title: Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: the AViDD trial.
abstract: BACKGROUND
  Antenatal vitamin D status may be associated with the risk of adverse pregnancy and neonatal outcomes; however, the benefits of vitamin D supplementation during pregnancy remain unknown.
  
  
  METHODS
  We conducted a double-blind placebo-controlled randomized trial to evaluate the effect of high-dose prenatal 3rd trimester vitamin D3 supplementation on maternal and neonatal (cord blood) serum 25-hydroxyvitamin D (25(OH)D) concentration (primary biochemical efficacy outcome) and maternal serum calcium concentration (primary safety measure). Eligibility criteria were pregnant women aged 18 to <35 years, at 26 to 29 weeks gestation, and residing in Dhaka, Bangladesh. 160 women were randomized by 1:1 allocation to one of two parallel intervention groups; placebo (n = 80) or 35,000 IU/week of vitamin D3 (n = 80) until delivery. All participants, study personnel and study investigators were blind to treatment allocation.
  
  
  RESULTS
  Mean maternal 25(OH)D concentration was similar in the vitamin D and placebo groups at baseline (45 vs. 44 nmol/L; p = 0.66), but was significantly higher in the vitamin D group vs. placebo group among mothers at delivery (134 vs. 38 nmol/L; p < 0.001) and newborns (cord blood: 103 vs. 39; p < 0.001). In the vitamin D group, 95% of neonates and 100% of mothers attained 25(OH)D >50 nmol/L, versus 21% mothers and 19% of neonates in the placebo group. No participants met criteria for hypercalcemia, there were no known supplement-related adverse events, and major pregnancy outcomes were similar between groups.
  
  
  CONCLUSIONS
  Antenatal 3rd-trimester vitamin D3 supplementation (35,000 IU/week) significantly raised maternal and cord serum 25(OH)D concentrations above 50 nmol/L in almost all participants without inducing hypercalcemia or other observed safety concerns. Doses up to 35,000 IU/week may be cautiously used in further research aimed at establishing the clinical effects and safety of vitamin D3 supplementation in pregnancy.
  
  
  BACKGROUND
  This trial was registered at ClinicalTrials.gov (NCT01126528).
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Roth
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mahmud
authors.forename: Rubhana
authors.initials: R
authors.lastname: Raqib
authors.forename: Evana
authors.initials: E
authors.lastname: Akhtar
authors.forename: Nandita
authors.initials: N
authors.lastname: Perumal
authors.forename: Brendon
authors.initials: B
authors.lastname: Pezzack
authors.forename: Abdullah H
authors.initials: AH
authors.lastname: Baqui
mesh_terms: D000293:Adolescent; D000328:Adult; D001459:Bangladesh; D002118:Calcium / Q000097:blood / Q000652:urine; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D010281:Parathyroid Hormone / Q000097:blood; D011247:Pregnancy; D011256:Pregnancy Outcome; D011263:Pregnancy Trimester, Third; D012709:Serum Albumin / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D010281:Parathyroid Hormone; D012709:Serum Albumin; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D003404:Creatinine; D002118:Calcium