부산대학교 도서관

Background: Shigella infections cause inflammation, which has been hypothesized to mediate the associations between Shigella and child development outcomes among children in low-resource settings. We aimed to assess whether early life inflammation and Shigella infections affect school-aged growth and cognitive outcomes from 6–8 years of age. Methodology/principal findings: We conducted follow-up assessments of anthropometry, reasoning skills, and verbal fluency in 451 children at 6–8 years of age in the Brazil, Tanzania, and South Africa sites of MAL-ED, a longitudinal birth cohort study. We estimated the associations between Shigella burden and inflammation with linear growth at 2, 5, and 6–8 years of age, and with the cognitive test scores using linear regression and adjusting for potential confounding variables. We also assessed whether inflammation mediated the associations between Shigella and school-aged outcomes using a regression-based approach to mediation analysis. A high prevalence of Shigella was associated with a 0.32 (95% CI: 0.08, 0.56) z-score lower height-for-age z-score (HAZ) at 6–8 years compared to a low prevalence of Shigella. Intestinal inflammation had a smaller association with HAZ at 6–8 years. Shigella burden had small and consistently negative associations with cognitive outcomes in Brazil and Tanzania, but not South Africa, and the estimates were not statistically significant. Systemic inflammation was strongly associated with lower verbal fluency scores in Brazil (semantic fluency z-score difference: -0.57, 95% CI: -1.05, -0.10; phonemic fluency z-score difference: -0.48, 95% CI: -0.93, -0.03). There was no evidence that intestinal inflammation mediated the association between Shigella and HAZ or cognitive outcomes. Conclusions/significance: While Shigella infections were consistently associated with long-term deficits in linear growth, the estimates of the negative associations between Shigella and cognitive outcomes were imprecise and only observed in the Brazil and Tanzania sites. Systemic inflammation was strongly associated with lower semantic and phonemic fluency scores in Brazil only, highlighting the site-specificity of effects. Author summary: Shigella infections are common among children in low-resource settings and cause inflammation, which may contribute to poor child development outcomes. We studied children from birth to 6–8 years of age in Brazil, Tanzania, and South Africa to assess whether Shigella infections and markers of inflammation in the first 2 years of life were associated with child development outcomes at school age, including height and cognitive assessment scores. Shigella infections were consistently associated with long-term deficits in linear growth. However, the associations between Shigella and cognitive outcomes were smaller, not statistically significant, and inconsistent across the three sites. There was no evidence that inflammation caused by Shigella explained the associations between Shigella and school-aged outcomes. Systemic inflammation was strongly associated with lower cognitive assessment scores in Brazil but not in the other sites, highlighting the differences in determinants of child development across settings. Quantifying the impact and understanding mechanisms for the effect of early life exposures to Shigella on long-term cognitive outcomes remains challenging. [ABSTRACT FROM AUTHOR]