The association of Helicobacter pylori infection and inflammation with cognitive development in preadolescents

Objective Limited evidence suggests an association between Helicobacter pylori ( H. pylori ) infection and diminished cognitive function in children; nonetheless, the role of gastric inflammation remains unclear. We examined the association of H. pylori infection and serum pepsinogens, markers of gastric inflammation, with cognitive function in children aged 10–12 years. Methods A prospective cohort study was conducted among 233 infants from Arab towns in Israel, who were followed up at ages 10–12 years. Cognitive function was assessed using the Wechsler Intelligence Scale for Children-IV edition. H. pylori in infancy and at school age was detected via stool antigen detection enzyme immunoassay. Serum pepsinogens I (PGI) and PGII, markers of gastric inflammation, were measured using ELISA. Covariates included sociodemographics, nutritional status, and systemic inflammation. Results Overall, 134 participants were enrolled, 81 (60.4%) tested H. pylori -positive. Compared to uninfected participants, those with H. pylori- positivity at school age and with a ratio of PGI:PGII≤4.43 (indicating more severe inflammation) had lower full-scale IQ scores: beta coefficient -5.9 (95% CI -11.7, -0.01), as well as those with a PGI:PGII ratio>4.43 (milder inflammation) -7.5 (-12.7, -2.2), adjusting for confounders. Results were similar for the verbal comprehension and working memory scores, and in inverse probability weighted analysis that accounted for the non-inclusion of participants from the original cohort. Children with persistent infection from infancy to school age had the lowest cognitive performance. Conclusions H. pylori infection is associated with reduced cognitive performance in school-age children, regardless of gastric inflammation, highlighting its potential role in extra-gastrointestinal outcomes.