TY - JOUR
T1 - Early pregnancy Vitamin D status and risk of preeclampsia
AU - Mirzakhani, Hooman
AU - Litonjua, Augusto A.
AU - McElrath, Thomas F.
AU - O'Connor, George
AU - Lee-Parritz, Aviva
AU - Iverson, Ronald
AU - MacOnes, George
AU - Strunk, Robert C.
AU - Bacharier, Leonard B.
AU - Zeiger, Robert
AU - Hollis, Bruce W.
AU - Handy, Diane E.
AU - Sharma, Amitabh
AU - Laranjo, Nancy
AU - Carey, Vincent
AU - Qiu, Weilliang
AU - Santolini, Marc
AU - Liu, Shikang
AU - Chhabra, Divya
AU - Enquobahrie, Daniel A.
AU - Williams, Michelle A.
AU - Loscalzo, Joseph
AU - Weiss, Scott T.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - 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 casecontrol 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.
AB - 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 casecontrol 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.
UR - http://www.scopus.com/inward/record.url?scp=85002566143&partnerID=8YFLogxK
U2 - 10.1172/JCI89031
DO - 10.1172/JCI89031
M3 - Article
C2 - 27841759
AN - SCOPUS:85002566143
SN - 0021-9738
VL - 126
SP - 4702
EP - 4715
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -