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Maternal 25-Hydroxyvitamin D and Preterm Birth in Twin Gestations

Bodnar, Lisa M. PhD; Rouse, Dwight J. MD; Momirova, Valerija MS; Peaceman, Alan M. MD; Sciscione, Anthony DO; Spong, Catherine Y. MD; Varner, Michael W. MD; Malone, Fergal D. MD; Iams, Jay D. MD; Mercer, Brian M. MD; Thorp, John M. Jr MD; Sorokin, Yoram MD; Carpenter, Marshall W. MD; Lo, Julie MD; Ramin, Susan M. MD; Harper, Margaret MDMSc

doi: 10.1097/AOG.0b013e3182941d9a
Original Research

OBJECTIVE: To assess whether there was an independent association between maternal 25-hydroxyvitamin D concentrations at 24–28 weeks of gestation and preterm birth in a multicenter U.S. cohort of twin pregnancies.

METHODS: Serum samples from women who participated in a clinical trial of 17 α-hydroxyprogesterone caproate for the prevention of preterm birth in twin gestations (2004–2006) were assayed for 25-hydroxyvitamin D concentrations using liquid chromatography tandem mass spectrometry (n=211). Gestational age was determined early in pregnancy using a rigorous algorithm. Preterm birth was defined as delivery of the first twin or death of either twin at less than 35 weeks of gestation.

RESULTS: The mean serum 25-hydroxyvitamin D concentration was 82.7 nmol/L (standard deviation 31.5); 40.3% of women had concentrations less than 75 nmol/L. Preterm birth at less than 35 weeks of gestation occurred in 49.4% of women with 25-hydroxyvitamin D concentrations less than 75 nmol/L compared with 26.2% among those with concentrations of 75 nmol/L or more (P<.001). After adjustment for maternal race and ethnicity, study site, parity, prepregnancy body mass index, season, marital status, education, gestational age at blood sampling, smoking status, and 17 α-hydroxyprogesterone caproate treatment, maternal 25-hydroxyvitamin D concentration of 75 nmol/L or more was associated with a 60% reduction in the odds of preterm birth compared with concentrations less than 75 nmol/L (adjusted odds ratio [OR] 0.4, 95% confidence interval [CI] 0.2–0.8). A similar protective association was observed when studying preterm birth at less than 32 weeks of gestation (OR 0.2, 95% CI 0.1–0.6) and after confounder adjustment.

CONCLUSIONS: Late second-trimester maternal 25-hydroxyvitamin D concentrations less than 75 nmol/L are associated with an increase in the risk of preterm birth in this cohort of twin pregnancies.


Supplemental Digital Content is Available in the Text.Maternal serum 25-hydroxyvitamin D level less than 75 nmol/L at 24–28 weeks of gestation is associated with an increased risk of early preterm birth in twin gestations.

Departments of Epidemiology and Obstetrics and Gynecology, University of Pittsburgh Pittsburgh, Pennsylvania, University of Alabama at Birmingham, Birmingham, Alabama, Northwestern University, Chicago, Illinois, Drexel University, Philadelphia, Pennsylvania, University of Utah, Salt Lake City, Utah, Columbia University, New York, New York, The Ohio State University, Columbus, Ohio, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio, University of North Carolina, Chapel Hill, North Carolina, Wayne State University, Detroit, Michigan, Brown University, Providence, Rhode Island, University of Texas Southwestern Medical Center, Dallas, Texas, University of Texas Health Science Center at Houston, Houston, Texas, and Wake Forest University Health Sciences, Winston-Salem, North Carolina; the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.

Corresponding author: Lisa Bodnar, PhD, MPH, RD, Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, 130 DeSoto Street, A742 Crabtree Hall, Pittsburgh, PA 15261; e-mail:

Supported by National Institutes of Health grant R01 HD056999 (Principal Investigator: Bodnar) and by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, HD36801) and the National Center for Research Resources (M01 RR00080, UL1 RR024989), and its contents do not necessarily represent the official view of Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Heart, Lung, and Blood Institute, National Center for Research Resources, or National Institutes of Health.

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

The authors thank Margaret Cotroneo, RN, and Allison T. Northen, MSN, RN, for protocol development and coordination between clinical research centers; Elizabeth Thom, PhD, for protocol and data management and statistical analysis; and Steve N. Caritis, MD, for protocol development and oversight.

For a list of other members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal Fetal Medical Unit Network, see the Appendix online at

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

© 2013 by The American College of Obstetricians and Gynecologists.