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Fetal Alcohol Syndrome

  • Author: Keith K Vaux, MD; Chief Editor: Ted Rosenkrantz, MD  more...
 
Updated: Jan 16, 2015
 

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 3 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).

Facial characteristics of a child with fetal alcoh 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 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.

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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 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.

Studies have shown that prenatal alcohol exposure affects the hypothalamic-pituitary-adrenal (HPA) axis as well as alters basal and poststress cortisol levels.[3] 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.[3]

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Epidemiology

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.

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Contributor Information and Disclosures
Author

Keith K Vaux, MD Professor of Medicine, Clinical Chief and Division Director, Division of Medical Genetics, Department of Medicine, University of California, San Diego, School of Medicine; Director, Rare Disease Program, Rady Children's Hospital San Diego and UC San Diego

Keith K Vaux, MD is a member of the following medical societies: American Academy of Pediatrics, Western Society for Pediatric Research

Disclosure: Nothing to disclose.

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

Christina Chambers, MPH, PhD is a member of the following medical societies: Society for Epidemiologic Research, Teratology Society, Research Society on Alcoholism, International Society for Pharmacoepidemiology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Arun K Pramanik, MD, MBBS Professor of Pediatrics, Louisiana State University Health Sciences Center

Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

The authors gratefully acknowledge the contributions of Christine D Dittmer, MD, and Sarah L Lentz-Kapua, MD, to the writing and development of this article.

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Facial characteristics of a child with fetal alcohol syndrome.
 
 
 
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