Iron Supplementation in Iron-Replete and Nonanemic Pregnant Women in Tanzania: A Randomized Clinical Trial.

Randomized clinical trial in Dar es Salaam, Tanzania, enrolling HIV-negative primigravidae or secundigravidae at or before 27 weeks' gestation who were nonanemic and iron-replete at screening. For the iron group, 750 participants were randomized; birth outcomes were analyzed in 731 and placental samples in 493.

Daily oral iron supplementation with 60 mg elemental iron as ferrous sulfate from enrollment until delivery, compared with placebo. The regimen was given in pregnant women receiving standard antenatal care and malaria-control measures.

Iron supplementation did not increase placental malaria or other major adverse outcomes, and it improved maternal iron status at delivery. Placental malaria was similar with iron vs placebo for any placental malaria (33 [6.7] vs 33 [6.5]; RR 1.03, 0.65-1.65; P=.89), microscopic placental malaria (11 [2.3] vs 10 [2.1]; RR 1.14, 0.49-2.65; P=.77), and submicroscopic placental malaria (26 [5.3] vs 24 [4.8]; RR 1.12, 0.65-1.92; P=.69). Maternal hemoglobin at delivery was higher with iron (11.8 [2.0] g/dL vs 10.9 [1.9] g/dL; P<.001), ferritin was higher (92.5 [171.1] μg/L vs 54.1 [90.3] μg/L; P<.001), and risks of iron deficiency and anemia at delivery were lower (iron deficiency 33 [6.8] vs 73 [14.3]; RR 0.48, 0.32-0.70; P=.001; anemia 144 [29.9] vs 248 [49.5]; RR 0.60, 0.51-0.71; P<.001). Birth weight and other major perinatal outcomes were not improved, including mean birth weight (3155 [545] g vs 3137 [519] g; P=.89) and preterm birth <37 weeks (100 [15.0] vs 113 [16.5]; RR 0.91, 0.71-1.17; P=.46).

The placental analysis subset was smaller than the full randomized cohort, with placental samples available for 493 participants and birth outcomes for 731, which limits precision for rarer outcomes. The trial was conducted in one malaria-endemic urban setting with strong malaria-control measures, so generalizability to other settings may be limited. Several clinically important outcomes were uncommon, reducing power to detect modest harms or benefits.