For many centuries, perhaps several millennia, ethanol has served as the euphoriant of choice by human adults throughout the world. Undoubtedly, over that period of time countless human fetuses have been exposed in utero to ethanol, but it was less than 30 years ago that P. Lemoine and colleagues in France and K.L. Jones and D.W. Smith in the United States reported the first evidence that ethanol can have deleterious effects on the human fetus. For several years after these authors described the fetal alcohol syndrome there was a tendency to disbelieve that ethanol could cause such dramatic changes in the human fetus. Their description of the syndrome focused on craniofacial malformations and severe neurobehavioral disturbances, including frank mental retardation, as the primary clinical manifestations. In subsequent research it was determined that all fetuses affected by ethanol do not show all features of the syndrome. For example, some may show either craniofacial malformations or CNS effects, but not both. Moreover, sometimes the CNS effects were limited to relatively mild degrees of learning impairment and/or hyperactivity/attention deficit disorder. By convention, the term fetal alcohol syndrome (FAS) has been used to refer to the full syndrome featuring both dysmorphogenic and neuro-behavioral aspects, and an alternate term, fetal alcohol effects (FAE), has sometimes been used to refer to partial or less severe syndromes that tend to feature primarily neurobehavioral aspects. A Committee of the Institute of Medicine, National Academy of Sciences proposed in 1996 that partial syndromes affecting primarily the CNS be termed alcohol-related neurodevelopmental disorder (ARND). Regardless of terminology, it is generally recognized that the CNS effects are the most debilitating component of the syndrome. It is not known what percentage of births currently or in the past qualify for a diagnosis of ARND, but there is little doubt that ethanol has contributed to more cases of developmental neuro-psychiatric impairment than any other substance in the human environment and perhaps more than all other substances combined.
FAS research initially focused on efforts to identify the critical period when the developing fetus is vulnerable to the toxic effects of ethanol. Initially, there was a tendency to assume that there was only one window of vulnerability during which all aspects of the syndrome were caused. However, when it was realized that some fetuses may have predominantly craniofa-cial malformations and others subtle neurobehavioral disturbances, it became evident that ethanol may act by more than one mechanism and each mechanism may have its own critical period of vulnerability. Because the progenitor cells that form the skull and bony skeleton differentiate much earlier than those that give rise to neurons in the brain, it was logical to assume that the vulnerability time window for producing the craniofacial malformations must be early, within the first trimester, whereas the vulnerable period for causing neurobehavioral disturbances would have to be later, perhaps in the second or third trimester, when neuronal progenitor cells are differentiating, migrating, and undergoing maturation. While mechanisms giving rise in the first trimester to the craniofacial malformations remain largely unknown, insights described below have been gained into third trimester mechanisms responsible for the deleterious effects of ethanol on the developing brain.
Was this article helpful?