Prenatal Alcohol Exposure and Abnormal Brain Development – Findings from Basic Research

The focus of this chapter is on description of normal and alcohol-induced abnormal embryogenesis of the brain and face. Emphasis is placed on early mammalian developmental stages and the vulnerability of early embryos to birth defects caused by maternal alcohol use. Regarding normal development, the prenatal stages described are present from the 3rd through the 6th weeks of human gestation (i.e., mid 5th through 8th weeks after the beginning of the last normal menstrual period [LNMP]; a time that is prior to pregnancy recognition by many women). This presentation of basic embryology concepts is designed to provide a foundation for the appreciation of alcohol-induced teratogenesis. The alcohol-induced abnormalities described result from accurately timed acute prenatal exposures in mice that were subsequent to maternal alcohol administration at times that correspond to the mid-3rd to early 4th week post-fertilization (mid-5th to early 6th week post-LNMP) in humans. The animal model-based research findings show that the characteristic facial features of Fetal Alcohol Syndrome result from insult as early as the mid-3rd week of human development; that later exposures affecting development in the 4th week yield a different pattern of facial defects; and that at both of these exposure periods embryos are vulnerable to induction of structural brain abnormalities. Demonstration of the vulnerability to alcohol-induced birth defects of embryos at developmental stages that are present at a time prior to typical human pregnancy recognition has major implications for Fetal Alcohol Spectrum Disorder prevention approaches and is important for legal and ethical considerations involving both mothers and their affected offspring.