The pathogenesis of brain abnormalities in the fetal alcohol syndrome: an integrating hypothesis

The most obvious characteristics of the fetal alcohol syndrome are a cluster of minor, physical malformations that are rather nonspecific and that vary greatly in the frequency and severity of expression. The most common characteristics are general body and organ growth deficits, including microcephaly. The most debilitating characteristics, however, are central nervous system (CNS) dysfunctions, such as behavioral and intellectual impairments, which appear to be closely related to the growth deficits. The mechanisms whereby alcohol exerts its deleterious effects on intrauterine growth and development are being intensively investigated. Because of its pharmacological properties, maternal consumption of alcohol is associated with widespread effects throughout the maternal-placental-fetal organism, many of which can secondarily alter the in utero environment. Both direct and indirect mechanisms are discussed with respect to their contribution to alcohol-related effects on embryofetal growth and development. It is suggested that impairment in the protein synthetic machinery, resulting in cellular growth restriction at critical periods of development is the common mechanism underlying alcohol's teratogenicity. Because the development of the CNS is so prolonged and complex compared to other organ systems, it is exquisitely vulnerable to derangement throughout pregnancy.