EFFECTS OF PRENATAL EXPOSURE TO ALCOHOL PLUS CAFFEINE IN RATS - PREGNANCY OUTCOME AND EARLY OFFSPRING DEVELOPMENT

The factors determining susceptibility to fetal alcohol syndrome (FAS) are not fully understood. We used an animal model of alcohol-related birth defects to assess the coteratogenic potential of caffeine as a risk factor in FAS. Rats were exposed prenatally to alcohol (similar to 15 g/kg/day) with or without caffeine (similar to 84 mg/kg/day) from gestation days 6 through 20 via liquid diet. All control groups were pair-fed to the alcohol-exposed groups. In addition, some controls had free access to lab chow and water. Prenatal exposure to alcohol or caffeine reduced both maternal weight gain during pregnancy and birthweight of offspring. The combination of alcohol plus caffeine produced an additive effect in reducing birthweight and synergistic effects in increasing postnatal offspring mortality. Prenatal alcohol exposure had a significant negative impact on several developmental indices, including grip strength and negative geotaxis. Prenatal caffeine exposure did not affect maturational measures and did reduce offspring serum levels of the zinc-dependent enzyme alkaline phosphatase. This study in rats demonstrated that caffeine can exacerbate some of the effects of alcohol on prenatal development, specifically reduced birthweight, litter size, and postnatal survival, but that caffeine does not appear to alter prenatal alcohol-induced delays in early postnatal maturation of survivors. The relative impact of intralitter birthweight rank on developmental outcome was also assessed. Birthweight influenced development, but did not interact significantly with either prenatal alcohol or caffeine. The results imply that high levels of maternal caffeine intake in humans could increase the likelihood that a child exposed prenatally to alcohol would be born with significantly lowered birthweight, one of the cardinal diagnostic criteria for FAS.