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
ReviewClinical presentation, diagnosis, and management of fetal alcohol spectrum disorder
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
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