Blood Levels of Environmental Heavy Metals are Associated with Poorer Iron Status in Ugandan Children: A Cross-Sectional Study

• Published in: The Journal of nutrition Vol. 153; no. 10; pp. 3023 - 3031
• Main Authors: Park, Saeun, Mupere, Ezekiel, Lund, Troy C., Hodges, James S., Moody, Emily C., Colicino, Elena, Georgieff, Michael K., Cusick, Sarah E.
• Format: Journal Article
• Language: English
• Published: Bethesda Elsevier Inc 01.10.2023; American Institute of Nutrition
• Subjects: Anemia; Biomarkers; Blood; Blood levels; Cadmium; child neurodevelopment; Children; Children & youth; Cobalt; Cross-sectional studies; Dietary minerals; Divalent metal transporter-1; Ferritin; Heavy metals; Hepcidin; Intestinal absorption; Iron; Iron deficiency; Manganese; Metal concentrations; metal mixtures; Mixtures; neurotoxicity; Nutrient deficiency; Regression; Regression analysis; Transferrin; Vitamin deficiency; Cd; Mn; metal mixtures; log-ferritin; biomarkers; DMT1; IS; Co; child neurodevelopment; MLR; Pb; neurotoxicity; log-sTfR; BPb; Hb; iron deficiency; ID; log-hepcidin
• ISSN: 0022-3166; 1541-6100
• DOI: 10.1016/j.tjnut.2023.08.014

Iron deficiency (ID) and environmental exposure to metals frequently co-occur among Ugandan children, but little is known about their associations, although iron and other divalent metals share the same intestinal absorption transporter, divalent metal transporter 1 (DMT1). We examined associations between iron status and blood concentrations of lead, manganese (Mn), cobalt (Co), and cadmium, both singly and as a mixture. We used data on sociodemographic status, iron biomarkers, and blood concentrations of heavy metals collected from a cross-sectional survey of 100 children aged 6–59 mo in Kampala, Uganda. We compared blood concentrations of metals in ID with iron-sufficient children. We examined associations between a metal mixture and iron biomarkers using multiple linear regression and weighted quintile sum regression. The median (interquartile range) blood Mn (μg/L) was higher in ID children defined by soluble transferrin receptor (sTfR) and ferritin (ID compared with iron-sufficient children): (sTfR [21.3 {15.1, 28.8}, 11.2 {8.6, 18.5}], ferritin [19.5 {15.0, 27.2}, 11.2 {8.8, 19.6}]; P < 0.001 for both). Similarly, the median (interquartile range) blood Co (μg/L) was higher in ID children by ferritin ([0.5 {0.4, 0.9}, 0.4 {0.3, 0.5}], P = 0.05). Based on the multiple linear regression results, higher blood Co and Mn were associated with poorer iron status (defined by all 4 iron indicators for Co and by sTfR for Mn). The weighted quintile sum regression result showed that higher blood concentrations of a metal mixture were associated with poorer iron status represented by sTfR, ferritin, and hepcidin, mainly driven by Co and Mn. Our study findings suggest that poorer iron status is associated with overall heavy metal burden, predominantly Co and Mn, among Ugandan children. Further prospective studies should confirm our primary findings and investigate the combined effects of coexposures to neurotoxicants on the neurodevelopment of young children.