The Relationship Between Ferritin and Body Mass Index is Mediated by Inflammation Among Women in Higher-Income Countries, But Not in Most Lower-Income Countries Nor Among Young Children: A Multi-Country Analysis

Abstract Background In the presence of inflammation, serum or plasma ferritin concentration (‘ferritin’) transiently increases, confounding its interpretation as an iron status marker. The extent to which adiposity-related inflammation may influence ferritin interpretation is uncertain. Objective To describe relationships between weight status, inflammation, and ferritin among non-pregnant women of reproductive age (15-49 years, WRA) and preschool-age children (6-59 months, PSC) with normal weight to overweight or obesity (OWOB) in differing geographic settings. Methods Cross-sectional data were separately analyzed from n = 18 surveys (WRA) and n = 25 surveys (PSC) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project, excluding observations with underweight, wasting, pregnancy, or malaria. Relationships were assessed between BMI (WRA) or BMI-for-age z-score (BAZ, PSC), inflammatory biomarkers C-reactive protein (CRP) and/or α-1-acid glycoprotein (AGP), and ferritin by linear regression, and potential mediation by CRP and/or AGP in relationships between BMI or BAZ and ferritin with structural equation modeling. Regression and mediation models accounted for complex survey designs. Results were grouped by World Bank income classifications. Included Kenya trial data registered at http://clinicaltrials.gov, identifier NCT01088958. Results In 5 of 6 surveys among WRA from upper-middle and high-income countries, ferritin was significantly positively associated with BMI, and this relationship was partially (or fully in the United States) mediated by CRP and/or AGP. Mediation was present in 4 of 12 surveys for WRA in low- and lower-middle income countries. Among PSC, ferritin was positively associated with CRP and/or AGP in all surveys, but there were no significant CRP- or AGP-mediated relationships between ferritin and BAZ, except a negative relationship in the Philippines. Conclusions Where OWOB are common among WRA, measurement of inflammatory biomarkers and their use in interpreting ferritin may improve iron status assessment. While these relationships were inconsistent among PSC, inflammation was common and should be measured to interpret iron status.