Fetal Alcohol Spectrum Disorder | Fetal alcohol syndrome

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Introduction

Fetal alcohol spectrum disorder (FASD) is an umbrella term for a group of conditions caused by prenatal alcohol exposure.¹

These conditions include:

• Fetal alcohol syndrome (FAS)
• Partial FAS
• Alcohol-related neurodevelopmental disorder
• Alcohol-related birth defects
• Neurobehavioural disorder associated with prenatal alcohol exposure

FASD is characterised by a broad spectrum of physical, behavioural, and cognitive impairments.²

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Aetiology

FASD results from antenatal alcohol exposure, which causes direct damage to the developing brain.³ Alcohol, a teratogenic substance, freely crosses the placenta, leading to fetal blood alcohol levels similar to maternal levels.⁴

Unlike adults, the fetal liver lacks the enzymes required to metabolise alcohol efficiently, leading to prolonged exposure to toxic metabolites.⁵ The severity of FASD depends on the dose, frequency and timing of alcohol exposure:

• First-trimester exposure (especially within the first two months of gestation) is strongly associated with craniofacial and brain anomalies
• Second-trimester exposure is associated with increased incidences of spontaneous abortions
• Third-trimester exposure is associated with decreased height, weight, and brain volume ^6-7

Neurobehavioural deficits associated with FASD occur at any point in the pregnancy when there is a wide range of exposure of alcohol to the fetus.⁷

Pathophysiology

Exposure to alcohol affects all stages of central nervous system (CNS) development in the fetus. Alcohol-induced brain damage includes disrupted glial development, leading to agenesis of the corpus callosum.⁸

High maternal blood alcohol concentration can cause hypoxia and ischaemia, resulting in structural damage to areas such as the hippocampus, cerebellum, and frontal cortex, which are crucial for memory, motor coordination, and executive function.⁹ Alcohol also disrupts several neurotransmitter systems, leading to decreased levels of serotonin, dopamine and noradrenaline, contributing to cognitive, emotional and behavioural impairments.⁴

Beyond direct neurotoxicity, alcohol alters placental structure and function, impairing nutrient and hormone transport and reducing placental weight, which can contribute to growth restriction and CNS damage.¹⁰

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Risk factors

The likelihood of developing FASD is influenced by:

• Maternal alcohol intake during pregnancy: there is no safe level of alcohol consumption. Women who consume alcohol throughout all three trimesters have a higher risk of having a child with FASD, and drinking five or more alcoholic beverages in one session significantly increases the risk of severe developmental problems.
• Previous child with FASD: women with a child affected by FASD are more likely to continue drinking, have higher current alcohol consumption, and report episodes of binge drinking
• Higher parity and gravidity: women with multiple previous pregnancies have a greater risk of having a child with FASD
• Higher birth order: later-born children are at a higher risk, particularly if the mother’s drinking patterns remain unchanged or worsen over time
• Maternal genetics: certain alcohol dehydrogenase (ADH) genotypes (ADH1B1/ADH1B3 or ADH1B1/ADH1B1) may influence alcohol metabolism, potentially modifying fetal risk
• Increasing maternal age: older mothers who consume alcohol during pregnancy may have a slightly increased risk
• Low maternal socioeconomic status: may be associated with poorer prenatal care and higher rates of alcohol use disorders
• Maternal family history of alcohol consumption: may increase the likelihood of maternal drinking behaviours during pregnancy ^{4, 11}

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Clinical features

Symptoms

Typical symptoms of FASD include:

• Delayed motor milestones and/or delayed speech and language development
• Difficulty with abstract concepts, such as mathematics and time management
• Poor problem-solving skills and impaired executive function
• Hearing or vision impairment
• Difficulty learning from consequences and confused social skills

Individuals with FASD frequently experience:

• Emotional and behavioural difficulties
• Involvement with the juvenile justice or foster care system
• A sibling diagnosed with FASD
• Recurrent unemployment
• A history of substance abuse
• Inappropriate sexual behaviours, such as improper touching or inappropriate exposure

Clinical examination

The three sentinel facial features of FASD are:

• Short palpebral fissures (reduced eye width)
• Smooth philtrum (absence of the normal ridge between the nose and upper lip)
• Thin upper lip

Other clinical findings of FASD include:

• Smaller head circumference (microcephaly)
• Structural abnormalities of the brain, heart, or kidneys
• Vision or hearing impairments

The presence of all three facial sentinel features is highly specific for prenatal alcohol exposure and FASD, meaning confirmation of maternal alcohol consumption is not required for diagnosis.

Figure 1. Features of fetal alcohol spectrum disorder

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Differential diagnoses

Due to the facial features, growth deficits, and neurodevelopmental impairments associated with FASD, several differential diagnoses should be considered.

Conditions associated with growth deficits include:

• Turner syndrome
• Idiopathic short stature
• Growth hormone deficiency
• Low birth weight

Conditions associated with dysmorphic facial features include:

• Williams syndrome
• Noonan syndrome
• DiGeorge syndrome (22q11.2 deletion syndrome)

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Investigations  

The diagnosis of fetal alcohol spectrum disorder (FASD) is clinical, based on a detailed history and examination. There is no single diagnostic test for FASD. However, specific assessments and investigations may be considered based on the child’s presenting symptoms.

A formal multidisciplinary assessment is typically required, involving:

• Educational psychologists
• Neuropsychologists
• Sub-specialist paediatricians

Bedside investigations

Relevant bedside investigations include:

• ECG: if congenital heart defects are suspected
• Facial photographic assessment: when sentinel facial features are present, allowing measurement of the philtrum area to identify abnormalities

Laboratory investigations

Blood tests may be requested to exclude common treatable causes of developmental disorders, and can include: 

• Full blood count: to exclude anaemia
• Urea and electrolytes: to exclude electrolyte imbalances 
• Bone profile: to exclude metabolic bone disease, which can present with motor delays 
• Creatine kinase and urate: to screen for muscular dystrophies and metabolic disorders 
• Thyroid function tests: to exclude hypothyroidism 
• Liver function tests: to exclude metabolic or genetic conditions affecting the liver e.g. Wilson’s disease 
• Fragile X gene testing: as it is the most common cause of inherited intellectual disability
• Lead toxicity screening: consider if there is a history of pica 

Imaging

Relevant imaging includes:

• Echocardiogram: if structural congenital heart defects are suspected
• Electroencephalogram (EEG): in cases of suspected seizures
• Neuroimaging (MRI/CT head): used to determine extent of effect on brain or to exclude other disorders, although not necessary in standard assessment of FASD

Specialist investigations

Specialist investigations can include:

• Genetic testing: to exclude alternative diagnoses such as Williams syndrome or other chromosomal disorders

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Diagnosis

The Scottish Intercollegiate Guidelines Network (SIGN) recommends the following criteria for diagnosing FASD.¹⁴

Prenatal alcohol exposure

Confirmation of prenatal alcohol exposure, based on one or more of the following:

1. Reliable clinical observation

2. Self-report by the mother or reports from a reliable source

3. Medical records documenting positive blood alcohol concentrations

4. History of alcohol treatment or social, legal, or medical issues related to alcohol use during pregnancy

FASD-related clinical features

Presence of FASD-related clinical features in the child, including:

1. Facial dysmorphology (short palpebral fissures, smooth philtrum, thin upper lip)

2. Growth impairment (low birth weight, failure to thrive, microcephaly)

3. Neurodevelopmental abnormalities (cognitive, behavioural, and motor impairments)

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Management  

FASD is a lifelong condition with a wide range of medical, developmental, behavioural, and learning difficulties. Management is individualised, as each person’s needs evolve over time, requiring input from multiple healthcare and support services.

Early diagnosis and long-term support are crucial in improving outcomes and maximising quality of life.

Learning and behavioural support

Learning and behavioural support includes:

• Cognitive control therapy: to improve behavioural regulation
• Language and literacy interventions: to support academic development
• Child friendship training: for social skills deficits to help improve social skills and peer interactions

Multidisciplinary support

A multidisciplinary approach is essential, involving:

• Paediatricians: for overall developmental monitoring and medical care
• Speech and language therapists: to support communication difficulties
• Educational psychologists: to tailor learning strategies in school settings
• Occupational therapists: to aid motor development and daily living skills
• Clinical psychologists and behavioural therapists: to address emotional regulation and mental health

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Complications

Complications experienced by those with FASD may include:

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Reviewer

Dr Selvi Radhika Vikram

Consultant Obstetrician and Gynaecologist

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Editor

Dr Jamie Scriven

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References

1. Streissguth AP, O’Malley K. Neuropsychiatric implications and long-term consequences of fetal alcohol spectrum disorders. Seminars in Clinical Neuropsychiatry. 2000. Available from: [LINK].
2. National Institute on Alcohol Abuse and Alcoholism. Understanding Fetal Alcohol Spectrum Disorders. 2023. Available from: [LINK].
3. Jones KL, Smith DW. Recognition of the Fetal Alcohol Syndrome in Early Infancy. The Lancet. 1973. Available from: [LINK].
4. BMJ Best Practice. Fetal alcohol spectrum disorder. 2023. Available from: [LINK].
5. Popova S, Dozet D, Shield K, et al. Alcohol’s Impact on the Fetus. Nutrients. 2021. Available from: [LINK].
6. Coles C. Critical Periods for Prenatal Alcohol Exposure: Evidence from Animal and Human Studies. Alcohol Health and Research World. 1994. Available from: [LINK].
7. Vorgias D, Bynum FD, Bernstein B. Fetal Alcohol Syndrome. StatPearls. 2023. Available from: [LINK].
8. Popova S, Charness ME, Burd L, et al. Fetal alcohol spectrum disorders. Nature Reviews Disease Primers. 2023. Available from: [LINK].
9. Guerri C. Neuroanatomical and Neurophysiological Mechanisms Involved in Central Nervous System Dysfunctions Induced by Prenatal Alcohol Exposure. Alcoholism: Clinical and Experimental Research. 2006. Available from: [LINK].
10. Burd L, Roberts D, Olson M, et al. Ethanol and the placenta: A review. The Journal of Maternal-Fetal & Neonatal Medicine. 2009. Available from: [LINK].
11. May PA, Gossage JP, Marais AS, et al. Maternal Risk Factors for Fetal Alcohol Syndrome and Partial Fetal Alcohol Syndrome in South Africa: a Third Study. Alcoholism: Clinical and Experimental Research. 2008. Available from: [LINK].
12. Gomez KU, Goodwin L, Chisholm A, et al. Alcohol use during pregnancy and motherhood: Attitudes and experiences of pregnant women, mothers, and healthcare professionals. PLOS ONE. 2022. Available from: [LINK].
13. NICE. Fetal alcohol spectrum disorder. 2022. Available from: [LINK].
14. SIGN. Children and young people exposed prenatally to alcohol. 2019. Available from: [LINK].

Image references

• Figure 1. Hariadhi. Features of Fetal Alcohol Spectrum Disorder. Licence: [CC BY-SA 4.0].

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