Basics
Description
- The four major features of classic fetal alcohol syndrome (FAS) are as follows:
- CNS neurodevelopmental abnormalities
- Facial dysmorphisms
- Growth retardation
- Maternal alcohol use during pregnancy.
- First described in 1973; classic FAS has since been recognized as one of the fetal alcohol spectrum disorders (FASDs), which include the following:
- FAS, partial FAS (pFAS), alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD)
- Taken together, FASDs are three times more common than classic FAS, and the effects range from very mild symptoms to very severe.
Epidemiology
Incidence
- Classic FAS: 3.1 per 1,000 live births
- FASDs: 9.1 per 1,000 live births
Risk Factors
- Binge drinking seems to be the primary risk factor.
- The highest prevalence of reported alcohol use during pregnancy are among those who are aged 35-44 years, white, college graduates, or employed.
- Poor maternal nutrition appears to increase risk in the presence of maternal binge drinking.
- Maternal polymorphisms of the alcohol dehydrogenase gene (ADH): The presence of the ADH1B*3 allele appears to protect the fetus.
- Concordance of FAS is higher in monozygotic than in dizygotic twins.
General Prevention
- Women who are pregnant or may become pregnant should avoid alcohol. No "safe"Ě level of alcohol consumption has been determined during pregnancy.
- Women with alcohol addiction who are or may become pregnant should enter a treatment program.
- According to the Centers for Disease Control and Prevention (CDC), 7.6% of pregnant women reported alcohol use during the month prior to being surveyed and 1.4% reported binge drinking.
- The highest risk for FAS occurs in children whose mothers consume ≥4 drinks per occasion per week (peak blood alcohol level is more important than a lower sustained blood alcohol level).
- In the United States, Alcoholic Beverage Labeling Act passed in 1998 requires heath warning labels, including risk of alcohol consumption during pregnancy.
Pathophysiology
- Malformation of the developing brain is the primary pathophysiologic event resulting in secondary neurodevelopmental pathology and facial dysmorphisms in classic FAS.
- May involve increased susceptibility to cell damage by free radicals in the developing fetus, especially in the first trimester
- Alcohol and its metabolite acetaldehyde are teratogens.
Diagnosis
History
- Neurodevelopmental and behavioral symptoms. No specific neurobehavioral pattern has been defined. See below for examples of age-specific presentations.
- Fine motor function abnormalities may be present.
- Birth and subsequent growth deficit (weight, height, head circumference)
- Maternal history of alcohol use (binge drinking, average number of drinks per day, timing in pregnancy) and other drug use
- Family history
- Neurobehavioral abnormalities may not be typical of other family members who were not exposed to alcohol prenatally.
- Neurobehavioral problems in infancy:
- May or may not have alcohol withdrawal as newborn
- Irritability, irregular sleep, poor feeding, hypotonia, delayed motor function
- Neurobehavioral problems in preschool and school age:
- Hyperactivity
- Slow verbal learning
- Slow visual-spatial learning
- Poor abstract thinking (planning and organizing)
- Perseveration (inability to abandon ineffective strategies)
- Attention problems
- Difficulty with peer interactions
- Neurobehavioral problems in adolescence and adulthood:
- Substance abuse
- Criminal behavior
- Inability to work
- Inability to live independently
Physical Exam
- Birth weight (‚ȧ10th percentile)
- Birth length (‚ȧ10th percentile)
- Microcephaly at birth (‚ȧ10th percentile)
- Postnatal growth deficiency persists throughout life.
- Facial manifestations include the following:
- Short palpebral fissures (measurement from inner to outer canthus of eyes)
- Long and smooth philtrum (area from nasal septum to vermillion border of lip)
- Thin vermillion border (upper lip)
- Ptosis, epicanthal folds, and flat face are also common in FAS.
Diagnostic Tests & Interpretation
Neuropsychological testing †
- Simple IQ tests cannot distinguish children with FAS from those with other developmental disabilities.
- No specific neurobehavioral phenotype yet defined
Lab
No laboratory marker exists for FAS. †
Diagnostic Procedures/Other
Classic FAS diagnosis requires all four of the following markers. †
- Facial features:
- Short palpebral fissures (‚ȧ10th percentile)
- Thin vermilion border upper lip (score of 4 or 5 on the lip/philtrum guide [see Astley reference])
- Smooth philtrum (4 or 5 on lip/philtrum guide)
- Other findings such as ptosis; maxillary hypoplasia; and short, upturned nose are not diagnostic but are commonly seen in children with FAS.
- Documentation of growth deficits
- Height or weight ‚ȧ10th percentile at any time in patient's history
- Documentation of CNS abnormality (any 1 below)
- Structural
- Structural brain abnormalities (e.g., agenesis of corpus callosum, cerebellar hypoplasia)
- Neurologic
- Seizures, poor coordination, impaired memory, or other soft neurologic signs not attributable to postnatal insult or fever
- Functional: performance substantially below that expected for an individual's age and circumstances, as evidenced by either
- Global cognitive deficits (IQ or developmental delays in multiple domains) >2 standard deviations (SD) below the mean OR
- Functional deficits 1 SD below the mean in at least 3 specific domains (e.g., attention, executive functioning, motor functioning, social skills, language, or specific learning disabilities)
- Maternal alcohol exposure
- Confirmed maternal exposure to alcohol is defined as substantial regular intake or heavy episodic drinking.
- Evidence may include self-report or that of a reliable informant, medical records showing an elevated blood alcohol level or alcohol-related medical problems (e.g., hepatic disease), and legal problems related to drinking.
- If there is no available history, or conflicting reports, then diagnosis can be "FAS without confirmed maternal alcohol exposure."Ě
Differential Diagnosis
- By physical features
- Normal variant
- Aarskog syndrome
- Williams syndrome
- Noonan syndrome
- Brachmann-De Lange syndrome
- Dubowitz syndrome
- Fetal valproate syndrome
- Fetal hydantoin syndrome
- Maternal phenylketonuria fetal effects
- Toluene embryopathy
- By neurobehavioral features
- Fragile X syndrome
- 22q11 deletion syndromes
- Turner syndrome
- Opitz syndrome
Treatment
General Measures
- The role of the pediatrician is early identification, appropriate referrals, and development of a multidisciplinary case plan, including the pediatrician, specialists, early intervention providers, psychologists, and social and educational resources in the community to support family and child.
- Specific medical referrals should include
- Comprehensive neuropsychological evaluation (IQ, achievement, executive function, memory, adaptive function, language, reasoning and judgment, behavior)
- Ophthalmologic exam (consider routine screening prior to school, then every 2 years)
- Hearing test (consider brainstem auditory evoked response [BAER] at 6-12 months)
Ongoing Care
Follow-up Recommendations
Patient Monitoring
- Growth and nutrition in infancy: Failure to thrive is a common problem.
- Regular evaluations of vision and hearing: Problems occur at a high rate.
- As indicated by other medical/psychological problems
Prognosis
- 50% have intellectual disability (IQ <70). Average IQ in individuals with FAS is in the 60s (mild mental retardation); however, a wide range of IQ exists, from 16 to 115.
- 62% have severe behavioral problems, even if a normal IQ exists.
- The major disabilities of FAS caused by the neurocognitive/neurobehavioral effects can lead to poor academic performance, legal problems, employment difficulties, and secondary mental health problems.
- Many are unable to live independently as adults.
Additional Reading
- American Academy of Pediatrics. Fetal alcohol syndrome and alcohol-related neurodevelopmental disorders. Pediatrics. 2000;106(2, Pt 1):358-361. †[View Abstract]
- Astley †SJ, Clarren †SK. Diagnosing the full spectrum of fetal-alcohol exposed individuals: introducing the 4-digit code. Alcohol Alcohol. 2000;35(4):400-410. †[View Abstract]
- Bertrand †J, Floyd †RL, Weber †MK, et al; National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Atlanta, GA: Centers for Disease Control and Prevention; 2004. http://www.cdc.gov/ncbddd/fasd/documents/FAS_guidelines_accessible.pdf. Accessed February 14, 2015.
- Bertrand †J, Floyd †RL, Weber †MK, et al; National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol †Effect. Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. 3rd rev ed. Atlanta, GA: Centers for Disease Control and Prevention; 2005.
- Hoyme †HE, May †PA, Kalberg †WO, et al. A practical clinical approach to diagnosis of fetal alcohol spectrum disorders: clarification of the 1996 Institute of Medicine criteria. Pediatrics. 2005;115(1):39-47. †[View Abstract]
- National Institute on Alcohol Abuse and Alcoholism. Fetal Alcohol Exposure and the Brain. Alcohol Alert no. 50. Bethesda, MD: National Institutes of Health; 2000.
- Riley †EP, Infante †MA, Warren †KR. Fetal alcohol spectrum disorders: an overview. Neuropsychol Rev. 2011;21(2):73. †[View Abstract]
- Sampson †PD, Streissguth †AP, Bookstein †FL, et al. Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder. Teratology. 1997;56(5):317-326. †[View Abstract]
Codes
ICD09
- 760.71 Alcohol affecting fetus or newborn via placenta or breast milk
ICD10
- Q86.0 Fetal alcohol syndrome (dysmorphic)
- P04.3 Newborn affected by maternal use of alcohol
SNOMED
- 268796000 Fetal or neonatal effect of placental or breast transfer of alcohol (disorder)
- 205791004 Fetal or neonatal effect of maternal use of alcohol (disorder)
FAQ
- Q: What is partial FAS?
- A: No diagnostic consensus; however, criteria include two of the key facial features, growth retardation OR CNS involvement, and confirmed prenatal alcohol exposure.
- Q: What is ARND?
- A: No diagnostic consensus; however, criteria include CNS involvement with functional impairment and onset in childhood, facial features and growth retardation not necessary (but may be present), not better explained by other conditions (teratogens, genetic, neglect), and confirmed prenatal alcohol exposure.
- Q: How much alcohol does it take to produce damage?
- A: The highest risk for FAS occurs in children whose mothers consume ≥4 drinks per occasion at least once per week. However, NO minimum safe level of alcohol consumption has been determined
- Q: Do most children with FAS have ADHD?
- A: Although hyperactivity appears to be common in FAS, many of these children are misdiagnosed as having ADHD. Instead of difficulty focusing and sustaining attention, children with FAS often have difficulty shifting attention from one task to another. Use of stimulant medication is not routinely supported, although a small proportion may respond to stimulant medication in educational settings.