Effect of calcium supplementation in pregnancy on maternal anaemia and iron status: Findings from two randomized trials in India and Tanzania

Abstract

Introduction: Iron-folic acid (IFA) and calcium supplementation are recommended during pregnancy; however, calcium may inhibit iron absorption. While recent trials have shown daily 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 anaemia 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 counselled to take calcium supplements several hours apart from the IFA. All participants had haemoglobin 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 haemoglobin and inflammation-adjusted serum ferritin concentrations using generalised linear models, and on anaemia, and iron deficiency anaemia using log-binomial models. Results: Third-trimester haemoglobin and serum ferritin were measured in 8,953 and 1,336 participants in India, respectively. In Tanzania, 8,496 participants had haemoglobin and 882 had ferritin assessed. In both trials, there was no difference between 500 and 1500 mg calcium supplementation on third-trimester haemoglobin [India: mean difference (MD) 0.01 (95% confidence intervals (CIs): -0.03, 0.04); Tanzania: MD -0.02 (95% CIs: -0.07, 0.03)], anaemia [India: relative risk (RR) 1.01 (95% CIs: 0.95, 1.07); Tanzania: RR 1.00 (95% CIs: 0.96, 1.05)], or iron deficiency anaemia [India: RR 1.20 (95% CIs: 0.93, 1.57); Tanzania: RR 0.94 (95% CIs: 0.77, 1.15)]. Conclusion: Low and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess co-administering or combining calcium and IFA into a single tablet on adherence and maternal iron status.