Antioxidant supplementation and premature rupture of the membranes: a planned secondary analysis

Am J Obstet Gynecol. 2008 Oct;199(4):433.e1-8. doi: 10.1016/j.ajog.2008.07.011.


Objective: The purpose of this study was to determine if antioxidant supplementation during pregnancy reduces the incidence of premature rupture of the membranes (PROM).

Study design: A placebo-controlled, double-blind trial was conducted. PROM and preterm PROM (PPROM) were planned secondary outcomes of the trial. Women between 12(0/7) and 19(6/7) weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomized to daily treatment with both vitamin C (1000 mg) and E (400 IU) or placebo.

Results: Outcome data for PROM were available for 697 of 739 patients. The rates of PROM (37/349 [10.6%] vs 19/348 [5.5%]; adjusted risk ratio [RR] 1.89 [95.42% CI, 1.11-3.23]; P = .015), and PPROM (16/349 [4.6%] vs 6/348 [1.7%]; RR 2.68 [1.07-6.71]; P = .025) were increased in the antioxidant group.

Conclusion: Contrary to expectations, vitamins C and E supplementation in this dose combination may be associated with an increased risk of PROM and PPROM.

Trial registration: NCT00097110.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antioxidants / administration & dosage*
  • Ascorbic Acid / administration & dosage*
  • Dietary Supplements*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fetal Membranes, Premature Rupture / epidemiology
  • Fetal Membranes, Premature Rupture / prevention & control*
  • Humans
  • Pregnancy
  • Pregnancy Outcome
  • Prospective Studies
  • Vitamin E / administration & dosage*


  • Antioxidants
  • Vitamin E
  • Ascorbic Acid

Associated data