eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Fetal Alcohol Syndrome

Author: Keith K Vaux, MD, Associate Professor of Pediatrics, University of California San Diego School of Medicine; Attending Physician, Rady Children's Hospital and Health Center; Assistant Clinical Professor of Pediatrics, Uniformed Services School of the Health Sciences
Coauthor(s): Christina Chambers, MPH, PhD, Associate Professor of Pediatrics and Family and Preventive Medicine, University of California at San Diego; Assistant Professor, Graduate School of Public Health, San Diego State University
Contributor Information and Disclosures

Updated: Sep 16, 2009

Introduction

Background

Adverse neonatal and pediatric effects occur with maternal alcohol consumption during pregnancy. The diagnosis of fetal alcohol syndrome (FAS) is based on findings in the following 3 areas: (1) characteristic facial anomalies, (2) growth retardation (intrauterine growth restriction and failure to have catch-up growth), and (3) CNS involvement (cognitive impairment, learning disabilities, or behavioral abnormalities).

Prenatal exposure to alcohol is associated with a variable spectrum of effects referred to as fetal alcohol spectrum disorders (FASD), with fetal alcohol syndrome at the most severe end of that spectrum. Children with fetal alcohol syndrome disorder may have clinically significant CNS involvement but few or no characteristic physical features.

Lemoine et al first described the pattern of malformation associated with heavy prenatal alcohol exposure in France in 1968, and Jones and Smith first described it in the United States in 1973.¹ Prenatal alcohol exposure is of substantial public health concern for the following reasons: (1) FAS is the leading known cause of mental retardation, (2) fetal alcohol syndrome or fetal alcohol syndrome disorder is associated with persistent physical and neurodevelopmental abnormalities,² and (3) fetal alcohol syndrome disorder crosses all socioeconomic groups and affects all races and ethnicities. The costs for 1 child with fetal alcohol syndrome are estimated to be $2 million over a lifetime, and costs of fetal alcohol syndrome to the American taxpayer are more than $321 million each year

Pathophysiology

Alcohol crosses the placenta and rapidly reaches the fetus. Extensive studies have demonstrated equivalent fetal and maternal alcohol concentrations, suggesting an unimpeded bidirectional movement of alcohol between the 2 compartments. The fetus appears to depend on maternal hepatic detoxification because the activity of alcohol dehydrogenase (ADH) in the fetal liver is less than 10% of that observed in the adult liver. Furthermore, the amniotic fluid acts as a reservoir for alcohol, prolonging fetal exposure.

The mechanism for the spectrum of adverse effects on virtually all organ systems of the developing fetus is unknown. Ethanol and its metabolite acetaldehyde can alter fetal development by disrupting cellular differentiation and growth, disrupting DNA and protein synthesis and inhibiting cell migration. Both ethanol and acetaldehyde modify the intermediary metabolism of carbohydrates, proteins, and fats. Both also decrease the transfer of amino acids, glucose, folic acid, zinc, and other nutrients across the placental barrier, indirectly affecting fetal growth due to intrauterine nutrient deprivation. Elevated levels of erythropoietin in the cord blood of newborns exposed to alcohol are reported and suggest a state of chronic fetal hypoxia.

Frequency

United States

Although careful comprehensive studies have not been performed and though passive surveillance systems are inadequate to measure the incidence of fetal alcohol syndrome or fetal alcohol syndrome disorder, the incidence of fetal alcohol syndrome in the United States is estimated to be 1-2 cases per 1000 live births. The incidence is related to the population studied, with highest incidence reported in areas where heavy drinking during pregnancy is common and where attention to diagnosis is greatest.

To date, no comprehensive population-based study with careful and standardized diagnostic methods applied to a large, representative sample of children has been performed. Likewise, the incidence of the broad spectrum of fetal alcohol syndrome disorder has not been well studied. However, data in one sample demonstrated that approximately 1 in 100 children have alcohol-related effects.

Among the subset of high-risk pregnant drinkers, estimated incidences of fetal alcohol syndrome differ because of variable definitions of heavy drinking and inconsistent methods of diagnosis. Therefore, rates range from 4% to as much as 44%.

International

Estimated rates of fetal alcohol syndrome in international settings are sparse in the literature. They are based on variable definitions and methods of ascertainment and range from 1 in 1000 to less than 1 in 10,000 live births. However, in some extremely high-risk areas, such as selected communities in South Africa where binge drinking in pregnancy is relatively common, careful in-school assessments have shown that rates of fetal alcohol syndrome may be as high as 4-5% of all children in the normal first grade in school.

Mortality/Morbidity

Adverse effects on the outcome of pregnancy, in addition to fetal alcohol syndrome disorder, have been noted with chronic or heavy alcohol use. These effects include an increased risk for spontaneous abortion, placental abruption, preterm delivery, amnionitis, stillbirth, and sudden infant death syndrome.

Commonly associated factors, such as maternal tobacco or other substance abuse, low socioeconomic status, and poor nutrition, complicate the morbidity and mortality associated with prenatal alcohol exposure.

Race

Regardless of race or ethnicity, fetal alcohol syndrome and fetal alcohol syndrome disorder occur in women who drink heavily during pregnancy. Rates of fetal alcohol syndrome appear to be highest among groups of low socioeconomic status. What is unknown is how these findings are related to a high prevalence of risky drinking in some populations; compromised nutritional status or general health; and, therefore, reduced resiliency to the effects of alcohol, possible genetic susceptibility, or a combination of these and other factors.

Clinical

History

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)

Physical

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

Causes

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

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