Randomized controlled trial of 2 prenatal iron supplements: is there a dose-response relation with maternal hemoglobin?

Abstract

Background: The most appropriate dose of iron to prevent maternal anemia is still unclear.

Objective: We assessed the dose-response relation between maternal hemoglobin and 2 prenatal iron supplements.

Design: An intention-to-treat, double-blind, randomized controlled trial compared 30 mg Fe + folic acid and 13 other micronutrients (UNIMMAP; UNICEF/WHO/UNU multiple micronutrient supplement for pregnant and lactating women) with 60 mg Fe + folic acid (IFA) only in rural Burkina Faso. Home visitors directly observed tablet intake. Mixed-effects models were used for the data analysis.

Results: At inclusion, 43.2% of the 1268 participants were anemic. On average, the hemoglobin concentration decreased over gestation by 0.019 g/dL (95% CI: 0.012, 0.025 g/dL) per week in the IFA and UNIMMAP groups. An increment in hemoglobin concentration per micronutrient tablet [β (±SE) = 0.006 ± 0.001 g/dL; P < 0001] was observed only in women who were anemic at inclusion, whereas a decrease was observed in the other mothers (-0.003 ± 0.001 g/dL; P = 0.002, P for interaction < 0.0001); the finding was similar in both the IFA and UNIMMAP groups. Women with baseline anemia achieved the same hemoglobin concentration (mean ± SD: 11.1 ± 0.64 g/dL) as their counterparts who received ±180 tablets of either UNIMMAP or IFA. Despite this, micronutrient intake did not significantly prevent anemia (51.0% in the third trimester). It was, however, a risk factor for hemoconcentration (odds ratio per tertile of tablet intake: 2.10; 95% CI: 1.12, 3.94), independently of supplement type or initial hemoglobin concentration.

Conclusions: UNIMMAP triggered the same hemoglobin dose response with half the amount of iron as provided by IFA treatment. The benefit of iron supplements in nonanemic women is unclear. Despite micronutrient supplementation, anemia remained highly prevalent during gestation, partly because of physiologic hemodilution. This trial was registered at clinicaltrials.gov as NCT00642408.