title: Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort.
abstract: BACKGROUND
  Miscarriage is the most common negative outcome of pregnancy, and identification of modifiable risk factors is potentially of great importance for public health. Low vitamin D concentrations in pregnancy are widespread worldwide, and vitamin D deficiency is implicated in immune cell regulation at the feto-maternal interface and several diseases of pregnancy.
  
  
  OBJECTIVE
  We investigated whether 25-hydroxyvitamin D serum concentration was a modifiable risk factor for early miscarriage.
  
  
  METHODS
  In a prospective cohort study of 1683 pregnant women donating serum before gestational week 22, we investigated the association between maternal serum concentrations of serum 25-hydroxyvitamin D [25(OH)D] and the risk of subsequent miscarriage (n = 58).
  
  
  RESULTS
  The adjusted hazard of first-trimester miscarriage was lower with higher 25(OH)D concentrations (HR: 0.98; 95% CI: 0.96, 0.99). Concentrations of 25(OH)D <50 nmol/L were associated with a >2-fold increased adjusted HR for miscarriage (HR: 2.50; 95% CI: 1.10, 5.69). Concentrations of 25(OH)D were not associated with an increased risk of second-trimester miscarriage.
  
  
  CONCLUSIONS
  We found an association between 25(OH)D and first-trimester miscarriages, suggesting vitamin D as a modifiable risk factor for miscarriage. To test this hypothesis, randomized controlled trials should investigate the possible effect of vitamin D supplementation to increase 25(OH)D concentrations in early pregnancy, or before conception, to decrease risk of miscarriage. This trial was registered at clinicaltrials.gov as NCT02434900.
authors.affiliation: Institute for Clinical Research and Hans Christian Andersen Children's Hospital.
authors.forename: Louise B
authors.initials: LB
authors.lastname: Andersen
authors.affiliation: Institute for Clinical Research and Department of Obstetrics and Gynecology.
authors.forename: Jan S
authors.initials: JS
authors.lastname: Jørgensen
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark;
authors.forename: Tina K
authors.initials: TK
authors.lastname: Jensen
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark;
authors.forename: Christine
authors.initials: C
authors.lastname: Dalgård
authors.affiliation: Odense Patient Data Explorative Network (OPEN), Department of Clinical Immunology, and.
authors.forename: Torben
authors.initials: T
authors.lastname: Barington
authors.affiliation: Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark;
authors.forename: Jan
authors.initials: J
authors.lastname: Nielsen
authors.affiliation: Institute for Clinical Research and Department of Pediatrics, Hospital of Southwest Denmark, Esbjerg, Denmark;
authors.forename: Signe S
authors.initials: SS
authors.lastname: Beck-Nielsen
authors.affiliation: Institute for Clinical Research and Hans Christian Andersen Children's Hospital, Odense Child Cohort, Hans Christian Andersen Children's Hospital, Odense, Denmark;
authors.forename: Steffen
authors.initials: S
authors.lastname: Husby
authors.affiliation: Institute for Clinical Research and Odense Patient Data Explorative Network (OPEN), Department of Medicine, Holbæk Hospital, Holbæk, Denmark; and.
authors.forename: Bo
authors.initials: B
authors.lastname: Abrahamsen
authors.affiliation: Institute for Clinical Research and Division of Surgery, University College London, Northwick Park Institute of Medical Research Campus, United Kingdom.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Lamont
authors.affiliation: Institute for Clinical Research and Hans Christian Andersen Children's Hospital, henrik.christesen@rsyd.dk.
authors.forename: Henrik T
authors.identifier: http://orcid.org/0000-0001-5330-6853
authors.initials: HT
authors.lastname: Christesen
mesh_terms: D000022:Abortion, Spontaneous / Q000097:blood* / Q000453:epidemiology*; D000328:Adult; D003718:Denmark / Q000453:epidemiology; D019587:Dietary Supplements; D005260:Female; D005865:Gestational Age; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood* / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D014807:Vitamin D
keywords: cohort study; endocrinology; miscarriage; pregnancy; spontaneous abortion; vitamin D