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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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 (www.epidem.com). 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: email@example.com.