Vitamin C and E Supplementation May Not Prevent Spontaneous Preterm Birth

From Medscape Medical News
Laurie Barclay, MD

August 27, 2010 — Vitamins C and E supplementation beginning at 9 to 16 weeks of gestation in nulliparous women at low risk may not reduce spontaneous preterm births, according to the results of a randomized, double-masked, placebo-controlled trial reported in the September issue of Obstetrics & Gynecology.

"Preterm [premature rupture of membranes (PROM)] has been associated with many factors, including ascorbic acid deficiency (vitamin C)," write John C. Hauth, MD, from the University of Alabama at Birmingham, and colleagues from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.
"These observations are of great importance because if vitamin C supplementation reduces the occurrence of preterm PROM, then a deficiency of vitamin C is a modifiable risk factor and supplementation would be a corrective interventional behavior.
Our intent was to assess further the hypothesis that daily maternal antioxidant supplementation with vitamins C and E from early pregnancy would reduce the incidence of spontaneous preterm birth attributable to either spontaneous labor or preterm PROM."

In the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network trial, nulliparous women at low risk were randomly assigned to daily vitamin C and E supplementation or matching placebo to determine the effect on adverse outcomes from pregnancy-associated hypertension.
Participants (n = 10,154) received 1000 mg of vitamin C and 400 IU of vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery.
In this secondary analysis, the studied endpoints included preterm birth attributable to PROM and total spontaneous preterm births (attributable either to PROM or spontaneous labor).

Of 9968 participants with available outcome data, 4992 were in the vitamin group and 4976 in the placebo group. Of 1038 women (10.4%) who delivered preterm, 698 (7.0%) had spontaneous preterm birth, including 356 (7.1%) randomly assigned to daily vitamin C and E supplementation and 342 (6.9%) assigned to placebo. Delivery after preterm PROM occurred in 253 women (2.5%), and delivery after spontaneous preterm labor occurred in 445 (4.5%).

Compared with the placebo group, the supplementation group had similar births attributed to preterm PROM at less than 37 and 35 weeks of gestation, but fewer births before 32 weeks of gestation (0.3% vs 0.6%; adjusted odds ratio, 0.3 - 0.9). Preterm PROM occurring before 32 weeks of gestation was also less frequent in women in the vitamin group (0.36% vs 0.64%; P = .046).

Total spontaneous preterm births across gestation were similar in the placebo group and in the supplementation group.

"Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk did not reduce spontaneous preterm births," the study authors write.

Limitations of this study include possible type 1 (alpha) error, as well as the clinical imprecision of determining the spontaneous preterm birth subcategories of preterm PROM or spontaneous preterm labor.

"Our results, taken in context with similar trials regarding vitamin C and E supplementation, do not support either the clinical use for prevention of spontaneous preterm birth or its neonatal sequelae or further trials of this treatment in similar populations at low risk," the study authors conclude.

Obstet Gynecol. 2010;116:653-658. Abstract