Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 95, Issue 4, Pages 817-826Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.16-0218
Keywords
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Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Bill & Melinda Gates Foundation [29202]
- Grand Challenges in Global Health Initiative [1364]
- National Institutes of Health Fogarty International Center [D43 TW005509]
- National Institutes of Health [R01A152059]
- National Institutes of Health Oxford Cambridge Scholars Program
- Medical Research Council, United Kingdom
- MRC [G0901149, G0800270, MC_UU_12010/10, MR/L003120/1] Funding Source: UKRI
- British Heart Foundation [RG/08/014/24067, RG/13/13/30194] Funding Source: researchfish
- Medical Research Council [G0800270, MR/L003120/1, MC_UU_12010/10, G0901149] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10165] Funding Source: researchfish
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Hepcidin, the master regulator of bioavailable iron, is a key mediator of anemia and also plays a central role in host defense against infection. We hypothesized that measuring hepcidin levels in cord blood could provide an early indication of interindividual differences in iron regulation with quantifiable implications for anemia, malaria, and mortality-related risk. Hepcidin concentrations were measured in cord plasma from a birth cohort (N = 710), which was followed for up to 4 years in a region of perennial malaria transmission in Muheza, Tanzania (2002-2006). At the time of delivery, cord hepcidin levels were correlated with inflammatory mediators, iron markers, and maternal health conditions. Hepcidin levels were 30% (95% confidence interval [CI]: 12%, 44%) lower in children born to anemic mothers and 48% (95% CI: 11%, 97%) higher in placental malaria-exposed children. Relative to children in the lowest third, children in the highest third of cord hepcidin had on average 2.5 g/L (95% CI: 0.1, 4.8) lower hemoglobin levels over the duration of follow-up, increased risk of anemia and severe anemia (adjusted hazard ratio [HR] [95% CI]: 1.18 [1.03, 1.36] and 1.34 [1.08, 1.66], respectively), and decreased risk of malaria and all-cause mortality (adjusted HR [95% CI]: 0.78 [0.67, 0.91] and 0.34 [0.14, 0.84], respectively). Although longitudinal measurements of hepcidin and iron stores are required to strengthen causal inference, these results suggest that hepcidin may have utility as a biomarker indicating children's susceptibility to anemia and infection in early life.
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