Fetal Alcohol Syndrome Does Alcohol Withdrawal Play a Role? Jennifer D. Thomas, Ph.D., and Edward P. Riley, Ph.D. Alcohol use by a pregnant woman may interfere with the development of her fetus. Newborns whose mothers are intoxicated during delivery can experience withdrawal symptoms, such as tremors and even seizures. It is likely that withdrawal also can occur during fetal development. Thus, the possibility exists that withdrawal by the pregnant woman may exacerbate alcohol’s adverse effects on her fetus. One potential mechanism through which alcohol withdrawal might damage the fetus involves the receptor for the neurotransmitter glutamate (i.e., the N-methyl-D-aspartate [NMDA] receptor). This receptor plays a crucial role during neuronal development. Excessive activation of the NMDA receptor, which occurs during withdrawal, may lead to neuronal cell death. Animal studies suggest that these effects may contribute to behavioral deficits following prenatal exposure to alcohol. KEY WORDS: fetal alcohol syndrome; AOD withdrawal syndrome; symptom; gestation; fetus; neonate; mother; prenatal alcohol exposure; heavy AOD use; binge AOD use; congenital anomaly; fetal development; central nervous system; NMDA receptors; cytolysis; cell growth and differentiation; teratogenesis; brain damage; AOD abstinence; animal model; literature review woman who drinks alcoholic Withdrawal Symptoms estimated to consume two or more beverages during pregnancy in Pregnant Women drinks per day (Abel 1990). A exposes not only herself but and Newborns One of the consequences of heavy also her fetus to alcohol. Alcohol read- alcohol use is the potential for experi- ily crosses the placenta; consequently, encing withdrawal symptoms during the blood alcohol levels (BAL’s) of the Pregnant Women periods of abstinence. Symptoms of fetus are similar to those of the mother. Likewise, if the woman suddenly Despite warning labels on alcoholic abstains from alcohol, both she and beverages and an increased awareness JENNIFER D. THOMAS, PH.D., is a her fetus may undergo withdrawal. among the general population of alco- research assistant professor and EDWARD This article briefly describes the with- hol’s deleterious effects on the devel- P. R ILEY, PH.D., is a professor and the drawal symptoms observed in pregnant oping fetus, the women who are the director of the Center for Behavioral women and newborns, discusses the heaviest alcohol abusers frequently do Teratology, Department of Psychology, birth defects associated with prenatal San Diego State University, San Diego, not change their drinking practices alcohol exposure, and explores the California. possibility that alcohol withdrawal during pregnancy. Such women are at (AW) may contribute to the adverse the greatest risk for giving birth to a This work was partially supported by effects of prenatal alcohol exposure child with alcohol-related problems. National Institute on Alcohol Abuse on fetal brain function and behavioral In the United States, approximately and Alcoholism grants AA–06902, development. 3.3 percent of pregnant women are AA–03249, and AA–11634. Vol. 22, No. 1, 1998 47 mild to moderate withdrawal from sedatives or tranquilizers has been used subsequent behavioral alterations are alcohol may include tremors, sweating, only for infants with the most serious among the challenges that researchers stomach pain, anxiety, and sleep dis- symptoms (e.g., seizures and vomiting). currently face. turbances. Severe withdrawal symptoms The observations described here may include delirium tremors and violent leave little doubt that newborns can agitation (i.e., seizures). These effects undergo AW, and similar effects may Can Alcohol Withdrawal may begin within hours of the last drink occur in the fetus. The effects of Damage the Fetus or and may persist for several days. Various maternal or fetal withdrawal (and its Newborn? tranquilizers and sedatives, including treatment) on the developing fetus, alcohol itself, have been used to man- however, remain unknown. There is little doubt that alcohol age these symptoms (Thorp 1995). interferes with normal fetal development (i.e., is a teratogenic agent). Fetal alcohol Consequences of Prenatal exposure can adversely affect numer- Newborns Alcohol Exposure ous developmental processes, such as When a pregnant woman undergoes the multiplication (i.e., proliferation), AW, so does her fetus. To date, no studies Women who drink alcohol during migration, and survival of cells, as well have analyzed the symptoms and effects pregnancy place their fetuses at risk as the cells’ development into specific of withdrawal on fetuses in utero. for numerous developmental problems, cell types (i.e., differentiation). The However, researchers have studied ranging from prenatal mortality to mechanisms by which alcohol disrupts withdrawal in newborns whose mothers disruptions in physical and behavioral these processes have yet to be fully were intoxicated during delivery. For development. The most serious con- elucidated. Given alcohol’s ubiquitous example, Beattie (1986) reported the sequence of heavy maternal drinking distribution throughout all body regions, case of a newborn who had a BAL of is a cluster of characteristic anomalies however, it likely interferes with devel- more than 200 milligrams per deciliter termed fetal alcohol syndrome (FAS) opment through many direct and indi- (mg/dL) (i.e., over 0.2 percent1) and (Jones and Smith 1973). Symptoms rect actions (for a review, see West et exhibited signs of AW—including of FAS include prenatal and postnatal al. 1994). tremors, irritability, frequent mouth growth retardation, characteristic facial Like alcohol itself, withdrawal from movements, and vomiting—between abnormalities, and CNS anomalies. alcohol initiates a cascade of physio- 24 and 48 hours after delivery. The distinct facial characteristics of logical events that might also affect The onset of withdrawal symptoms children with FAS include such features the developing organism. Although in newborns may be delayed compared as a flat midface, thin upper lip, and there is no direct evidence that with- with adults, because alcohol metabolism small eye openings (i.e., palpebral drawal contributes to alcohol’s adverse in newborns is slower than in adults. fissures). CNS anomalies associated effects on development, the possibility Neonatal AW typically manifests itself with FAS include an abnormally small demands further investigation. as hyperexcitability of the central ner- head (i.e., microcephaly) and behavioral The clearest indications that with- vous system (CNS) and gastrointestinal problems, such as attention deficits, drawal from drugs can have long-term symptoms. CNS hyperexcitability hyperactivity, motor dysfunction, adverse effects on the developing fetus results in symptoms such as tremors, mental retardation, and learning and have come from animal studies exam- excessive muscle tension, irritability, social skills deficits. Although some ining the teratogenic effects of narcotics. increased respiratory rate, poor sleeping of the physical characteristics of FAS For example, a series of studies evalu- patterns, and increased sense of hearing become less pronounced as the child ating the effects of prenatal opiate (i.e., hyperacusis). These infants also matures into adulthood, many of the exposure have shown that withdrawal may exhibit spontaneous seizures behavioral problems persist. contributes considerably to the adverse accompanied by cessation of breathing Even if they do not meet all the effects of these agents, increasing (i.e., apnea) and arching of the back (i.e., criteria for a diagnosis of FAS, children mortality and morbidity in fetal and opisthotonos). Gastrointestinal symp- exposed to alcohol in utero may exhibit newborn rat pups (for a review, see toms may include abdominal distention a wide range of developmental prob- Sparber 1986). In those studies, pregnant and, in a few cases, vomiting (Robe et lems, particularly behavioral disorders. rats (and their fetuses) were exposed al. 1981; see also Coles et al. 1984). These developmental problems often throughout gestation to high doses of Newborns undergoing AW are best are referred to as fetal alcohol effects a long-acting opiate (i.e., 1-alpha- treated by being placed in a calm envi- or alcohol-related birth defects. The acetylmethadol [LAAM]). Of the rat ronment with decreased sensory stim- identification of the factors that place pups, 50 percent died within 24 hours ulation. Pharmacological treatment with a fetus at risk for the harmful effects of birth, a time during which the pups of prenatal alcohol exposure and the were undergoing withdrawal. This 1In most States, the legal BAL for driving ranges elucidation of the mechanisms by which mortality rate decreased to 30 percent from 0.08 to 0.1 percent. alcohol causes CNS dysfunction and when the rats were injected with 48 Alcohol Health & Research World The Role of Alcohol Withdrawal in FAS opiates to alleviate withdrawal. Con- with more chronic alcohol consumption. example, acute AW is associated with versely, injection of naloxone, an In animals, for example, a lower dose changes in many of the hormones agent that increases withdrawal severity, of alcohol consumed in a bingelike related to stress. The possibility exists increased the pups’ mortality rate to manner that produces a high peak that the stress to the mother and/or more than 90 percent. Moreover, when BAL causes more severe microencephaly, the fetus associated with a withdrawal