World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women.
ABSTRACT The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery.
Randomized placebo-controlled, double-blinded trial in nulliparous normotensive women from populations with dietary calcium < 600 mg/d. Women who were recruited before gestational week 20 received supplements (1.5 g calcium/d or placebo) throughout pregnancy. Primary outcomes were preeclampsia and preterm delivery; secondary outcomes focused on severe morbidity and maternal and neonatal mortality rates.
The groups comprised 8325 women who were assigned randomly. Both groups had similar gestational ages, demographic characteristics, and blood pressure levels at entry. Compliance were both 85% and follow-up losses (calcium, 3.4%; placebo, 3.7%). Calcium supplementation was associated with a non-statistically significant small reduction in preeclampsia (4.1% vs 4.5%) that was evident by 35 weeks of gestation (1.2% vs 2.8%; P = .04). Eclampsia (risk ratio, 0.68: 95% CI, 0.48-0.97) and severe gestational hypertension (risk ratio, 0.71; 95% CI, 0.61-0.82) were significantly lower in the calcium group. Overall, there was a reduction in the severe preeclamptic complications index (risk ratio, 0.76; 95% CI, 0.66-0.89; life-table analysis, log rank test; P = .04). The severe maternal morbidity and mortality index was also reduced in the supplementation group (risk ratio, 0.80; 95% CI, 0.70-0.91). Preterm delivery (the neonatal primary outcome) and early preterm delivery tended to be reduced among women who were < or = 20 years of age (risk ratio, 0.82; 95% CI, 0.67-1.01; risk ratio, 0.64; 95% CI, 0.42-0.98, respectively). The neonatal mortality rate was lower (risk ratio, 0.70; 95% CI, 0.56-0.88) in the calcium group.
A 1.5-g calcium/day supplement did not prevent preeclampsia but did reduce its severity, maternal morbidity, and neonatal mortality, albeit these were secondary outcomes.
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ABSTRACT: A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct P values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis.JAMA The Journal of the American Medical Association 08/1991; 266(1):93-8. · 29.98 Impact Factor
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