari, M. H. K. & Ilkhanizadeh, B. The protective effect of vitamin E against prenatal and early postnatal ethanol treatment-induced heart abnormality in rats: a 3-month follow-up study. Int. Immunopharmacol. 26 , 72–79 (2015).

Wentzel, P., Rydberg, U. & Eriksson, U. J. Antioxidative treatment diminishes ethanol-induced congenital malformations in the rat. Alcohol Clin. Exp. Res. 30 , 1752–1760 (2006).

Luo, G. et al. Resveratrol attenuates excessive ethanol exposure induced insulin resistance in rats via improving NAD + /NADH ratio. Mol. Nutr. Food Res. 61 , 1700087 (2017).

Yuan, H. et al. Neuroprotective effects of resveratrol on embryonic dorsal root ganglion neurons with neurotoxicity induced by ethanol. Food Chem. Toxicol. 55 , 192–201 (2013).

Cantacorps, L., Montagud-Romero, S. & Valverde, O. Curcumin treatment attenuates alcohol-induced alterations in a mouse model of foetal alcohol spectrum disorders. Prog. Neuropsychopharmacol. Biol. Psychiatry 100 , 109899 (2020).

Tiwari, V. & Chopra, K. Protective effect of curcumin against chronic alcohol-induced cognitive deficits and neuroinflammation in the adult rat brain. Neuroscience 244 , 147–158 (2013).

Gupta, K. K., Gupta, V. K. & Shirasaka, T. An update on fetal alcohol syndrome-pathogenesis, risks, and treatment. Alcohol Clin. Exp. Res. 40 , 1594–1602 (2016).

Popova, S. et al. Health, social and legal outcomes of individuals with diagnosed or at risk for fetal alcohol spectrum disorder: Canadian example. Drug Alcohol Depend. 219 , 108487 (2021).

Popova, S., Lange, S., Bekmuradov, D., Mihic, A. & Rehm, J. Fetal alcohol spectrum disorder prevalence estimates in correctional systems: a systematic literature review. Can. J. Public Health 102 , 336–340 (2011).

Weeks, O. et al. Fetal alcohol spectrum disorder predisposes to metabolic abnormalities in adulthood. J. Clin. Invest. 130 , 2252–2269 (2020).

Carson, G. et al. No. 245-Alcohol use and pregnancy consensus clinical guidelines. J. Obstet. Gynaecol. Can. 39 , e220–e254 (2017).

Gomez, D., Petrenko, C., Monteiro, M. & Rahman, O. Assessment of Fetal Alcohol Spectrum Disorders. Report No. 978-92-75-12224-2 (Pan American Health Organization, 2020).

Download references

Acknowledgements

M.E.C. and E.P.R.: part of the work on mechanisms of alcohol harm was done in conjunction with the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD), which is funded by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Support was provided by U24 AA014811 (E.P.R. and M.E.C.). Additional information about CIFASD, including information on how to request data, can be found at www.cifasd.org . H.E.H.: the section on diagnostic guidelines was partially supported by the National Institute on Alcohol Abuse and Alcoholism grants R01 AA11685, R01/U01 AA01115134, and U01 AA019879-01/NIH-NIAAA (Collaboration on Fetal Alcohol Spectrum Disorders Prevalence (CoFASP)), and by the Oxnard Foundation, Newport Beach, CA, USA. E.J.E. is supported by an Australian Medical Research Futures Fund Next Generation Fellowship (#MRF1135959) and National Health and Medical Research Council of Australia funding for a Centre of Research Excellence in FASD (#GNT1110341).

Author information

Authors and affiliations.

Institute for Mental Health Policy Research, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

Svetlana Popova

VA Boston Healthcare System, West Roxbury, MA, USA

Michael E. Charness

Department of Neurology, Harvard Medical School, Boston, MA, USA

Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA

Department of Neurology, Brigham and Women’s Hospital, Boston, MA, USA

North Dakota Fetal Alcohol Syndrome Center, Department of Pediatrics, University of North Dakota School of Medicine and Health Sciences, Pediatric Therapy Services, Altru Health System, Grand Forks, ND, USA

Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

Andi Crawford

Sanford Children’s Genomic Medicine Consortium, Sanford Health, and University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA

H. Eugene Hoyme

National UK FASD Clinic, Surrey and Borders Partnership NHS Foundation Trust, Redhill, Surrey, UK

Raja A. S. Mukherjee

Center for Behavioral Teratology, San Diego State University, San Diego, CA, USA

Edward P. Riley

Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia

Elizabeth J. Elliott

New South Wales FASD Assessment Service, CICADA Centre for Care and Intervention for Children and Adolescents affected by Drugs and Alcohol, Sydney Children’s Hospitals Network, Westmead, Sydney, New South Wales, Australia

You can also search for this author in PubMed   Google Scholar

Contributions

Introduction (E.P.R. and E.J.E.); Epidemiology (S.P.); Mechanisms/pathophysiology (M.E.C.); Diagnosis, screening and prevention (E.J.E., M.E.C., H.E.H., E.P.R., S.P., A.C. and L.B.); Management (R.A.S.M., A.C. and E.J.E.); Quality of life (S.P., L.B. and R.A.S.M.); Outlook (E.J.E. and M.E.C.); Overview of Primer (S.P. and E.J.E.).

Corresponding author

Correspondence to Svetlana Popova .

Ethics declarations

Competing interests.

The authors declare no competing interests

Peer review

Peer review information.

Nature Reviews Disease Primers thanks C. Chambers, O. Garcia-Algar, J. Kable, C. Valenzuela and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Informed consent.

The authors affirm that human research participants provided informed consent, for publication of the images in Figure 4 .

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary information, rights and permissions.

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Cite this article.

Popova, S., Charness, M.E., Burd, L. et al. Fetal alcohol spectrum disorders. Nat Rev Dis Primers 9 , 11 (2023). https://doi.org/10.1038/s41572-023-00420-x

Download citation

Accepted : 16 January 2023

Published : 23 February 2023

DOI : https://doi.org/10.1038/s41572-023-00420-x

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

Prevention of alcohol exposed pregnancies in europe: the far seas guidelines.

• Carla Bruguera
• Lidia Segura-García

BMC Pregnancy and Childbirth (2024)

Scoping review on the role of the family doctor in the prevention and care of patients with foetal alcohol spectrum disorder

• Sébastien Leruste
• Bérénice Doray
• Michel Spodenkiewicz

BMC Primary Care (2024)

Functional connectivity of cognition-related brain networks in adults with fetal alcohol syndrome

• Benedikt Sundermann
• Reinhold Feldmann
• Bettina Pfleiderer

BMC Medicine (2023)

Assessment of the corpus callosum size in male individuals with high intelligence quotient (members of Mensa International)

• Andrzej Urbanik
• Wiesław Guz
• Monika Ostrogórska

Die Radiologie (2023)

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Disclaimer » Advertising

• HealthyChildren.org

• Previous Article
• Next Article

History and Terminology

Epidemiology, fasd diagnosis, medical, behavioral, and cognitive problems, secondary and co-occurring conditions, economic effects, the role of the pediatrician and the medical home, selected public domain resources, lead authors, committee on substance abuse, 2014–2015, former committee member, contributors, council on children with disabilities, fetal alcohol spectrum disorders expert panel – aap/cdc cooperative agreement, 2021 reference update acknowledgment, abbreviations, fetal alcohol spectrum disorders.

• Split-Screen
• Article contents
• Figures & tables
• Supplementary Data
• Peer Review
• CME Quiz Close Quiz
• Open the PDF for in another window
• Get Permissions
• Cite Icon Cite
• Search Site

Janet F. Williams , Vincent C. Smith , the COMMITTEE ON SUBSTANCE ABUSE; Fetal Alcohol Spectrum Disorders. Pediatrics November 2015; 136 (5): e20153113. 10.1542/peds.2015-3113

Download citation file:

• Ris (Zotero)
• Reference Manager

Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.

Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.

Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.

○ no amount of alcohol intake should be considered safe;

○ there is no safe trimester to drink alcohol;

○ all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and

○ binge drinking poses dose-related risk to the developing fetus.

This clinical report has been reaffirmed with reference and data updates. New or updated references or datapoints are indicated in bold typeface. No other changes have been made to the text or content.

The AAP would like to acknowledge Carol Cohen Weitzman, MD, FAAP, for these updates.

Fetal alcohol spectrum disorders (FASDs) is an overarching phrase that encompasses a range of possible diagnoses, including fetal alcohol syndrome (FAS), partial fetal alcohol syndrome, alcohol-related birth defects (ARBD), alcohol-related neurodevelopmental disorder (ARND), and neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE). FAS refers to a clinical diagnosis based on a specific constellation of physical, behavioral, and cognitive abnormalities resulting from prenatal alcohol exposure (PAE). 1 By 1973, sufficient research evidence had accrued to devise basic diagnostic criteria such that FAS became established as a diagnostic entity. 1 The US Surgeon General issued the first public health advisory in 1981 (reissued in 2005) that alcohol during pregnancy was a cause of birth defects. 2 , 3 In 1989, Congress mandated that alcohol product labels include a warning about potential birth defects. Nineteen states and the District of Columbia have now enacted laws requiring these warnings at the point of sale, including bars and restaurants. 4  

As it became evident that PAE resulted in a spectrum of lifelong manifestations, varying from mild to severe and encompassing a broad variety of physical defects and cognitive, behavioral, emotional, and adaptive functioning deficits, the term “fetal alcohol effects” was adopted to describe children who had PAE manifestations yet did not meet the FAS diagnostic criteria, primarily by lacking physical abnormalities associated with FAS. Because the term was too broad and vague for practical clinical or epidemiologic use, it was retired from use in 1996 and replaced with 2 pathophysiologically based diagnostic categories: ARBD and ARND. 5 , – 7  

Despite greater public awareness, improved terminology, and an accruing body of research, the lack of uniformly accepted diagnostic criteria for FAS and other related disorders has critically limited efforts to determine accurate prevalence figures, expand awareness and prevention campaigns, actuate early identification and intervention programs, and delineate the full continuum of alcohol-related conditions. As part of the fiscal year 2002 appropriations legislation, Congress mandated that the Centers for Disease Control and Prevention (CDC) develop diagnostic guidelines for FAS and related disorders and integrate them broadly across medical and allied health professions’ training curricula. Under the auspices of the CDC, acting through the National Center on Birth Defects and Developmental Disabilities FAS Prevention Team, in conjunction with the National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effects, a multidisciplinary scientific working group of key national experts engaged in an intensive collaborative effort to draw conclusions about PAE effects. This collaborative conducted a comprehensive review of scientific and clinical evidence and extensively consulted with clinicians, experts, and families to delineate clear diagnostic criteria for FAS on the basis of a combination of 3 cardinal facial features, growth problems, and central nervous system abnormalities qualified by confirmed or unknown PAE ( Fig 1 ). 8 Through this effort, practical clinical approaches were endorsed so that those children with PAE could be more readily identified, the condition could be diagnosed with greater accuracy, and children could be referred for appropriate services. 9 , 10  

Child presenting with the 3 diagnostic facial features of FAS: (1) short palpebral fissure lengths, (2) smooth philtrum (Rank 4 or 5 on the Lip-Philtrum Guide), and (3) thin upper lip (Rank 4 or 5 on the Lip-Philtrum Guide). Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

In April 2004, the National Institutes of Health, CDC, and the Substance Abuse and Mental Health Services Administration, along with additional experts in the field, were convened by the National Organization on Fetal Alcohol Syndrome to develop the following consensus definition of FASD: “FASD is an umbrella term describing the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects include physical, mental, behavioral, and/or learning disabilities with possible lifelong implications. The term FASD encompasses all other diagnostic terms, such as FAS, and is not intended for use as a clinical diagnosis.” 11  

Research continued to accrue about ARND, that is, individuals with PAE-associated neurodevelopmental and behavioral abnormalities yet without the FAS facial phenotype, so that in late 2011, the Interagency Coordinating Committee on Fetal Alcohol Spectrum Disorders organized a consensus conference to define ARND diagnostic criteria and related screening and referral needs. 7 As an outgrowth of this conference, a subcommittee collaborated with the American Psychiatric Association in preparing the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition , reorganized on a neurologic disorders framework. The manual includes FASD under the term “FAS (ND-PAE).” 12 , 13 FASD terminology continues to evolve, and research evidence suggests that ARBD may be declining in use while ARND/ND-PAE terminology remains incompletely defined. ND-PAE may become the accepted diagnostic term for moderate PAE findings, and “static encephalopathy” associated with PAE is a suggested diagnostic term for severe PAE effects. 14  

FASDs remain among the most commonly identifiable causes of developmental delay and intellectual disability yet are generally accepted to be vastly underrecognized. FAS, ARBD, and ARND prevalence rates and occurrence patterns have been the subject of many studies since the late 1970s. The wide variance in reported rates reflects the specific diagnoses studied and the different research methodologies used, the 3 most common methodologies being clinic-based studies, passive surveillance of existing records often limited to a geographic area, and active case ascertainment studies. 15 , 16 Although the prevalence of FAS in the United States during the 1980s and 1990s was reported as 0.5 to 2 cases per 1000 live births, recent studies aggressively diagnosing FASD have reported FAS rates and FASD estimates of 6 to 9 cases and 24 to 48 cases per 1000 children (or up to 5%), respectively, while continuing to consider these rates underestimates. 15 , – 18 Rates as high as 9 cases per 1000 live births have long been documented among vulnerable populations, usually related to isolation and socioeconomic impoverishment, such as can be more often found among certain American Indian and other racial/ethnic minority populations. 19 , – 21 An FAS prevalence of 1.0% to 1.5% has been reported among children in foster care. 22 A recent study among a population of foster and adopted youth referred to a children’s mental health center reported a FASD misdiagnosis rate of 6.4% and a missed diagnoses rate of 80.1%. 23 FAS is the FASD with the most explicit diagnostic criteria, so it only represents a fraction of individuals affected by PAE. FASDs other than FAS are more challenging to diagnose, so the true FASD prevalence remains unknown and the actual impact underappreciated. 15 , – 18  

Approximately half of all US women of childbearing age have reported past month alcohol consumption, and use ranged from sporadic intake to 15% reporting binge drinking. 24 Binge drinking is a pattern of drinking that raises a person’s blood alcohol concentration to 0.08% or greater and was originally defined as 5 or more standard drinks per occasion (generally within 2 hours). 25 A “standard drink” contains approximately 0.5 fluid oz of pure ethanol, which is the amount found in a 1.5-oz shot of distilled spirits, 5 oz of wine, or 12 oz of beer. In 2004, the National Institute on Alcohol Abuse and Alcoholism changed the binge drinking definition for women to “the ingestion of 4 or more drinks per occasion” to account for known physiologic gender-related differences affecting alcohol absorption. 26 Setting this lower threshold for binge drinking among women also served to increase prevalence. 27 Binge drinking in the preconception period is associated with unintended pregnancy and a higher likelihood of risky behaviors, including drinking during pregnancy. 28 Often, PAE is unintentional, occurring before the woman knows that she is pregnant. Women continue to drink alcohol and binge drink during pregnancy despite the US Surgeon General’s warnings and their awareness that risk for potential harm exists. 29 , – 31 Although most women report cutting down or abstaining from alcohol use during pregnancy, 7.6% of pregnant women report continued alcohol use, and 1.4% report binge drinking. 24  

FASD as such is not heritable, and having an FASD does not increase a woman’s risk of having a child with FASD. No genetic factors are known to be predictive of which particular children with PAE will have FASDs or the extent of effects. Multiple studies and meta-analyses have focused on how various patterns of drinking during pregnancy might affect fetal and child development. 32 , – 43 Mills et al prospectively studied approximately 31 000 pregnancies to determine how much alcohol pregnant women could safely consume and found increased risk of infant growth retardation even when consumption was limited to 1 standard drink daily. 32 Although a consensus is still lacking about the effects of low levels of PAE, harmful effects are well documented related to moderate or greater PAE and to binge drinking. 34 , – 42 The potential for fetal harm increases as maternal alcohol consumption rises. 34 , 42 Despite methodologic differences, potentially confounding factors, and variable sensitivity among the detection methods applied, these studies support advising that the healthiest choice regarding alcohol use during pregnancy is to abstain.

Ongoing work seeks to define specific diagnostic criteria for each of the FASD conditions along the continuum, such as has been possible for FAS. The FAS diagnosis is made only when an individual meets all 3 diagnostic criteria: prenatal and/or postnatal growth deficiency, the 3 cardinal facial features (reduced palpebral fissure length, smooth philtrum, and thin upper vermillion lip border [ Figs 2 , 3 , 4A , 4B and 5 ]), and any of a range of recognized structural, neurologic, and/or functional central nervous system deficits. 8 , – 10 , 44 Confirmed PAE strengthens the evidence, but FAS can be diagnosed without this history when all of the specific FAS diagnostic criteria have been met. Diagnosing FAS also means a comprehensive history has documented any other in utero substance exposures, including tobacco, medications, or illicit substances of abuse, and that other possible genetic and environmental etiologies have been excluded, specifically Williams, Noonan, 22q deletion syndromes, trisomy 21, and fetal toluene embryopathy, because some dysmorphological features are shared with FAS. 45  

The palpebral fissure length is defined by the distance between the endocanthion (en) and exocanthion (ex) landmarks. Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

The palpebral fissure length (the distance from the inner corner to outer corner of the eye) being measured with a small plastic ruler. Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

Lip-Philtrum Guide 1 is one of two Guides (see Fig 4B ) used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guide reflects the full range of lip thickness and philtrum depth observed among Caucasians with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. Guide 1 is used for Caucasians and all other races with lips like Caucasians. This guide is available from fasdpn.org as a free digital image for use on smartphones. © 2015 Susan Astley, PhD, University of Washington. Legend written by Susan Astley, PhD.

Lip-Philtrum Guide 2 is one of two Guides (see Fig 4A ) used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guide reflects the full range of lip thickness and philtrum depth observed among African Americans with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. Guide 2 is used for African Americans and all other races with thicker lips like African Americans. This guide is available from fasdpn.org as a free digital image for use on smartphones. © 2015 Susan Astley, PhD, University of Washington. Legend written by Susan Astley, PhD.

All other FASD conditions have a range of PAE-associated findings that meet only some of the FAS diagnostic criteria. A computer-based 3-dimensional facial image analysis is showing promise in identifying PAE-affected children who have cognitive impairments but lack the FAS diagnostic facial features. 46 ARBD refers to children with confirmed PAE and certain physical findings related to congenital structural malformations and dysplasias affecting organ systems and/or specific minor anomalies but normal neurodevelopment. 10 , 14 , 33 A confirmed history of PAE should also prompt careful developmental screening and assessment for ARND/ND-PAE, which is among the possible diagnoses when there are no physical stigmata of FAS, yet evidence of brain abnormalities, and either structural or functional neurocognitive disabilities manifest as problems with neurodevelopment, behavior, adaptive skills, and/or self-regulation. 7 , 9 , 10 Other individuals whose features meet most but not all of the diagnostic criteria for FAS are described as having partial fetal alcohol syndrome. Fetal exposure to alcohol and to one or more additional substances complicates the causal explanation of clinical findings because the potential teratogenic, fetal growth, and neurobehavioral effects might be attributable to exposure to the other drug(s) alone, to multiple different exposures, or to drug combinations, including alcohol.

Although a classic FAS diagnostic triad has long been identified, other findings, including microcephaly, behavioral abnormalities, and “noncardinal” abnormal facial features, such as maxillary hypoplasia, cleft palate, or micrognathia, are also well recognized to co-occur with PAE. 1 , 45 , 47 A wide range of developmental and/or medical problems can accompany FAS as a result of alcohol’s structural and/or functional effects on the brain and various other organs or systems, particularly the cardiovascular, renal, musculoskeletal, ocular, and auditory systems. 1 , 45 , 48 A growing body of FASD research has focused on delineating how various brain volume deficits are related to neurocognitive function and facial dysmorphology, and close correlations with alcohol use in the first trimester of pregnancy have been found. 49 , 50 Fetal death is the most extreme PAE outcome, and PAE is also associated with sudden infant death syndrome ( Fig 5 ). 35 , 51  

Young man presenting with the 3 facial features of FAS (small eyes, smooth philtrum, and thin upperlip) at 2 years of age and 20 years of age. Legend written by Susan Astley, PhD. © 2015, Susan Astley PhD, University of Washington.

Children and adolescents with known PAE experience a variety of behavioral and cognitive difficulties, ranging from subtle learning and/or behavioral problems to significant intellectual disability. 10 , 49 , 52 , – 56 PAE is associated with a higher incidence of attention-deficit/hyperactivity disorder (ADHD) and specific learning disabilities, such as mathematics difficulties. 52 , 54 , – 58 The neurocognitive profile associated with FASDs results from deficits in visual-spatial and executive functioning, including impaired impulse control, memory skills, and problem-solving, but also difficulties with abstract reasoning, auditory comprehension, and pragmatic language use. 49 , 58 PAE-associated executive dysfunction is evident as slow information processing and integration, and children with FASD show deficits in cognitive planning, concept formation, set shifting, verbal and nonverbal fluency, social interaction skills, and peer relationships. 49 , 58 Because attention deficits are considered a common characteristic of people with FASD, these skills have been extensively investigated. Children with FASD have demonstrated attention deficiencies with their capacity to hold information temporarily in memory while coding it or performing a mental operation on it and with the ability to shift attention flexibly compared with those with ADHD, who display greater difficulty with focus, concentration, and staying on task. 57 , – 59 Children and adolescents with PAE have difficulty rapidly processing relatively complex information and perform worse on visual than on auditory sustained attention tasks. 60 Although a few case reports have associated extreme PAE with autism spectrum disorders, most reports have delineated qualitative differences in the social difficulties experienced by those with FAS compared with individuals with autism spectrum disorders. 61 , 62  

Compared with the general population, although similar to those with other intellectual disability, individuals with FASD have a higher incidence of concurrent psychiatric, emotional, and behavioral problems. 13 , 49 , 54 , 56 , 63 , – 65 Children and adolescents with FASD have a 95% lifetime likelihood to experience mental health issues, and among the most prevalent are anxiety and mood disorders, particularly depression, as well as ADHD, substance use, addiction, and suicide. Individuals with PAE have greater rates of school disruptions, trouble with the law, and under- or unemployment. 54 , 64 , 65 Failure to achieve age-appropriate socialization and communication skills results in maladaptive and impaired social functioning. Substance use; inappropriate sexual behaviors, such as inappropriate exposure, improper touching, and promiscuity; and consequent legal problems have been reported in adults diagnosed with FAS. 54 , 65 , 66 Delayed diagnosis and misdiagnosis contribute to the higher risk for secondary and co-occurring conditions.

An integrated multifactorial FASD model that includes genetic, PAE, and environmental factors, among others, provides an approach to understanding and assisting this complex and diverse high-risk population. FASDs have no cure, but affected individuals experience improved medical, psychological, and vocational outcomes through longitudinal intervention and treatment that maximize protective factors and build capacity in identified strengths. 67 , – 71 Multimodal symptom treatments that improve long-term outcomes include optimizing environmental modifications, parenting strategies, social support, and developmental and educational interventions that address the neurologically based problems related to FASDs. 67 , – 72 Children with FASDs prescribed neuroleptic medication have shown improved outcomes, but stimulant medication either failed to improve or worsened ADHD symptoms. 73 The heterogeneity of FASD manifestations calls for tailoring treatments to meet individual needs and addressing these constellations of lifelong disabilities across the life span.

Washington State continues to be a national and international leader in FASD diagnostic, prevention, and intervention practices through a long-standing coordinated effort of diverse programs focused on their collective FASD-associated needs and building a strong FASD research and evidence basis. The 2014 recommendations from the Washington State Fetal Alcohol Spectrum Disorders Interagency Work Group highlight evidence-based practices that include identifying risk and protective factors, engaging early intervention, addressing the high FASD risk for substance abuse problems, and applying screening-informed treatment planning, including neuropsychological assessment-guided treatment plans. 74  

Children with FASD are not explicitly designated to receive special education services in the Individuals with Disabilities Education Act; however, some school districts serve affected children through the “Other Health Impaired” category. PAE is not specifically listed in this category but does qualify a child as “at risk” and eligible for early intervention services (Part C). The developmental and behavior difficulties in young children with FASDs qualify for special education services (Part C and Part B). Various school-based educational accommodations have been effective in helping children with FASDs reach their developmental and educational potential, but the transition to the posteducational setting and adulthood poses additional challenges where support services such as vocational training and life skills development are needed. 54 , 69 , 71 , 72 , 74  

The constellation of medical, surgical, behavioral, educational, custodial, judicial, and other services required to care for an individual with FASD results in a large economic burden to the individual, the family, and society. 75 In the 1980s, the estimated annual FAS-related expenses for the United States increased from $75 million to $4 billion, with the lifetime cost of care approaching $1.4 million. 54 , 75 , 76 Cost estimates are similarly high in Canada but also vary widely depending on the methodologies used. 77 During 2005, children with FAS incurred average medical expenditures 9 times higher than those without FAS. 78 When FAS with intellectual disability was considered in making these calculations, average expenditures increased an additional 2.8 times the costs for FAS alone. 79 Because FAS is only 1 subset of FASD, the true economic effect of FASD is much larger. It has been documented in Canada that an FASD evaluation requires 32 to 47 hours for 1 individual to be screened, referred, evaluated, and given the diagnosis of an FASD, resulting in a total cost of $3110 to $4570 per person. 79 On the basis of the cost of a comprehensive multidisciplinary FASD assessment in Canada, the total cost estimate of all FASD screening and diagnosis ranges from $3.6 to $7.3 million per year, excluding treatment costs. 79 The estimated lifetime cost of care, including social and health care services, for each child born with FASD is up to $2.44 million. 75 , 80 The calculated expense of raising a child with FASD is 30 times the cost of preventing the FASD. 81 In 2005, the annual Medicaid cost to care for a child with FASD was 9 times that of a child without FASD. 78  

The main role of a pediatrician and the medical home regarding FASD is to be knowledgeable about the disorder to guide prevention, to suspect and screen for FASD, and to recognize, manage, and refer patients. Pediatricians, medical home team members, and other health professionals are in prime position to provide both primary and secondary FASD prevention education and counseling because young women of childbearing age are among their patient population. 82 Pediatricians build trusted relationships with their adolescent and young adult patients and the parents of these patients, and a routine and expected part of medical home care is to discuss personal health responsibilities, including preventing pregnancy, alcohol, and other substance use and abstaining from sexual activity. Many women have misconceptions about the “safety” of alcohol use and as a result continue to consume alcohol during pregnancy despite the Surgeon General’s warnings. 24 Refraining from alcohol use during pregnancy is an important message to be delivered by health care providers as a part of prenatal care and other health visits during pregnancy. Clear guidance to correct misunderstandings about the risks of alcohol use during pregnancy and educate people about the importance of abstaining from alcohol during pregnancy may prevent further PAE and related outcomes. Earlier termination of alcohol use in pregnancy is associated with fewer alcohol-related complications for the mother and her baby. Specifically, first trimester drinking (vs no drinking) produces 12 times the odds of giving birth to a child with FASD, first and second trimester drinking increases FASD odds 61 times, and drinking in all trimesters increases FASD odds 65 times. 83  

Adolescent patient care standards include providing consistent patient and family education and anticipatory guidance about alcohol use risks, screening for alcohol use and addiction, and intervention to address use and refer patients to treatment. Because adolescents who drink alcohol while pregnant could have a child with a FASD, policies from the American Academy of Pediatrics (AAP) and public domain tools are available to promote pediatrician skills and practices related to alcohol and other drug use screening, brief intervention, and referral to treatment. 84 , – 86  

Given the prevalence in the United States of alcohol use by women who are sexually active or pregnant, pediatricians, through the medical home, should maintain a high level of suspicion for FASD, become familiar with FASD features, and conduct screening to detect PAE and FASD patients as early as possible. Maternal markers that increase the likelihood of a child having had PAE include the mother’s past history of alcohol or drug use problems, such as addiction, multiple drug use, a previous alcohol-exposed pregnancy, little or no prenatal care, unemployment, a transient lifestyle, incarceration, and/or a heavily drinking partner or family member. 66 Primary care providers should consider the possibility for FASD whenever a child has suggestive physical stigmata and/or is being assessed for poor growth, developmental delays, or behavioral concerns, including attention deficit or school failure. Any history of adoption, especially from an environment of socioeconomic impoverishment, whether domestic or international, and any history of involvement with a US child social services system can indicate a higher likelihood of having had PAE and a need for careful screening for FASD. 23 , 53 , 87 A history of involvement with child protective services related to parental substance use or to child neglect, abuse, or abandonment is a strong marker for risk, as is a history of any out-of-home or foster care placement, including kinship care. 87 Many people are not aware of the requirement for health care providers to report FASD to child protective service systems. 88 The 2010 reauthorization of the federal Child Abuse Prevention and Treatment Act legislation included specific policy revisions and mandates about FASD, including “a requirement that health care providers involved in the delivery or care of such infants notify the child protective service system,” make appropriate referrals to this system and other services, and develop a plan of safe care. 88  

Medical home care relevant to FASD patients includes documenting a PAE and other substance exposure history and other historical details as well as physical examination findings, diagnosing FAS in patients when possible, and/or referring for comprehensive FASD assessment and diagnostic evaluation for intervention. 10 , 13 , 72 Effective medical home practices include optimizing the electronic health record use to facilitate documentation of PAE screening as a practice routine and integrating checklists or other tools to facilitate coordinated collaborative care, follow-up connections, and care transitions. Similar to other patients with complex conditions, those with FASDs are best served through periodic well-child care surveillance and coordinated collaborative patient management through referral to medical subspecialists and other health professionals to diagnose and/or manage comorbidities, facilitating access to and enrollment in developmental and educational services, consultation with social work risk assessment services, and coordination with legal and other community resources for the child and family. Partnering with the patient and family helps medical home physicians understand this lifelong diagnosis and how to manage any stigma and emotional responses, such as anger, shame, or blame that may arise from many sources, including themselves. 62 , 89 Working closely with families to engage their child in appropriate developmental and educational services is an ongoing role, and it is important to anticipate and coordinate the eventual transition of individuals with an FASD from pediatric to adult care services. Pediatricians may also refer FASD-diagnosed patients to the Supplemental Security Income (SSI) system so they can obtain income assistance and medical insurance. Many infants and children with FASD may be eligible for SSI. Furthermore, SSI can help adolescents and young adults with income support and medical insurance beyond 26 years of age, if not available through their parents. Early referral to the SSI system is important.

Assessment of physician training needs has shown that although pediatricians are knowledgeable about FASD and PAE risks, they inconsistently provide anticipatory guidance for FASD prevention with adolescent patients and lack confidence about integrating into routine practice the care management and treatment coordination needed by patients affected by FASDs. 90 , 91 To address these gaps, the CDC-funded FASD Regional Training Centers have published a curriculum development guide to create trainings for medical and allied health students and providers. 92 Other educational modalities and practice tools to enhance practitioner confidence with providing FASD care have been cooperatively developed by the CDC and the AAP. 92 Available through the AAP Web site, the FASD Toolkit and clinical algorithm are among the modalities developed to guide FASD screening, diagnosis, and management in the medical home.

There is no known absolutely safe quantity, frequency, type, or timing of alcohol consumption during pregnancy, but having no PAE translates into no FASD. Despite research evidence clearly documenting the spectrum of detrimental consequences of PAE, too many women continue to drink alcohol during pregnancy. Progress continues to be made in understanding the mechanisms of alcohol’s deleterious effects and identifying the most efficacious intervention strategies for preventing and ameliorating deficits associated with FASDs, but each discovery also reveals new challenges. From an economic, societal, educational, family, or health or medical home perspective, FASDs represent a major public health burden. 93 The pediatrician and the medical home as well as cooperative care with practitioners such as obstetricians and family medicine providers play important roles in the success of FASD prevention, intervention and treatment modalities but also in the research progress needed to discover additional means to address the lifelong consequences of FASDs.

AAP FASD Toolkit. www.aap.org/fasd

Astley SJ, Grant T. Recommendations From the Washington State Fetal Alcohol Spectrum Disorders Interagency Work Group, December 2014. Seattle, WA: Washington State Fetal Alcohol Spectrum Disorders Interagency Work Group. http://depts.washington.edu/fasdpn/pdfs/FASD-IAWG-Dec2014-Report.pdf

American College of Obstetricians and Gynecologists. At-Risk Drinking and Alcohol Dependence: Obstetric and Gynecological Implications. www.acog.org/Resources-And- Publications/Committee-Opinions/ Committee-on-Health-Care-for- Underserved-Women/At-Risk- Drinking-and-Alcohol-Dependence- Obstetric-and-Gynecologic- Implications

Centers for Disease Control and Prevention. www.cdc.gov/fasd

FAS Diagnostic and Prevention Network. FAS Facial Photography and Measurement Instruction (using images and animations to teach accurate measurement of FAS facial features). http://depts.washington.edu/fasdpn/htmls/photo-face.htm

National Dissemination Center for Children with Disabilities. www.parentcenterhub.org/nichcy- resources (All About the IEP— Individualized Educational Program: www.parentcenterhub.org/repository/iep/ )

NIAAA Collaborative Initiative on Fetal Alcohol Spectrum Disorders: www.cifasd.org

NOFAS National and State Resource Directory: www.nofas.org/resource-directory

Substance Abuse and Mental Health Services Administration (SAMHSA), Fetal Alcohol Spectrum Disorders (FASD) Center for Excellence: www.fascenter.samhsa.gov

Substance Abuse and Mental Health Services Administration. Addressing Fetal Alcohol Spectrum Disorders (FASD). Treatment Improvement Protocol (TIP) Series 58. HHS Publication No. (SMA) 13-4803. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2014. http://store.samhsa.gov/product/TIP-58- Addressing-Fetal-Alcohol-Spectrum- Disorders-FASD-/SMA13-4803

SAMHSA Treatment Locator: www.samhsa.gov/treatment/index.aspx

Janet F. Williams, MD, FAAP Vincent C. Smith, MD, MPH, FAAP

Sharon Levy, MD, MPH, FAAP, Chairperson Seth D. Ammerman, MD, FAAP Pamela K. Gonzalez, MD, FAAP Sheryl A. Ryan, MD, FAAP Lorena M. Siqueira, MD, MSPH, FAAP Vincent C. Smith, MD, MPH, FAAP

Janet F. Williams, MD, FAAP

Vivian B. Faden, PhD – National Institute of Alcohol Abuse and Alcoholism Gregory Tau, MD, PhD – American Academy of Child and Adolescent Psychiatry

Renee Jarrett, MPH

Sandra L. Friedman, MD, MPH, FAAP

Philip John Matthias, MD, FAAP Paul Seale, MD Yasmin Suzanne Nable Senturias, MD, FAAP Vincent C. Smith, MD, MPH, FAAP Renee M. Turchi, MD, MPH, FAAP David Wargowski, MD Janet F. Williams, MD, FAAP

Jacquelyn Bertrand, PhD – Centers for Disease Control and Prevention Elizabeth Parra Dang, MPH – Centers for Disease Control and Prevention Jeanne Mahoney – American College of Obstetricians and Gynecologists

Rachel Daskalov, MHA Faiza Khan, MPH

Carol Cohen Weitzman, MD, FAAP

American Academy of Pediatrics

attention-deficit/hyperactivity disorder

alcohol-related birth defect

alcohol-related neurodevelopmental disorder

Centers for Disease Control and Prevention

fetal alcohol syndrome

fetal alcohol spectrum disorder

neurobehavioral disorder associated with prenatal alcohol exposure

prenatal alcohol exposure

Advertising Disclaimer »

Citing articles via

Email alerts.

Affiliations

• Editorial Board
• Editorial Policies
• Journal Blogs
• Pediatrics On Call
• Online ISSN 1098-4275
• Print ISSN 0031-4005
• Pediatrics Open Science
• Hospital Pediatrics
• Pediatrics in Review
• AAP Grand Rounds
• Latest News
• Pediatric Care Online
• Red Book Online
• Pediatric Patient Education
• AAP Toolkits
• AAP Pediatric Coding Newsletter

First 1,000 Days Knowledge Center

Institutions/librarians, group practices, licensing/permissions, integrations, advertising.

• Privacy Statement | Accessibility Statement | Terms of Use | Support Center | Contact Us
• © Copyright American Academy of Pediatrics

This Feature Is Available To Subscribers Only

Sign In or Create an Account

Advertisement

Questioning Fetal Alcohol Syndrome: a Case Report of Multiple Etiological Factors

• Published: 22 March 2019
• Volume 5 , pages 41–51, ( 2019 )

Cite this article

• Jack C. Lennon   ORCID: orcid.org/0000-0002-8490-2807 1 &
• Bradford Czochara 2  

752 Accesses

6 Altmetric

Explore all metrics

A 14-year-old, Caucasian, right-handed male presented for neuropsychological evaluation for diagnostic clarification due to attention-deficit/hyperactivity disorder, bipolar I disorder, and oppositional defiant disorder diagnoses and to rule-out fetal alcohol syndrome (FAS) due to aggression, impulsivity, difficulties with authority, and history of legal issues.

Patient was born at 29 weeks gestation without complications. Patient’s adoptive mother reported delays in walking, as well as regression in talking, with suspected prenatal alcohol exposure, neglect, and abuse in first 2 years of life prior to being adopted. Patient is currently in detention setting due to recent homicidal ideation toward family member.

Neuropsychological and psychological tests were administered to assess for FAS and clarify previous diagnoses, for which psychostimulant and antipsychotic medications have proven ineffective. Results suggest minimal intellectual impairment beyond low general processing speed abilities, minor academic achievement concerns in only sentence comprehension, executive dysfunction specifically in inhibition, inefficient learning with early plateau, and externalizing behaviors. Adaptive functioning difficulties are limited to self-direction and safety. No evidence of brain atrophy, delayed physical development, or facial dysmorphia in childhood but significant behavioral concerns suggestive of FASDs.

A wide range of etiological factors with unconfirmed prenatal alcohol exposure, such as neglect, trauma, and poor school attendance, suggests that FAS may be diagnostically restrictive as it pertains to the broad spectrum of prenatal alcohol effects and common comorbidities. FAS criteria may be revisited as it relates to confirmed alcohol exposure when history does not permit.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price includes VAT (Russian Federation)

Instant access to the full article PDF.

Rent this article via DeepDyve

Institutional subscriptions

Similar content being viewed by others

Fetal alcohol spectrum disorders: a case study.

Leila Glass & Sarah N. Mattson

Neuropsychological Aspects of Prevention and Intervention for Fetal Alcohol Spectrum Disorders in Australia

James P. Fitzpatrick & Carmela F. Pestell

In Fetal Alcohol Spectrum Disorder: Comorbidity Determines Complexity

Achenbach, T. M. (1999). The child behavior checklist and related instruments. In M. E. Maruish (Ed.), The use of psychological testing for treatment planning and outcomes assessment (pp. 429–466). Mahwah: Lawrence Erlbaum Associates Publishers.

Google Scholar  

Adleman, N. E., Menon, V., Blasey, C. M., White, C. D., Warsofsky, I. S., Glover, G. H., & Reiss, A. L. (2002). A developmental fMRI study of the Stroop Color-Word task. Neuroimage, 16 (1), 61–75.

Article   PubMed   Google Scholar  

Amato, N., Riva, N., Cursi, M., Martins-Silva, A., Martinelli, V., Comola, M., et al. (2013). Differential frontal involvement in ALS and PLS revealed by Stroop event-related potentials and reaction times. Frontiers in Aging Neuroscience, 5 , 82. https://doi.org/10.3389/fnagi.2013.00082 .

Article   PubMed   PubMed Central   Google Scholar  

American Academy of Pediatrics. (2019a). Common definitions. Retrieved from https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/fetal-alcohol-spectrum-disorders-toolkit/Pages/Common-Definitions.aspx . Accessed 3 Oct 2018.

American Academy of Pediatrics. (2019b). Identification and diagnostic issues . Retrieved from https://www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/fetal-alcohol-spectrum-disorders-toolkit/Pages/Frequently-Asked-Questions.aspx . Accessed 3 Oct 2018.

American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed.). Arlington: American Psychiatric Publishing.

Book   Google Scholar  

Andrews, G., & Robins, C. J. (2010). FAS behavioral survey of traits: screening for effects of prenatal exposure to alcohol. Journal of FAS International Test retrieved from http://www.fetalalcoholsyndrome.org/?page_id=22 ; Scoring retrieved from https://www.uaa.alaska.edu/academics/college-of-health/departments/center-for-human-development/Reducing-Recidivism-Conference/_documents/Christine_King_Session1_FASD_BeST_AdminScoring.pdf . Accessed 1 Feb 2019.

Astley, S. J. (2010). Profile of the first 1,400 patients receiving diagnostic evaluations for fetal alcohol spectrum disorders at the Washington State Fetal Alcohol Syndrome Diagnostic & Prevention Network. Journal of Population Therapeutics and Clinical Pharmacology, 17 , e-132-ee64.

Azorin, J. -M., Perret, L. C., Fakra, E., Tassy, S., Simon, N., Adida, M., & Belzeaux, R. (2017). Alcohol use and bipolar disorders: risk factors associated with their co-occurrence and sequence of onsets. Drug and Alcohol Dependence, 179 , 205–212. https://doi.org/10.1016/j.drugalcdep.2017/07.005 .

Barkley, R. A. (2010). Why emotional impulsiveness should be a central feature of ADHD. The ADHD Report, 18 (4), 1–5.

Article   Google Scholar  

Beck, J. S., Beck, A. T., Jolly, J., & Steer, R. A. (2005). Beck youth inventories for children and adolescents . San Antonio: PsychCorp.

Biederman, J., Spencer, T., Lomedico, A., Day, H., Petty, C. R., & Faraone, S. V. (2012a). Deficient emotional self-regulation and pediatric attention deficit hyperactivity disorder: a family risk analysis. Psychological Medicine, 42 (3), 639–646.

Biederman, J., Spencer, T. J., Petty, C., Hyder, L. L., O’Connor, K. B., Surman, C. B. H., & Faraone, S. V. (2012b). Longitudinal course of deficient emotional self-regulation CBCL profile in youth with ADHD: a prospective controlled study. Neuropsychiatric Disease and Treatment, 8 , 267–276.

Biffen, S. C., Warton, C. M. R., Lindinger, N. M., Randall, S. R., Lewis, C. E., Molteno, C. D., et al. (2018). Reductions in corpus callosum volume partially mediate effects of prenatal alcohol exposure on IQ. Frontiers in Neuroanatomy, 11 , 132. https://doi.org/10.3389/fnana.2017.00132 .

Birmaher, B., Brent, D. A., Chiappetta, L., Bridge, J., Monga, S., & Baugher, M. (1999). Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. Journal of the American Academy of Child & Adolescent Psychiatry, 38 (10), 1230–1236.

Boone, K. B., Salazar, X., Lu, P., Warner-Chacon, K., & Razani, J. (2010). The Rey-15-item recognition trial: a technique to enhance sensitivity of the Rey 15-item memorization test. Journal of Clinical and Experimental Neuropsychology, 24 (5), 561–573.

Boronat, S., Sánchez-Montañez, A., Gómez-Barros, N., Janas, C., Martínez-Ribot, L., Vázquez, E., & Del Campo, M. (2017). Correlation between morphological MRI findings and specific diagnostic categories in fetal spectrum disorders. European Journal of Medical Genetics, 60 (1), 65–71. https://doi.org/10.1016/j.ejmg.2016.09.003 .

Burd, L. (2012). Fetal alcohol spectrum disorders (FASD): a guide for pediatricians and mental health providers. Retrieved from http://www.online-clinic.com/docs/forms/fas_Pediatricians_Layout_1.pdf . Accessed 1 Feb 2019.

Burd, L. (2013). Neurocognitive impairments and prenatal alcohol exposure. Retrieved from http://www.qicct.org/sites/default/files/Neuro%20Impair%20and%20PAE%282%29.pdf . Accessed 1 Feb 2019.

Conners, C. K. (2008). Conners 3rd edition manual . Toronto: Multi-Health Systems.

Crocker, N., Riley, E. P., & Mattson, S. N. (2015). Visual-spatial abilities relate to mathematics achievement in children with heavy prenatal alcohol exposure. Neuropsychology, 29 (1), 108–116. https://doi.org/10.1037/neu0000094 .

Donald, K. A., Eastman, E., Howells, F. M., Adnams, C., Riley, E. P., Woods, R. P., et al. (2015). Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review. Acta Neuropsychiatrica, 27 (5), 251–269. https://doi.org/10.1017/neu.2015.12 .

Ghazi, S. F., Aarabi, M. H., Hosein, Y. M., & Haghshomar, M. (2019). White matter microstructure in fetal alcohol spectrum disorders: a systematic review of diffusion tensor imaging studies. Human Brain Mapping, 40 (3), 1017–1036. https://doi.org/10.1002/hbm.24409 .

Gioia, G., Isquith, P. K., Guy, S. C., & Kenworthy, L. (2000). Behavior Rating Inventory of Executive Function. Child Neuropsychology, 6 (3), 235–238.

Green, C. R., Mihic, A. M., Nikkel, S. M., Stade, B. C., Rasmussen, C., Munoz, D. P., et al. (2009). Executive function deficits in children with fetal alcohol spectrum disorders (FASD) measured using the Cambridge Neuropsychological Tests Automated Battery (CANTAB). Journal of Child Psychology & Psychiatry, 50 (6), 688–697.

Hosenbocus, S., & Chahal, R. (2012). A review of executive function deficits and pharmacological management in children and adolescents. Journal of the Canadian Academy of Child & Adolescent Psychiatry, 21 (3), 223–229.

Hoyme, H. E., May, P. A., Kalberg, W. O., Kodituwakku, P., Gossage, J. P., Trujillo, P. M., et al. (2005). A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 Institute of Medicine criteria. Pediatrics, 115 (1), 39–47.

Hoyme, H.E., Kalberg, W.O., Elliott, A.J., Blankenship, J., Buckley, D., Marais, A.-S., et al. (2016). Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics , 138(2). https://doi.org/10.1542/peds.2015-4256 .

Jacobson, S. W., Jacobson, J. L., Molteno, C. D., Warton, C. M. R., Wintermark, P., Hoyme, H. E., et al. (2017). Heavy prenatal alcohol exposure is related to smaller corpus callosum in newborn MRI scans. Alcoholism, Clinical and Experimental Research, 41 (5), 965–975. https://doi.org/10.1111/acer.13363 .

Jarmasz, J. S., Basalah, D. A., Chudley, A. E., & Del Bigio, M. R. (2017). Human brain abnormalities associated with prenatal alcohol exposure and fetal alcohol spectrum disorder. Journal of Neuropathology & Experimental Neurology, 76 (9), 813–833. https://doi.org/10.1093/jnen/nlx064 .

Kaneria, R. M., Patel, N. C., & Keck, P. E. (2005). Bipolar disorder: new strategy for checking serum valproate. Current Psychiatry, 4 (12), 31–44.

Masi, G., Pisano, S., Milone, A., & Muratori, P. (2015). Child behavior checklist dysregulation profile in children with disruptive behaviors: a longitudinal study. Journal of Affective Disorders, 186 (1), 249–253. https://doi.org/10.1016/j.jad.2015.05.069 .

Mattson, S. N., Riley, E. P., Gramling, L., Delis, D. C., & Jones, K. L. (1998). Neuropsychological comparison of alcohol-exposed children with or without physical features of fetal alcohol syndrome. Neuropsychology, 12 , 146–153.

Mattson, S. N., Crocker, N., & Nguyen, T. T. (2011). Fetal alcohol spectrum disorders: neuropsychological and behavioral features. Neuropsychology Review, 21 (2), 81–101. https://doi.org/10.1007/211065-011-9167-9 .

May, P. A., Chambers, C. D., & Kalberg, W. O. (2018). Prevalence of fetal alcohol spectrum disorders in 4 US communities. Journal of the American Medical Association, 319 (5), 474–482. https://doi.org/10.1001/jama.2017.21896 .

Measurement Instrument Database for the Social Sciences. (2012). The Screen for Child Anxiety Related Disorders (SCARED) [Data file]. Retrieved from http://www.midss.org/sites/default/files/scaredchild1.pdf . Accessed 1 Feb 2019.

Menezes, I. C., von Werne Baes, C., Lacchini, R., & Juruena, M. F. (2019). Genetic biomarkers for differential diagnosis of major depressive disorder and bipolar disorder: a systematic and critical review. Behavioural Brain Research, 357-358 , 29–38. https://doi.org/10.1016/j.bbr.2018.01.008 .

Murphy, A., Steele, H., Steele, M., Allman, B., Kastner, T., & Dube, S. R. (2016). The Clinical Adverse Childhood Experiences (ACEs) Questionnaire: implications for trauma-informed healthcare. In R. D. Briggs (Ed.), Integrated early childhood behavioral health in primary care: a guide to implementation and evaluation (pp. 7–16). Cham: Springer International Publishing. https://doi.org/10.1007/978-3-319-31815-8_2 .

Chapter   Google Scholar  

Nash, K., Rovet, J., Greenbaum, R., Fantus, E., Nulman, I., & Koren, G. (2006). Identifying the behavioral phenotype in fetal alcohol spectrum disorder: sensitivity, specificity and screening potential. Archives of Women's Mental Health, 9 (4), 181–186.

National Organisation for Fetal Alcohol Spectrum Disorder. (2018). FASD: a checklist. Retrieved from https://www.nofasd.org.au/wp-content/uploads/2018/05/FASD-checklist.pdf . Accessed 1 Feb 2019.

National Organization on Fetal Alcohol Syndrome. (2019). Recognizing FASD: identifying individuals with prenatal alcohol exposure. Retrieved from https://www.nofas.org/recognizing-fasd/ Accessed 1 Feb 2019.

Nitch, S., Boone, K. B., Wen, J., Arnold, G., & Alfano, K. (2005). The utility of the Rey Word Recognition Test in the detection of suspect effort. The Clinical Neuropsychologist, 20 (4), 873–887.

Norman, A. L., Crocker, N., Mattson, S. N., & Riley, E. P. (2009). Neuroimaging and fetal alcohol spectrum disorders. Developmental Disabilities Research Reviews, 15 (3), 209–217. https://doi.org/10.1002/ddrr.72 .

O’Connor, M. J., Shah, B., Whaley, S., Cronin, P., Gunderson, B., & Graham, J. (2002). Psychiatric illness in a clinical sample of children with prenatal alcohol exposure. American Journal of Drug & Alcohol Abuse, 28 (4), 743–754. https://doi.org/10.1081/ADA-120015880 .

Peadon, E., & Elliott, E. J. (2010). Distinguishing between attention-deficit hyperactivity and fetal alcohol spectrum disorders in children: clinical guidelines. Neuropsychiatric Disease and Treatment, 6 , 509–515.

Rasmussen, C., Andrew, G., Zwaigenbaum, L., & Tough, S. (2008). Neurobehavioral outcomes of children with fetal alcohol spectrum disorders: a Canadian perspective. Paediatrics & Child Health, 13 (3), 185–191.

Rasmussen, C., Benz, J., Pei, J., Andrew, G., Schuller, G., Abele-Webster, L., et al. (2010). The impact of an ADHD co-morbidity on the diagnosis of FASD. The Canadian Journal of Clinical Pharmacology, 17 (1), e165–e176.

PubMed   Google Scholar  

Reid, N., Shelton, D., Warner, J., O’Callaghan, F., & Dawe, S. (2017). Profile of children diagnosed with a fetal alcohol spectrum disorder: a retrospective chart review. Drug and Alcohol Review, 5 (1), 22. https://doi.org/10.1186/s40359-017-0191-2 .

Reitan, R. M. (1958). Validity of the Trail Making test as an indicator of organic brain damage. Perceptual & Motor Skills, 8 , 271–276 Retrieved from http://apps.usd.edu/coglab/schieber/psyc423/pdf/IowaTrailMaking.pdf . Accessed 1 Feb 2019.

Reynolds, C. R., & Kamphaus, R. W. (2015). Behavior Assessment System for Children, Third Edition (BASC-3) . Bloomington: Pearson.

Riley, E. P., Mattson, S. N., Sowell, E. R., Jemigan, T. L., Sobel, D. F., & Jones, K. L. (1995). Abnormalities of the corpus callosum in children prenatally exposed to alcohol. Alcoholism, Clinical and Experimental Research, 19 (5), 1198–1202.

Saunders, E. H., Scott, L. J., McInnis, M. G., & Burmeister, M. (2008). Familiality and diagnostic patterns of subphenotypes in the National Institutes of Mental Health bipolar sample. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 147B (1), 18–26.

Stratton, K.R., Howe, C.J., Battaglia, F.C. (1996). Fetal alcohol syndrome - diagnosis, epidemiology, prevention, and treatment. Washington, DC: National Academy Press.

Stroop, J. R. (1935). Studies of interference in serial verbal reactions. Journal of Experimental Psychology, 18 , 643–662.

Sulik, K. K., Johnston, M. C., & Webb, M. A. (1981). Fetal alcohol syndrome: embryogenesis in a mouse model. Science, 214 , 936–938.

Surman, C. B. H., Biederman, J., Spencer, T., Miller, C. A., Petty, C. R., & Faraone, S. V. (2015). Neuropsychological deficits are not predictive of deficient emotional self-regulation in adults with ADHD. Journal of Attention Disorders, 19 (12), 1046–1053.

Tsang, T. W., Lucas, B. R., Olson, H. C., Pinto, R. Z., & Elliott, E. J. (2016). Prenatal alcohol exposure, FASD, and child behavior: a meta-analysis. Pediatrics, 137 (3), e20152542. https://doi.org/10.1542/peds.2015-2542 .

Vaurio, L., Riley, E. P., & Mattson, S. N. (2008). Differences in executive functioning in children with heavy prenatal alcohol exposure or attention-deficit/hyperactivity disorder. Journal of the International Neuropsychological Society, 14 , 119–129.

Wechsler, D. (2014). Wechsler Intelligence Scale for Children-Fifth Edition . Bloomington: Pearson.

Wilkinson, G. S., & Robertson, G. J. (2006). Wide Range Achievement Test 4 professional manual . Lutz: Psychological Assessment Resources.

Williams, J. F., Smith, V. C., & The Committee on Substance Abuse. (2015). Fetal alcohol spectrum disorders. Pediatrics, 136 (5). https://doi.org/10.1542/peds.2015-3113 .

Willoughby, K. A., Sheard, E. D., Nash, K., & Rovet, J. (2008). Effects of prenatal alcohol exposure on hippocampal volume, verbal learning, and verbal and spatial recall in late childhood. Journal of the International Neuropsychological Society, 14 (6), 1022–1033.

Download references

Acknowledgments

This work was not supported by any funding sources.

Author information

Authors and affiliations.

Department of Clinical Neuropsychology, Illinois School of Professional Psychology at Argosy University, 225 North Michigan Avenue, Suite 1300, Chicago, IL, 60601, USA

Jack C. Lennon

Department of Clinical Psychology, Midwestern University, 555 31st Street, Downers Grove, IL, 60515, USA

Bradford Czochara

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Jack C. Lennon .

Ethics declarations

Conflict of interest.

The authors declare that they have no conflicts of interest.

Human and Animal Rights in Informed Consent

In this case report, the cited articles contain studies with human and/or animal work approved by institutional review boards prior to publication.

Informed Consent

Informed consent to neuropsychological testing was obtained from the patient and legal guardian in regard to the clinical referral question at-hand. Informed consent for research was also obtained from the patient and legal guardian. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Lennon, J.C., Czochara, B. Questioning Fetal Alcohol Syndrome: a Case Report of Multiple Etiological Factors. J Pediatr Neuropsychol 5 , 41–51 (2019). https://doi.org/10.1007/s40817-019-00065-3

Download citation

Received : 13 December 2018

Revised : 06 February 2019

Accepted : 18 February 2019

Published : 22 March 2019

Issue Date : 15 June 2019

DOI : https://doi.org/10.1007/s40817-019-00065-3

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Fetal alcohol spectrum disorders
• Substance use
• Find a journal
• Publish with us
• Track your research

LEEANNE DENNY, MD, SARAH COLES, MD, AND ROBIN BLITZ, MD

This is a corrected version of the article that appeared in print. Figure 2 has been updated.

Am Fam Physician. 2017;96(8):515-522A

AAFP Resource: See related resources from the American Academy of Family Physicians on alcohol misuse.

Patient information: A handout on this topic is available at https://familydoctor.org/condition/fetal-alcohol-syndrome .

Author disclosure: No relevant financial affiliations.

Fetal alcohol syndrome (FAS) and fetal alcohol spectrum disorders (FASD) result from intrauterine exposure to alcohol and are the most common nonheritable causes of intellectual disability. The percentage of women who drink or binge drink during pregnancy has increased since 2012. FAS is commonly missed or misdiagnosed, preventing affected children from receiving needed services in a timely fashion. Diagnosis is based on the presence of the following clinical features, all of which must be present: prenatal and/or postnatal growth retardation, facial dysmorphology, central nervous system dysfunction, and neurobehavioral disabilities. FASD is a broader diagnosis that encompasses patients with FAS and others who are affected by prenatal alcohol exposure but do not meet the full criteria for FAS. Management is multidisciplinary and includes managing comorbid conditions, providing nutritional support, managing behavioral problems and educational difficulties, referring patients for habilitative therapies, and educating parents. The Centers for Disease Control and Prevention and other organizations recognize no safe amount of alcohol consumption during pregnancy and recommend complete abstinence from alcohol. All women should be screened for alcohol use during preconception counseling and prenatal care, and alcohol use should be addressed with brief interventions.

Fetal alcohol spectrum disorders (FASD) result from prenatal exposure to alcohol and include fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (PFAS), alcohol-related neurodevelopmental disorder, and alcohol-related birth defects. 1 FAS is the most severe form of FASD. 2

WHAT IS NEW ON THIS TOPIC: FETAL ALCOHOL SPECTRUM DISORDERS

According to the Centers for Disease Control and Prevention, the percentage of pregnant women who consume alcohol increased from 7.6% in 2012 to 10.2% in 2015, and the number of pregnant women reporting binge drinking (at least four alcoholic beverages at once) increased from 1.4% to 3.1%.

A study demonstrated that more than one-half of children with fetal alcohol spectrum disorders do not consume the recommended dietary allowance of fiber, calcium, or vitamins D, E, and K.

According to the Centers for Disease Control and Prevention, the percentage of pregnant women who consume alcohol increased from 7.6% in 2012 to 10.2% in 2015, and the number of pregnant women reporting binge drinking (four or more alcoholic beverages at once) increased from 1.4% to 3.1%. 3 , 4 These trends are concerning because alcohol is the most common teratogen, and FASD is the most common cause of nonheritable intellectual disability. 5 Binge drinking is associated with the development of behavioral problems and physical deformities. 6

Although there is wide variation in the estimated prevalence of FAS/FASD, FAS is thought to occur in 0.3 to 0.8 per 1,000 children in the United States and in 2.9 per 1,000 globally. 7 , 8 The prevalence of FASD is estimated at 33.5 per 1,000 children in the United States and 22.8 per 1,000 globally. 8 In the United States, FASD is least prevalent in Hispanic children and most prevalent in Native Americans and Alaska Natives. 4 FAS is diagnosed at an average age of 48.3 months 9 ; however, it is commonly missed or misdiagnosed, preventing affected children from receiving needed services in a timely fashion.

FASD carries a significant economic burden. Children with FAS who are enrolled in Medicaid have annual mean medical expenses nine times higher than those for children without FAS, equating to a median annual expenditure of $6,670 per child (vs. $518 for those without FAS). 10

Any child who was exposed to alcohol pre-natally or presents with growth retardation, facial dysmorphology, central nervous system dysfunction, or neurobehavioral disabilities—the key manifestations of FASD—should prompt consideration of FASD. 11 The assessment and diagnosis require a multidisciplinary team ( Table 1 1 , 12 ) and should include neuropsychological assessment. 1

Diagnosis begins with assessment of prenatal alcohol exposure, including quantity of alcohol consumed per occasion, frequency of use, and timing of consumption during pregnancy. Prenatal alcohol exposure is defined as at least one of the following documented findings: (1) six or more drinks per week for two or more weeks during pregnancy; (2) three or more drinks per occasion on two or more occasions during pregnancy; (3) alcohol-related social or legal problems around the time of pregnancy; (4) intoxication during pregnancy documented by blood, breath, or urinary alcohol testing; (5) positive test for alcohol exposure biomarkers during pregnancy (fatty acid ethyl esters, phosphatidylethanol, and ethyl glucuronide in maternal hair, fingernails, urine, or blood, or in placenta or meconium); (6) increased prenatal risk associated with alcohol use during pregnancy as assessed by a validated screening tool. Documentation includes drinking levels reported by the mother three months before pregnancy recognition or at the time of a positive pregnancy test. Information must be obtained by the mother or a reliable source, such as family member, social service agency, or medical record. 1

Exposure to other teratogens should also be assessed, because women who consume alcohol during pregnancy are more likely to use other drugs. 1 The diagnostic criteria for FAS or PFAS do not require confirmed alcohol use if characteristic findings are present. 1 , 11 However, a confirmed absence of alcohol exposure rules out the diagnoses. Confirmation of alcohol exposure is required for diagnosis of alcohol-related neurodevelopmental disorder and alcohol-related birth defects. 1

KEY DIAGNOSTIC CRITERIA

As previously noted, FASD comprises four distinct categories: FAS, PFAS, alcohol-related neurodevelopmental disorder, and alcohol-related birth defects. Each category is distinguished by the presence or absence of characteristic facial dysmorphology, growth retardation, central nervous system dysfunction, and neurobehavioral disabilities ( Table 2 ) . 1

Characteristic facial dysmorphology associated with FASD includes short palpebral fissures (10th percentile or less for age and racial norms), a thin vermilion border of the upper lip, and a smooth philtrum 1 ( Figure 1 13 ) . Two of the three characteristic features are required for the diagnosis of FAS or PFAS. Palpebral fissures can be measured using a small plastic ruler, noting the distance between the endocanthion (where the eyelids meet medially) and exocanthion (where they meet laterally). The ruler should be angled to follow the curve of the zygoma. 1 The presence of a thin vermilion border and smooth philtrum is scored objectively using the lip-philtrum scoring guide ( Figure 2 ) . 14 Scores of 4 or 5 are consistent with FAS or PFAS.

Growth retardation is defined as the 10th percentile or less using height and weight measurements on standard growth curves. 1 For central nervous system dysfunction to qualify as consistent with FASD, it must include deficient brain growth, abnormal structure, or abnormal neurophysiology. This can be documented as a head circumference in the 10th percentile or less on appropriate growth curves, structural brain abnormalities, or recurrent nonfebrile seizures with no other identifiable cause. 1 Magnetic resonance imaging has identified structural brain abnormalities in children with FASD (e.g., temporal lobe asymmetry, change in size or shape of corpus callosum, cerebellum, or basal ganglia), and it may be used in the evaluation of suspected FASD; it can also be helpful if there is a question about the differential diagnosis. 1 , 15 – 17

Neurobehavioral disabilities in FASD include deficient global intellectual ability and cognition, and poor behavior, self-regulation, and adaptive skills. These domains should be measured using standardized testing, which often cannot be administered until after three years of age. A deficiency on these tests is characterized by scores of at least 1.5 standard deviations below the mean. 1 Alcohol-related neurodevelopmental disorder is diagnosed with documented prenatal alcohol exposure and neurobehavioral impairment in at least two domains in the absence of other defining characteristics for FAS.

Although they are not included in the diagnostic criteria for FAS or PFAS, multiple congenital abnormalities associated with prenatal alcohol exposure have been described for nearly every organ system ( Table 3 ) . 15 , 18 – 21 In the absence of defining criteria for FAS or PFAS, documented prenatal alcohol exposure and the presence of one or more major malformations known to result from prenatal alcohol exposure are diagnostic for alcohol-related birth defects 1 ( eTable A , Figure 3 13 ).

Differential Diagnosis

The differential diagnosis for FASD includes a variety of chromosomal abnormalities, exposure to other teratogens, and behavioral and psychiatric diagnoses ( Table 4 ) . 2 , 22 – 28 If the diagnosis is uncertain, the workup should include referral to a developmental pediatrician or geneticist for further evaluation, which may involve a chromosomal microarray, cranial neuroimaging, and cardiac/abdominal ultrasonography. 2

There is no cure for FASD. 5 There is a lack of evidence on which to base recommendations for optimal management; therefore, much of the management is based on expert opinion. Treatment consists of providing a medical home for the patient and family, managing comorbid conditions, providing nutritional support, addressing behavioral and emotional problems, arranging referrals for habilitative therapies (therapeutic intervention for those who have never developed a specific skill), coordinating care with a multidisciplinary team, and educating parents ( Table 5 ) . Early intervention is necessary to optimize health outcomes. 11 , 29

MANAGING COMORBID CONDITIONS

Children with FASD can have a range of comorbid conditions ( Table 3 ) 15 , 18 – 21 ; referrals to members of the multidisciplinary team are based on the specific needs identified. Because hearing and vision impairments are correlated with prenatal alcohol exposure, all children with suspected FASD should have hearing and vision screening. 30 , 31

NUTRITIONAL SUPPORT

Children with FASD are nutritionally and socially vulnerable and may benefit from nutritional education and support. By midchildhood, most of these children have spent, on average, one-fourth of their life with unmet basic needs and one-third of their life with someone who abuses alcohol or drugs. 29 One study showed that more than 50% of children with FASD do not consume the recommended dietary allowance of fiber, calcium, or vitamins D, E, and K. 32 It is important to regularly assess the child's height, weight, and body mass index and refer for support (e.g., nutritionist, social worker) when nutritional problems are identified. 33 Some children will require high-calorie foods and supplements.

MANAGING BEHAVIORAL PROBLEMS

Children with FASD should be monitored and screened for behavioral problems. They have an increased risk of attention-deficit/hyperactivity disorder (40% to 95%), 34 , 35 mood disorders (50%), 36 and oppositional defiant disorder (38%). 35 Medications can improve hyperactivity and impulsivity, but not symptoms of inattention. 37 , 38 Children with FASD and attention-deficit/hyperactivity disorder or other disruptive behaviors should be referred to a developmental pediatrician, psychologist, and/or psychiatrist. Behavioral interventions such as play therapy, children's friendship training, and specially trained case managers have reasonable evidence of effectiveness, but these resources have variable availability. 37

FAMILY SUPPORT

Children with FASD are at increased risk of physical and sexual violence, with 61% experiencing physical or sexual abuse or witnessing domestic violence by 12 years of age. 29 , 39 Sexual abuse should be considered in children who present with inappropriate sexual behaviors. Children with FASD who remain in the care of their biologic mother are more likely to experience family dysfunction and instability (e.g., divorce, unemployment, drug and alcohol use). 25 , 29 Those who are raised in stable homes have improved outcomes and are less likely to be expelled from or drop out of school, be arrested, or develop substance use problems. 29 Interventions should be aimed at stabilizing the home environment and improving parent-child interactions. 11 Such interventions include parental substance abuse referrals, child discipline courses, parent support groups, and child protective services.

Prognosis varies with the degree of impairment. Persons with FASD are more likely to require special education, receive disability pensions, and be unemployed. 40 Those who receive early diagnosis and intervention (before 12 years of age) have significantly better outcomes, including a two- to fourfold reduction in rates of imprisonment and substance abuse. 29

The Centers for Disease Control and Prevention, the American Academy of Family Physicians, the American Academy of Pediatrics, and the American Congress of Obstetricians and Gynecologists recognize no safe amount of alcohol consumption during pregnancy and recommend complete abstinence. 26 , 41 – 43 Although many women abstain from alcohol when they learn they are pregnant, some consume alcohol before they find out. Contraception should be offered to women of child-bearing age who drink; if they desire pregnancy, abstinence from alcohol should be recommended. 44 The American Congress of Obstetricians and Gynecologists recommends screening women in the first trimester for alcohol use, and Canadian guidelines recommend screening all pregnant women for alcohol use. 42 , 45 A useful screening tool is the TACER-3, which identifies women whose drinking may put their fetus at risk of FASD ( Table 6 ) . 46

If alcohol use in pregnancy is identified, physicians should recommend cessation and offer group-based interventions such as Alcoholics Anonymous and alcohol rehabilitation centers. 47 Brief interventions that include the patient's partner improve FASD-related birth outcomes and should include assessing maternal understanding of healthy pregnancy behaviors, assisting the mother in setting the goal of abstinence from alcohol, planning alternative behaviors for when the temptation to drink arises, and inviting the partner to find methods to support the mother's abstinence from alcohol. 48 , 49

This article updates a previous article on this topic by Wattendorf and Muenke . 13

Data Sources: Sources searched include PubMed (OVID), Evidence Summary from the AFP 's editors, Essential Evidence Plus, Cochrane database, and the Agency for Healthcare Research and Quality. Search terms included: fetal alcohol syndrome, fetal alcohol spectrum disorder, alcohol-related birth defects, maternal alcohol consumption, prenatal alcohol exposure. Search dates: February 2016, April 2016, May 2016, June 2016, July 2016, November 2016, and December 2016.

Figures 1 and 3 courtesy of Darryl Leja, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md.

Hoyme HE, Kalberg WO, Elliott AJ, et al. Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics. 2016;138(2):e20154256.

de Sanctis L, Memo L, Pichini S, Tarani L, Vagnarelli F. Fetal alcohol syndrome: new perspectives for an ancient and underestimated problem. J Matern Fetal Neonatal Med. 2011;24(suppl 1):34-37.

Tan CH, Denny CH, Cheal NE, Sniezek JE, Kanny D. Alcohol use and binge drinking among women of childbearing age—United States, 2011–2013. MMWR Morb Mortal Wkly Rep. 2015;64(37):1042-1046.

Centers for Disease Control and Prevention (CDC). Alcohol use and binge drinking among women of childbearing age—United States, 2006–2010. MMWR Morb Mortal Wkly Rep. 2012;61(28):534-538.

Joya X, Garcia-Algar O, Salat-Batlle J, Pujades C, Vall O. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention. Birth Defects Res A Clin Mol Teratol. 2015;103(3):163-177.

Alvik A, Aalen OO, Lindemann R. Early fetal binge alcohol exposure predicts high behavioral symptom scores in 5.5-year-old children. Alcohol Clin Exp Res. 2013;37(11):1954-1962.

Fox DJ, Pettygrove S, Cunniff C, et al.; Centers for Disease Control and Prevention (CDC). Fetal alcohol syndrome among children aged 7–9 years—Arizona, Colorado, and New York, 2010. MMWR Morb Mortal Wkly Rep. 2015;64(3):54-57.

Roozen S, Peters GJ, Kok G, Townend D, Nijhuis J, Curfs L. Worldwide prevalence of fetal alcohol spectrum disorders: a systematic literature review including meta-analysis [published correction appears in Alcohol Clin Exp Res . 2016;40(7):1587]. Alcohol Clin Exp Res. 2016;40(1):18-32.

Moberg DP, Bowser J, Burd L, Elliott AJ, Punyko J, Wilton G Fetal Alcohol Syndrome Surveillance Program-FASSLink Team. Fetal alcohol syndrome surveillance: age of syndrome manifestation in case ascertainment. Birth Defects Res. 2014;100(9):663-669.

Amendah DD, Grosse SD, Bertrand J. Medical expenditures of children in the United States with fetal alcohol syndrome. Neurotoxicol Teratol. 2011;33(2):322-324.

Bertrand J, Floyd LL, Weber MK Fetal Alcohol Syndrome Prevention Team, Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention (CDC). Guidelines for identifying and referring persons with fetal alcohol syndrome [published correction appears in MMWR Morb Mortal Wkly Rep . 2006;55(20):568]. MMWR Recomm Rep. 2005;54(RR-11):1-14.

Chasnoff IJ, Wells AM, King L. Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure. Pediatrics. 2015;135(2):264-270.

Wattendorf DJ, Muenke M. Fetal alcohol spectrum disorders. Am Fam Physician. 2005;72(2):279-282.

FAS Diagnostic & Prevention Network. Lip-philtrum guides. http://depts.washington.edu/fasdpn/htmls/lip-philtrum-guides.htm . Accessed January 30, 2017.

Norman AL, Crocker N, Mattson SN, Riley EP. Neuroimaging and fetal alcohol spectrum disorders. Dev Disabil Res Rev. 2009;15(3):209-217.

Stoos C, Nelsen L, Schissler KA, Elliot AJ, Kinney HC. Fetal alcohol syndrome and secondary schizophrenia: a unique neuropathological study. J Child Neurol. 2015;30(5):601-605.

Cook JL, Green CR, Lilley CM, et al.; Canada Fetal Alcohol Spectrum Disorder Research Network. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. CMAJ. 2016;188(3):191-197.

Popova S, Lange S, Shield K, et al. Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. Lancet. 2016;387(10022):978-987.

American Academy of Pediatrics Committee on Substance Abuse and Committee on Children with Disabilities. Fetal alcohol syndrome and alcohol-related neurodevelopmental disorders. Pediatrics. 2000;106(2 pt 1):358-361.

Caputo C, Wood E, Jabbour L. Impact of fetal alcohol exposure on body systems: a systematic review. Birth Defects Res C Embryo Today. 2016;108(2):174-180.

Gummel K, Ygge J. Ophthalmologic findings in Russian children with fetal alcohol syndrome. Eur J Ophthalmol. 2013;23(6):823-830.

Douzgou S, Breen C, Crow YJ, et al. Diagnosing fetal alcohol syndrome: new insights from newer genetic technologies. Arch Dis Child. 2012;97(9):812-817.

Burd L, Cotsonas-Hassler TM, Martsolf JT, Kerbeshian J. Recognition and management of fetal alcohol syndrome. Neurotoxicol Teratol. 2003;25(6):681-688.

Jones KL. Fetal alcohol syndrome. In: Smith's Recognizable Patterns of Human Malformation . 6th ed. Philadelphia, Pa.: Elsevier Saunders; 2006:646.

Toutain S, Lejeune C. Family management of infants with fetal alcohol syndrome or fetal alcohol spectrum disorders. J Dev Phys Disabil. 2008;20(5):425-436.

National Center on Birth Defects and Developmental Disabilities; Centers for Disease Control and Prevention; U.S. Department of Health and Human Services; National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect. Fetal alcohol syndrome: guidelines for referral and diagnosis. July 2004. http://www.cdc.gov/ncbddd/fasd/documents/FAS_guidelines_accessible.pdf . Accessed July 23, 2016.

Thackray H, Tifft C. Fetal alcohol syndrome. Pediatr Rev. 2001;22(2):47-55.

Adams DJ, Clark DA. Common genetic and epigenetic syndromes. Pediatr Clin North Am. 2015;62(2):411-426.

Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O'Malley K, Young JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. J Dev Behav Pediatr. 2004;25(4):228-238.

Pruett D, Waterman EH, Caughey AB. Fetal alcohol exposure: consequences, diagnosis, and treatment. Obstet Gynecol Surv. 2013;68(1):62-69.

Carter RC, Jacobson SW, Molteno CD, Chiodo LM, Viljoen D, Jacobson JL. Effects of prenatal alcohol exposure on infant visual acuity. J Pediatr. 2005;147(4):473-479.

Fuglestad AJ, Fink BA, Eckerle JK, et al. Inadequate intake of nutrients essential for neurodevelopment in children with fetal alcohol spectrum disorders (FASD). Neurotoxicol Teratol. 2013;39:128-132.

Young JK, Giesbrecht HE, Eskin MN, Aliani M, Suh M. Nutrition implications for fetal alcohol spectrum disorder. Adv Nutr. 2014;5(6):675-692.

Fryer SL, McGee CL, Matt GE, Riley EP, Mattson SN. Evaluation of psychopathological conditions in children with heavy prenatal alcohol exposure. Pediatrics. 2007;119(3):e733-e741.

O'Connor MJ, Shah B, Whaley S, Cronin P, Gunderson B, Graham J. Psychiatric illness in a clinical sample of children with prenatal alcohol exposure. Am J Drug Alcohol Abuse. 2002;28(4):743-754.

Davis K, Desrocher M, Moore T. Fetal alcohol spectrum disorder: a review of neurodevelopmental findings and interventions. J Dev Phys Disabil. 2011;23(2):143-167.

Oesterheld JR, Kofoed L, Tervo R, Fogas B, Wilson A, Fiechtner H. Effectiveness of methylphenidate in Native American children with fetal alcohol syndrome and attention deficit/hyperactivity disorder: a controlled pilot study. J Child Adolesc Psychopharmacol. 1998;8(1):39-48.

Freunscht I, Feldmann R. Young adults with fetal alcohol syndrome (FAS): social, emotional and occupational development. Klin Padiatr. 2011;223(1):33-37.

Rangmar J, Hjern A, Vinnerljung B, Strömland K, Aronson M, Fahlke C. Psychosocial outcomes of fetal alcohol syndrome in adulthood. Pediatrics. 2015;135(1):e52-e58.

Williams JF, Smith VC Committee on Substance Abuse. Fetal alcohol spectrum disorders. Pediatrics. 2015;136(5):e1395-e1406.

American College of Obstetricians and Gynecologists; Committee on Health Care for Underserved Women. Committee opinion no. 496: at-risk drinking and alcohol dependence: obstetric and gynecologic implications. Obstet Gynecol. 2011;118(2 pt 1):383-388.

American Academy of Family Physicians. Substance abuse and addiction. https://www.aafp.org/about/policies/all/substance-abuse.html . Accessed December 9, 2016.

Green P, McKnight-Eily L, Tan C, Mejia R, Denny C. Vital signs: alcohol-exposed pregnancies—United States, 2011–2013. MMWR Morb Mortal Wkly Rep. 2016;65(4):91-97.

Carson G, Cox LV, Crane J, et al.; Society of Obstetricians and Gynaecologists of Canada. Alcohol use and pregnancy consensus clinical guidelines. J Obstet Gynaecol Can. 2010;32(8 suppl 3):S1-S31.

Chiodo LM, Delaney-Black V, Sokol RJ, Janisse J, Pardo Y, Hannigan JH. Increased cut-point of the TACER-3 screen reduces false positives without losing sensitivity in predicting risk alcohol drinking in pregnancy. Alcohol Clin Exp Res. 2014;38(5):1401-1408.

Committee opinion no. 633: alcohol abuse and other substance use disorders: ethical issues in obstetric and gynecologic practice. Obstet Gynecol. 2015;125(6):1529-1537.

Chang G, McNamara TK, Orav EJ, et al. Brief intervention for prenatal alcohol use: a randomized trial. Obstet Gynecol. 2005;105(5 pt 1):991-998.

O'Connor MJ, Whaley SE. Brief intervention for alcohol use by pregnant women. Am J Public Health. 2007;97(2):252-258.

Continue Reading

More in AFP

More in pubmed.

Copyright © 2017 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions  for copyright questions and/or permission requests.

Copyright © 2024 American Academy of Family Physicians. All Rights Reserved.

Understanding Fetal Alcohol Spectrum Disorders (FASD)

A Comprehensive Guide for Pre-K-8 Educators

Home » Chapter 7: Case Study I

• Introduction
• Chapter 1: Physical, Neuropsychological, & Behavioral Manifestations of Children with FASD
• Chapter 2: Pattern of Prenatal Alcohol Exposure Determines the FASD Phenotype
• Chapter 3: Effects of Prenatal Alcohol Exposure on Brain Development and Post-Natal Function
• Chapter 4: The FASD Student & the Classroom
• Chapter 5: The FASD Student & Learning Issues
• Chapter 6: The FASD Student & Behavioral Issues
• Student Study Team
• Individual Education Plan (IEP)
• Reason for Referral
• Chapter 8: Case Study 2
• Chapter 9: Strategies for Other Educational Professionals

Chapter 7: Case Study I

Lynn is an 8 year old 1st grade student attending Oakview Elementary School. Very little information is known about her biological mother. It is reported that her mother had a history of substance abuse, and Lynn was possibly exposed to alcohol in utero. It is known that Lynn has a sibling who was born when she was 1 years old. Shortly after her sibling was born, Lynn was placed with a foster family. She was adopted by the Copelands when she was 3 years old.

Lynn was the Copelands’ first child and they were not certain when developmental milestones should be achieved. The Copelands brought Lynn to a pediatrician. They wanted her to have a thorough check-up given her high activity level and their concern with her short stature and low weight. The pediatrician reassured the Copelands that Lynn was adjusting to her new home and that she was “on the charts” with height and weight at the 5th percentile, not to worry.

As the Copelands spent more time with Lynn, they were concerned that she had special needs. They decided to take Lynn to another pediatrician. This pediatrician took note of the limited known history of her biological mother and observed that Lynn had some mild dysmorphia. The pediatrician, familiar with FASD, assessed that Lynn had some behavioral and cognitive features consistent with prenatal alcohol exposure. Lynn was given the diagnosis of Fetal Alcohol Spectrum Disorder.

When Lynn first arrived at the Copelands’, she was quite active; in fact, she was described as rambunctious. She ran from one activity to the next. Although quite verbal, language difficulties became apparent. Lynn had a slight articulation difficulty, but more problematic was her difficulty remembering the names for things and communicating effectively. She was impulsive—always getting into things. The parents describe Lynn as not yet knowing how to tie her shoes, very slow to learn how to do simple chores, and unable to tell her right from her left.

The pediatrician suggested that Lynn attend the Strawberry Preschool when she was 5 years old. The class was small and developmentally oriented. Usually, the children worked in groups of 4 and received a lot of adult attention. The teachers were engaged with the students. The daily routine was consistent. Every day there was music and art. The parents report that their goal for Lynn was to develop her social skills and interact with other children. Lynn did develop a friendship with one girl. She loved going to school.

The following year when Lynn was 6 years old she began kindergarten at a public school. The day was short and the class size was small, although not as small as Strawberry Preschool. Lynn was described as friendly but immature, not interested in pre-academic skills, and had many developmental delays. At the kindergarten teacher’s request, a Student Study Team meeting was held at the end of Lynn’s 1st year in kindergarten. The team decided that Lynn would repeat kindergarten with the hope that an extra year would give her time to catch up with her peers. Lynn’s 2nd year in kindergarten proved to be beneficial in terms of lengthening her attention span, improving her social skills, beginning to learn sound/symbol association, and developing some pre-academic skills.

This year, Lynn’s 1st grade teacher, Ms. Meltzer, is requesting a 2nd student study team to dis- cuss Lynn’s educational and behavioral strengths and concerns. Halfway through 1st grade, Lynn has made many gains. Ms. Meltzer describes Lynn as learning although her learning is at a very slow pace. Lynn is beginning to read CVC and CVCC words. She is able to read some common irregular words (e.g. the, of, come). She works best when reading with 1:1 help or small group work. Lynn loves to listen to the teacher read big picture book stories. She not only looks carefully at the illustrations she even touches them. When asked questions about the story, Lynn remembers pieces of it. She is not able to sequence the events of the story.

Math skills are a weaker area for Lynn. She has difficulty understanding number concepts (i.e., bigger than and smaller than) and remembering the math symbols for addition and subtraction. At the beginning of the school year , Lynn would work on math with the class. Lynn enjoyed working with manipulatives but was not on task. She would build with the blocks or play with the manipulatives; she did not follow the directions given. When paper and pencil tasks were presented in mathematics, Lynn became very frustrated. This led to tearing up math papers and refusing to work. Now , Lynn works 1:1 on math skills with the classroom aide. She also enjoys working on math programs on the computer. Lynn responds to positive reinforcement.

Lynn’s 1st grade teacher reports that poor focus and attention continue to be a hindrance to her learning. She loses her focus quickly. Lynn’s attention span varies depending on the activity. She gets out of her seat and wanders. She visits with other students, is very chatty, and likes to hug them. She also likes to take the pet rabbit and guinea pig out of the cage even when it’s not a “free time.” During “free time,” Lynn darts from one activity to the next.

Due to her small stature, petite frame, and immature behavior , Lynn is regarded as a younger child and is babied by her peers. A few of her classmates want to hold her hand and lead her to the music room or the lunchroom; they want to help her when she’s “stuck” or confused. When Lynn invades her classmates’ space, they become annoyed with her. Some classmates keep their distance from her. Her peers do not include her in recess games unless an adult organizes an activity and encourages everyone to join in. During recess, Lynn usually plays in the sandbox with some of the kindergarten children.

During her 2nd year of kindergarten, Lynn was evaluated by the Speech and Language Specialist. She now receives speech and language assistance 2 times a week for 30 minutes. Even though Lynn is very verbal, her language interferes with her social skills. She is not an effective communicator, as she gets off subject and is unaware of her listener. She often has difficulty finding the word she wants to say, forgetting the names of her classmates. Many of her classmates fill in her words. Her slight articulation difficulties are age appropriate and do not interfere with her communication.

When Lynn enters the classroom, it seems as if it’s a new experience each time. She needs to be reminded to put her lunch pail in the lunch box. Then, she needs to be directed to the coat hooks and take off her coat. Next, Lynn begins a process of wandering or flitting about the classroom unless she is directed to an activity with adult supervision.

During group lessons, Lynn will sit and listen for a short period of time. She can follow a 1- step direction. However, multi-step directions are very difficult for Lynn. She does not seem to remember the 1st part of what was said. She never asks for help. She will focus her attention on something else that interests her even if all the students are working on a class project. Lynn rarely finishes an assignment. When she does work, it takes her a long time to finish a project. When she’s frustrated, she cries.

Safety is a concern. During field trips, it is imperative for Lynn to be paired with an adult the entire time. On her 1st field trip to the zoo, Lynn wandered away from the group. They found her happily talking to an animal trainer and petting a llama. She did not demonstrate an under- standing of why the teacher was upset.

Gross motor skills are a strength for Lynn. Her parents have enrolled her in swim lessons, which she seems to enjoy. She is also starting to skate. Fine motor control is coordinated yet slow. Lynn likes to draw with big magic markers. She does have an awkward pencil grip and seems to tire easily.

Powered by WordPress / Academica WordPress Theme by WPZOOM

Join Our Mailing List

David Martin

Fetal Alcohol Spectrum Disorder (FASD) is a term currently used to refer to a variety of physical features and neurological and/or psychometric patterns of brain damage associated with fetal exposure to alcohol during pregnancy. Such damage to the brain can result in a range of structural, physiological, learning and behaviour disabilities in individuals. FASD is an umbrella term to indicate the spectrum of physical, cognitive and behavioural characteristics that can be seen in such individuals.

Fetal Alcohol Syndrome (FAS) is the medical term used to describe a specific identifiable group of people who all share certain characteristics: a specific set of possible facial features, central nervous system (CNS) dysfunction, and often growth deficiency and possibly other birth defects. In addition to FAS there are three other medical diagnostic terms; Partial FAS, Alcohol Related Birth Defects (ARBD) and Alcohol Related Neurodevelopment Defects (ARND).

Working with children diagnosed on the spectrum presents with many challenges as each one is so uniquely different. They can present with a variety of characteristics including some of the following:

some of the children are very verbal, but lack understanding as to what is being said to them they have difficulty with abstract reasoning, concepts of time, and/or understanding figures of speech as they tend to live in the literal world

while they seem to grasp a concept one day, the next day it is as if they never heard of it, but a few days later they might remember it again

difficulty listening, staying focused and engaging with others

they tend to be about half their chronological age with respect to emotional maturity

as they move into their teenage years, this maturity factor causes many children to be ostracized by their peer group, or they will tend to isolate themselves

The reality in Canada today is that many children, while presenting with some of these characteristics, may never receive any type of diagnosis. According to a report in the Canadian Medical Association Journal authored by Christine Lock, Julianne Conry, Jocelyn L. Cook, Albert E. Chudley and Ted Rosales:

The diagnosis of FAS has not been monitored consistently on a provincial or national basis, which has resulted in significant under-reporting and, therefore, an inadequate allocation of resources. A standardized interdisciplinary approach to early diagnosis is essential for more accurate surveillance of FASD. (CMAJ “March 1, 2005; 172 (5). doi:10.1503/cmaj.050135).

Despite this assertion Environics Research group in May 2006 reported

Fetal Alcohol Syndrome (FAS) is the leading cause of developmental disability among Canadian children. (Public Health Agency of Canada Prepared by: Environics Research Group May 2006pn5877).

In 2004, the Saskatchewan Institute on Prevention of Handicaps stated: “There may be students in your classroom affected by prenatal exposure to alcohol who may never be diagnosed. It is extremely important that educators are aware of this fact and develop an understanding of this often unrecognized disability.”

This article will highlight the strategies and interventions which were found to be helpful for this particular young person, but can also be applied to other children regardless of whether they have a diagnosis or not. In order to illustrate the practical reality of working with a child who has been diagnosed on the spectrum, a case study is presented. The child has a diagnosis of FAS.

Case study: Andrew Andrew was an 8 year old boy living in a small rural community. The community has access to a major highway which results in many strangers travelling through the community on a regular basis. The parents are very engaged and active in the life of their child.

Andrew is very small for his age. As with many children presenting on the spectrum, Andrew is developmentally about half his chronological age. Academically, he is behind in many aspects compared to his peers. He has difficulty following directions, staying focused and completing assigned tasks.

He is a very likeable, engaging young boy. He has no fear of strangers and will engage in conversation with anyone at any time. In school he will stop to talk to everyone in the hallway between classes, before and after school. This causes him to be late for class on most occasions.In the community everyone knows Andrew. He presents with the same behaviours. He will stop to talk with anyone, and will even enter a persons” home uninvited to engage in conversation.

In a discussion with the family, school officials and other support agencies the question of what area of intervention should be the priority for Andrew was raised. There were two specific areas given consideration:

Given the number of strangers travelling through the community on any given day, and Andrews” lack of ability to discriminate between stranger and friend, teaching him to recognize the difference was one priority.

In school, the time spent in his classroom was being severely impacted by his constant stopping to talk with anyone who happened to be near him as he travelled the hallways. Teaching him to reduce this would enable him to spend more time accessing his special education support. Success with this would translate into more time accessing the curriculum.

One of the challenges of working with children who present with multiple issues is trying to determine which to focus on first. The biggest mistake that is often made is trying to attempt to deal with all the issues at the same time. One of the goals of any intervention would be to have that intervention, when successfully implemented, transfer to other situations. It becomes a building block in the foundation of the child's future experiences.

Since it was taking upwards of 13 minutes to have Andrew proceed from one classroom to another, it was agreed to try and reduce this time. As the school was a controlled environment versus the open community, it was felt if he was successful here, there was a better possibility of having success when it came to addressing the issue of talking to strangers.

The intervention It was decided by staff at the school, and supported by the parents, to use two strategies to assist him in managing his behaviour. The staff began by teaching Andrew self-talk. Self-talk introduces a statement which when repeated enough times, will be internalized in the child's thinking.

As a first strategy the staff first introduced this question: –Andrew, when you leave your classroom to go to the music class (they would change the destination, i.e. art class, or phys. ed. class) what will you try to do as you walk down the hallway?”

Then the staff, with Andrew’s participation, developed the following statement for him: “When I leave my classroom to go to my next class, I will try to walk down the hallway without talking to anyone along the way.”

It is critical with this approach that the word “try” is in the question and in his answer. Andrew’s talking to people is a predictable behaviour. We know he will not automatically stop talking to people just because we have introduced the statement. When he talks to people we have to encourage him to try again. If we were to create the phrase using the word “will” instead of “try”, knowing he is not going to be successful in mastering this approach the first number of times, then we have set him up for failure. “Will” means he must. Using that phrase teaches him he “can’t”. The “try” gives him multiple opportunities to keep trying his best until he starts to make progress.

The time frame for teaching Andrew to answer the question with his response was estimated to be 2-3 weeks. His parents practiced at home. It was discussed with the parents that the practices take place in a relaxed atmosphere. The question could be asked at supper, or a quiet time in the evening. It should not take the form of a lecture or a demand. At school, the practice took place as part of regular conversation. It was also included with his social story, the second strategy.

The social story is a written version of the self talk. It has only one topic: in this case the social story was about what to do when walking down the corridor, on the way to class. It included the “try” statement. For more detailed information about Social Stories go to http://www.thegraycenter.org/social-stories .

The social story was then written with Andrew’s participation. Once written it could be placed where Andrew could refer to it from time to time. Here is an example of his social story:

In school, I walk the hallway with my classmates on the way to our next class When I see someone in the hallway, I get excited and I stop to talk with them Before I know it my classmates are gone, and I am late for class I will try not to talk to people as I walk along the hallway This will help me be on time for class with my classmates

To further encourage a positive result, the staff would practice walking Andrew through the hallway. To further enhance the likelihood of success, he was provided with a pictorial representation of when to engage or not to engage with people between classes. It is important to note, all these interventions were presented from a positive perspective. Andrew is eight and he would not always want to participate in the activities. There were no repercussions for Andrew if he did not want to participate or if he did not “succeed”. Staff would engage him when they felt he was most receptive.

Finally, the day for Andrew to have his first real attempt at walking the corridor had arrived. That morning before he left for school his parents, having his class schedule at home, asked him to repeat what he was going to try and do when he had to leave his class second period and go down the hallway to his music class. It probably required a little prompting and help, but they were careful not to make it into a demand which might create a heightened level of anxiety. At school during first period, he was asked to use his self talk to voice what he was going to try and do. Also, his social story was reviewed with him.

At the end of the first period he left the class with his mates and headed out into the hallway. He walked down the hallway and never spoke to anyone “not so! The first person he saw, he excitedly stopped to chat.

At this point, it is critical to understand the amount of preparations carried out by other staff members in anticipation of this day. All staff was given a protocol to use when they encountered Andrew in the hallway between classes:

They allowed Andrew to calm down, as his excitement level increased when he stopped to speak with people.

They would then calmly ask him what he was supposed to do when in the hallway between classes. (This probably meant some prompting until he could reasonably use his self talk).They would then encourage him to speak his statement out loud.

They would not send him back to his class as some form of punishment, but rather tell him it was a good try and then ask him to continue down the hallway to his next class.

In the early days of this intervention, Andrew stopped to talk with any number of people along the way. However, all staff used the 3 steps above as best they could. At about the six month period, Andrew had improved from taking 13 minutes to move along the hallway to less than 2 minutes. All during this time, the family and staff continued to work with him on his self-talk and social story.

Whenever, and wherever possible, connecting the behaviour to the planned response (consequence) is very important. The more immediate the response is to the behaviour the more likely it is that he will be able make the connection. By stopping Andrew at the time he began to speak with others in the hallway, referring to his self talk and then allowing him time to process, he was starting to make the connection. If staff chose to send him along and speak to him later in the day, it is likely the intended connection to his behaviour would not be made.

While the immediate goal was to get down the hallway in a reasonable amount of time which we would consider a functional goal, the long term goal was teaching him self-regulation. Andrew was learning to manage his environment, draw less attention to himself, and interact with adults and peers in a more appropriate manner. As part of this intervention, Andrew was encouraged to speak with people at more appropriate times, such as before class, during recess and at lunch time.

His success gave Andrew a strong foundation to build upon his next challenge which was dealing with strangers. That is another story.

Living with FASD: Brenna

Brenna, a young teen living with an FASD.

F etal alcohol spectrum disorders (FASDs) are disabilities that last a lifetime. Children with FASDs can have behavioral, intellectual, and neurological problems. FASDs can occur when a developing baby is exposed to alcohol during pregnancy.

Brenna was diagnosed with an FASD when she was 12 years old. She and her mother, Heather, share Brenna’s story.

Brenna’s Story

Heather and her husband, Jason, adopted Brenna and her three siblings from foster care. Weighing just 4 pounds and 13 ounces at birth, Brenna was so small that she came home wearing a doll’s clothes.

For years, Brenna’s parents struggled to get her accurately diagnosed. She had been slow to reach many milestones as an infant and participated in early childhood services for speech and physical therapy. She was small for her age throughout elementary school. Brenna also struggled academically. She had trouble staying on task, getting easily frustrated, and having outbursts and tantrums both in school and at home.

It was also difficult for her to understand concepts such as time, money, and organization. “When Brenna was in elementary school, she preferred to play with preschoolers rather than kids her own age,” her mother, Heather, recalls. She also took everything literally. For instance, according to Heather when she said, “her classmates might be talking behind her back, Brenna had replied by saying that wasn’t true, because she would hear them.” It took Heather a bit to figure out that when Brenna said that she thought she would hear them, it was because she took it to mean they would be right behind her back talking.

Brenna’s older sister was first of the children to be diagnosed with an FASD; Brenna was diagnosed later at the age of 12 years. Deciding if a child has an FASD takes both a physical and developmental evaluation. Since there is no biological test to diagnose FASDs, clinicians must assess a child’s exposure history, behavioral and intellectual function, as well as look for neurological and physical features. Also, many other disorders have similar symptoms which must be ruled out. Among several other tests, Brenna’s evaluation included an independent living/life skills test.

Benefits of a Diagnosis

At birth, Brenna weighed just 4 pounds and 13 ounces. She came home wearing a doll’s clothes.

According to Brenna’s mother, “Getting the diagnosis helped understand where Brenna was coming from.” Heather said that it helped them reframe the challenges they faced. It wasn’t that Brenna was being defiant or wouldn’t do things they asked of her, but rather that Brenna couldn’t do it or lacked the skills and ability. They had to give Brenna the space and time to do it.

Heather also commented that, “It was helpful to get the diagnosis since it made available many resources in our area, including a support group. Being part of the support group has helped us learn more about FASDs. It is a relief to know there are other children with similar issues, who, for instance, must also be reminded of personal hygiene, even though they are almost in high school.” The diagnosis also helps explain why Brenna could be disruptive in school, as the classes might be too hard for her to follow.

According to Heather, “Hearing about similar examples helped one not feel so alone. For instance, many of the children can’t find their coats, shoes, homework, or favorite toy they just had. Or how when they are done with something, they just walk away, leaving it for you to pick up, clean up, or put away. What takes typical kids weeks to master, may take your child months or even years.”

In addition to the support group, the diagnosis helped Brenna get access to local services and ensured the school system had the information they needed to best support her.

Increasing Awareness in Her Community

Brenna wearing her FASD strong T-shirt.

Brave and cheerful, Brenna has been instrumental in increasing awareness about FASDs in her school. After her diagnosis, she proudly wore her FASD T-shirt depicting a strong woman and handed out buttons and flyers about this condition. Her mother says, “I was a bit worried, wondering if she would be able to handle the comments or teasing, but Brenna did great!”

Brenna is a kind and happy teen. She loves helping people and cares about her friends and is always checking up on them. She also calls and checks on her grandmother daily.

Brenna enjoys playing the piano and being in the choir. She also recently took up junior varsity color guard and is looking forward to the competitions.

CDC would like to give a special thanks to Brenna and her family and to FASD United (formerly NOFAS ) for sharing this story with us.

Brenna practicing junior varsity color guard.

CDC addresses alcohol and other substance use during pregnancy and FASDs. Example activities include:

• Understanding alcohol use during pregnancy:  CDC estimates how much and how often pregnant people report alcohol use and binge drinking as well as use multiple substances. These data are important to help reduce prenatal alcohol use by identifying groups at increased risk and designing prevention programs to reduce risk behaviors.
• Promoting evidence-based care:  CDC and partners support the implementation, adoption, and promotion of evidence-based interventions to reduce alcohol use during pregnancy, including  alcohol screening and brief counseling . We are also working together to promote effective  treatments  for children, adolescents, and young adults living with FASDs and their families. Early identification and management of FASDs can help children and families living with FASDs receive the care and services they need to thrive.
• Providing training and resources:  CDC enhances healthcare provider education, including free  online training courses  on preventing prenatal alcohol use and identifying and caring for people with FASDs. We are also offering  FASD-related educational information  and  materials  as well as disseminating guidelines on alcohol use, including the  Dietary Guidelines for Americans .
• Disseminating accurate, up-to-date information:  CDC educates and informs the general public and policymakers about effective strategies for reducing excessive alcohol use, such as those recommended by the  Community Preventive Services Task Force  (e.g., limiting alcohol sales).

More Information

• CDC Fetal Alcohol Spectrum Disorders
• FASD United (formerly NOFAS)
• CDC Alcohol Portal
• Excessive Alcohol Use
• Binge Drinking
• Drinking & Driving
• Underage Drinking
• Alcohol & Pregnancy

Learn more about the FASD Competency-Based Curriculum Development Guide for Medical and Allied Health Education and Practice

Exit Notification / Disclaimer Policy

• The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
• Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
• You will be subject to the destination website's privacy policy when you follow the link.
• CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Int J Environ Res Public Health

The Prevalence of Fetal Alcohol Syndrome and Its Impact on a Child’s Classroom Performance: A Case Study of a Rural South African School

Melissa lubbe.

1 School of Economics, University of Cape Town, Cape Town 7700, South Africa; moc.liamg@1assilemebbul (M.L.); moc.liamg@keeblawc (C.v.W.)

Corné van Walbeek

2 Southern Africa Labour and Development Research Unit, University of Cape Town, Cape Town 7700, South Africa

Nicole Vellios

Alcohol consumption is high among farm labourers in the Western and Northern Cape of South Africa. Excessive alcohol consumption during pregnancy is common, resulting in a high prevalence of Fetal Alcohol Syndrome (FAS) among children. FAS causes intellectual and behavioural problems, which create considerable obstacles to a child’s education. The aim of this study is to provide a prevalence estimate of FAS in a rural school and to examine the effects of FAS on learners’ educational outcomes. The study was conducted at a farm school near Clanwilliam in the Western Cape of South Africa. The sample comprises 166 learners from Grades 1 to 4. Educational outcomes include class scores (Afrikaans home language and mathematics), reading ability, and classroom behaviour. A physician diagnosed FAS using a three-stage process. We find FAS prevalence of 127 per 1000 (12.7%). Children with FAS score significantly lower (at the 10% level) for home language and behaviour than children who do not have FAS. Large-scale interventions in rural areas of the Western and Northern Cape that specifically target females of child-bearing age, as well as children with FAS, are necessary.

1. Introduction

Fetal Alcohol Syndrome (FAS) is a birth defect caused by mothers drinking alcohol whilst pregnant. The continuum of effects of prenatal alcohol exposure is referred to as Fetal Alcohol Spectrum Disorder (FASD), which encompasses FAS (most severe), Partial FAS (PFAS), Alcohol-related Neurodevelopmental Disorder (ARND) and Alcohol-related Birth Defects (ARBD) [ 1 ]. The effects on the Central Nervous System (CNS) caused by the syndrome, which include developmental delays, hyperactivity, attention deficits, learning disabilities, intellectual deficits, and sometimes seizures, complicate the educational experience of a child [ 2 ].

Mothers in South Africa often consume alcohol during pregnancy, a phenomenon frequently attributed to the “dop system” of the Western and Northern Cape where wages of farm workers were supplemented with alcohol [ 3 ]. The name “dop” originates from the Afrikaans word for a tot of alcohol. The “dop” or “tot” system originated in the 1700s when European settlers colonised fertile land in South Africa to create an agricultural economy [ 4 ]. Wine farmers, not having enough cash to pay for labour, used surplus wine as payment. The dop system also provided a way for farmers to dispose of excess wine that was deemed unfit to drink [ 5 ]. Not only were alcoholic labourers less productive, but their offspring, many of whom had FASD conditions, were unable to perform as required. The Labour Commission of 1893 acknowledged the dominance of the farmer over workers through this system, as alcohol dependency ensured that workers were prepared to work under harsh conditions to support their habit [ 6 ]. Although the use of alcohol as payment was outlawed in 1961, the free dispensation of wine “as a gift” resulted in the ongoing application of the practice [ 7 ]. Only in 2004, when the President signed the Liquor Act of 2003, was the practice of using alcohol as an inducement to employment finally prohibited [ 8 ]. The repercussions of this system still ripple through many rural communities, where the extensive use of alcohol has become a way of life for many, especially in the form of binge drinking over weekends [ 9 ].

Although laws that segregated communities on the basis of skin colour officially ended in 1994, the town of Clanwilliam in the Cederberg (like so many South African towns and cities) remains racially divided, both geographically and socially. The Cederberg is a remote agricultural area, approximately 250 km north of Cape Town. Clanwilliam is a small town with a population of about 7500 of which about 70% are of mixed race ancestry (known in South Africa as “Coloured”), 23% are African, 6% are White, and 1% are Asian/Other [ 10 ]. The vast majority (85%) of the community identified Afrikaans as their home language [ 10 ]. Over the decade spanning 2001 to 2011, the population in the Cederberg grew by 26.6% [ 10 ]. However, the town’s economic growth potential is low, weakened by factors such as high unemployment, poor literacy, a low skills base, high levels of poverty, a high incidence of HIV/AIDS, and high crime levels. An anchor employer in Clanwilliam is the Rooibos factory, purchasing most of the annual crop of Rooibos tea, the main crop of the region, which it exports to over 60 countries [ 11 ]. The town’s population is heavily dependent on government grants (especially the Child Support Grant and the Old Age Pension). The Gini coefficient (indicating income inequality) of the Cederberg is the highest in the district at 0.64 [ 10 ].

In this social context, coupled with a lack of knowledge among healthcare workers and a strained healthcare system, children’s health is often neglected, resulting in FAS often going undiagnosed. The medical diagnosis of FAS outlines three main spheres of influence: microcephaly (small head and underdeveloped brain), physical and facial abnormalities, and possible CNS abnormalities, which manifest in developmental delays, hyperactivity, low intelligence, reduced attention spans, and possible seizures [ 12 ]. Every learner with FAS or FASD presents unique challenges within the classroom, including difficulties with speech and language [ 12 ]. Research focusing on adolescents and adults with FAS shows that learning plateaus prematurely, though the age at which this happens depends on the extent of damage sustained from prenatal alcohol exposure [ 12 ]. As concrete thinkers, children with FAS find abstraction difficult [ 12 ]. Their inability to generalise from one situation to another causes considerable challenges in understanding concepts, such as time, space, figurative language, and cause and effect. Their inability to understand time means that learners cannot plan ahead and, thus, rely heavily on routine. Hyperactivity in learners with FAS resembles Attention Deficit Hyperactivity Disorder, for which it is often mistaken [ 13 ].

Although the dop system that was applied in the Western Cape for 300 years is no longer in place today, its devastating repercussions are still very pervasive [ 4 ]. In 2017, Popova et al. estimated that South Africa has the highest FAS prevalence in the world, at 58.5 per 1000 people. In fact, estimated FAS prevalence in South Africa is five times higher than Croatia, the country with the second highest prevalence of 11.5 per 1000 people [ 14 ]. Compared to the rest of the African region, South Africa is the only country with FAS prevalence greater than five cases per 1000 births [ 14 ].

In this case study, the prevalence of FAS in a rural school in Clanwilliam is estimated, together with the effects of FAS on educational outcomes of learners.

2. Study Context and Methods

2.1. study context.

South African public schools are divided into five broadly equal groups (quintiles) for the allocation of financial resources, based on the poverty of the surrounding community. Quintile 5 is the “least poor” whilst quintile 1 is the “poorest” and comprises 8.6% of Western Cape Schools. The primary school sampled in this study is a quintile 1 school located in a remote farming region outside Clanwilliam.

The school offers schooling from Grade R (the year before a learner goes to Grade 1) to Grade 7. In 2015 there were 262 learners and 25 staff members. Two thirds of learners live in the boarding house. Most students come from homes where their physical and emotional wellbeing is often neglected (some are given nothing but sugar-water over the weekend), and where physical and sometimes sexual abuse is common. The boarding house offers security, supervision, structure, routine, and meals at set times. Since boarding is only offered during the week, learners are collected from the surrounding farms and Clanwilliam on Sunday evenings and transported home on Friday afternoons. The often dysfunctional home environment, lack of school preparation, and lack of parental support (often related to the functional illiteracy of the parents) results in discipline problems at school, with many learners repeating, many being progressed to a higher grade before they are ready, and a high dropout rate.

Although the dop system is outlawed, alcohol is still readily available to farmworkers. Every Friday (which is the weekly pay day), tradesmen hawk alcohol and other goods from farm to farm. Illegal homemade alcohol is also brewed and sold for a profit. Alcohol is usually consumed in the form of five-liter bottles of sweet, cheap wine. Four or more people usually consume a whole bottle, drinking from mugs, over the course of a weekend afternoon, often in view of children.

2.2. Methods

The first author spent a total of seven months at the primary school in 2015 to gather comprehensive insight into the effects of FAS on classroom performance from 166 learners: Grade 1 ( n = 47), Grade 2 ( n = 32), Grade 3 ( n = 33), and Grade 4 ( n = 54). Data on educational outcomes was obtained by collecting existing data from teachers (class scores for Afrikaans home language and mathematics), generating new data (reading score), and observing learners in the class (classroom behaviour). The learners’ class marks for mathematics and Afrikaans home language were obtained at the end of the second term, which reflect their half-year marks. There are a number of coding schemes to observe learners’ classroom behaviour directly [ 15 ]. The Behavioural Observation of Students in School (BOSS) was selected and adapted for this study since it is sensitive to the behaviours often displayed in the foundation phase (Grades 1–3) and offers a sensitive measure to detect subtle behavioural differences [ 15 ]. Each learner was subject to two 15-min BOSS sessions conducted by the first author over a period of six months. Every 10 seconds for 15 min, the first author coded behaviour according to one of six categories: (1) active engaged time (e.g., reading); (2) passive engaged time (e.g., listening to a teacher); (3) off-task motor (e.g., leaving seat); (4) off-task verbal (e.g., humming, talking to classmates); (5) off-task passive (e.g., looking out the window); or (6) teacher-directed instruction [ 15 ]. A weighting designed by the first author was assigned to each of the different behaviours based on their desirability and influence on the rest of the class (good behaviour was weighted a high number and bad behaviour a lower number). The classroom behaviour score for each child over the 15 min period was calculated to give a measure of how well the child behaved on average.

FAS diagnosis was conducted independently by a qualified medical doctor who resides and works in the district. A number was assigned to learners during the diagnosis period to protect their identity. All data was recorded on a FAS assessment form, specifically developed based on diagnosis requirements [ 16 ]. Measuring anthropometrics and dysmorphology is common in diagnosing FAS in South Africa and globally [ 17 , 18 , 19 ]. The diagnosis occurred in three phases: screening, examination, and review of hospital records. Screening of the 166 learners from Grades 1 to 4 involved basic anthropometry (i.e., weight, height, and head circumference). Any child falling below two standard deviations of the normal value for their age was included in the examination round, which was conducted during a repeat visit by the doctor. This round involved repeated anthropometric measurements, examination for typical facial characteristics (short palpebral fissure, thin upper lip, smooth philtrum, epicanthal folds, flat midface, micrognathia, flat nasal bridge, and short upturned nose) and examination for systemic manifestations (cardiac, skeletal, renal, ocular, auditory, and neurological exams) of fetal alcohol exposure [ 16 ]. The final phase was a review of maternity, clinic, and hospital notes (to which the doctor was granted access) on the mother and child.

Descriptive statistics are provided for educational outcomes (home language score, math score, behaviour score, and reading score) and physical measurements (height, weight, and head circumference). We use multiple regression analysis to predict the value of dependent variables (home language score, math score, behaviour score, and reading score) based on the value of the independent variables (gender, grade, number of days absent from school, farm/town, boarder/non-boarder, Afrikaans as home language, and years too old for grade). The data was analysed using Stata v14.1 (StataCorp LLC, College Station TX, USA). The lower and upper bounds of the 95% confidence intervals are reported for each statistic in square brackets.

Ethical clearance was obtained from the University of Cape Town (UCT) Commerce Faculty Ethical Clearance Committee (1952L Lubbe and Van Walbeek). Permission to conduct this study was also obtained from the school and from the parents of participating learners. Only one parent refused to allow the child’s participation.

A local physician tested 166 learners for FAS using three rounds of investigation: the initial screening phase resulted in 52 learners (31.3% of the full sample) as possibly having FAS, the examination round further reduced the number of learners to 31 (18.7% of the full sample), and the final round of reviewing hospital records resulted in a final diagnosis of FAS in 21 learners or 12.7% of the full sample (11 boys and 10 girls) ( Table 1 ). Some children had already been diagnosed with FAS by another doctor. The prevalence of FAS among children from farms is 16.2%, which is substantially higher than among children from town (6.6%). On all four educational outcomes children with FAS perform worse than children who do not have FAS, although not all the results are significant. The score for Afrikaans home language of learners with FAS is 7.2 marks lower than that of learners without FAS (44.9% vs. 52.1%) ( p = 0.060). The behaviour (BOSS) score is 4.2 marks lower for FAS learners ( p = 0.081). The reading score for girls with FAS is 15.8 marks lower than for girls who do not have FAS ( p = 0.080), but the effect for boys is not significant.

Descriptive statistics of learners, Grades 1–4 in 2015.

Note: Values in bold and italic are significant at the 10% level.

Children with FAS are, on average, 5.2 cm shorter ( p = 0.027), weigh 6.3 kg less ( p = 0.001) and have a 2.3 cm smaller head circumference ( p = 0.000) than children without FAS.

Table 2 presents multiple regression analyses for four educational outcomes for children in Grades 1 to 4. All scores are out of 100, so the numbers can be read as marks or percentages. Other than number of days absent and years too old for grade , all explanatory variables are dummy variables taking on a value of 1 if the characteristic is present, and 0 if the characteristic is not present. For example, if a learner has FAS, the variable Fetal Alcohol Syndrome takes on a value of 1. The coefficient in Table 2 indicates by how many marks the learner’s score changes if that characteristic is present compared to a learner who does not have that characteristic.

Multiple regression analysis for educational outcomes.

Standard errors in parentheses *** p < 0.01, ** p < 0.05, * p < 0.1. Values in bold are significant at the 10% level.

Home language score (column 1) decreases by 7.1 marks if a child has FAS [−14.5, 0.3], holding other factors constant. The BOSS score (column 3), which is a measure of behaviour, is reduced by 4.0 marks if a child has FAS [−8.2, 0.2]. These results are significant at the 10% level. While math (column 2) and reading scores (column 4) are also lower for children who have FAS, these results are not significant.

Females score significantly higher than males for all outcomes except math. Although we control for grades in all regressions, we do not show the coefficients on grade for regressions 1, 2 and 4 as the level of difficulty on these tests increases as a child moves through the grades, making any interpretation of those coefficients meaningless. The behaviour score is measured consistently over all four grades. Grade 2 children score 9.6 more points on average than Grade 1 children [5.6, 13.6], Grade 3 children score 11.9 more points [7.8, 16.0], and Grade 4 children score 8.1 more points [3.8, 12.4].

Children that have repeated grades score, on average, 5.2 points less [−8.9, −1.4] on home language than children who have not repeated a grade. While scores for the other educational outcomes are also lower if children have repeated grades, the results are not significant. Being a boarder significantly decreases the math score by 6.8 marks [−12.5, −1.1] but has no significant impact on the other educational outcomes. The number of days absent, living on a farm, or having Afrikaans as a home language do not appear to affect any of the four educational outcomes.

4. Discussion

Our estimate of 127 per 1000 births [83.6, 187.0] is close to the upper bound compared to other published studies, surpassed only by a study published in 2017 [ 17 ]. FAS prevalence in South Africa ranges from 26.5 to 129 per 1000 people ( Table 3 ). In 2016, Roozen et al. published a worldwide systematic literature review of FASDs. Only two studies report a higher FAS prevalence than our estimate: one in the US in 1995, which reported a prevalence of 139.2 per 1000 (27/194) [ 20 ], and one in Sweden (2010) reporting a prevalence of 295.8 per 1000 (21/71) [ 21 ].

FAS prevalence rates from studies in South Africa.

Since the dop system has its roots in viticulture, there is a general expectation that FAS prevalence is higher in these regions. However, this study, and other published studies [ 22 , 23 , 24 , 25 ], suggest that the prevalence of FAS in non-viticulture communities is similar to that in viticulture farming communities.

FAS learners typically perform worse than non-FAS learners, but this effect is only significant at the 10% level for home language score and classroom behaviour. May et al. found that children with FAS perform significantly worse ( p < 0.001) than children without FAS on verbal IQ, non-verbal IQ, behaviour, and total dysmorphology scores [ 28 ]. We expected that the impact of FAS on scholastic performance would be more pronounced. The lack of significance is possibly because many learners in the school (not only those diagnosed with FAS) come from extremely deprived and dysfunctional backgrounds. Children with maltreatment histories (e.g., sexual abuse, physical abuse, emotional abuse, exposure to intimate partner violence, and neglect) often experience impairments in both their academic performance and mental well-being [ 30 ]. The deprived environment that most of the children come from decreases the average performance to the extent that it becomes difficult to identify the even lower performance of children with FAS. Had children with FAS from this study attended well-functioning, high-performing suburban schools, the scholastic difference would have likely been greater.

Having spent significant time in the classroom environment, the main author found that FAS-affected children are oversensitive to touch and other stimulation, which is a common trait of FAS [ 12 ]. Learners with FAS would shut their eyes or block their ears when the stimulation became overwhelming. They would often shut down by engaging in a non-productive activity, such as rolling a pretend-cigarette when they were over-stimulated. Children with FAS struggle to understand figurative language. Visuospatial memory difficulties mean that learners cannot focus on the details of something they are trying to copy from the board [ 12 ].

Ideally, FAS-affected children should be removed from loud or crowded classrooms to a safe haven. Unfortunately, this is not the case. Like many other rural areas in South Africa, there is no children’s home or special needs school in Clanwilliam. As a result, children with FAS are left to struggle at schools that cannot meet their specific developmental needs, which greatly reduces their chances of becoming productive members of society. In addition, there is little help for adults struggling with alcohol dependence. Many South African government-run treatment centres for alcohol-related problems have closed, and those that are left are not adequately distributed across the country. Although the number of private treatment centres has increased, the poor cannot afford the cost of these services. Specific programmes have been developed which target pregnant women, but these programmes do not reach small towns like Clanwilliam.

Although there is an awareness of FAS by health professionals in the area of Clanwilliam (some cases of FAS had been previously diagnosed), there is little being done to address the specific needs of FAS-affected learners.

We note several limitations to this study. Firstly, the sample size is small, representing 166 learners from the same school. Secondly, since we only diagnosed FAS (and not FASD) our results are not fully comparable to other studies that diagnose the full FASD spectrum. Thirdly, there may be some measurement error. Since different teachers assessed the different grades (home language and maths scores) there could be some teacher bias. There may also be desirability bias among learners (BOSS and reading scores) as learners might have improved their behaviour since they knew they were being observed. This effect is likely to be ameliorated since the first author spent a considerable amount of time in the classroom and was identified as a teacher rather than as an observer/researcher before observations commenced. There may also be some measurement error in diagnosing FAS since some hospital folders and information had been lost (in these cases the diagnosis was made on the clinical examination only). Complicated cases were also a burden, for example, a learner was excluded despite possibly having FAS because of birth abnormalities, prematurity, bacterial blood stream infection at birth, and meningitis, making the case too complicated for direct correlation to be drawn between cognitive impairment and FAS. Fourthly, definitive confirmation of maternal drinking could not be ascertained. Fifthly, the research design was such that changes in educational outcomes over a long period of time were not observed.

Further research could investigate whether the abilities of learners with FAS continue to diverge from those of their classmates, or whether they catch up. Since this is a small, and relatively closed, community, most children will presumably live in the same area in five years’ time.

5. Conclusions

We report an extremely high rate of FAS. Low educational attainment, low socio-economic status, easy access to cheap alcohol, and a culture of drinking rooted in the dop system have resulted in excessive alcohol use among the population of Clanwilliam. Alcohol policy responses in South Africa need to be strengthened to decrease alcohol consumption, especially among young people and women.

Not only are interventions needed to help FAS-affected children, but also to prevent future generations from continuing the cycle. This calls for a comprehensive prevention program to reduce excessive drinking and to initiate change, especially among women of child-bearing age, such as the prevention program that was successfully carried out at community health clinics in the Western Cape province for women with high-risk drinking behaviour [ 31 ]. The intervention was effective in helping women stop drinking, or drink less, during pregnancy, reducing the risk of FASD. Such interventions are urgently required in high-risk populations like that of Clanwillian.

Acknowledgments

Without the cooperation of the parents/guardians and participating children this study would not have been possible. Special acknowledgement goes to the dedicated staff of the primary school. Our deepest thanks are extended to Ross Murray.

Author Contributions

Melissa Lubbe and Corné van Walbeek conceptualized the study. Melissa Lubbe conducted the data collection. Melissa Lubbe and Nicole Vellios performed the data analysis. All authors contributed to writing the manuscript.

Conflicts of Interest

All authors declare no conflict of interest.

This research was supported by the University of Cape Town.