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Maternal gestational vitamin D supplementation and offspring bone health: a multicentre randomised, double-blind, placebo-controlled trial (MAVIDOS)

Maternal gestational vitamin D supplementation and offspring bone health: a multicentre randomised, double-blind, placebo-controlled trial (MAVIDOS)
Maternal gestational vitamin D supplementation and offspring bone health: a multicentre randomised, double-blind, placebo-controlled trial (MAVIDOS)
Background: Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation.

Methods: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25–100 nmol/L at 10–17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007–001716–23.

Findings: Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3–62·8] vs 60·5 g [59·3–61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related.

Interpretation: Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited.

Funding: Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.
2213-8587
393-402
Cooper, C.
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Harvey, N.C.
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Bishop, N.J.
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Kennedy, S.
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Papageorghiou, A.T.
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Schoenmakers, I.
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Fraser, R.
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Gandhi, S.V.
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Carr, A.
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D'Angelo, S.
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Crozier, S.R.
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Moon, R.J.
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Arden, N.K.
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Dennison, E.M.
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Godfrey, K.M.
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Inskip, H.M.
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Prentice, A.
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Zulf Mughal, M.
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Eastell, R.
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Reid, D.M.
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Javaid, M.K.
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MAVIDOS Trial Group
Cooper, C.
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Harvey, N.C.
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Bishop, N.J.
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Kennedy, S.
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Papageorghiou, A.T.
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Schoenmakers, I.
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Fraser, R.
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Gandhi, S.V.
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Carr, A.
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D'Angelo, S.
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Crozier, S.R.
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Moon, R.J.
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Arden, N.K.
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Dennison, E.M.
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Godfrey, K.M.
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Inskip, H.M.
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Prentice, A.
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Zulf Mughal, M.
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Eastell, R.
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Reid, D.M.
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Javaid, M.K.
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Cooper, C., Harvey, N.C., Bishop, N.J., Kennedy, S., Papageorghiou, A.T., Schoenmakers, I., Fraser, R., Gandhi, S.V., Carr, A., D'Angelo, S., Crozier, S.R., Moon, R.J., Arden, N.K., Dennison, E.M., Godfrey, K.M., Inskip, H.M., Prentice, A., Zulf Mughal, M., Eastell, R., Reid, D.M. and Javaid, M.K. , MAVIDOS Trial Group (2016) Maternal gestational vitamin D supplementation and offspring bone health: a multicentre randomised, double-blind, placebo-controlled trial (MAVIDOS). The Lancet Diabetes & Endocrinology, 4 (5), 393-402. (doi:10.1016/S2213-8587(16)00044-9).

Record type: Article

Abstract

Background: Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation.

Methods: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25–100 nmol/L at 10–17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007–001716–23.

Findings: Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3–62·8] vs 60·5 g [59·3–61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related.

Interpretation: Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited.

Funding: Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.

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More information

Accepted/In Press date: 23 February 2016
e-pub ahead of print date: 1 March 2016
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 389328
URI: http://eprints.soton.ac.uk/id/eprint/389328
ISSN: 2213-8587
PURE UUID: 3283bc0c-2cc6-4aa3-8f22-4d64a94c70fa
ORCID for C. Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for N.C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for S. D'Angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for S.R. Crozier: ORCID iD orcid.org/0000-0002-9524-1127
ORCID for E.M. Dennison: ORCID iD orcid.org/0000-0002-3048-4961
ORCID for K.M. Godfrey: ORCID iD orcid.org/0000-0002-4643-0618
ORCID for H.M. Inskip: ORCID iD orcid.org/0000-0001-8897-1749

Catalogue record

Date deposited: 04 Mar 2016 11:45
Last modified: 13 Nov 2021 05:02

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Contributors

Author: C. Cooper ORCID iD
Author: N.C. Harvey ORCID iD
Author: N.J. Bishop
Author: S. Kennedy
Author: A.T. Papageorghiou
Author: I. Schoenmakers
Author: R. Fraser
Author: S.V. Gandhi
Author: A. Carr
Author: S. D'Angelo ORCID iD
Author: S.R. Crozier ORCID iD
Author: R.J. Moon
Author: N.K. Arden
Author: E.M. Dennison ORCID iD
Author: K.M. Godfrey ORCID iD
Author: H.M. Inskip ORCID iD
Author: A. Prentice
Author: M. Zulf Mughal
Author: R. Eastell
Author: D.M. Reid
Author: M.K. Javaid
Corporate Author: MAVIDOS Trial Group

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