Abstract
Background
For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and increased tolerogenic immune-mediator concentrations.
Methods
Pregnant women enrolled at 10–14 weeks gestation were randomized to 400 or 4400 IU vitamin D3/day. Data on health, safety, circulating 25(OH)D, and 9 immune-mediators were collected at each trimester. Associations between immune-mediators and 25(OH)D at baseline and at second and third trimesters were examined.
Results
Baseline TGF-β and second and third trimesters IFN-γ and IL-2 were associated with baseline 25(OH)D. Baseline immune-mediators were associated with immune-mediators at second and third trimesters for all immune-mediators except IL-5 and IL-10. Race was associated with baseline TGF-β, VEGF and IL-10 and with IL-10 at second and third trimesters.
Conclusions
Both treatment groups had increased 25(OH)D at second and third trimesters, greatest in the 4400 IU group. Though associations between baseline 25(OH)D and baseline TGF-β and second and third trimester IFN-γ and IL-2 were noted, vitamin D supplementation throughout pregnancy did not impact immune-mediators at later trimesters. Supplementing with vitamin D before conception conceivably influences immune-mediator responses during pregnancy.
Impact
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In this vitamin D supplementation clinical trial, baseline (first trimester) but not increasing plasma 25(OH)D concentration impacted select plasma immune-mediator profiles in pregnant women.
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Baseline 25(OH)D was associated with baseline TGF-β and with IFN-γ and IL-2 at second and third trimesters.
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Baseline IFN-γ, CRP, TGF-β, TNF-α, VEGF, IL-2, and IL-4 were associated with concentrations at second and third trimesters for respective immune-mediators; however, 25(OH)D concentration at second and third trimesters were not.
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Some racial differences existed in immune-mediator concentrations at baseline and at second and third trimesters.
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This study assesses the impact of vitamin D supplementation on multiple immune-mediators in pregnant women of different racial/ethnic groups using longitudinal data from a relatively large randomized controlled trial.
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This study found that race was associated with baseline TGF-β, VEGF, and IL-10 and with IL-10 at second and third trimesters, a novel finding that sheds light where relationships were less well defined.
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The results of this study suggest that vitamin D supplementation before conception or early in pregnancy, rather than during pregnancy, may be necessary to significantly impact immune-mediator response.
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This study sets premise for future clinical trials to evaluate the effect of vitamin D supplementation before conception or prior to pregnancy.
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Acknowledgements
We thank Patrick Simpson, MS, of the W. K. Kellogg Foundation and Myla D. Ebeling, data manager in the Department of Pediatrics at the Medical University of South Carolina (MUSC), for their support during the conduct of this study. We also thank the women who participated in this study, without whose participation we could not have learned what we did. We also are thankful to Church & Dwight, Inc. (Princeton, NJ), who provided the vitamin D and placebo gummies for this study. This publication was also supported, in part, by the W. K. Kellogg Foundation Grant P3020828, “Preventing Health Disparities during Pregnancy through Vitamin D supplementation” and the South Carolina Clinical & Translational Research Institute (SCTR), MUSC’s Clinical and Translational Science Awards Hub, NIH/NCRR Grant Number 1UL1TR001450. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the Kellogg Foundation, NIH, or NCRR.
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Conception and design: C.L.W., J.K.M., J.R.S., M.H., J.E.B., D.A.N., B.H.W. Acquisition of the data: J.K.M., J.R.S., J.E.B., D.A.N., C.L.W. Analysis and interpretation of data: A.K., B.J.W., J.K.M., M.H., J.E.B., D.A.N., C.H., C.L.W. Drafting the article/revising important intellectual content: A.K., B.J.W., J.K.M., J.R.S., M.H., J.E.B., D.A.N., C.H., C.L.W. Final approval of version to be published: all authors.
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Khatiwada, A., Wolf, B.J., Mulligan, J.K. et al. Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy. Pediatr Res 89, 554–562 (2021). https://doi.org/10.1038/s41390-020-0885-7
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DOI: https://doi.org/10.1038/s41390-020-0885-7
