title: Vitamin D and pre-eclampsia: original data, systematic review and meta-analysis.
abstract: OBJECTIVE
  Vitamin D may protect from pre-eclampsia through influences on immune modulation and vascular function. To evaluate the role of vitamin D in the development of pre-eclampsia, we conducted a systematic review and meta-analysis including novel data from 2 large-scale epidemiological studies.
  
  
  METHODS
  PubMed, EMBASE and the Cochrane Central Register of Controlled Trials were searched for prospective observational studies of association between vitamin D supplementation or status (measured by maternal 25-hydroxyvitamin D, 25(OH)D) with a subsequent risk of pre-eclampsia, or randomised controlled trials using vitamin D supplementation to prevent pre-eclampsia. The Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA) and the Avon Longitudinal Study of Parents and Children (ALSPAC) were included in meta-analyses with published studies.
  
  
  RESULTS
  Mothers receiving vitamin D supplementation earlier in pregnancy had lower odds of pre-eclampsia [pooled odds ratios (OR) 0.81 and 95% confidence interval (CI) 0.75-0.87, p = 2.4 × 10(-8), 2 studies] in the meta-analysis of published studies with HCCSCA. The meta-analysis of published studies with ALSPAC suggested an association between higher serum 25(OH)D levels and a reduced risk of pre-eclampsia (pooled OR 0.52 and 95% CI 0.30-0.89, p = 0.02, 6 studies). Randomised trials of supplementation were suggestive of protective association (pooled OR 0.66 and 95% CI 0.52-0.83, p = 0.001, 4 studies).
  
  
  CONCLUSIONS
  This study suggests that low maternal serum 25(OH)D concentrations increase pre-eclampsia risk and that vitamin D supplementation lowers this risk. The quality of evidence is insufficient to determine a causal association, which highlights the need for adequately powered clinical trials.
authors.affiliation: School of Population Health and Sansom Institute, University of South Australia, Adelaide, S.A., Australia.
authors.forename: Elina
authors.initials: E
authors.lastname: Hyppönen
authors.forename: Alana
authors.initials: A
authors.lastname: Cavadino
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Abigail
authors.initials: A
authors.lastname: Fraser
authors.forename: Attila
authors.initials: A
authors.lastname: Vereczkey
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bánhidy
authors.forename: Deborah
authors.initials: D
authors.lastname: Lawlor
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Czeizel
mesh_terms: D019587:Dietary Supplements; D005260:Female; D006801:Humans; D009752:Nutritional Status; D064887:Observational Studies as Topic; D011225:Pre-Eclampsia / Q000097:blood* / Q000517:prevention & control*; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014807:Vitamin D / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D014807:Vitamin D