Elsevier

The Lancet Neurology

Volume 18, Issue 8, August 2019, Pages 760-770
The Lancet Neurology

Review
Clinical presentation, diagnosis, and management of fetal alcohol spectrum disorder

https://doi.org/10.1016/S1474-4422(19)30150-4Get rights and content

Summary

Although prenatal alcohol exposure causes craniofacial anomalies, growth retardation, neurological abnormalities, cognitive impairment, and birth defects, fetal alcohol spectrum disorder is underdiagnosed. Global prevalence of fetal alcohol spectrum disorder is 0·77%, with a higher prevalence of 2–5% in Europe and North America, highlighting the need for increased diagnosis and treatment. However, diagnosis remains challenging because of the poor reliability of self-reported maternal drinking histories, an absence of sensitive biomarkers, and the infrequency of diagnostic dysmorphic facial features among individuals with fetal alcohol spectrum disorder. Different diagnostic systems and disagreements over criteria have slowed progress in the diagnosis and management of the disorder. Neuroimaging shows abnormalities in brain structure, cortical development, white matter microstructure, and functional connectivity in individuals with fetal alcohol spectrum disorder. These abnormalities modify developmental trajectories and are associated with deficits in cognition, executive function, memory, vision, hearing, motor skills, behaviour, and social adaptation. Promising trials of nutritional interventions and cognitive rehabilitation therapies are underway, with the aim of treating cognitive deficits in fetal alcohol spectrum disorders.

Introduction

Fetal alcohol spectrum disorder can result from prenatal alcohol exposure and comprises a range of symptoms, including minor craniofacial anomalies, growth retardation, neurological abnormalities, cognitive and behavioural impairment, and birth defects.1 The prevalence of fetal alcohol spectrum disorder in the global population is 0·77%,2 with variation by country and epidemiological method; the prevalence in Europe and North America is 2·0–5·0%.3 The public health burden of fetal alcohol spectrum disorder can include lifelong physical and cognitive disability, psychiatric and medical comorbidity, diminished productivity, unemployment, homelessness, and incarceration.4 Although fetal alcohol spectrum disorder is as common as autism spectrum disorder with a global prevalence of 0·6%,5 fetal alcohol spectrum disorder remains underdiagnosed6 because of social stigma, diagnostic complexity, reliance on facial features, and characteristics that overlap with those of alternative diagnoses, including attention deficit hyperactivity disorder.7 Many individuals with fetal alcohol spectrum disorder develop subtle neurodevelopmental effects, including small deficits (<1 SD) in intelligence quotient, attention, or memory that do not prompt clinical attention on their own.6, 8 Efforts to improve diagnosis of fetal alcohol spectrum disorder include studies of traditionally undiagnosed individuals who have not been referred to clinics, such as school-based populations,2 international studies examining high-risk populations,9 advanced three-dimensional facial imaging for screening,10 and neurobehavioural screening tools for school-age children that could help clinicians to identify fetal alcohol spectrum disorder via cognitive and behavioural profiles.11

This Review summarises advances in fetal alcohol spectrum disorder research, particularly with regards to epidemiology and clinical presentation. We discuss classifications and diagnostic systems, brain anomalies in individuals with fetal alcohol spectrum disorder, pathophysiology, and management of the disorder. Although fetal alcohol spectrum disorder is typically identified clinically during childhood, we include discussion of adult fetal alcohol spectrum disorder because the clinical manifestations persist into adulthood,4 and adult neurologists are often unfamiliar with the disorder. Prenatal alcohol exposure often occurs with polysubstance use, further complicating neurodevelopmental outcomes. However, because prenatal alcohol exposure alone can cause fetal alcohol spectrum disorder,12 and prenatal alcohol exposure is a greater risk to neurodevelopment than exposure to tobacco, cannabis, or methamphetamine, this Review focuses on the independent consequences of prenatal alcohol exposure on fetal alcohol spectrum disorder.

Section snippets

Epidemiology

In a meta-analysis of 24 studies (1416 children), the global prevalence of fetal alcohol syndrome, the most severe form of fetal alcohol spectrum disorder, was found to be 0·15%, whereas the prevalence of all prenatal alcohol exposure-related conditions was found to be 0·77%.3 There are large regional differences in prevalence; in South Africa, the prevalence of fetal alcohol spectrum disorder was 11·1%, whereas it was 0·01% in eastern Mediterranean countries (eg, Syria and Saudi Arabia) and

Craniofacial dysmorphology

Craniofacial dysmorphology in fetal alcohol spectrum disorder is most commonly characterised by short palpebral fissures, a smooth philtrum, and a thin upper lip vermilion.1, 26 Clinical recognition of craniofacial dysmorphology is important because it narrows differential diagnosis in the presence of developmental brain abnormalities, neurobehavioural deficits, or a history that suggests prenatal alcohol exposure. However, dysmorphic features (typically evaluated by dysmorphologists,

Diagnosis and classification

Multiple fetal alcohol spectrum disorder diagnostic and classification systems are available, each with different criteria across the four domains: magnitude of prenatal alcohol exposure, growth impairment, dysmorphic facial features, and neurodevelopmental abnormalities. Commonly used diagnostic and classification systems for fetal alcohol spectrum disorder include the fetal alcohol spectrum disorder 4-Digit Diagnostic Code,59 the Institute of Medicine criteria revised by Hoyme and colleagues,1

Pathophysiology

In both animals and humans, alcohol equilibrates freely from maternal to fetal circulation, disrupting maternal, placental, and fetal physiology.79 In animal models, the extent of disruption is determined in part by the dose, pattern, and timing of prenatal alcohol exposure.12 In rodents, alcohol exposure during gastrulation (approximately equivalent to day 17 of human gestation) can result in the cardinal craniofacial features of fetal alcohol syndrome, such as small palpebral fissures and

Management

Interventions for fetal alcohol spectrum disorder are multifaceted. The treatment approach accommodates an individual's specific profile of needs (eg, behavioural, cognitive, mental health, and adaptive), in a similar manner to the tailored approach used for other developmental disorders, such as intellectual disability or autism.67, 92 For children and adolescents with fetal alcohol spectrum disorder, interventions might include education and behaviour management training for parents,

Conclusions and future directions

Fetal alcohol spectrum disorder, caused by prenatal alcohol exposure, is a global public health problem that is under-recognised and underdiagnosed despite high prevalence and burden to society.3, 4, 6 Prenatal alcohol exposure, a common teratogenic event, leads to cardinal craniofacial abnormalities (eg, small palpebral fissures, flattened philtrum, and thin upper lip) in some cases,1, 26 and a range of neuropathological abnormalities and associated cognitive, behavioural, and social

Search strategy and selection criteria

We searched PubMed and the Cochrane Library for articles published in English between Jan 1, 2013, to Dec 15, 2018 with the search terms “fetal alcohol syndrome”, “fetal alcohol spectrum disorder”, “alcohol-related neurodevelopmental disorder”, and “prenatal alcohol”. We also identified articles through reference lists, review articles, the authors' own published research, and textbooks. The final reference list was generated on the basis of the relevance of papers to the topics that are

References (102)

  • JH Hannigan et al.

    Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors

    Physiol Behav

    (2015)
  • S Popova et al.

    Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis

    Lancet

    (2016)
  • L Glass et al.

    Neurobehavioral, neurologic, and neuroimaging characteristics of fetal alcohol spectrum disorders

    Handb Clin Neurol

    (2014)
  • S Boronat et al.

    Correlation between morphological MRI findings and specific diagnostic categories in fetal alcohol spectrum disorders

    Eur J Med Genet

    (2017)
  • VT Nguyen et al.

    Radiological studies of fetal alcohol spectrum disorders in humans and animal models: an updated comprehensive review

    Magn Reson Imaging

    (2017)
  • NC Dodge et al.

    Protective effects of the alcohol dehydrogenase-ADH1B*3 allele on attention and behavior problems in adolescents exposed to alcohol during pregnancy

    Neurotoxicol Teratol

    (2014)
  • P Gautam et al.

    Executive function and cortical thickness in youths prenatally exposed to cocaine, alcohol and tobacco

    Dev Cogn Neurosci

    (2015)
  • MA Infante et al.

    Altered functional connectivity during spatial working memory in children with heavy prenatal alcohol exposure

    Alcohol

    (2017)
  • KJ Woods et al.

    Parietal dysfunction during number processing in children with fetal alcohol spectrum disorders

    Neuroimage Clin

    (2015)
  • A Schoeps et al.

    Prenatal alcohol consumption and infant and child behavior: evidence from the Growing Up in New Zealand Cohort

    Early Hum Dev

    (2018)
  • S Boronat et al.

    Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders

    Eur J Med Genet

    (2017)
  • S Goril et al.

    Sleep and melatonin secretion abnormalities in children and adolescents with fetal alcohol spectrum disorders

    Sleep Med

    (2016)
  • CL Petrenko et al.

    Interventions in fetal alcohol spectrum disorders: an international perspective

    Eur J Med Genet

    (2017)
  • JR Wozniak et al.

    Choline supplementation in children with fetal alcohol spectrum disorders: a randomized, double-blind, placebo-controlled trial

    Am J Clin Nutr

    (2015)
  • K Kully-Martens 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

    (2018)
  • HE Hoyme et al.

    Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders

    Pediatrics

    (2016)
  • PA May et al.

    Prevalence of fetal alcohol spectrum disorders in 4 US communities

    JAMA

    (2018)
  • S Lange et al.

    Global prevalence of fetal alcohol spectrum disorder among children and youth: a systematic review and meta-analysis

    JAMA Pediatr

    (2017)
  • J Rangmar et al.

    Psychosocial outcomes of fetal alcohol syndrome in adulthood

    Pediatrics

    (2015)
  • Autism spectrum disorders

    (2017)
  • IJ Chasnoff et al.

    Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure

    Pediatrics

    (2015)
  • JD McLennan

    Misattributions and potential consequences: the case of child mental health problems and fetal alcohol spectrum disorders

    Can J Psychiatry

    (2015)
  • M Suttie et al.

    Facial dysmorphism across the fetal alcohol spectrum

    Pediatrics

    (2013)
  • CM Adnams

    Fetal alcohol spectrum disorder in Africa

    Curr Opin Psychiatry

    (2017)
  • S Pichini et al.

    Global prevalence of fetal alcohol spectrum disorder in Italy

    JAMA Pediatr

    (2018)
  • PP Green et al.

    Vital signs: alcohol-exposed pregnancies: United States, 2011–2013

    MMWR Morb Mortal Wkly Rep

    (2016)
  • LB Finer et al.

    Declines in unintended pregnancy in the United States, 2008–2011

    N Engl J Med

    (2016)
  • Alcohol and pregnancy

    (2015)
  • Guidelines for the identification and management of substance use and substance use disorders in pregnancy

    (2014)
  • JF Williams et al.

    Fetal alcohol spectrum disorders

    Pediatrics

    (2015)
  • D Shelton et al.

    Responding to fetal alcohol spectrum disorder in Australia

    J Paediatr Child Health

    (2018)
  • KR Warren

    A review of the history of attitudes toward drinking in pregnancy

    Alcohol Clin Exp Res

    (2015)
  • L Burd

    FASD and ADHD: are they related and how?

    BMC Psychiatry

    (2016)
  • K Strömland et al.

    Fetal alcohol spectrum disorders among children in a Brazilian orphanage

    Birth Defects Res A Clin Mol Teratol

    (2015)
  • K Strömland et al.

    Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies

    Alcohol Alcohol

    (2002)
  • S Yoshida et al.

    Prenatal alcohol exposure and suspected hearing impairment among children: a population-based retrospective cohort study

    Alcohol Alcohol

    (2018)
  • CD Tesche et al.

    Sex-related differences in auditory processing in adolescents with fetal alcohol spectrum disorder: a magnetoencephalographic study

    Neuroimage Clin

    (2014)
  • CD Coles et al.

    Dose and timing of prenatal alcohol exposure and maternal nutritional supplements: developmental effects on 6-month-old infants

    Matern Child Health

    (2015)
  • AL Panczakiewicz et al.

    Neurobehavioral deficits consistent across age and sex in youth with prenatal alcohol exposure

    Alcohol Clin Exp Res

    (2016)
  • JJ Boseck et al.

    Cognitive and adaptive skill profile differences in children with attention-deficit hyperactivity disorder with and without comorbid fetal alcohol spectrum disorder

    Appl Neuropsychol Child

    (2015)
  • Cited by (158)

    View all citing articles on Scopus
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