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A.E. Armitage et al.
protocols; parents and/or legal guardians gave written informed consent for infants. Studies were performed in accordance with the Declaration of Helsinki.
Results
Decline in hepcidin and iron status through infancy
High plasma concentrations of hepcidin and ferritin in
the absence of inflammation suggest that the majority of infants were iron replete at birth and up to two months of age (Figure 1A and B). Hepcidin concentrations declined from two to 12 months of age in both VPM and VA infant cohorts. In both cohorts, declines were most marked in males born in the lower birthweight group (Figure 1A). Similar patterns of decline were observed for ferritin, indi- cating rapid depletion of iron stores through infancy (Figure 1B). The decline in hepcidin and ferritin occurred
A
B
CD
E
F
GH
Figure 1. Changes in hepcidin and iron/inflammatory biomarkers across the first year of life in Gambian infants. Plots summarize changes in (A) hepcidin, (B) fer- ritin, (C) C-reactive protein (CRP), (D) α(1)-acid glycoprotein (AGP), (E) plasma iron, (F) soluble transferrin receptor (sTfR), and (G) transferrin (VPM only), and (H) hemo- globin (VA cohort) occurring across the first year of life in two cohorts of Gambian infants, VPM (left panels) and VA (right panels). Plots depict mean for cross-sec- tional data at each time point, stratifying by sex (male: blue; female: red) and birthweight group [World Health Organization weight-for-age z-score (WAZ) -0.5: above -0.5: solid line, or below -0.5: dashed line], summarizing 100 datasets in which any missing data was imputed by multiple imputation, combined using Rubin’s com- bination rules, as described in detail in the Methods section and the Online Supplementary Methods. 95% Confidence Intervals are omitted for clarity, but are given in Online Supplementary Table S4. Equivalent plots based on the original data prior to multiple imputation are shown in Online Supplementary Figure S1. VPM: Vaccination and Paediatric Microbiome study; VA: a vitamin A supplementation randomized controlled trial.22
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