Fetal Alcohol Syndrome Clinical Presentation

In the absence of sensitive and specific biomarkers of fetal alcohol syndrome (FAS), and given the common reluctance or inability of women to accurately disclose the quantity and frequency of their alcohol consumption, validating maternal reports of alcohol use is difficult. Furthermore, this information may not be available for children who are not in the care of their biologic mothers. Therefore, the US Institute of Medicine guidelines allow for a diagnosis of fetal alcohol syndrome in cases in which a documented history of exposure to alcohol is not available. The following 3 diagnostic subcategories are based on the history obtained and give the criteria for diagnosis in each category, as described in the guidelines of the US Institute of Medicine.

• Fetal alcohol syndrome with confirmed maternal alcohol exposure

  • Confirmed maternal alcohol exposure
  • Evidence of characteristic facial anomalies
  • Evidence of prenatal or postnatal growth retardation
  • Evidence of CNS neurodevelopmental abnormalities
• Fetal alcohol syndrome without confirmed maternal alcohol exposure

  • Evidence of characteristic facial anomalies
  • Evidence of prenatal or postnatal growth retardation
  • Evidence of CNS neurodevelopmental abnormalities
• Partial fetal alcohol syndrome with confirmed maternal alcohol exposure

  • Confirmed maternal alcohol exposure
  • Evidence of components of characteristic facial anomalies
  • Evidence of prenatal or postnatal growth retardation, evidence of CNS neurodevelopmental abnormalities, or evidence of an otherwise unexplained pattern of behavior or cognitive abnormalities
• Other categories that can be used when heavy maternal alcohol use is documented and other causes are ruled out

  • Alcohol-related neurodevelopmental disorder (ARND)
  • Alcohol-related birth defects (ARBD)

In newborns, alcohol withdrawal is uncommon. Neonates of women who have been drinking immediately before delivery may have alcohol on their breath for several hours, and blood levels of these babies are similar to those of the mother. Hypoglycemia and acidosis may be present. Withdrawal symptoms are agitation, hyperactivity, and marked tremors lasting 72 hours followed by approximately 48 hours of lethargy. Seizures may develop.

Although a wide variety of structural, growth, and functional abnormalities are reported to occur more frequently in infants and children prenatally exposed to alcohol than in others, the principal features of children with fetal alcohol syndrome or fetal alcohol syndrome disorder (FASD) are as follows:

• Key characteristic craniofacial abnormalities

  • Smooth philtrum
  • Thin, smooth vermilion border of the upper lip
  • Short palpebral fissures (< 10th percentile for age)
• Other craniofacial abnormalities

  • Midface hypoplasia
  • Microphthalmia
  • Strabismus
  • Ptosis
• CNS and neurobehavioral abnormalities

  • Microcephaly
  • Intellectual impairment (mild-to-moderate mental retardation)
  • Cognitive impairment
  • Developmental delay
  • Irritability in infancy
  • Hyperactivity in childhood or attention deficit hyperactivity disorder (ADHD)
  • Seizures
  • Delayed or deficient myelination
  • Agenesis or hypoplasia of the corpus callosum
• Skeletal abnormalities

  • Radioulnar synostosis
  • Flexion contractures
  • Camptodactyly
  • Aberrant palmar creases, especially hockey-stick palmar crease
  • Clinodactyly
  • Klippel-Feil anomaly
  • Hemivertebrae
  • Scoliosis
  • Dislocated joints
• Other major congenital anomalies

  • Cleft palate
  • Heart defects
  • Renal anomalies
  • DiGeorge sequence
• Functional problems

  • Refractive problems (eg, myopia, astigmatism)
  • Hearing loss
• Growth deficiency

  • Infant small for gestational age (< 10th percentile for weight or length)
  • Postnatal growth deficiency

Although many factors may modify the risk, the primary and only necessary cause of fetal alcohol syndrome or fetal alcohol syndrome disorder is maternal alcohol consumption.

• The quantity and pattern of maternal drinking and, therefore, the dose and duration of exposure to alcohol are the critical factors in conferring risk.

  • Current evidence supports the conclusion that women who drink heavily during pregnancy may produce children with features of fetal alcohol syndrome. Low-to-moderate levels of maternal alcohol consumption have not been well studied in human pregnancy, but evidence has not suggested a threshold dose below which no effects on cognitive performance or behavior are seen. In the absence of adequate data, no level of alcohol consumption in pregnancy is known to be safe, and the US Surgeon General advises women who are pregnant or who may be pregnant to abstain from alcohol consumption throughout the gestation.
  • Numerous studies demonstrated that the risk of alcohol-related effects increases according to maternal consumption in a dose-dependent fashion. Furthermore, heavy episodic, or binge, drinking is the riskiest pattern of consumption. Therefore, women who have the potential to become pregnant and who are binge drinkers may continue this pattern of consumption in the early weeks of an unrecognized pregnancy and therefore be at risk for fetal alcohol syndrome or fetal alcohol syndrome disorder.
  • Evidence indicates that alcohol primarily affects brain development. Therefore, drinking in all 3 trimesters poses a risk. As a consequence, women can reduce their risk for alcohol-related birth outcomes by reducing the dose or by discontinuing the consumption of alcohol as soon as possible in the pregnancy.
• Several conditions or characteristics may modify risk for fetal alcohol syndrome or fetal alcohol syndrome disorder among women who consume sufficient quantities of alcohol in pregnancy.

  • Women older than 30 years and/or those with a long history of alcohol consumption may be most likely to give birth to a child with fetal alcohol syndrome or fetal alcohol syndrome disorder.
  • Poor maternal nutritional status may also increase the likelihood of having an alcohol-affected child.
  • Having 1 child with fetal alcohol syndrome further increases the risk of producing subsequent children with fetal alcohol syndrome.
  • Genetic susceptibility to fetal alcohol syndrome has been suggested in some studies, with alcohol dehydrogenase (ADH) polymorphisms as a risk factor. In particular, the ADH 2*2 and 2*3 alleles, which result in rapid metabolism of alcohol to acetaldehyde, were shown to be protective against FAS. However, the mechanism by which this protective effect occurs is unknown. Some suggest that rapid metabolism of alcohol to acetaldehyde lowers peak blood alcohol levels and therefore lowers fetal exposure. As an alternative, rapid metabolism may increase levels of acetaldehyde with associated noxious effects on the mother and therefore reduce levels of alcohol consumption, which lowers fetal exposure.
  • Mouse models have demonstrated deficiencies in neuronal nitric oxide synthase worsens microcephaly and neuronal loss when exposed to alcohol.^[3]