Villar 2006.

Methods	Type of study: multicentre, randomised, placebo‐controlled, double‐blind trial. Central randomisation at WHO Geneva. Method of treatment allocation: computer‐generated random number blocking with randomly varying groups of 6 to 8 women and were used to restrict randomisation in the strata (country). The technique consisted of allocating consecutively numbered treatment boxes for each woman. Randomisation codes remained at the WHO Clinical trial Unit until the time of analysis and were not available to any person until the analyses were completed. Boxes and tablets were prepared and numbered by Magistra SA, GENEVA and were shipped to each centre. Stratification: yes, by country. Placebo: yes, starch tablets. Sample size calculation: not stated. Intention‐to‐treat analyses: yes. Losses to follow‐up: 13 in 8325 = 0.16%. Before treatment started, 2 women in the calcium group were not pregnant. 2 women in the placebo group were excluded from the analyses. 143 (3.4%) in calcium group (4157‐143) were lost to follow‐up and no delivery information; 4008 pregnancies available for analyses. 155 (3.7%) in placebo group (4168‐155) lost to follow‐up and no delivery information; 4006 pregnancies available for analyses of preterm labour and 4161 pregnancies  available for analyses of PIH (final analyses) of preterm labour and 4151 pregnancies available for analyses of PIH (final analyses). Post randomised exclusion: 4 in calcium were not pregnant, 5 in placebo group.
Participants	Location: Rosiario, Argentina; Assiut , Egypt; Nagpur and Vellor, India; Lima, Peru; Johannesburg, South Africa; Ho Chiminh City, Vietnam; where population intake calcium < 600 mg/d. Time frame: November 2001 to July 2003. Eligible criteria: healthy nulliparity, normal single viable pregnancy with known menstrual period date (LMP), registering at antenatal clinic before 20 weeks of gestation. Exclusion criteria: BP > 140/90 mmHg, had history or evidence of chronic hypertension, renal disease, signs and symptoms of nephrolithiasis, parathyroid disease and disease that require digoxin, phenytoin, or tetracycline therapy. Total recruited: 8325 pregnant women were randomised, treatment group, n = 4157, control group, n = 4168.
Interventions	1.5 g of calcium carbonate (1 x 500 mg tablet, 3 times per day at meal time), chewable tablets started at 20 weeks until delivery, and > 3 hours after any iron supplement. Compared with 3 tablets of placebo (contained lactose, sorbitol, cellulose plus other calcium free ingredient) per day, same form, colour and taste.
Outcomes	Incidence of pre‐eclampsia/eclampsia. Pregnancy outcomes; GA, preterm birth, birthweight, birth length, maternal admission to intensive care unit, maternal death, stillbirth, neonatal death.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Central randomisation at WHO Geneva. Computer‐generated random number blocking with randomly varying groups of 6 to 8  women and were used to restrict randomisation in the strata (country)."
Allocation concealment (selection bias)	Low risk	Quote: "The technique consisted of allocating consecutively numbered treatment boxes for each woman. Randomization codes remained at the WHO Clinical trial Unit until the time of analysis and were not available to any person until the analyses were completed. Boxes and tablets were prepared and numbered by Magistra SA, GENEVAand were shipped to each centre."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "Women were assigned randomly to receive calcium tablets or placebo.They were identical in form, color and taste." Randomisation code kept until study end.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Women were assigned randomly to receive calcium tablets or placebo.They were identical in form, color and taste." Blood pressure was recorded by trained nurses and doctors. Randomisation code kept until study end.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Of 8325 women assigned randomly to group, 4157 were assigned to the calcium group and 4168 were assigned to the placebo group. Nine women (5 in the placebo group; 4 in calcium group) were determined to not be pregnant, and 2 women from each group who were lost to follow‐up before starting any treatment were excluded from all analyses. Delivery information was unavailable for 143 (3.4%) in the placebo group; therefore, they did not contribute to the preterm analyses, but the available data were included in the analyses for other outcomes. Thus, 4151 women in the calcium group and 4161 women in the placebo group contribute to the final analyses." Missing data 13 in 8325 = 0.16%.
Selective reporting (reporting bias)	Low risk	None identified.
Other bias	Low risk	None identified.