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.