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J Allergy Clin Immunol. 2018 Jan;141(1):269-278.e1. doi: 10.1016/j.jaci.2017.02.039. Epub 2017 May 26.

Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial.

Author information

1
MRC and Asthma UK Centre for Allergic Mechanisms in Asthma, King's College London, London, United Kingdom.
2
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass.
3
Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Mass.
4
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
5
MRC and Asthma UK Centre for Allergic Mechanisms in Asthma, King's College London, London, United Kingdom. Electronic address: catherine.hawrylowicz@kcl.ac.uk.

Abstract

BACKGROUND:

Programming of the immune system during fetal development can influence asthma-related risk factors and outcomes in later life. Vitamin D is a well-recognized immune modulator, and deficiency of this nutrient during pregnancy is hypothesized to influence disease development in offspring.

OBJECTIVE:

We sought to investigate the effect on neonatal immunity of maternal supplementation with 4400 IU/d vitamin D3 during the second and third trimesters of pregnancy by using a subset of cord blood samples from a randomized, double-blind, placebo-controlled clinical trial (the Vitamin D Antenatal Asthma Reduction Trial).

METHODS:

Cord blood samples from neonates born to mothers supplemented with 4400 IU/d (n = 26) or 400 IU/d (n = 25) of vitamin D3 were analyzed for immune cell composition by flow cytometry, Toll-like receptor (TLR) expression by quantitative PCR, and cytokine secretion after stimulation with mitogenic, TLR, and T-cell stimuli by cytometric bead array. Responsiveness to the glucocorticoid dexamethasone was determined.

RESULTS:

Supplementation of mothers with 4400 IU of vitamin D3 resulted in an enhanced broad-spectrum proinflammatory cytokine response of cord blood mononuclear cells to innate and mitogenic stimuli (P = .0009), with an average 1.7- to 2.1-fold increase in levels of several proinflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-6, and IL-8) across stimuli, a higher gene expression level of TLR2 (P = .02) and TLR9 (P = .02), a greater than 4-fold increase in IL-17A (P = .03) production after polyclonal T-cell stimulation, and an enhanced IL-10 response of cord blood mononuclear cells to dexamethasone treatment in culture (P = .018).

CONCLUSION:

Vitamin D exposure during fetal development influences the immune system of the neonate, which can contribute to protection from asthma-related, including infectious, outcomes in early life.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00920621.

KEYWORDS:

Vitamin D; asthma; innate immunity; pregnancy

PMID:
28552588
DOI:
10.1016/j.jaci.2017.02.039
[Indexed for MEDLINE]
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