Brain Growth Abnormalities in Fetal Alcohol Syndrome Suggest the Teratogenic Effects of Alcohol Persist Long After the Prenatal Brain Insults:

Background: Fetal Alcohol Syndrome (FAS) is a permanent birth defect caused by maternal consumption of alcohol during pregnancy, and it is a leading cause of preventable developmental disabilities. Symptoms of the syndrome include prenatal growth deficiency and developmental delay. Caniofacial anomalies (i.e., microcephaly, epicanthal folds, short palpebral fissures) are a hallmark marker of the disorder, but not all children with severe prenatal alcohol exposure have the facial dysmorphology required for a diagnosis of FAS. Roughly 10 to 40% of children born to alcohol abusing mothers meet criteria for the diagnosis. Brain abnormalities, most commonly microcephaly and neuronal migration anomalies, have been documented in post mortem studies. Mental retardation is common among FAS individuals and subtler neuropsychological abnormalities have also been reported. Prominent in the cognitive and behavioral literature are implications that children with prenatal alcohol exposure have difficulties with response inhibition, behavioral control, and executive functions, all known to be related to frontal lobe functioning. Yet, brain imaging studies using traditional volumetric methods have not documented frontal lobe abnormalities to accompany the frontal lobe system dysfunction in FAS individuals.

Advance: We assessed regional brain shape abnormalities in children and adolescents with FAS using high resolution, 3D, structural magnetic resonance imaging data and novel, whole-brain, surface-based image analysis procedures. Significant brain size and shape abnormalities were observed in the alcohol-exposed subjects in inferior parietal/perisylvian regions bilaterally where their brains appeared to be narrower than the controls.' Highly significant decreased brain surface extent or reduced brain growth was also observed in the ventral aspects of the frontal lobes most prominent in the left hemisphere. The brain shape abnormalities, particularly in the frontal lobe, have previously been obscured, likely by the relatively low spatial resolution typical of volumetric studies used in the past to assess brain morphologic abnormalities.

Implications: Despite the common lay perception that the teratogenic effects of alcohol on the fetus are static, our recent studies have shown that brain growth continues to be adversely affected during childhood and adolescence, long after the prenatal insult of alcohol exposure to the developing brain. Our studies have shown that FAS individuals do indeed have frontal lobe dysmorphology that could account for their difficulties with executive cognitive functioning. Our increased understanding of the influence of alcohol exposure on brain structure and function during childhood and adolescence as a result of these studies is of critical importance. It is possible that patterns of brain structural abnormalities now characterized in FAS subjects may serve as better biological markers for the severity of prenatal alcohol exposure than the strict adherence to markers of facial dysmorphology that tend to exclude all those without it from educational and social support helpful to families caring for these individuals.

(A.W.. Toga)