von Siebenthal Hanna K, Galetti Valeria, Zimmermann Michael B, Stoffel Nicole U
Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, ETH Zurich, Switzerland.
VMMT Research, Cagiallo, Switzerland; GroundWork, Fläsch, Switzerland.
Am J Clin Nutr. 2023 Mar;117(3):607-615. doi: 10.1016/j.ajcnut.2022.10.003. Epub 2022 Dec 15.
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.
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.
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).
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.
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.
低收入和中等收入国家的铁项目通常以婴幼儿为目标人群。来自人类婴儿和小鼠模型的有限数据表明，婴儿早期铁吸收的稳态控制并不完全。婴儿期铁吸收过多可能会产生有害影响。
我们的目标是：1）研究3至15个月龄婴儿铁吸收的决定因素，并评估在此期间铁吸收的调节是否完全成熟；2）确定婴儿期触发铁吸收上调的铁蛋白和铁调素浓度阈值。
我们对本实验室在婴幼儿中进行的标准化、稳定铁同位素吸收研究进行了汇总分析。我们使用广义相加混合模型（GAMM）来研究铁蛋白、铁调素和铁分数吸收（FIA）之间的关系。
纳入了年龄在2.9至15.1个月的肯尼亚和泰国婴儿（n = 269）；66.8%的婴儿缺铁，50.4%的婴儿贫血。在回归模型中，铁调素、铁蛋白和血清转铁蛋白受体是FIA的显著预测因子，而C反应蛋白不是。在包含铁调素的模型中，铁调素是FIA最强的预测因子（β = -0.435）。在所有模型中，包括年龄在内的交互项不是FIA或铁调素的显著预测因子。铁蛋白与FIA的拟合GAMM趋势显示，直到铁蛋白达到46.3μg/L（95%CI：42.1，50.5μg/L）时才有显著的负斜率，这对应于FIA从26.5%降至8.3%；高于该铁蛋白值时，FIA保持稳定。铁调素与FIA的拟合GAMM趋势显示，直到铁调素达到3.15nmol/L（95%CI：2.67，3.63nmol/L）时才有显著的负斜率，高于该值时FIA保持稳定。
我们的研究结果表明，婴儿期铁吸收的调节途径是完整的。在婴儿中，铁吸收分别在铁蛋白阈值约为46μg/L和铁调素阈值约为3nmol/L时开始增加，这与成人值相似。
