Poster Presentation Second Round 16th Lorne Infection and Immunity 2026

Hepcidin links iron immunity, enteric infection, and fetal vulnerability in early pregnancy (#124)

Sara Young 1 , Shahjahan Siraj 2 , Kelly Davidson 1 , Meghan Gerety 3 , Rebecca Carpenter 4 , Mostofa Shakil 2 , Rachel Boone 1 , Uma Nayak 1 , Rashidul Haque 2 , William Petri 1
  1. University of Virginia, Charlottesville, VIRGINIA, United States
  2. icddr,b, Dhaka, Bangladesh
  3. University of Pennsylvania, Philadelphia, Pennsylvania, USA
  4. The University of Texas Medical Branch, Galveston, Texas, USA

Background

Poor fetal outcomes have been linked to dysfunctional immune signaling early in pregnancy.1 Hepcidin, the master regulator of iron homeostasis, integrates inflammatory and infectious cues to restrict iron during infection but is physiologically modulated in pregnancy to support fetal demands.2 In settings with a high burden of chronic enteric infections, it remains unclear how pregnancy-associated immune adaptations reshape hepcidin regulation and how hepcidin reflects immune and vascular states relevant to fetal outcomes.

Methods

We conducted a prospective cohort study of 412 women enrolled during the first trimester (<13 weeks of gestation). Enteric pathogens were assessed through stool testing in a subset of participants (n=367). Pathogen burden analyses excluded universally detected, commensal, and non-enteric targets.

Results

Hemoglobin and inflammatory biomarkers were similar despite hepcidin variations. Higher first-trimester hepcidin was associated with significantly lower odds of iron deficiency and iron deficiency anemia (p<0.001), an inverse association with angiotensin II (p<0.001), and a reduced incidence of small vulnerable neonates (birth weight <2.5g or gestational age <34 weeks; p=0.042). Among 266 women with at least one enteric pathogen detected, an increasing pathogen burden was associated with lower hepcidin levels (p=0.038), while STEC prevalence decreased with increasing hepcidin levels (p=0.022). CRP and AGP did not vary significantly with pathogen burden.

Discussion

Higher first-trimester hepcidin was associated with reduced enteric pathogen burden, improved iron status, lower angiotensin II, and fewer adverse fetal outcomes. Elevated hepcidin may limit iron availability to enteric pathogens, consistent with reduced pathogen burden and STEC prevalence, while the inverse association with angiotensin II may reflect vascular adaptations that support placental perfusion. Hepcidin may serve as an integrated biomarker of a pregnancy-adapted state where iron immunity is balanced with infection tolerance to support fetal demands. Future studies are needed to distinguish pregnancy-specific immune adaptation from infection-driven iron regulation and clarify mechanistic links.

  1. Gerety MK, Kim DK, Carpenter RM, et al. Systemic inflammation, enteropathogenic E. Coli, and micronutrient insufficiencies in the first trimester as possible predictors of preterm birth in rural Bangladesh: a prospective study. BMC Pregnancy Childbirth. 2024;24:82. doi:10.1186/s12884-024-06266-9
  2. Koenig MD, Tussing-Humphreys L, Day J, Cadwell B, Nemeth E. Hepcidin and Iron Homeostasis during Pregnancy. Nutrients. 2014;6(8):3062-3083. doi:10.3390/nu6083062