Alcohol-induced microencephaly during the third trimester equivalent: relationship to dose and blood alcohol concentration.

Alcohol was administered in different doses to groups of neonatal rat pups from postnatal days 4-10 using an artificial rearing technique. Blood alcohol concentrations (BACs) were monitored in pups on postnatal day 6. Brain weights were measured on postnatal day 10 and the extent of microencephaly was correlated with dose and BAC. Doses of 7.4 g/kg/day and above resulted in microencephaly. Although BACs varied considerably among individual animals at each dose tested, the amount of microencephaly increased with the BAC, and the amount of brain growth reduction was more dependent on BAC than dose. The BAC threshold for producing microencephaly was between 140 and 197 mg/dl. Deficits in the brain weight to body weight ratio ranged from 14% to 25% as BACs increased to approximately 280 mg/dl. Higher BACs did not produce significantly more microencephaly, although BACs above 425 mg/dl were lethal. Sex-related differences were also examined. There were significant differences in the brain weights and the BACs between males and females of the same dose groups. These data indicate that increasing the amount of alcohol during the third trimester equivalent increases the amount of microencephaly. However, BAC is a better predictor than dose of the adverse affects of alcohol on brain growth.