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Review
. 2018 Jun 1;126(1):57-77.
doi: 10.1093/bmb/ldy010.

Maternal vitamin D supplementation during pregnancy

Elizabeth M Curtis  1 , Rebecca J Moon  1   2 , Nicholas C Harvey  1   3 , Cyrus Cooper  1   3   4
Affiliations
Review

Maternal vitamin D supplementation during pregnancy

Elizabeth M Curtis et al. Br Med Bull. .

Abstract

Introduction: Maternal vitamin D status in pregnancy has been linked to many health outcomes in mother and offspring. A wealth of observational studies have reported on both obstetric outcomes and complications, including pre-eclampsia, gestational diabetes, mode and timing of delivery. Many foetal and childhood outcomes are also linked to vitamin D status, including measures of foetal size, body composition and skeletal mineralization, in addition to later childhood outcomes, such as asthma.

Sources of data: Synthesis of systematic and narrative reviews.

Areas of agreement and controversy: The findings are generally inconsistent in most areas, and, at present, there is a lack of data from high-quality intervention studies to confirm a causal role for vitamin D in these outcomes. In most areas, the evidence tends towards maternal vitamin D being of overall benefit, but often does not reach statistical significance in meta-analyses.

Growing points and areas timely for developing research: The most conclusive evidence is in the role of maternal vitamin D supplementation in the prevention of neonatal hypocalcaemia; as a consequence the UK department of health recommends that pregnant women take 400 IU vitamin D daily. High-quality randomized placebo-controlled trials, such as the UK-based MAVIDOS trial, will inform the potential efficacy and safety of vitamin D supplementation in pregnancy across a variety of outcomes.

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Conflict of interest statement

Disclosures:

EMC and RM have no disclosures. NH has no disclosures directly related to this work, and has received consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, UCB, Consilient Healthcare and Internis Pharma; CC has no disclosures directly related to this work, and has received consultancy, lecture fees and honoraria from AMGEN, GSK, Alliance for Better Bone Health, MSD, Eli Lilly, Pfizer, Novartis, Servier, Medtronic and Roche.

Figures

Figure 1
Figure 1
Factors affecting response to 25(OH)D supplementation (1000 IU daily from 14 to 34 weeks) in the MAVIDOS trial. Adapted with permission from Moon et al .
Figure 2
Figure 2
Associations between SNPs and change in 25(OH)D from 14 to 34 weeks of gestation following supplementation with 1000 IU/d cholecalciferol. Shown as β and 95% CI. The homozygous low-frequency allele was used as the reference group, with the β representing the change in 25(OH)D (nmol/L) per common allele (additive model). Models were adjusted for age, physical activity, smoking status, educational attainment, season of blood sampling, compliance, and pregnancy weight gain. Adapted with permission from Moon et al, 2017
Figure 3
Figure 3
Forest plot of the association between maternal vitamin D status and risk of pre-eclampsia (observational studies (adjusted), ES, effect size). Reproduced with permission from Harvey et al; Health Technology Assessment 2014
Figure 4
Figure 4
Neonatal whole-body bone mineral content (BMC) of neonates born in the summer (June-November) or winter (December-May) in the UK Southampton Women’s Survey. Data are mean and 95% CI.
Figure 5
Figure 5
Neonatal whole body bone mineral content (BMC), bone area and bone mineral density (BMD) by intervention group and season of birth in the MAVIDOS trial. Data are shown as mean and 95% confidence interval. Winter is December to February, spring is March to May, summer is June to August and autumn is September to November. Reproduced with permission from Cooper et al, 2016 and in accordance with a Creative Commons Licence; https://creativecommons.org/licenses/by/4.0/; https://doi.org/10.1016/S2213-8587(16)00044-9
Figure 6
Figure 6
Percent DNA methylation at RXRA & offspring size corrected bone mineral content (a); maternal 25(OH)D & RXRA DNA methylation (b). scBMC, size-corrected Bone Mineral Content. Adapted with permission from Harvey et al, 2014
See this image and copyright information in PMC

References

    1. Harvey NC, Sheppard A, Godfrey KM, et al. Childhood bone mineral content is associated with methylation status of the RXRA promoter at birth. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014;29(3):600–7. - PMC - PubMed
    1. Moon RJ, Harvey NC, Cooper C, et al. Response to Antenatal Cholecalciferol Supplementation Is Associated With Common Vitamin D-Related Genetic Variants. The Journal of clinical endocrinology and metabolism. 2017;102(8):2941–9. - PMC - PubMed
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