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The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis

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Abstract

Summary

Systematic review and meta-analysis of the effect of moderate- to high-dose vitamin D supplementation in pregnancy on offspring bone mineralisation found a positive effect of vitamin D supplementation on offspring bone mineral density (BMD) at age 4–6 years, with a smaller effect on bone mineral content.

Purpose

A systematic review and meta-analysis was performed to assess the effect of pregnancy vitamin D supplementation on offspring bone mineral density (BMD) in childhood.

Methods

A literature search was conducted for published RCTs of antenatal vitamin D supplementation with assessment of offspring BMD or bone mineral content (BMC) by dual-energy X-ray absorptiometry (DXA) using MEDLINE and EMBASE up to 13th July 2022. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Study findings were grouped in two age groups of offspring assessment: neonatal period and early childhood (3–6 years). Random-effects meta-analysis of the effect on BMC/BMD at 3–6 years was performed using RevMan 5.4.1, yielding standardised mean difference (SMD) (95% CI).

Results

Five RCTs were identified with offspring assessment of BMD or BMC; 3250 women were randomised within these studies. Risk of bias was low in 2 studies and “of concern” in 3. Supplementation regimes and the control used (3 studies used placebo and 2 used 400 IU/day cholecalciferol) varied, but in all studies the intervention increased maternal 25-hydroxvitamin D status compared to the control group. Two trials assessing BMD in the neonatal period (total n = 690) found no difference between groups, but meta-analysis was not performed as one trial represented 96.4% of those studied at this age. Three trials assessed offspring whole-body-less-head BMD at age 4–6 years. BMD was higher in children born to mothers supplemented with vitamin D [0.16 SD (95% confidence interval 0.05, 0.27), n = 1358] with a smaller effect on BMC [0.07 SD (95% CI − 0.04, 0.19), n = 1351].

Conclusions

There are few RCTs published to address this question, and these are inconsistent in methodology and findings. However, meta-analysis of three trials suggests moderate- to high-dose vitamin D supplementation in pregnancy might increase offspring BMD in early childhood, but further trials are required to confirm this finding. (Prospero CRD42021288682; no funding received).

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Funding

We are grateful for the following funding: UKRI Medical Research Council (MRC) [MC_PC_21022; MC_PC_21003; MC_PC_21001]; National Institute for Health and Care Research (NIHR) Southampton Biomedical Research Centre, University of Southampton, and University Hospital Southampton NHS Foundation Trust; NIHR Oxford Biomedical Research Centre, University of Oxford; and Versus Arthritis (17702 and 21231). The work leading to these results was supported by the European Union’s Seventh Framework Programme (FP7/2007–2013), projects EarlyNutrition, ODIN and LifeCycle under grant agreements numbers 289346, 613977 and 733206, and by the BBSRC (HDHL-Biomarkers, BB/P028179/1 and BB/P028187/1), as part of the ALPHABET project, supported by an award made through the ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 grant agreement number 696295. RJM is funded by Health Education England (HEE)/National Institute for Health Research (NIHR) for this research project. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF-SI-0515–10042) and NIHR Southampton Biomedical Research Centre (IS-BRC-1215–20004)), the European Union (Erasmus + Programme ImpENSA 598488-EPP-1–2018-1-DE-EPPKA2-CBHE-JP), British Heart Foundation (RG/15/17/3174, SP/F/21/150013) and the US National Institute On Aging of the National Institutes of Health (Award No. U24AG047867). For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.

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Authors and Affiliations

  1. MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton, UK

    Rebecca J. Moon, Harry D. Green, Stefania D’Angelo, Keith M. Godfrey, Elizabeth M. Curtis, Cyrus Cooper & Nicholas C. Harvey

  2. Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, UK

    Rebecca J. Moon & Justin H. Davies

  3. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK

    Keith M. Godfrey, Cyrus Cooper & Nicholas C. Harvey

  4. Faculty of Medicine, University of Southampton, Southampton, UK

    Justin H. Davies

  5. National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, University of Oxford, Oxford, UK

    Cyrus Cooper

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Correspondence to Rebecca J. Moon.

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This systematic review and meta-analysis contains no original data and thus issues of ethics, informed consent and patient confidentiality do not apply.

Conflicts of interest

HDG and SD have no conflicts of interest. RJM has received travel bursaires from Kyowa Kirin. KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products, and is part of an academic consortium that has received research funding from Abbott Nutrition, Nestec, BenevolentAI Bio Ltd. and Danone, outside the submitted work. JHD has received travel bursaries from Novo Nordisk, SANDOZ and Pfizer unrelated to this work. EMC reports honoraria/travel support from Eli Lilly, Pfizer and UCB outside the submitted work. CC reports personal fees from ABBH, Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier and Takeda, outside the submitted work. NCH reports personal fees, consultancy, lecture fees and honoraria from Alliance for Better Bone Health, AMGEN, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare and Internis Pharma, outside the submitted work.

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Moon, R.J., Green, H.D., D’Angelo, S. et al. The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis. Osteoporos Int 34, 1269–1279 (2023). https://doi.org/10.1007/s00198-023-06751-5

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