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. 2019 Oct 3;2019(10):CD013446. doi: 10.1002/14651858.CD013446

March 2010.

Methods Double‐blind randomised controlled trial (blocked by ethnicity as either European or non‐European)
Participants 226 healthy pregnant women age of 18–45 years from Greater Vancouver, British Columbia, Canada, from 13 to 24 weeks of gestation (based on LMP). Women taking vitamin D supplements > 10 ug/d, with any metabolic, inflammatory or genetic problems (e.g. diabetes, TB, cardiac or renal disease, HIV/AIDS, chronic hypertension, inflammatory bowel disease, autoimmune disease, liver disease, or epilepsy) or with digestive and intestinal problems that may affect vitamin D absorption (e.g. coeliac disease or gastric bypass) were excluded from the study. Additionally, those with history of adverse pregnancy outcome (e.g. preterm delivery < 37 weeks of gestation; stillbirth; haemolytic anaemia, elevated liver enzymes and low platelet count syndrome; severe pre‐eclampsia or eclampsia) were excluded.
Interventions Within each block, women were randomly allocated to 1 of the 3 vitamin D doses:
‐ 10 mcg/d (n = 76);
‐ 25 mcg/d (n = 76);
‐ 50 mcg/d (n = 74).
Health worker cadre: women attended the study clinics at BC Women’s Hospital in Canada (north of tropics). Although not explicitly mentioned, study staff facilitated the self‐administration of questionnaires; measured height and weight at each visit according to standardise procedures with a calibrated standing weight scale and stadiometer after enrolment, at 36 weeks of gestation, and 8 weeks postpartum; collected maternal non‐fasting venous blood and urine at each time point, and cord blood at birth and 8 weeks after birth; and dispensed and counted the supplements at different time points.
Outcomes Maternal
  • serum 25OHD

  • hypercalcaemia


Infant
  • cord blood 25OHD


Laboratory method used for assessment of vitamin D concentrations:Serum 25(OH)D concentrations were determined using a LIAISON 25‐OH Vitamin D Vitamin D TOTAL assay (DiaSorin), a competitive chemiluminescence immunoassay that equally detects 25‐OHD2 and 25‐OHD metabolites.
Notes • Start of supplementation: Started at 13‐24 weeks of gestation
• Pre‐gestational BMI (kg/m2): mostly healthy weight (62% to 78%) and the rest OW/OB
• Supplementation scheme/regimen: daily
• Skin pigmentation based on Fitzpatrick skin tone chart (Fitzpatrick 1988):No skin pigmentation assessed
• Latitude: north of Tropics
• Season at the start of pregnancy: varied
Source of funding: supported by the Canadian Institutes for Health Research (CIHR) and Frederick Banting and Charles Best Canada Graduate Scholarship from the CIHR (KMM). Supplements were provided by Natural Factors (Coquitlam, Canada). Natural Factors had no role in the study design, implementation, or interpretation of the study findings.
Dates of the study: June 2010 and March 2013, included 3 calendar years with 4 full seasons each year: summer,fall, winter, and spring.
Declarations of interest among primary researchers: MRL receives consulting fees from the Factors Group of Nutritional Companies (Canada’s leading manufacturer of natural health products). All other authors declared no conflicts of interest related to this study.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Women were blocked by ethnicity as either European or non‐European; then, within each block, they were randomly allocated to 1 of the 3 vitamin D doses.
Allocation concealment (selection bias) Low risk The supplements were coded by the manufacturer to ensure blinding of all study participants.
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk The supplements were coded by the manufacturer to ensure blinding of all study staff; tablets all identical in size and colour but containing 10, 25, or 50 mg vitamin D3/d.
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Not mentioned but it is unlikely that the staff and the participants knew of their treatment group during periodic assessments and laboratory testing.    
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Across the treatment groups, the dropout rate was similar: 7.5%(n = 17) in the 10 mg/d group, 8.4% (n = 19) in the 25 mg/d group, and 8.0% (n = 18) in the 50 mg/d group. In the 10 mg/d group, 13 women were lost to follow‐up, and 4 withdrew from the study for personal reasons. In the 25 mg/d group, 17 women were lost to follow‐up, and 2 withdrew from the study for personal reasons. In the 50 mg/d group, 16 women were lost to follow‐up, and 2 withdrew from the study for personal reasons.
Selective reporting (reporting bias) Low risk All outcomes included in the methods were reported.
Other bias Low risk No other source of bias were identified