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 · 153 citas
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- Genome Canada
- Organización sin fines de lucro
- Fondation du cancer du sein du Québec
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- National Institute of General Medical Sciences
- Gobierno
- NHLBI NIH HHS
- Gobierno
- NIGMS NIH HHS
- Subvenciones
- 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)
Según 6 financiadores declarados.
Publicación
- Publicado
- 2016-11-13 · J Clin Invest · vol. 126 · número 12 · págs. 4702–4715
- Editorial
- American Society for Clinical Investigation
- Citado
- 213 citas · más que el 99% de estudios similares · 14.0× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 59 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Vitamin D Research Studies · Pregnancy and preeclampsia studies · Iron Metabolism and Disorders
- Palabras clave
- 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 autores
- Hooman Mirzakhani
- Augusto A. Litonjua🇺🇸Pulmonary and Critical Care Associates
- Thomas Frederick McElrath🇺🇸Brigham and Women's Hospital; Harvard University
- George T. O’Connor🇺🇸Boston Medical Center
- Aviva Lee-Parritz🇺🇸Boston Medical Center
- Ronald E. Iverson🇺🇸Boston Medical Center
- George A. Macones🇺🇸Society for Maternal-Fetal Medicine
- Robert C. Strunk🇺🇸Washington University in St. Louis; Pulmonary and Allergy Associates
- Leonard B. Bacharier🇺🇸Washington University in St. Louis; Pulmonary and Allergy Associates
- Robert S. Zeiger🇺🇸Kaiser Permanente; Kaiser Permanente San Diego Medical Center
- Bruce W. Hollis🇺🇸Medical University of South Carolina
- Diane E. Handy🇺🇸Brigham and Women's Hospital
- Amitabh Sharma
- Nancy Laranjo
- Vincent J. Carey
- Weilliang Qiu
- Marc Santolini🇺🇸Northeastern University
- Shikang Liu🇺🇸Northeastern University
- Divya Chhabra🇺🇸University of California System; University of California San Diego
- Daniel A. Enquobahrie🇺🇸University of Washington
- Michelle Anne Williams🇺🇸Harvard Global Health Institute
- Joseph Loscalzo🇺🇸Brigham and Women's Hospital; Harvard University; Harvard Global Health Institute
- Scott T. Weiss🇺🇸 · autor de correspondenciaMass General Brigham
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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