Fetal Alcohol Syndrome

Updated: Feb 03, 2023
  • Author: Keith K Vaux, MD; Chief Editor: Santina A Zanelli, MD  more...
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Overview

Background

Adverse fetal, 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 three areas: (1) characteristic facial anomalies (see image below), (2) growth retardation (intrauterine growth restriction and failure to have catch-up growth), and (3) CNS involvement (cognitive impairment, learning disabilities, or behavioral abnormalities). [1, 2]

Fetal Alcohol Syndrome. Facial characteristics of Fetal Alcohol Syndrome. Facial characteristics of a child with fetal alcohol syndrome.

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 FASD 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. [3] Prenatal alcohol exposure is of substantial public health concern for the following reasons: (1) FAS is the leading known cause of intellectual disability, (2) fetal alcohol syndrome or fetal alcohol spectrum disorder is associated with persistent physical and neurodevelopmental abnormalities, [4] and (3) fetal alcohol spectrum disorder crosses all socioeconomic groups and affects all races and ethnicities. The costs for one individual with fetal alcohol spectrum disorder are estimated to be more than $30,000 per year; cost of FASD to American society is estimated to be $205 billion each year. [5]

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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 two 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.

Studies have shown that prenatal alcohol exposure affects the hypothalamic-pituitary-adrenal (HPA) axis as well as alters basal and poststress cortisol levels. [6] In a Canadian study involving 26 children (aged 6-14 y) and 32 control children, Keiver et al found significantly elevated cortisol levels in the afternoon and at bedtime in those with known high prenatal exposure to alcohol (alcohol exposure rank 4) relative to those with low/unknown levels of prenatal alcohol exposure (alcohol exposure rank 3) and the control group. The investigators suggest these findings provide evidence for HPA dysregulation due to chronic fetal alcohol exposure, which may lead to long-term psychologic and medical morbidity. [6]

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Etiology

Although many factors may modify the risk, the primary and only necessary cause of fetal alcohol syndrome (FAS) or fetal alcohol spectrum disorder (FASD) is maternal alcohol consumption. [7, 8]

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. [8] 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. [7]

Numerous studies demonstrated that the risk of alcohol-related effects increases according to maternal consumption in a dose-dependent fashion. [9] 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 spectrum disorder.

Evidence indicates that alcohol primarily affects brain development. Therefore, drinking in all three 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 spectrum 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 spectrum disorder.

Poor maternal nutritional status may also increase the likelihood of having an alcohol-affected child.

Having one 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. [10]

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Epidemiology

United States data

Although careful comprehensive studies have not been performed and though passive surveillance systems are inadequate to measure the incidence of fetal alcohol syndrome (FAS) or fetal alcohol spectrum disorder (FASD), the incidence of FAS in the United States is estimated to be 6-9 cases per 1000 live births; the incidence of FASD is estimated to range from 24 to 48 cases per 1000. [2] 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 spectrum disorder has not been well studied. However, it is estimated that 2% to 5% of schoolchildren in the United States have alcohol-related effects. [11]

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 data

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. In some extremely high-risk areas, such as South Africa, Croatia, and Ireland, rates of fetal alcohol spectrum disorders are estimated at 111.1, 53.3, and 47.5 cases per 1000, respectively. [12]

Race

Regardless of race or ethnicity, fetal alcohol syndrome and fetal alcohol spectrum disorder occur in women who drink heavily during pregnancy. Rates of fetal alcohol syndrome appear to be highest among groups of low socioeconomic status. [13] 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.

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Prognosis

The prognosis for individuals with fetal alcohol syndrome (FAS) or fetal alcohol spectrum disorder (FASD) is wide ranging. Some data suggest that having a confirmed diagnosis of fetal alcohol syndrome improves the prognosis, perhaps because this improves access to services. Other studies of fetal alcohol syndrome suggest that early diagnosis improves the prognosis because implementation of early intervention programs occurs at a younger age.

In one study, researchers followed up the natural history of a group of individuals with fetal alcohol syndrome or fetal alcohol spectrum disorder aged 12-51 years. Although no comparison group was included, rates of various mental, social, and legal problems were documented as follows:

  • Mental health problems (95%)

  • Confinement in prison, a drug or alcohol treatment center, or a mental institution (55%)

  • Trouble with the law (60%)

  • Inappropriate sexual behavior (52%)

  • Inability to live independently (82%)

  • Problems with employment (70%)

  • Alcohol and drug problems (>50% of male subjects, 70% of female subjects)

In a more recent study, Swedish investigators evaluating the psychosocial outcomes of 79 adults with fetal alcohol syndrome also found higher rates of special education, unemployment, disability, prescriptions for psychotropic drugs, and hospitalizations for alcohol abuse and psychiatric disorders compared to their age-, sex-, and birth place – matched cohorts. [14] However, both groups had similar levels of criminal offences.

Morbidity/mortality

Adverse effects on the outcome of pregnancy, in addition to fetal alcohol spectrum 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.

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Patient Education

Keys to working successfully with children who have fetal alcohol syndrome or fetal alcohol spectrum disorder are structure, consistency, variety, brevity, and persistence. Because children with fetal alcohol syndrome or fetal alcohol spectrum disorder lack internal structure, caretakers need to provide external structure for them. Be consistent in response and routine so that the child believes the world is predictable.

Because of serious problems maintaining attention, be brief in explanations and directions but also use various ways to get and keep the child's attention.

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