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

BACKGROUND

Although 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.

OBJECTIVES

This study evaluated the effects of 500 mg daily calcium supplementation as compared to 1500 mg calcium supplementation during pregnancy on maternal anemia and iron indices.

METHODS

We conducted two individually randomized, noninferiority trials in India and Tanzania (N = 11,000 each) comparing daily 500 to 1500 mg calcium supplementation during pregnancy. All participants received standard iron and folic acid (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 wk of gestation, whereas 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 with 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 8953 and 1336 participants in India, respectively. In Tanzania, 8496 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)].

CONCLUSIONS

Low- and high-dose calcium supplementation showed no differences in third-trimester hematologic outcomes. Future studies should assess the effects of coadministering or combining calcium and IFA into a single tablet on adherence and bioavailability of iron. This trial was registered at ClinicalTrials.gov as NCT03350516; at Clinical Trials Registry India as CTRI/018/2/12119; and at Tanzania Medicines and Medical Devices Au-thority Trials Registry as TFDA0018/TR/010/.