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Maternal Vitamin D Status and the Risk of Mild and Severe Preeclampsia

Bodnar, Lisa M.a,b,c; Simhan, Hyagriv N.b,c; Catov, Janet M.a,b,c; Roberts, James M.a,b,c; Platt, Robert W.d; Diesel, Jill C.a; Klebanoff, Mark A.e,f

doi: 10.1097/EDE.0000000000000039

Background: We sought to determine the association between maternal vitamin D status at ≤26 weeks’ gestation and the risk of preeclampsia by clinical subtype.

Methods: We conducted a case–cohort study among women enrolled at 12 US sites from 1959 to 1966 in the Collaborative Perinatal Project. In serum collected at ≤26 weeks’ gestation (median 20.9 weeks) from 717 women who later developed preeclampsia (560 mild and 157 severe cases) and from 2986 mothers without preeclampsia, we measured serum 25-hydroxyvitamin D, over 40 years later, using liquid chromatography–tandem mass spectrometry.

Results: Half of women in the subcohort had 25-hydroxyvitamin D (25(OH)D) >50 nmol/L. Maternal 25(OH)D 50 to 74.9 nmol/L was associated with a reduction in the absolute and relative risk of preeclampsia and mild preeclampsia compared with 25(OH)D <30 nmol/L in the crude analysis but not after adjustment for confounders, including race, prepregnancy body mass index, and parity. For severe preeclampsia, 25(OH)D ≥50 nmol/L was associated with a reduction in three cases per 1000 pregnancies (adjusted risk difference = −0.003 [95% confidence interval = −0.005 to 0.0002]) and a 40% reduction in risk (0.65 [0.43 to 0.98]) compared with 25(OH)D <50 nmol/L. Conclusions were unchanged (1) after restricting to women with 25(OH)D measured before 22 weeks’ gestation or (2) with formal sensitivity analyses for unmeasured confounding.

Conclusions: Maternal vitamin D deficiency may be a risk factor for severe preeclampsia but not for its mild subtypes. Contemporary cohorts with large numbers of severe preeclampsia cases would be needed to confirm or refute these findings.

Supplemental Digital Content is available in the text.

From the aDepartment of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; bDepartment of Obstetrics, Gynecology, and Reproductive Sciences, School of Medicine, University of Pittsburgh, Pittsburgh, PA; cMagee-Womens Research Institute, Pittsburgh, PA; dDepartment of Pediatrics and Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada; eCenter for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, OH; and fDepartment of Pediatrics, The Ohio State University College of Medicine, Columbus, OH.

This research was supported by NIH grant HD 056999 (PI: L.M.B.).

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Lisa M. Bodnar, Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, A742 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA15261. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc