Regulation of iron absorption in infants

Abstract

Background: Iron programs in low- and middle-income countries often target infants and young children. Limited data from human infants and mouse models suggest that homeostatic control of iron absorption is incomplete in early infancy. Excess iron absorption during infancy may have detrimental effects.

Objectives: Our aims were to 1) investigate determinants of iron absorption in infants aged 3-15 mo and assess whether regulation of iron absorption is fully mature during this period and 2) define the threshold ferritin and hepcidin concentrations in infancy that trigger upregulation of iron absorption.

Methods: We performed a pooled analysis of standardized, stable iron isotope absorption studies performed by our laboratory in infants and toddlers. We used generalized additive mixed modeling (GAMM) to examine relationships between ferritin, hepcidin, and fractional iron absorption (FIA).

Results: Kenyan and Thai infants aged 2.9-15.1 mo (n = 269) were included; 66.8% were iron deficient and 50.4% were anemic. In regression models, hepcidin, ferritin, and serum transferrin receptor were significant predictors of FIA, whereas C-reactive protein was not. In the model including hepcidin, hepcidin was the strongest predictor of FIA (β = -0.435). In all models, interaction terms, including age, were not significant predictors of FIA or hepcidin. The fitted GAMM trend of ferritin versus FIA showed a significant negative slope until ferritin of 46.3 μg/L (95% CI: 42.1, 50.5 μg/L), which corresponded to an FIA decrease from 26.5% to 8.3%; above this ferritin value, FIA remained stable. The fitted GAMM trend of hepcidin versus FIA showed a significant negative slope until hepcidin of 3.15 nmol/L (95% CI: 2.67, 3.63 nmol/L), above which FIA remained stable.

Conclusions: Our findings suggest that the regulatory pathways of iron absorption are intact in infancy. In infants, iron absorption begins to increase at threshold ferritin and hepcidin values of ∼46 μg/L and ∼3 nmol/L, respectively, similar to adult values.

Keywords: absorption; anemia; ferritin; hepcidin; homeostasis; infancy; iron; iron deficiency; iron supplement; stable isotopes.