Role of hepcidin on benefits and risks of supplementation with iron syrup and multiple micronutrient powders in Bangladeshi children: a substudy to a randomized controlled trial.

Background: Hepcidin can determine individuals' responses to iron supplementation, but limited evidence exists from pediatric trials.

Objectives: We aimed to examine the influence of hepcidin on the effects of supplementation with iron syrup and multiple micronutrient powders (MNPs) on hemoglobin and ferritin concentrations and the incidence of diarrhea in young children.

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

Results: Hepcidin modified the effect of MNPs, but not iron syrup, compared with placebo on hemoglobin and ferritin concentrations immediately postintervention. The treatment effect of MNPs compared with placebo in the change from baseline to month 3 was larger among children with low compared with not-low baseline hepcidin [hemoglobin: mean difference 11.6 g/L (7.2, 15.9) compared with 4.3 (3.09, 5.7), P-interaction = 0.002; ferritin: geometric mean ratio 2.4 (1.6, 3.6) compared with 1.5 (1.3, 1.7), P-interaction = 0.024]. This effect modification was not sustained at month 12. Hepcidin did not modify the effects of either intervention on the incidence of diarrhea.

Conclusions: Immediate effects of MNPs on child hemoglobin and iron status are larger among those with low compared with not-low hepcidin, indicating that preintervention screening could help identify those who would benefit most from MNPs. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12617000660381.