ISSN 2052-1219 (online)

Bone Abstracts (2016) 5 HTHT4 | DOI: 10.1530/boneabs.5.HT4

Vitamin D supplementation in pregnancy leads to greater bone mass in UK infants born during winter months: the MAVIDOS multicentre, randomised, double-blind, placebo-controlled trial

Cyrus Cooper1,2, Nicholas Harvey1,2, Nicholas Bishop4, Stephen Kennedy5, Aris Papageorghiou5, Inez Schoenmakers6, Robert Fraser7, Saurabh Gandhi7, Stefania D’Angelo1, Sarah Crozier1, Rebecca Moon1, Nigel Arden3, Elaine Dennison1, Keith Godfrey1,2, Hazel Inskip1,2, Ann Prentice6, Zulf Mughal8, Richard Eastell9, David Reid10 & Kassim Javaid3

1MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; 2NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; 3Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK; 4Academic Unit of Child Health, Sheffield Children’s Hospital, University of Sheffield, Sheffield, UK; 5Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Oxford, UK; 6MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK; 7Sheffield Hospitals NHS Trust (University of Sheffield), Sheffield, UK; 8Department of Paediatric Endocrinology, Royal Manchester Children’s Hospitals, Manchester, UK; 9Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK; 10School of Medicine, Medical Science & Nutrition, University of Aberdeen, Aberdeen, UK

Maternal vitamin D status has been positively associated with infant bone mass in observational studies. We therefore evaluated whether 1000 IU/day cholecalciferol during pregnancy would lead to greater offspring bone mass at birth, in a UK, multicentre, randomised, double-blind, placebo-controlled trial (MAVIDOS, ISRCTN82927713).

At 12 weeks’ gestation, pregnant women with a serum 25-hydroxyvitamin D [25(OH)D] 25-100 nmol/l were randomised to either 1000 IU cholecalciferol or matched placebo daily until delivery. Plasma 25(OH)D concentration was measured centrally at 14 and 34 weeks’ gestation (Diasorin Liaison). Within 2 weeks after birth, infant whole body bone mineral content (BMC) was assessed by Dual-Energy X-ray Absorptiometry (Hologic Discovery, Hologic; or iDXA, GE-Lunar; measurements standardised).

Infants born to mothers supplemented with cholecalciferol had non-significantly greater whole body BMC than infants born to mothers taking placebo (total n=665; mean (S.D.) 61.6 (11.7)g vs 60.5 (11.1)g, respectively, P=0.21). However, in a pre-specified analysis, there was an interaction between season of birth and treatment allocation (P=0.04): infants born in winter (December–February) to mothers randomised to cholecalciferol had greater BMC than those randomised to placebo (63.0±10.8 g vs 57.5±10.9 g, P=0.004), a difference>0.5S.D. Similar patterns were observed for bone area and bone mineral density. At 34 weeks’ gestation, the proportion of women with vitamin D sufficiency [25(OH)D>50 nmol/l] was increased (83.4% vs 36.5%, P<0.001) amongst those who received cholecalciferol compared to placebo. In the placebo group, 25(OH)D declined from 14 to 34 weeks’ gestation in women who gave birth in winter or spring, but rose in those taking cholecalciferol, irrespective of birth season (P<0.001). No safety issues were identified.

Maternal gestational supplementation with 1000 IU cholecalciferol increases bone mass in UK infants born during winter months, and prevents the seasonal decline in 25(OH)D in these mothers. The findings inform public health policy relating to antenatal vitamin D supplementation. *CC and NCH are joint first author.

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