Table 1 Characteristics of randomized controlled trials included in the review.

Methods

Randomization

Numbered, sealed opaque envelopes, containing randomization codes.

Numbered treatment packs in computer-generated simple randomization sequence.

Lost to follow-up – women

Of 593 (calcium) vs. 601 (placebo) enrolled, 14 vs. 13 were lost before starting treatment and excluded from analysis; 577 vs. 588 had at least partial follow up. Follow up was incomplete for 52 vs. 46, but delivery data were available in 17 vs. 12 of these, giving delivery data for 544 vs. 554.

calcium 132/2,295 vs. placebo 121/2,294.

Lost to follow-up – offspring

Of 614 randomized in one center (calcium 309/placebo 305), 301/299 completed the first study, 2/6 infant deaths and 1/0 maternal deaths had occurred, leaving 298/293 eligible for follow up. 289/285 were contacted, 10/5 refused to participate, 22/19 lived outside the country, and 257/261 were assessed.

559 randomized in study site. Of 497 invited to participate in the follow-up study, BP was measured in 260 infants at 3 months of age and 57 toddlers at 2 years of age.

Participants

Mothers

Nulliparous women, < 20 weeks pregnant; blood pressure < 140/90 mmHg (mean of 5 measurements); no present or past disease; not taking medication; normal oral glucose tolerance tests.

Pregnant nulliparas (45% black, 35% non-Hispanic white, 17% Hispanic white). Passed compliance test (took 75% of placebo over 6–14 days); BP 134/84 mmHg or less; urine protein dipstick negative or trace; 13–21 weeks pregnant.

Exclusion criteria: taking medications; obstetric or pre-existing diseases or personal characteristics which could influence study end-points, absorption or metabolism of calcium; any risk associated with calcium supplementation, or compliance; elevated serum creatinine (1.0 mg per decilitre or more) or calcium (10.6 mg per decilitre or more); renal disease; haematuria; history or family history of urolithiasis; frequent use of calcium supplements or antacids.

Of 11,959 women screened, 5,703 excluded initially and a further 1,667 after the compliance test. The remaining 4,589 women were enrolled.

Offspring

Two public and one private hospital participated in the original trial, but only babies born in the private hospital were included in the follow-up study at 7 years of age.

Five participating medical centers participated in the original trial, but only babies born in one center (Oregon) were included in the follow-up study. Additional criteria for inclusion: mothers who completed the original trial, delivered an infant without serious problems, and who read english. Follow-up was completed at 12 week postpartum and at 2 years of age.

Interventions

2 g calcium as 500 mg calcium carbonate tablets, vs. identical looking placebo tablets. Compliance was 84% (calcium) and 86% (placebo).

2 g/day elemental calcium as calcium carbonate, or placebo. Taken until delivery, development of pre-eclampsia or suspicion of urolithiasis. All women took 50 mg calcium per day as normal supplementation and were asked to drink 6 glasses of water per day.

Compliance was 64% in the calcium group and 67% in the placebo group. 20% of women took > 90% of the allocated treatment.

Outcomes

Systolic blood pressure, diastolic blood pressure, kidney stones, gall stones, hospital admissions

Systolic blood pressure, left ventricular wall mass. Diastolic blood pressure was measured at 2 years but group means were not reported.

Allocation Concealment

A

A