2: An international trial of vitamins C and E in the prevention of preeclampsia (INTAPP trial)


      To investigate whether antioxidant supplementation (vitamins C and E) during pregnancy reduces the incidence of preeclampsia (PE) and its adverse conditions among patients at increased or low risk for PE.

      Study Design

      A randomized, placebo-controlled trial was conducted in 17 centres in Canada and 10 centres in Mexico. Women between 12-18 weeks of gestation were stratified by the presence or absence of risk factors for PE (i.e. history of PE, chronic hypertension, multiple pregnancy, or diabetes) and then randomly assigned to daily treatment with both 1000 mg vitamin C and 400 IU vitamin E (RRR tocopherol) or placebo. Our primary composite outcome was gestational hypertension and at least one adverse condition. Analyses were conducted by intention to treat.


      Of 2647 women randomized, a total of 2363 women and their 2536 infants were included in the final analysis. There was no significant difference in the rate of gestational hypertension and adverse conditions in the treatment group (118 of 1167, 10.11%) compared with the placebo group (122 of 1196, 10.20%; relative risk: [0.99 (0.78-1.26]). The rates of PE and gestational hypertension were similar in the two groups. There were no differences in mean gestational age at delivery or rates of perinatal mortality, preterm delivery, small for gestational age, and other neonatal adverse conditions (e.g. convulsions, respiratory distress requiring oxygen, assisted ventilation24 hours, etc.). The effect estimate did not vary according to country, stratum or specific risk factors.


      This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of gestational hypertension, preeclampsia and adverse conditions among patients with or without risk factors.