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Current approaches to antenatal vitamin D supplementation do not account for interindividual differences in 25-hydroxyvitamin D (25(OH)D) response.We assessed which maternal and environmental characteristics were associated with 25(OH)D after supplementation with cholecalciferol.Within-randomization-group analysis of participants in the Maternal Vitamin D Osteoporosis Study trial of vitamin D supplementation in pregnancy.Hospital antenatal clinics.A total of 829 pregnant women (422 placebo, 407 cholecalciferol). At 14 and 34 weeks of gestation, maternal anthropometry, health, and lifestyle were assessed and 25(OH)D measured. Compliance was determined using pill counts at 19 and 34 weeks.1000 IU/d of cholecalciferol or matched placebo from 14 weeks of gestation until delivery.25(OH)D at 34 weeks, measured in a single batch (Diasorin Liaison).25(OH)D at 34 weeks of gestation was higher in the women randomized to vitamin D (mean [SD], 67.7 [21.3] nmol/L) compared with placebo (43.1 [22.5] nmol/L; P < .001). In women randomized to cholecalciferol, higher pregnancy weight gain from 14 to 34 weeks of gestation (kg) (β = -0.81 [95% confidence interval -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 in the winter vs the summer (β = -10.5 [-6.4, -14.6]) were independently associated with lower 25(OH)D at 34 weeks of gestation.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 supplemented with 1000 IU/d cholecalciferol. Future studies should aim to determine appropriate doses to enable consistent repletion of 25(OH)D during pregnancy.

Original publication




Journal article


The Journal of Clinical Endocrinology and Metabolism

Publication Date





5012 - 5020


Medical Research Council (MRC) Lifecourse Epidemiology Unit (University of Southampton) (R.J.M., N.C.H., C.C., S.D., S.R.C., H.M.I., E.M.D., K.M.G., S.M.R.), Southampton General Hospital; Paediatric Endocrinology (R.J.M.), University Hospital Southampton NHS Foundation Trust; and National Institute for Health Research (NIHR) Southampton Nutrition Biomedical Research Centre (N.C.H., C.C., K.M.G.), University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, United Kingdom; NIHR Musculoskeletal Biomedical Research Unit (C.C., N.K.A., A.C., M.K.J.), University of Oxford, Oxford OX3 7LD, United Kingdom; MRC Human Nutrition Research (I.S., A.P.), Elsie Widdowson Laboratory, Cambridge, United Kingdom CB1 9NL; Academic Unit of Child Health (N.J.B.), Sheffield Children's Hospital, University of Sheffield, Sheffield, United Kingdom S10 2TH; Academic Unit of Bone Metabolism (R.E.), University of Sheffield, Sheffield, United Kingdom S5 7AU; Sheffield Hospitals NHS Trust (University of Sheffield) (R.F., S.V.G.), Sheffield, United Kingdom S10 2SF; Nuffield Department of Obstetrics and Gynaecology (S.K., A.T.P.), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom OX3 9DU; Department of Paediatric Endocrinology (M.Z.M.), Royal Manchester Children's Hospitals, Manchester, United Kingdom M13 9WL; and School of Medicine and Dentistry (D.M.R.), Medical School, University of Aberdeen, Aberdeen, United Kingdom AB25 2ZD; Department of Medicine (I.S.), Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, United Kingdom NR4 7TJ.


Humans, Weight Gain, Cholecalciferol, Vitamins, Vitamin D, Double-Blind Method, Seasons, Pregnancy, Pregnancy Trimesters, Adult, Outcome Assessment (Health Care), Female, Young Adult