title: Early pregnancy vitamin D status and risk of preeclampsia.
abstract: Low vitamin D status in pregnancy was proposed as a risk factor of preeclampsia.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  ClinicalTrials.gov NCT00920621.
  
  
  
  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.
authors.forename: Hooman
authors.initials: H
authors.lastname: Mirzakhani
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McElrath
authors.forename: George
authors.initials: G
authors.lastname: O'Connor
authors.forename: Aviva
authors.initials: A
authors.lastname: Lee-Parritz
authors.forename: Ronald
authors.initials: R
authors.lastname: Iverson
authors.forename: George
authors.initials: G
authors.lastname: Macones
authors.forename: Robert C
authors.initials: RC
authors.lastname: Strunk
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Bacharier
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiger
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Hollis
authors.forename: Diane E
authors.initials: DE
authors.lastname: Handy
authors.forename: Amitabh
authors.initials: A
authors.lastname: Sharma
authors.forename: Nancy
authors.initials: N
authors.lastname: Laranjo
authors.forename: Vincent
authors.initials: V
authors.lastname: Carey
authors.forename: Weilliang
authors.initials: W
authors.lastname: Qiu
authors.forename: Marc
authors.initials: M
authors.lastname: Santolini
authors.forename: Shikang
authors.initials: S
authors.lastname: Liu
authors.forename: Divya
authors.initials: D
authors.lastname: Chhabra
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Enquobahrie
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Williams
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000328:Adult; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D015994:Incidence; D011225:Pre-Eclampsia / Q000097:blood / Q000453:epidemiology / Q000517:prevention & control*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood*; D011263:Pregnancy Trimester, Third / Q000097:blood*; D012307:Risk Factors; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D