Iron supplementation strategies in Gambian infants

Summary

Dietary iron inadequacy affects approximately 4.9 billion people globally, impairing red blood cell production, immune function, and cognitive development. The World Health Organization (WHO) recommends daily iron supplementation of 10–12.5 mg for infants aged 6–23 months in regions where anaemia prevalence exceeds 40%. However, in infection-endemic settings, low-grade inflammation induces hepcidin upregulation, blocking iron absorption. Additionally, while exclusive breastfeeding is recommended for the first six months of life, many infants in low-income settings are born with inadequate iron stores due to maternal iron deficiency or low birth weight, increasing their risk of iron deficiency. This thesis focuses on iron supplementation strategies in Gambian infants aged 6 weeks to 12 months. In Chapters 2 and 3, we conducted a double-blind randomised controlled trial (RCT) comparing 12 weeks of haem iron polypeptide (HIP) supplementation with 10 mg elemental iron (n = 104) to 10 mg elemental iron as ferrous sulphate (n = 104) in Gambian infants aged 6–12 months. HIP was not superior to ferrous sulphate regarding our primary endpoints: haemoglobin (mean difference: 0.13 g/dL; 95% CI: -0.14 to 0.40) and ferritin concentrations (difference in geometric mean ratio: 14.2%; 95% CI: -7.03% to 40.2%). However, HIP supplementation resulted in higher serum iron and transferrin saturation concentrations, along with lower soluble transferrin receptor (sTfR) and unsaturated iron-binding capacity (UIBC) concentrations four hours post-dose. Adverse events were comparable between groups. In Chapters 4 and 5, we conducted a double-blind RCT to determine the efficacy and safety of 7.5 mg/day ferrous sulphate (n = 50) compared to placebo (n = 51) over 14 weeks among rural Gambian infants aged 6–10 weeks. Serum iron concentrations were higher in the ferrous sulphate group (mean difference: 2.5 µmol/L; 95% CI: 0.6 to 4.3) compared to placebo. There were improvements in haematological and iron status markers, with no signal of adverse events. In Chapters 6 and 7, we explored the impact of early iron supplementation on maternal and stakeholder acceptability, as well as growth and exclusive breastfeeding duration. No statistical support was found that early iron supplementation affected weight (p = 0.79), length (p = 0.64), or changes in z-scores for weight-for-age (p = 0.99), length-for-age (p = 0.70), or weight-for-length (p = 0.89). The median duration of exclusive breastfeeding did not differ between the iron (67 days) and placebo (71 days) groups (p = 0.15). While parents found the intervention acceptable, concerns were raised about cost. Among stakeholders, concerns also emerged regarding nutritional messaging related to exclusive breastfeeding. In Chapter 8, we conducted a secondary data analysis to determine the diagnostic accuracy of HemoCue-301 compared to the Sysmex XN-Series 1500 among 227 Gambian infants aged 6–12 months. HemoCue-301 was associated with biased measurements, with this bias being more pronounced at lower haemoglobin levels. Among individuals with a haemoglobin level of 8.0 g/dL, the absolute bias was 1.12 g/dL (95% CI: 0.91 to 1.37), with a proportional bias of 14.0% (95% CI: 11.4% to 17.1%).