title: Cord Blood Hepcidin: Cross-Sectional Correlates and Associations with Anemia, Malaria, and Mortality in a Tanzanian Birth Cohort Study.
abstract: 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.
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland. Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Brickley
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland. Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. Department of Microbiology and Immunology, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Natasha
authors.initials: N
authors.lastname: Spottiswoode
authors.affiliation: Muheza Designated District Hospital, Muheza, Tanzania.
authors.forename: Edward
authors.initials: E
authors.lastname: Kabyemela
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Morrison
authors.affiliation: Rhode Island Hospital, Department of Pathology and Laboratory Medicine, Brown University Medical School, Providence, Rhode Island.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kurtis
authors.affiliation: Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Wood
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland.
authors.forename: Michal
authors.initials: M
authors.lastname: Fried
authors.affiliation: Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland. patrick.duffy@nih.gov.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Duffy
mesh_terms: D000740:Anemia / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry*; D064451:Hepcidins / Q000097:blood*; D006801:Humans; D007223:Infant; D007501:Iron / Q000097:blood*; D008288:Malaria / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D008297:Male; D012306:Risk; D013636:Tanzania / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D064451:Hepcidins; D007501:Iron