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. 2015 Feb 25;2015(2):CD007079. doi: 10.1002/14651858.CD007079.pub3

Levine 1997.

Methods Type of study: double‐blind, computer‐generated simple randomisation sequence.
Method of treatment allocation: packages of study tablets were prepared and numbered by manufacturer and then shipped to the medical centre.
 Stratification: not stated.
 Placebo: yes, starch tablets.
 Sample size calculation: not stated.
 Intention‐to‐treat analyses: yes.
 Losses to follow‐up: 253 in 4589 women (5.5%); 132 in the calcium group, 121 in the placebo group.
Participants Location: The Calcium for Preeclampsia Prevention (CPEP) Trial at 5 U.S medical centres.
Time frame: not stated.
 Eligibility criteria: nulliparity, normal single viable pregnancy with known menstrual period date (LMP), registering at antenatal clinic before 11 to 21 weeks of gestation and intended to undergo delivery at the same institution, normal glucose tolerance test and willing to participate in trial, BP below 134/84 mmHg and free of any underlying medical disorders, based on a comprehensive medical examination and routine laboratory tests.
 Exclusion criteria: taking medication, had bad obstetrical conditions, pre‐existing disease, elevated serum concentration of creatinine (> 1.0 mg/dL) or calcium (> 10.6 mg /dlL, pregnant women with renal disease, haematuria, or history of urolithiasis in themselves or in first‐degree relative and who report frequently use of calcium supplementation or antacid.
Total recruited: 4589 pregnant women; treatment group n = 2295, control group n = 2294.
Interventions 2 g of calcium (4 chewable tablets of calcium carbonate per day, 500 mg of elemental calcium), start at 13 to 20 weeks until delivery, 2 tablets with morning meal and 2 tablets with evening meal. Compared with 4 tablets of placebo (contained lactose and granulated starch) per day, same size, weight and colour.
Outcomes
  1. Incidence of PIH.

  2. Pregnancy outcomes; preterm birth, premature rupture of membrane, birthweight, birth length, admission to NICU, perinatal losses.

  3. Urolithiasis, renal insufficiency.

Notes Koo 1999 was another subset report of Levine 1997. Total recruited: 289 pregnant women. 13 refused consent; only 256 women and 256 infants were included (128 in each group).
  1. Fetal bone mineral density, bone mineral content.

  2. Pregnancy outcomes; GA, birthweight, birth length, and head circumference.

Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote: "Package of study tablets were prepared and numbered by manufacturer according to a computer‐generated simple randomisation sequence developed by statisticians."
Allocation concealment (selection bias) Low risk Quote: "Package of study tablets were prepared and numbered by manufacturer according to a computer‐generated simple randomisation sequence developed by statisticians and then were shipped to the medical centres. Upon enrolment, each woman was assigned the next number packages of medication at the centre and thus was randomised automatically to receive calcium or placebo according to the pre assigned random sequence."
Blinding of participants and personnel (performance bias) 
 All outcomes Low risk Quote: "Double‐blind, calcium supplementation versus placebo. Package of study tablets were prepared and numbered by manufacturer according to a computer‐generated simple randomisation sequence developed by statisticians. Women and staff blind to allocation."
Blinding of outcome assessment (detection bias) 
 All outcomes Low risk Quote: "All pregnant women received routines prenatal care. Staff blind to treatment allocation."
Incomplete outcome data (attrition bias) 
 All outcomes Low risk Quote: "Of 4589 women enrolled in the study, 253 women (5.5%) were lost to follow‐up; 132 in the calcium group, 121 in the placebo group."
Missing data 253 in 4589 = 5.5%.
Selective reporting (reporting bias) Low risk None identified.
Other bias Low risk None identified.