Antioxidant supplementation during pregnancy: Harmful rather than helpful?

Supplementation with the antioxidant vitamins C and E during pregnancy doesn't reduce the risks of preeclampsia, intrauterine growth restriction, infant death, or other serious infant outcomes in nulliparous women, according to the results of a recent multicenter, randomized trial. In fact, women taking the vitamins may be more likely to develop hypertension and to require treatment with antihypertensive drugs.

Researchers from Australia included in the study almost 2,000 women who were between 14 and 22 weeks' pregnant. Approximately half the group received 1,000 mg vitamin C and 400 IU vitamin E daily, while the other half received placebo.

The researchers found no significant differences between the vitamin and placebo groups in terms of incidence of preeclampsia (6% vs. 5%, respectively, RR 1.20; 95% CI; 0.82–1.75; P=0.57), infantile death or serious outcome (9.5% vs. 12.1%, RR 0.79; 95% CI; 0.61–1.02, P=0.20), or in birthweight below the 10th percentile for gestational age (8.7% vs. 9.9%, RR 0.87; 95% CI; 0.66–1.16, P=0.57). What they did find significant was the fact that more women in the vitamin group had to be admitted to the hospital antenatally with hypertension (5.2% vs. 3.4 %, RR 1.54; 95% CI; 1.00–2.39) or required treatment with antihypertensive agents (4.6% vs. 2.8%, RR 1.67; 95% CI; 1.03–2.69).

The authors of an editorial accompanying the study point out that the trial was powered to detect only a reduction of 50% or more in the risk of preeclampsia. Thus, the possibility that these antioxidants confer a smaller protective benefit to nulliparous, low-risk pregnant women cannot be excluded.

Rumbold AR, Crowther CA, Haslam RR, et al. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006;354:1796-1806.

Jeyabalan A, Caritis SN. Antioxidants and the prevention of preeclampsia-unresolved issues. N Engl J Med. 2006;354:1841-1843.

Commentary by Sharon Phelan MD, Professor, Department of Obstetrics and Gynecology, New Mexico School of Medicine, Albuquerque, NM:

"Because of the morbidity and mortality associated with preeclampsia, researchers continue to seek a way to prevent its occurrence. Given the optimistic findings about supplemental vitamin C and E in high-risk women, it was a natural extension to see if this protection carried over to low-risk women. However-as with low-dose aspirin-the use of supplemental vitamins C and E did not decrease occurrence or morbidity associated with preeclampsia."