Iron supplementation affects hematologic biomarker concentrations and pregnancy outcomes among iron-deficient tanzanian women^1-3

Background: Iron deficiency is a highly prevalent micronutrient abnormality and the most common cause of anemia globally, worsening the burden of adverse pregnancy and child outcomes. Objective: We sought to evaluate the response of hematologic biomarkers to iron supplementation and to examine the predictors of the response to iron supplementation among iron-deficient pregnant women. Methods: Weidentified 600 iron-deficient (serumferritin≤12μg/L) pregnant women, aged 18-45 y, presenting to 2 antenatal clinics in Dar es Salaam, Tanzania using rapid ferritin screening tests, and prospectively followed them through delivery and postpartum. All women received 60 mg Fe and 0.25 mg folate daily from enrollment until delivery. Proportions meeting the thresholds representing deficient hematologic status including hemoglobin <110 g/L, ferritin ≤12 μg/L, serum soluble transferrin receptor (sTfR) >4.4 mg/L, zinc protoporphyrin (ZPP) >70 mmol/L, or hepcidin ≤13.3 μg/L at baseline and delivery were assessed. The prospective change in biomarker concentration and the influence of baseline hematologic status on the change in biomarker concentrations were assessed. Regression models were estimated to assess the relation of change in biomarker concentrations and pregnancy outcomes. Results: Therewas significant improvement inmaternal biomarker concentrations between baseline and delivery, with increases in the concentrations of hemoglobin (mean difference: 15.2 g/L; 95% CI: 13.2, 17.2 g/L), serum ferritin (51.6 μg/L; 95% CI: 49.5, 58.8 μg/L), and serumhepcidin (14.0 μg/L; 95% CI: 12.4, 15.6 μg/L) and decreases in sTfR (21.7mg/L; 95% CI:22.0,21.3mg/L) and ZPP (217.8 mmol/L; 95% CI: 232.1, 3.5 mmol/L). The proportions of participants with low hemoglobin, ferritin, and hepcidin were 73%, 93%, and 99%, respectively, at baseline and 34%, 12%, and 46%, respectively, at delivery. The improvements in biomarker concentrationswere significantly greater among participants with poor hematologic status at baseline - up to 12.1 g/L and 14.5 μg/L for hemoglobin and ferritin concentrations, respectively. For every 10-g/L increase in hemoglobin concentration, therewas a 24% reduced risk of perinatal mortality (RR = 0.76; 95% CI: 0.59, 0.99) and a 23% reduced risk of early infantmortality (RR = 0.77; 95% CI: 0.60, 0.99). The risk of anemia at delivery despite supplementation was predicted by baseline anemia (RR = 2.11; 95% CI: 1.39, 3.18) and improvements in ferritin concentration were more likely to be observed in participants who took iron supplements for up to 90 d (RR = 1.41; 95% CI: 1.13, 1.76). Conclusion: Iron supplementation decreases the risk of maternal anemia and increases the likelihood of infant survival among iron-deficient Tanzanian pregnant women. Interventions to promote increased duration and adherence to iron supplements may also provide greater health benefits.