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

The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis.
The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis.
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).
BMD, Epidemiology, Osteoporosis, Pregnancy, RCT, Vitamin D
0937-941X
1269-1279
Moon, Rebecca J.
954fb3ed-9934-4649-886d-f65944985a6b
Green, Harry D.
65fef24c-6b88-40f4-896e-dd447990d88d
D'Angelo, Stefania
13375ecd-1117-4b6e-99c0-32239f52eed6
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Davies, Justin H.
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Curtis, Elizabeth M.
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Moon, Rebecca J.
954fb3ed-9934-4649-886d-f65944985a6b
Green, Harry D.
65fef24c-6b88-40f4-896e-dd447990d88d
D'Angelo, Stefania
13375ecd-1117-4b6e-99c0-32239f52eed6
Godfrey, Keith M.
0931701e-fe2c-44b5-8f0d-ec5c7477a6fd
Davies, Justin H.
9f18fcad-f488-4c72-ac23-c154995443a9
Curtis, Elizabeth M.
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145

Moon, Rebecca J., Green, Harry D., D'Angelo, Stefania, Godfrey, Keith M., Davies, Justin H., Curtis, Elizabeth M., Cooper, Cyrus and Harvey, Nicholas C. (2023) The effect of pregnancy vitamin D supplementation on offspring bone mineral density in childhood: a systematic review and meta-analysis. Osteoporosis International, 34 (7), 1269-1279. (doi:10.1007/s00198-023-06751-5).

Record type: Article

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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Vit D bone meta-analysis Feb 2023 - no tracked changes - Accepted Manuscript
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Accepted/In Press date: 6 April 2023
e-pub ahead of print date: 27 April 2023
Published date: July 2023
Additional Information: Funding Information: 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. Publisher Copyright: © 2023, International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.
Keywords: BMD, Epidemiology, Osteoporosis, Pregnancy, RCT, Vitamin D

Identifiers

Local EPrints ID: 476467
URI: http://eprints.soton.ac.uk/id/eprint/476467
ISSN: 0937-941X
PURE UUID: 0d798b9f-6d6d-4195-91e9-c6bd4776422f
ORCID for Stefania D'Angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for Keith M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for Elizabeth M. Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512

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Date deposited: 03 May 2023 16:42
Last modified: 18 Mar 2024 03:38

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Contributors

Author: Rebecca J. Moon
Author: Harry D. Green
Author: Stefania D'Angelo ORCID iD
Author: Cyrus Cooper ORCID iD

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