The recommended dose of Vitamin E in human pregnancy is 22-30 mg/day. High doses of Vitamin E (>or=400 IU/day) have been shown to attenuate or even prevent the damaging effect of ethanol and diabetes on the fetus in experimental animal models. The Motherisk program prospectively enrolled, and followed-up on, 82 pregnant women exposed to high doses (>or=400 IU/day) of Vitamin E during the first trimester of pregnancy. Pregnancy outcome was compared to a matched control group. The study group (n=82) was exposed to Vitamin E at doses ranging from 400-1200 IU/day. There was one pregnancy with major malformation (omphalocele) in study group. There was an apparent decrease in mean birth weight (3173+/-467 g) in Vitamin E group as compare to control (3417+/-565 g; P=0.0015); however, there were no significant differences in rates of live births, preterm deliveries, miscarriages and stillbirths. Therefore, it is concluded that consumption of high doses of Vitamin E during the first trimester of pregnancy does not appear to be associated with an increased risk for major malformations, but may be associated with decrease in birth weight.