An international case-control study of primary pediatric brain tumors included interviews with mothers of cases diagnosed from 1976 to 1994 and mothers of population controls. Data are available on maternal vitamin use during pregnancy for 1,051 cases and for 1,919 controls from 8 geographic areas in North America, Europe and Israel. While risk estimates varied by study center, combined results suggest that maternal supplementation for 2 trimesters decreased risk of brain tumor [odds ratio (OR) β«Ψβ¬ 0.7; 95% confidence interval (CI) β«Ψβ¬ 0.5, 0.9], with a trend of less risk with longer duration of use (p trend β«Ψβ¬ 0.0007). The greatest risk reduction was among children diagnosed under 5 years of age whose mothers used supplements during all 3 trimesters (OR β«Ψβ¬ 0.5; CI β«Ψβ¬ 0.3, 0.8). This effect did not vary by histology and was seen for supplementation during pregnancy rather than during the month before pregnancy or while breastfeeding. Our findings are largely driven by data from the United States, where most mothers took vitamins. The proportion of control mothers who took vitamins during pregnancy varied markedly from 3% in Israel and in France, 21% in Italy, 33% in Canada and 52% in Spain to 86-92% at the 3 U.S. centers. The composition of the various multivitamin compounds taken also varied: daily dose of vitamin C ranged from 0 to 600 mg; vitamin E from 0 to 70 mg; vitamin A from 0 to 30,000 IU; and folate from 0 to 2,000 g. Mothers also took individual micronutrient supplements (e.g., vitamin C tablets), but most mothers who took these also took multivitamins, making it impossible to determine the potential independent effects of these micronutrients. Int.