Global Nutrition (Oral Session 1)

(OR01-04-25) The Influence of Hepcidin on Benefits and Risks of Iron Supplementation in Bangladeshi Children

Saturday, May 31, 2025

10:36 AM – 10:48 AM ET

Location: S220 E-G

Presenting Author(s)

Leila M. Larson, PhD

Assistant Professor
University of South Carolina
Columbia, South Carolina, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

AB

Andrew Baldi, MBBS, FRACP, FRCPA

WEHI
Melbourne, Victoria, Australia
MH

Mohammed I. Hasan

Walter and Eliza Hall Institute of Medical Research, Australia
NJ

Naomi Jones

Walter and Eliza Hall Institute of Medical Research, Australia
EP

Emily Pickle

University of South Carolina, United States
RA

Ricardo Ataide

Walter and Eliza Hall Institute of Medical Research, Australia
CB

Cavan Bennett

Walter and Eliza Hall Institute of Medical Research, Australia
MB

Mohammad Bhuiyan

International Centre for Diarrhoeal Disease Research, Bangladesh
ST

SM Tipu

International Centre for Diarrhoeal Disease Research, Bangladesh
FT

Fahmida Tofail, MD, PhD

International Centre for Diarrhoeal Disease Research, Bangladesh, icddrb
Dhaka, Dhaka, Bangladesh
BB

Beverley-Ann Biggs, MBBS, PhD, FRACP

University of Melbourne
Melbourne, Victoria, Australia
JH

Jena D. Hamadani, MD, PhD

International Centre for Diarrhoeal Disease Research, Bangladesh, icddrb
Dhaka, Dhaka, Bangladesh
Sant-Rayn Pasricha, MBBS, MPH, PhD, FRACP, FRCPA

Division Head
Walter and Eliza Hall Institute of Medical Research
Melbourne, Victoria, Australia
SB

Sabine Braat

Walter and Eliza Hall Institute of Medical Research, Australia

Objectives: Hepcidin level may determine individual responses to iron supplementation, but limited evidence exists from pediatric trials. We examined the influence of hepcidin on the effects of supplementation with iron syrup and multiple micronutrient powders (MNPs) on hemoglobin and ferritin concentrations and incidence of diarrhea in young children.

Methods: Participants included a subsample of 1281 8-month-old children enrolled in a three-arm, double-blind, double-dummy, individually randomized controlled trial examining the efficacy of 3 months of universal supplementation with daily iron syrup (12.5mg iron), MNPs (containing 12.5mg iron), or placebo in children living in Bangladesh. In all participants at baseline, immediately post-intervention (month 3), and after a further 9 months of follow-up (month 12), serum hepcidin concentrations were measured by ELISA, venous hemoglobin by HemoCue® 301, ferritin by chemiluminescence assay, and incidence of diarrhea by caregiver report. We used a likelihood-based longitudinal data analysis model to examine effect modification from baseline hepcidin on effects of iron syrup or MNPs on hemoglobin and ferritin concentrations and log-binomial model on incidence of diarrhea at months 3 and 12.

Results: The proportion of children with low ( < 10ng/mL) hepcidin concentration was 9.6% and comparable between randomized groups. Hepcidin modified the effect of MNPs, but not iron syrup, compared to placebo on hemoglobin and ferritin concentrations at month 3. The treatment effect of MNPs compared to placebo was larger among children with low compared to not-low baseline hepcidin (hemoglobin: mean difference in change from baseline (95% confidence interval) 11.6g/L (7.2, 15.9) compared to 4.3 (3.09, 5.7), p-interaction=0.002; ferritin: geometric mean ratio 2.4 (1.6, 3.6) compared to 1.5 (1.3, 1.7), p-interaction=0.024). This effect modification was not sustained at month 12. Hepcidin did not modify effects of either intervention on incidence of diarrhea at months 3 and 12.

Conclusions: Immediate effects of MNPs on child hemoglobin and iron status are larger among those with low compared to not-low hepcidin, indicating that pre-intervention screening could help identify those who would benefit most from MNPs.

Funding Sources: NHMRC, Thrasher Research Fund