In malaria endemic countries, anemia in pregnant women occurs as a result of erythrocyte destruction by Plasmodium infections and other causes including malnutrition. Iron supplementation is recommended as treatment of iron-deficiency anemia. Erythrocyte destruction results in increased release of cytotoxic free heme that is scavenged by haptoglobin (Hp), hemopexin (Hx) and heme oxygenase-1 (HO-1). Paradoxically, iron supplementation in pregnant women has been reported to enhance parasitemia and increase levels of free heme. The relationship between free heme, heme scavengers, and birth outcomes has not been investigated, especially in women who are on iron supplementation. We hypothesized that parasite-infected pregnant women on routine iron supplementation have elevated heme and altered expression of heme scavengers. A cross-sectional study was conducted to determine the association between plasma levels of free heme, HO-1, Hp, Hx, and malaria status in pregnant women who received routine iron supplementation and their birth outcomes. Heme was quantified by colorimetric assay and scavenger protein concentration by ELISA. We demonstrated that iron-supplemented women with asymptomatic parasitemia had increased free heme (mean 75.6 µM; interquartile range [IQR] 38.8–96.5) compared with nonmalaria iron-supplemented women (mean 34.9 µM; IQR 17.4–43.8, P < 0.0001). Women with preterm delivery had lower levels of Hx (mean 656.0 µg/mL; IQR 410.9–861.3) compared with women with full-term delivery (mean: 860.9 µg/mL; IQR 715.2–1055.8, P = 0.0388). Our results indicate that iron supplementation without assessment of circulating levels of free heme and heme scavengers may increase the risk for adverse pregnancy outcomes.
Address correspondence to Annette M. Nti or Jonathan K. Stiles, Morehouse School of Medicine, 720 Westview Dr., Atlanta, GA 30324. E-mails: firstname.lastname@example.org or email@example.com
Financial support: Support for this study was provided by grant R01 NS091616 from National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, NIH-RCMI (RR033062), USAID grant LAG-G-00-96-90013-00, grant R25TW007501 UAB Framework Program for Global Health, NIH-NIGM-MBRS/RISE (GM58268) at Morehouse School of Medicine, Georgia Clinical and Translational Science Alliance ACTSI TL1 Training Grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.