Article ; Online: Early pregnancy vitamin D status and risk of preeclampsia.
The Journal of clinical investigation
2016 Volume 126, Issue 12, Page(s) 4702–4715
Abstract: Background: Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia.: Methods: We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of ... ...
| Abstract | Background: Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia. Methods: We assessed the effect of vitamin D supplementation (4,400 vs. 400 IU/day), initiated early in pregnancy (10-18 weeks), on the development of preeclampsia. The effects of serum vitamin D (25-hydroxyvitamin D [25OHD]) levels on preeclampsia incidence at trial entry and in the third trimester (32-38 weeks) were studied. We also conducted a nested case-control study of 157 women to investigate peripheral blood vitamin D-associated gene expression profiles at 10 to 18 weeks in 47 participants who developed preeclampsia. Results: Of 881 women randomized, outcome data were available for 816, with 67 (8.2%) developing preeclampsia. There was no significant difference between treatment (N = 408) or control (N = 408) groups in the incidence of preeclampsia (8.08% vs. 8.33%, respectively; relative risk: 0.97; 95% CI, 0.61-1.53). However, in a cohort analysis and after adjustment for confounders, a significant effect of sufficient vitamin D status (25OHD ≥30 ng/ml) was observed in both early and late pregnancy compared with insufficient levels (25OHD <30 ng/ml) (adjusted odds ratio, 0.28; 95% CI, 0.10-0.96). Differential expression of 348 vitamin D-associated genes (158 upregulated) was found in peripheral blood of women who developed preeclampsia (FDR <0.05 in the Vitamin D Antenatal Asthma Reduction Trial [VDAART]; P < 0.05 in a replication cohort). Functional enrichment and network analyses of this vitamin D-associated gene set suggests several highly functional modules related to systematic inflammatory and immune responses, including some nodes with a high degree of connectivity. Conclusions: Vitamin D supplementation initiated in weeks 10-18 of pregnancy did not reduce preeclampsia incidence in the intention-to-treat paradigm. However, vitamin D levels of 30 ng/ml or higher at trial entry and in late pregnancy were associated with a lower risk of preeclampsia. Differentially expressed vitamin D-associated transcriptomes implicated the emergence of an early pregnancy, distinctive immune response in women who went on to develop preeclampsia. Trial registration: ClinicalTrials.gov NCT00920621. Funding: Quebec Breast Cancer Foundation and Genome Canada Innovation Network. This trial was funded by the National Heart, Lung, and Blood Institute. For details see Acknowledgments. |
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| MeSH term(s) | Adolescent ; Adult ; Dietary Supplements ; Female ; Humans ; Incidence ; Pre-Eclampsia/blood ; Pre-Eclampsia/epidemiology ; Pre-Eclampsia/prevention & control ; Pregnancy ; Pregnancy Trimester, First/blood ; Pregnancy Trimester, Third/blood ; Risk Factors ; Vitamin D/administration & dosage ; Vitamin D/analogs & derivatives ; Vitamin D/pharmacokinetics | |||||
| Chemical Substances | Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H) | |||||
| Language | English | |||||
| Publishing date | 2016-11-14 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 3067-3 | |||||
| ISSN | 1558-8238 ; 0021-9738 | |||||
| ISSN (online) | 1558-8238 | |||||
| ISSN | 0021-9738 | |||||
| DOI | 10.1172/JCI89031 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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