Vitamins C, E Supplementation May Not Reduce Risk for Certain Pregnancy Complications

From Medscape Medical News
Laurie Barclay, MD

April 6, 2010 — Prenatal vitamin C and E supplementation does not reduce the rate of preeclampsia or gestational hypertension (GH) but is associated with greater risk for fetal loss or perinatal death and preterm prelabor rupture of membranes (PPROM), according to the results of a multicenter, randomized controlled trial reported in the March issue of the American Journal of Obstetrics & Gynecology.

"Several lines of evidence support the hypothesis that oxidative stress, an imbalance between prooxidant and antioxidant forces, plays an essential role in the development of hypertensive disorders of pregnancy," write Hairong Xu, MD, MSc, from Hôpital Ste-Justine and Université de Montréal in Quebec City, Canada, and colleagues from the International Trial of Antioxidants in the Prevention of Preeclampsia (INTAPP) study group. "We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of ...GH and its adverse conditions among high- and low-risk women."

Participants were stratified by risk status and were randomly assigned to receive daily supplementation with 1 g of vitamin C and 400 IU of vitamin E, or placebo. The main study endpoint was GH and its associated complications.

Among 2647 women randomly selected, data were analyzed for 2363 women because the trial was stopped prematurely when adverse outcomes from supplementation were recognized. The groups did not differ in the risk for GH and its complications (relative risk [RR], 0.99; 95% confidence interval, 0.78 - 1.26). However, vitamin C and E supplementation was associated with nonprespecified outcomes of an increased risk for fetal loss or perinatal death, as well as with PPROM.

Limitations of this study include reduced power because the trial was stopped prematurely.

"Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and ...PPROM," the study authors write. "Despite the fact that the underlying mechanisms remain largely unclear, there is increasing concern that supplementation of vitamins C and E at the doses studied [ie, 1000 mg vitamin C and 400 IU vitamin E (RRR alpha-tocopherol)] may increase the risk of other adverse pregnancy outcomes such as low birthweight and PPROM. Therefore, based on our present knowledge, vitamin C and E supplementation at the above doses cannot be recommended for pregnant women to prevent adverse pregnancy outcomes including [preeclampsia]."

The Canadian Institutes of Health Research supported this study. The study authors have disclosed no relevant financial relationships.

Am J Obstet Gynecol. 2010;202:239.e1-239.e10.