title: Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK; Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK. Electronic address: cc@mrc.soton.ac.uk.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Harvey
authors.affiliation: Academic Unit of Child Health, Sheffield Children's Hospital, University of Sheffield, Sheffield, UK.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Bishop
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
authors.forename: Aris T
authors.initials: AT
authors.lastname: Papageorghiou
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Inez
authors.initials: I
authors.lastname: Schoenmakers
authors.affiliation: Sheffield Hospitals NHS Trust, University of Sheffield, Sheffield, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Fraser
authors.affiliation: Sheffield Hospitals NHS Trust, University of Sheffield, Sheffield, UK.
authors.forename: Saurabh V
authors.initials: SV
authors.lastname: Gandhi
authors.affiliation: Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Stefania
authors.initials: S
authors.lastname: D'Angelo
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Crozier
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Moon
authors.affiliation: Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: Nigel K
authors.initials: NK
authors.lastname: Arden
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Dennison
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Godfrey
authors.affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Inskip
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Prentice
authors.affiliation: Department of Paediatric Endocrinology, Royal Manchester Children's Hospitals, Manchester, UK.
authors.forename: M Zulf
authors.initials: MZ
authors.lastname: Mughal
authors.affiliation: Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.affiliation: School of Medicine and Dentistry, Medical School, University of Aberdeen, Aberdeen, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.affiliation: Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: M Kassim
authors.initials: MK
authors.lastname: Javaid
mesh_terms: D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D012621:Seasons; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D050071:Bone Density Conservation Agents; D014807:Vitamin D