Perinatal & Pediatric
Pre-pregnancy calcium supplementation on the risk of gestational hypertension and proteinuria: A per-protocol analysis of a randomized trial Chase D. Latour* Chase Latour Latour Latour Latour Latour Latour Latour Latour chase.latour@pennmedicine.upenn.edu
Introduction: Adhering to pre- and early-pregnancy low-dose calcium supplementation may reduce the risk of preeclampsia. However, its effect on preeclampsia physiology—specifically, gestational hypertension and proteinuria—is unclear.
Methods: We analyzed data from a double-blind, placebo-controlled trial of daily, low-dose (500mg) calcium supplementation from pre-conception through 20 weeks’ gestation among women with prior preeclampsia in Zimbabwe, South Africa, and Argentina (2011-16). Persons who had chronic hypertension with proteinuria at screening were excluded. Gestational hypertension and proteinuria were assessed during study visits at 20 and 32 weeks’ and from medical records based on blood pressures (systolic ≥140 or diastolic ≥90 mmHg) and urine protein (≥2 on urine dipstick or elevated urinary protein laboratory values). Participants were adherent if they took their assigned tablets at least 5 days/week, on average, as determined by counts taken every 12 weeks. We used parametric g-computation to estimate per-protocol RRs for gestational hypertension and proteinuria. We addressed missing values via multiple imputation (m=10) and estimated CIs via bootstrap (n=500).
Results: Among 1,355 participants (678 calcium, 677 placebo), 60% adhered to their assigned treatment. Adhering to pre- and early-pregnancy low-dose calcium supplementation versus placebo had minimal to no effect on the risk of gestational hypertension (33.6% versus 35.2%, RR=0.95 [95% CI: 0.90, 1.05]) or gestational proteinuria (20.7% versus 21.6%, RR=0.95 [95% CI: 0.87, 1.04]).
Conclusions: Adhering to pre- and early-pregnancy low-dose calcium supplementation did not decrease the risk of gestational hypertension or proteinuria. These results seem to conflict with a previous analysis, finding adherence associated with a decreased risk of preeclampsia. However, discrepancies may reflect bias towards the null due to non-differential outcome misclassification in secondary trial outcomes.