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Epidemiology. 2014 Mar;25(2):207-14. doi: 10.1097/EDE.0000000000000039.

Maternal vitamin D status and the risk of mild and severe preeclampsia.

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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.



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


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.


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.


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.

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