Vitamins C and E to prevent complications of pregnancy-associated hypertension.

Multicenter randomized placebo-controlled trial in nulliparous pregnant women at low risk for preeclampsia with singleton pregnancies, enrolled before 16 weeks of gestation. The trial was conducted at 16 clinical centers in the MFMU Network, with enrollment from July 2003 through February 2008.

Participants in the active arm received oral capsules containing vitamin C 1000 mg daily as ascorbic acid plus vitamin E 400 IU daily as RRR-alpha-tocopherol acetate, started between 9 and 16 weeks of pregnancy and continued until delivery. For the vitamin C plus E group, 5088 women were randomized and 4993 were analyzed for the primary outcome.

Vitamin C plus vitamin E did not reduce the primary composite outcome of pregnancy-associated hypertension with adverse maternal, fetal, or neonatal outcomes. The primary outcome occurred in 305 women (6.1%) in the vitamin group versus 285 (5.7%) with placebo, RR 1.07 (95% CI 0.91 to 1.25; P = 0.42). Preeclampsia was also unchanged, 358 (7.2%) versus 332 (6.7%), RR 1.07 (0.93 to 1.24; P = 0.33), and most neonatal outcomes were similar. Pregnancy-associated hypertension was higher with vitamins, 1457 (29.2%) versus 1322 (26.6%), RR 1.10 (1.03 to 1.17; P = 0.004).

The intervention was tested in a specific low-risk, nulliparous singleton-pregnancy population, which limits generalizability. Some women were lost to follow-up and primary outcome data were not available for all randomized participants. Several reported outcomes were secondary, increasing the possibility of chance findings across multiple comparisons.