In a recently completed research study, ethanol was orally administered once per week to gravid pigtailed macaques (M.nemestrina). The results suggested that teratogenic effects in facial form and cognition occurred in exposures of 1.8 gm/kg (yielding peak plasma ethanol concentrations of about 200 mg/dl), and that the alterations were produced in the first six weeks of gestation. These results stimulate two clinical questions concerning the temporal patterns of alcohol consumption that can be effectively studied in this animal model: 1) Can the primate fetus recover from an initial gestational teratogenic exposure to alcohol through later gestational abstinence? This question will be explored by comparing groups of infant animals gestationally exposed to the 1.8 gm/kg ethanol dose for 0, 3, 6, or all (24) weeks in gestation. 2) How does the teratogenic effect of ethanol relate to the relative exposure to ethanol (the area under the metabolic curve), the peak plasma ethanol concentration, and the weekly frequency of ethanol exposures? This question will be examined by comparing groups of infants fetally exposed to the same cumulative weekly relative ethanol exposure as the infants who were fetally exposed to 1.8 gm/kg once per week throughout gestation as above, but scheduled in two different but typical human consumption patterns -- 1.2 gm/kg ethanol given on two consecutive days per week (modeling weekend drinking) or 0.6 gm/kg ethanol daily. Control dams will receive a daily sucrose solution. Infants in all groups in each study will be assessed on the same measures of physical appearance and cognitive function until they are 15 months of age. The results of these studies should provide information for the reasonable identification of human drinking schedules that are high risk to produce infants with birth defects, especially mental retardation.
