Determinants of the maternal 25-hydroxyvitamin D response to vitamin D supplementation during pregnancy

Rebecca J Moon, Nicholas C Harvey, Cyrus Cooper, Stefania D'Angelo, Sarah R Crozier, Hazel M Inskip, Inez Schoenmakers, Ann Prentice, Nigel K Arden, Nicholas J Bishop, Andrew Carr, Elaine M Dennison, Richard Eastell, Robert Fraser, Saurabh V Gandhi, Keith M Godfrey, Stephen Kennedy, M Zulf Mughal, Aris T Papageorghiou, David M ReidSian M Robinson, M Kassim Javaid, the MAVIDOS Trial Group

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Context: Current approaches to antenatal vitamin D supplementation do not account for inter-individual differences in 25-hydroxyvitamin D [25(OH)D] response. 
Objective: We assessed which maternal and environmental characteristics were associated with 25-hydroxyvitamin D [25(OH)D] following supplementation with cholecalciferol. 
Design: Within-randomisation-group analysis of participants in the MAVIDOS trial of vitamin Dsupplementation in pregnancy. 
Setting: Hospital antenatal clinics 
Participants: 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks’ gestation, maternal anthropometry, health and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks. 
Interventions: 1000IU/day cholecalciferol or matched placebo from 14 weeks’ gestation until delivery. 
Main outcome measure: 25-(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison).  
Results: 25(OH)D at 34 weeks’ gestation was higher in the women randomised to vitamin D [mean(SD): 67.7 (21.3) nmol/l] compared with placebo [43.1 (22.5) nmol/l, p<0.001]. In womenrandomised to cholecalciferol, higher pregnancy weight gain from 14 to 34 weeks’ gestation[kg] (β=-0.81 (95%CI -1.39, -0.22)), lower compliance with study medication [%] (β=-0.28 (-0.072, -0.48)), lower early pregnancy 25(OH)D [nmol/l] (β=0.28 (0.16, 0.40)) and delivery inthe winter vs the summer (β=-10.5 (-6.4, -14.6)) were independently associated with lower25(OH)D at 34 weeks’ gestation. 
Conclusions: Women who gained more weight during pregnancy, had lower 25(OH)D in early pregnancy and delivered in winter achieved a lower 25(OH)D in late pregnancy when supplementedwith 1000 IU/day cholecalciferol. Future studies should aim to determine appropriate dosesto enable consistent repletion of 25-hydroxyvitamin D during pregnancy.
Original languageEnglish
Pages (from-to)5012–5020
Number of pages9
JournalJournal of Clinical Endocrinology & Metabolism
Issue number12
Early online date28 Oct 2016
Publication statusPublished - Dec 2016


  • vitamin D
  • pregnancy
  • osteoporosis
  • epidemiology
  • supplementation

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