Serum hepcidin-25 in submicroscopic Plasmodium infection during first trimester pregnancy: An exploratory cross-sectional study in Southwest Sumba, Indonesia.

Malaria in pregnancy contributes to maternal anaemia and adverse birth outcomes, but the relationship between submicroscopic infection and hepcidin-mediated iron regulation in early pregnancy remains poorly characterised. This comparative cross-sectional study enrolled 80 first-trimester pregnant women attending antenatal care at Puskesmas Kori, Southwest Sumba, Indonesia, from May to August 2024. Species-specific 18S SSU rRNA quantitative polymerase chain reaction and Giemsa microscopy classified participants as submicroscopic P. falciparum mono-infection (n = 35), P. vivax mono-infection (n = 6), P. falciparum-P. vivax co-infection (n = 33), or aparasitaemic controls (n = 6). Serum hepcidin-25 was quantified in duplicate by sandwich ELISA. Hepcidin-25 concentrations differed across groups (Kruskal-Wallis H = 18.59, p < 0.001). The highest median concentration occurred in P. vivax mono-infection (5.293 ng/mL; IQR 5.040-5.380). In an exploratory direct comparison, the median was 2.334 ng/mL higher in P. vivax than in P. falciparum mono-infection (bootstrap 95% CI 0.918-2.564; Bonferroni-adjusted p = 0.0158). Haemoglobin and erythrocyte indices did not differ significantly across infection groups. Mean corpuscular haemoglobin showed a weak, non-significant inverse correlation with hepcidin-25 (rho = -0.190, p = 0.091). Chronic energy deficiency was associated with lower haemoglobin, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration, but not hepcidin-25. Serum hepcidin-25 therefore varied across submicroscopic infection groups, with the highest median in P. vivax mono-infection. This species-specific finding is exploratory and requires confirmation in larger prospective studies incorporating microscopy-positive comparators, iron-status indicators, inflammatory biomarkers, and antenatal supplementation data.