Perinatal & Pediatric
Calcium supplementation during pre-pregnancy and early pregnancy among women at high risk of preeclampsia: a per-protocol analysis of a randomized trial Kyle Busse* Kyle Busse Long Khuong Gabriela Cormick Stefanie Hinkle José Belizán Enrique Schisterman Sunni Mumford Ellen Caniglia
Calcium supplementation is recommended from 20 weeks’ gestation for prevention of preeclampsia. Potential benefits of supplementation before 20 weeks’ gestation are less clear. A randomized trial of pre-pregnancy and early pregnancy (<20 weeks) calcium supplementation showed no significant reduction in recurrent preeclampsia (intention-to-treat [ITT] risk ratio [RR]=0.80; 95% confidence interval [CI] 0.61-1.06); however, roughly half of participants took fewer than 80% of expected tablets. Our objective was to estimate the per-protocol effect of pre-pregnancy and early pregnancy calcium supplementation on risk of recurrent preeclampsia in that trial.
This was a secondary analysis of a randomized trial of 500mg daily calcium pre-pregnancy through 20 weeks’ gestation on risk of recurrent preeclampsia among 1355 parous women in South Africa, Zimbabwe, and Argentina. Adherence was assessed by pill count every 12 weeks. The parametric g-formula was used to estimate the per-protocol effect of calcium supplementation vs. placebo ≥5 days/week on risk of preeclampsia. Bootstrapping was used to estimate 95% CI. Multiple imputation was used for missing values.
Of the 1355 women, 331 of 678 in the calcium group and 320 of 677 in the placebo group had a pregnancy. Of these, 298 in the calcium group and 283 in the placebo group had a pregnancy beyond 20 weeks’ gestation. The percentage of women with adherence ≥5 days/week was 59% in the calcium group and 60% in the placebo group. When adhering ≥5 days/week, the incidence of preeclampsia was 10.5% and 14.9% in the calcium and placebo groups, respectively (RR=0.70 [95% CI 0.44-1.06]). For every 100 women, supplemental calcium ≥5 days/week until 20 weeks’ gestation resulted in 4 fewer cases of preeclampsia (risk difference=−4.4 [−9.7-0.6]).
The per-protocol effect suggests that calcium supplementation ≥5 days/week until 20 weeks’ gestation may reduce risk of preeclampsia, but, like the ITT effect, it was not statistically significant.