Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants
Rapid growth is a dominant predictor of hepcidin suppression and declining ferritin in Gambian infants
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DOI：
10.3324/haematol.2018.210146
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发表时间：
2019-07-31
期刊：
影响因子：
10.1
通讯作者：
Kwambana-Adams, Brenda Anna
中科院分区：
文献类型：
--
作者：
Armitage, Andrew E.;Agbla, Schadrac C.;Kwambana-Adams, Brenda Anna
缺铁和缺铁性贫血在低收入国家非常普遍，特别是在幼儿中。Hepcidin是系统铁稳态的主要调节因子。它控制膳食铁的吸收，决定吸收的铁是否可用于红细胞生成和其他需要铁的过程，并预测口服铁补充剂的反应。因此，了解hepcidin本身是如何调节的是很重要的，尤其是在幼儿中。我们利用冈比亚农村两个出生队列（n=114和n=193）的纵向数据，研究了铁相关参数、炎症和感染状态、季节性和生长的变化如何影响婴儿期血浆hepcidin和铁蛋白浓度。这种环境的特点是极端季节性、普遍的儿童贫血、营养不良和频繁感染。从婴儿出生时和定期收集血浆，直至12个月大。婴儿时期Hepcidin、铁蛋白和血浆铁浓度明显下降，可溶性转铁蛋白受体和转铁蛋白浓度相互增加，表明铁储量下降，组织铁需求增加。在5个月和12个月大的横断面分析中，我们确定了hepcidin与铁和炎症标志物的预期关系，但也观察到hepcidin与先前体重增加之间存在显著的负相关。相应地，纵向固定效应模型表明，体重增加是两个队列中婴儿期hepcidin和铁蛋白降低的最显著动态预测因子。在这种情况下快速生长的婴儿尤其有铁储备枯竭的风险，但由于hepcidin浓度随着体重增加而降低，他们也可能对口服铁干预反应最敏感。
Iron deficiency and iron deficiency anemia are highly prevalent in low-income countries, especially among young children. Hepcidin is the major regulator of systemic iron homeostasis. It controls dietary iron absorption, dictates whether absorbed iron is made available in circulation for erythropoiesis and other iron-demanding processes, and predicts response to oral iron supplementation. Understanding how hepcidin is itself regulated is therefore important, especially in young children. We investigated how changes in iron-related parameters, inflammation and infection status, seasonality, and growth influenced plasma hepcidin and ferritin concentrations during infancy using longitudinal data from two birth cohorts of infants in rural Gambia (n=114 and n=193). This setting is characterized by extreme seasonality, prevalent childhood anemia, undernutrition, and frequent infection. Plasma was collected from infants at birth and at regular intervals, up to 12 months of age. Hepcidin, ferritin and plasma iron concentrations declined markedly during infancy, with reciprocal increases in soluble transferrin receptor and transferrin concentrations, indicating declining iron stores and increasing tissue iron demand. In cross-sectional analyses at 5 and 12 months of age, we identified expected relationships of hepcidin with iron and inflammatory markers, but also observed significant negative associat ions between hepcidin and antecedent weight gain. Correspondingly, longitudinal fixed effects modeling demonstrated weight gain to be the most notable dynamic predictor of decreasing hepcidin and ferritin through infancy across both cohorts. Infants who grow rapidly in this setting are at particular risk of depletion of iron stores, but since hepcidin concentrations decrease with weight gain, they may also be the most responsive to oral iron interventions.