In the late 1960s, the effects of alcohol abuse on the fetus were rediscovered, so to speak. Lemoine and associates in France, and then Ulleland and Jones and Smith in the United States, described a distinctive pattern of abnormalities in infants born of severely alcoholic mothers. They stated that the affected infants are small in length in comparison to weight, and most of them fall below the third percentile for head circumference. They are distinguished also by the presence of short palpebral fissures (shortened distance between inner and outer canthi) and epicanthal folds; maxillary hypoplasia, micrognathia, indistinct philtrum, and thin upper lip; and longitudinally oriented palmar creases, flexion deformities of the fingers, and a limited range of motion of other joints. Minor anomalies (usually spontaneously closing cardiac septal defects), anomalous external genitalia, and cleft lip and palate are much more frequent than in the general population. All of these features have similarities to the syndrome described in a proportion of infants whose mothers had taken anticonvulsants during pregnancy, the “fetal anticonvulsant (antiepileptic) syndrome” (see Chap. 15). The newborn infants suck and sleep poorly, and many of them are irritable, restless, hyperactive, and tremulous; these last symptoms resemble those of alcohol withdrawal except that they persist.
The first long-term study of children with what has come to be called fetal alcohol syndrome (FAS) was reported by Jones and coworkers. Among 23 infants born to alcoholic mothers, there was a neonatal mortality of 17 percent; among the infants who survived the neonatal period, almost half failed to achieve normal weight, length, and head circumference or remained mentally retarded to a varying degree, even under optimal environmental conditions. Several large groups of severely affected children have now been observed for 20 years or longer (see Streissguth). Distractibility, inattentiveness, hyperactivity, and impairment of fine motor coordination are prominent features in early childhood. Most such children fall into the category of attention-deficit hyperactivity disorder. Slow growth of head circumference is a consistent finding throughout infancy and childhood. The physical stigmata of the syndrome become less distinctive after puberty, but practically all adolescents are left with some degree of mental retardation and behavioral abnormalities.
The pathologic changes that underlie the syndrome have been studied in a small number of cases and no uniform change has emerged. Of some interest are observations such as those of Ikonomidu and coworkers that demonstrate a profound effect of alcohol exposure on the deletion of millions of neurons in the developing rat brain by a mechanism of apoptosis. The main vulnerability occurs during periods of synaptogenesis, which in humans extends from the sixth month of gestation onward.
It is noteworthy that infants born to nonalcoholic mothers who had been subjected to severe dietary deprivation during pregnancy (during World War II) were small and often premature, but these infants did not show the pattern of malformations that characterizes FAS. Alcohol readily crosses the placenta in humans and animals; in the mouse, rat, chick, miniature swine, and beagle dog, alcohol has been shown to have both embryotoxic and teratogenic effects. Thus, the evidence to date favors a toxic effect of alcohol, although a possible toxic effect of acetaldehyde and smoking and a possible contributory role for nutritional deficiency have not been totally excluded.