Research in context
anaemia, diarrhoea, dysentery, malaria, inflammation, infection, dysbiosis, deaths
ANAEMIA, DYSENTERY, RESPIRATORY TRACT INFECTIONS, MALARIA, INFLAMMATION, INFECTION, IRON DEFICIENCY, INFLAMMATION OR INFECTION

WHO recommends that children living in areas where the prevalence of anaemia exceeds 20% should receive 90 sachets of multiple micronutrient powders containing 10·0–12·5 mg iron over 6 months. Meta-analyses of randomised trials using these and similar protocols conducted under supervised conditions indicate an efficacy of only 5·0 g/L increase in haemoglobin concentration or less. Real-life effectiveness is probably much lower due to a combination of poor implementation and compliance. Compliance is often low because supplemental iron can cause discomfort due to unabsorbed reactive iron in the small gut, dysbiosis in the large gut, or both. Several large trials in low-income settings have also reported an excess of serious adverse outcomes, including diarrhoea and dysentery, respiratory tract infections, malaria, hospitalisations, and deaths. The iron-regulatory hormone, hepcidin, is upregulated by infection and inflammation and downregulates absorption of iron in the duodenum. Low circulating concentrations of hepcidin typically indicate that children do not have infection or inflammation, have iron deficiency, and will absorb iron effectively—ie, that they are safe and ready to receive supplemental iron. We reasoned that a hepcidin-guided screen-and-treat approach might achieve equivalent efficacy to daily iron supplementation but at a lower dose; therefore, it might have an improved profile of side-effects and safety.
We tested two screen-and-treat regimens (12 mg/day and 6 mg/day iron when hepcidin was below a pre-established threshold, and none when above the threshold) versus the WHO standard-of-care approach of 12 mg/day. The screen-and-treat strategy was effective at targeting supplementation and, thus, reducing overall intake of supplemental iron. However, both screen-and-treat approaches were inferior to WHO's recommendation of standard daily iron supplementation at increasing haemoglobin, decreasing prevalence of anaemia, and decreasing prevalence of iron deficiency. There were no differences in morbidity or safety outcomes between the screen-and-treat regimens and the WHO recommended regimen.
Contrary to conceptual logic, a hepcidin-guided screen-and-treat approach to targeting iron administration was less effective than WHO's recommended practice of universal iron supplementation at 12 mg daily. However, because the standard approach has generally low efficacy, research into improved interventions must continue.