Effect of calcium supplementation in pregnancy on maternal anemia and iron status: Secondary analyses of two randomized trials in India and Tanzania.

INTRODUCTION: While recent trials have shown daily prenatal low-dose 500 mg calcium supplementation to be noninferior to the recommended high-dose 1500 mg regimen for prevention of preeclampsia, its effects on maternal anemia and iron status remain unclear. METHODS: We conducted two individually randomized, non-inferiority trials in India and Tanzania (N=11,000 each) comparing daily 500 mg to 1500 mg calcium supplementation during pregnancy. All participants received standard IFA (60 mg iron) and were counseled to take calcium supplements several hours apart from the IFA. All participants had hemoglobin measured at baseline and at 32 weeks of gestation, while a random subset of participants had ferritin quantified at the same time points. Using an intention-to-treat approach, we assessed effects of 500 mg compared to 1500 mg calcium supplementation on mean hemoglobin and inflammation-adjusted serum ferritin (log-scale) using generalized linear models, and on anemia and iron deficiency anemia using log-binomial models. RESULTS: Third-trimester hemoglobin and serum ferritin were measured in 8,953 and 1,336 participants in India, respectively. In Tanzania, 8,496 participants had hemoglobin, and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester hemoglobin [India: mean difference (MD) 0.01 (95% confidence interval (CI): -0.03, 0.04); Tanzania: MD -0.02 (95% CI: -0.07, 0.03)], anemia [India: relative risk (RR) 1.01 (95% CI: 0.95, 1.07); Tanzania: RR 1.00 (95% CI: 0.96, 1.05)], or iron deficiency anemia [India: RR 1.20 (95% CI: 0.93, 1.57); Tanzania: RR 0.94 (95% CI: 0.77, 1.15)]. CONCLUSION: Low and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of co-administering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier, NCT03350516; Clinical Trials Registry India number, CTRI/018/2/12119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/TR/010/.