Febrile illness and pro-inflammatory cytokines are associated with lower neurodevelopmental scores in Bangladeshi infants living in poverty

Abstract

BackgroundAn estimated one-third of children younger than 5 years in low- and middle-income countries fail to meet their full developmental potential. The first year of life is a period of critical brain development and is also when most of the morbidity from infection is suffered. We aimed to determine if clinical and biological markers of inflammation in the first year of life predict cognitive, language, and motor outcomes in children living in an urban slum in Bangladesh.MethodsChildren living in Dhaka, Bangladesh were observed from birth until 24 months of age. Febrile illness was used as a clinical marker of inflammation and elevated concentrations of inflammation-related cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10) in sera collected from a subset of the cohort (N = 127) at 6 months of age were used as biomarkers of inflammation. Psychologists assessed cognitive, language, and motor development using a culturally adapted version of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 12 (N = 398) and 24 months of age (N = 210). We tested for the ability of febrile illness and elevated cytokine levels to predict developmental outcomes, independent of known predictors of stunting, family income, and maternal education.ResultsEvery additional 10 days of fever was associated with a 1.9 decrease in language composite score and a 2.1 decrease in motor composite score (p = 0.005 and 0.0002, respectively). Elevated levels of the pro-inflammatory cytokines IL-1β (> 7.06 pg/mL) and IL-6 (> 10.52 pg/mL) were significantly associated with a 4.9 and 4.3 decrease in motor score, respectively. Conversely, an elevated level of the Th-2 cytokine IL-4 (> 0.70 pg/mL) was associated with a 3.6 increase in cognitive score (all p < 0.05).ConclusionsClinical and biological markers of inflammation in the first year of life were significantly associated with poor neurodevelopmental outcomes. Conversely, a Th2-like response was associated with a better outcome. These findings suggest that markers of inflammation could serve as prognostic indicators and potentially lead to immune-based therapies to prevent developmental delays in at-risk children.

Early Childhood Diarrhea Predicts Cognitive Delays in Later Childhood Independently of Malnutrition

“…33,34 Beyond statistical significance level, it is important to note that the differences that approach 10 points on a 100-point standardized cognitive test are often considered to be an important difference in cognitive performance. 35 Our interaction effect results do show that a child suffering from both a higher number of ECDs and stunting is 7-9 TONI points lower than those suffering from neither.…”

Neurodevelopment: The Impact of Nutrition and Inflammation During Infancy in Low-Resource Settings

“…In this cohort, fever and inflammation were strongly associated with significantly lower scores on language, cognitive, and motor tests. 40 In the same cohort, high rates of anemia and zinc deficiency were also observed, with rates being highest in the first year of life when processes of brain maturation are particularly active. 41 New insights regarding the links between inflammation and neurodevelopment will undoubtedly emerge in coming years, as prospective data linking growth, feeding, and nutrientintake patterns, gut function and the microbiota, inflammation, and developmental testing from other high-risk populations become available.…”

Environmental Enteric Dysfunction in Children

“…Petri et al recently reported associations of pro-inflammatory cytokines with neurodevelopment in a prospective cohort of Bangladeshi infants from birth until 24 months of age. They showed elevated levels of the pro-inflammatory cytokines IL-1β (> 7.06 pg/mL) and IL-6 (> 10.52 pg/mL) were significantly associated with decreases in motor score, conversely, an elevated level of the Th-2 cytokine IL-4 (> 0.70 pg/mL) was associated with a 3.6 increase in cognitive score (51). Limitations include lack of standardization and use in different clinical settings.…”