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Vitamin C and E Supplementation to Prevent Spontaneous Preterm Birth: A Randomized Controlled Trial

Hauth, John C. MD; Clifton, Rebecca G. PhD; Roberts, James M. MD; Spong, Catherine Y. MD; Myatt, Leslie PhD; Leveno, Kenneth J. MD; Pearson, Gail D. MD, ScD; Varner, Michael W. MD; Thorp, John M. Jr MD; Mercer, Brian M. MD; Peaceman, Alan M. MD; Ramin, Susan M. MD; Sciscione, Anthony DO; Harper, Margaret MD; Tolosa, Jorge E. MD, MSCE; Saade, George MD; Sorokin, Yoram MD; Anderson, Garland B. MD

doi: 10.1097/AOG.0b013e3181ed721d
Original Research

OBJECTIVE: To estimate whether maternally administered vitamins C and E lower the risk of spontaneous preterm birth.

METHODS: This is a secondary analysis of a randomized, double-masked, placebo-controlled trial in nulliparous women at low-risk administered 1,000 mg vitamin C and 400 international units vitamin E or placebo daily from 9 to 16 weeks of gestation until delivery. Outcomes include preterm birth attributable to premature rupture of membranes (PROM) and total spontaneous preterm births (spontaneous preterm birth attributable to PROM or spontaneous labor).

RESULTS: Of the 10,154 women randomized, outcome data were available for 9,968 (4,992 vitamin group and 4,976 placebo group). A total of 1,038 women (10.4%) delivered preterm, of whom 698 (7.0%) had spontaneous preterm birth. A spontaneous preterm birth occurred in 356 women (7.1%) assigned to daily vitamin C and E supplementation and in 342 (6.9%) assigned to placebo. There were 253 women (2.5%) who delivered after preterm PROM and 445 (4.5%) after a spontaneous preterm labor. In women supplemented with vitamins C and E, births attributed to preterm PROM were similar at less than 37 and 35 weeks of gestation, but births were less frequent before 32 weeks of gestation (0.3% compared with 0.6%, adjusted odds ratio 0.3–0.9). However, total spontaneous preterm births across gestation in women supplemented with vitamins C and E or a placebo were similar.

CONCLUSION: 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.



Maternal supplementation with vitamins C and E beginning at 9 to 16 weeks of gestation in nulliparous women at low risk does not reduce total spontaneous preterm births. SUPPLEMENTAL DIGITAL CONTENT IS AVAILABLE IN THE TEXT.

From the Departments of Obstetrics and Gynecology at the University of Alabama at Birmingham, Birmingham, Alabama; University of Pittsburgh, Pittsburgh, Pennsylvania; University of Cincinnati, Cincinnati, Ohio; University of Texas Southwestern Medical Center, Dallas, Texas; University of Utah, Salt Lake City, Utah; University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Case Western Reserve University, Cleveland, Ohio; Northwestern University, Chicago, Illinois; University of Texas Health Science Center at Houston, Houston, Texas; Drexel University, Philadelphia, Pennsylvania; Wake Forest University Health Sciences, Winston-Salem, North Carolina; Oregon Health and Science University, Portland, Oregon; University of Texas Medical Branch, Galveston, Texas; Wayne State University, Detroit, Michigan; University of Texas Medical Center, Galveston, Texas; The George Washington University Biostatistics Center, Washington, DC; National Heart, Lung, and Blood Institute, Bethesda, Maryland; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

* For a list of other members of the NICHD MFMU, see the Appendix online at

Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD34208, HD27869, HD40485, HD40560, HD40544, HD34116, HD40512, HD21410, HD40545, HD40500, HD27915, HD34136, HD27860, HD53118, HD53097, HD27917, and HD36801); the National Heart, Lung, and Blood Institute; and the National Center for Research Resources (M01 RR00080, UL1 RR024153, UL1 RR024989). The contents of this article do not necessarily represent the official view of National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, National Center for Research Resources, or National Institutes of Health.

The authors thank Sabine Bousleiman, MSN, and Margaret Cotroneo, RN, for protocol development and coordination between clinical research centers, and Elizabeth Thom, PhD, for protocol and data management and statistical analysis.

Presented as a poster at the Society for Maternal-Fetal Medicine 2010 Annual Meeting, February 1–6, 2010, Chicago, IL.

Dr. Spong, Associate Editor of Obstetrics & Gynecology, was not involved in the review or decision to publish this article.

Corresponding author: John C. Hauth, MD, University of Alabama at Birmingham, Department of Obstetrics and Gynecology, 619 19th Street South–176F, Suite 10360, Birmingham, AL 35249-7333; e-mail:

Financial Disclosure The authors did not report any potential conflicts of interest.

© 2010 by The American College of Obstetricians and Gynecologists.