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.
Highlights
An estimated one-third of children younger than 5 years in low- and middle-income countries fail to meet their full developmental potential
Average Length-for-age Z-score (LAZ) and Weight-for-age Z-score (WAZ) scores were below average (z-score of 0) at birth and declined over the following 24 months
We found that duration of febrile illness and elevated levels of the pro-inflammatory cytokines IL-1β and IL-6 in the first year of life are associated with lower neurodevelopmental scores
Summary
An 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 when most of the morbidity from infection is suffered. The first year of life is a period of critical and rapid brain development and is when most of the morbidity and mortality from infection is suffered [1,3]. While stunting has been associated with cognitive impairment, mechanisms that result in cerebral damage are not fully understood. It remains controversial whether infection has an independent effect on neurodevelopment through mechanisms such as chronic inflammation [5,6,7]. To the best of our knowledge, no studies have linked markers of inflammation during the post-neonatal period to child development
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