Early pregnancy vitamin D status and risk of preeclampsia
Mirzakhani H, Litonjua AA, McElrath TF, O'Connor G, Lee-Parritz A, Iverson R, Macones G, Strunk RC, Bacharier LB, Zeiger R, Hollis BW, Handy DE, Sharma A, Laranjo N, Carey V, Qiu W, Santolini M, Liu S, Chhabra D, Enquobahrie DA, Williams MA, Loscalzo J, Weiss ST
The Journal of clinical investigation · 151 citations
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Government
- Genome Canada
- Nonprofit
- Fondation du cancer du sein du Québec
- Government
- National Heart, Lung, and Blood Institute
- Government
- National Institute of General Medical Sciences
- Government
- NHLBI NIH HHS
- Government
- NIGMS NIH HHS
- Grants
- National Heart, Lung, and Blood Institute (R37 HL 061795); National Heart, Lung, and Blood Institute (T32HL007427); National Heart, Lung, and Blood Institute (R01 HL091528); National Heart, Lung, and Blood Institute (U01 HL091528); National Heart, Lung, and Blood Institute (GM107618); National Heart, Lung, and Blood Institute (HL007427); National Heart, Lung, and Blood Institute (R01 HL091075); National Institute of General Medical Sciences (P50GM107618)
Based on 6 listed funder(s).
Publication
- Published
- 2016-11-13 · J Clin Invest · vol. 126 · issue 12 · pp. 4702–4715
- Publisher
- American Society for Clinical Investigation
- Cited
- 213 citations · more than 99% of similar papers · 14.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 59 works
- Access
- Free to read
- Research areas
- Vitamin D Research Studies · Pregnancy and preeclampsia studies · Iron Metabolism and Disorders
- Keywords
- Preeclampsia, Medicine, Vitamin D and neurology, Pregnancy, Incidence (geometry), Obstetrics, vitamin D deficiency, Vitamin, Internal medicine, Endocrinology, Biology
- MeSH
- humans, pre-eclampsia, vitamin d, incidence, risk factors, pregnancy, pregnancy trimester, first, pregnancy trimester, third, dietary supplements, adolescent, adult, female
23 authors
From US
- Hooman Mirzakhani
- Augusto A. LitonjuaPulmonary and Critical Care Associates
- Thomas Frederick McElrathBrigham and Women's Hospital; Harvard University
- George T. O’ConnorBoston Medical Center
- Aviva Lee-ParritzBoston Medical Center
- Ronald E. IversonBoston Medical Center
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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