Abstract
.Exposure to profound adversity can negatively affect the neurodevelopment of children, but biologic mechanisms that underlie this association remain unknown. We sought to determine whether elevated levels of the inflammatory markers C-reactive protein (CRP) and soluble CD14 (sCD14) are associated with neurodevelopmental outcomes in Bangladeshi children. A total of 422 infant–mother pairs from an urban slum in Dhaka, Bangladesh were enrolled at birth and followed prospectively. Inflammation was measured with sCD14, interleukin (IL)-1β, and IL-6 at 18 weeks, and CRP at 6, 18, 40, and 53 weeks. Psychologists assessed cognitive, language, motor, and social emotional development using the Bayley Scales of Infant and Toddler Development at 78 and 104 weeks of age. We tested for the association of inflammatory markers with developmental outcomes, independent of previously identified associations such as malnutrition, family income, and maternal education. Every 10 pg/mL increase in sCD14 was associated with a 1.1–2.0 decrement in cognitive and motor scores at 78 weeks and in all domains at 104 weeks. The cumulative number of CRP elevations that a child experienced in the first year of life, as well as IL-1β and IL-6 at 18 weeks of age, were also negatively associated with Bayley Scales results. CRP, sCD14, IL-1β, and IL-6 were associated with lower neurodevelopmental outcomes. Our findings implicate a role of inflammation in the neurodevelopment of children growing up in adversity.
Highlights
Hundreds of millions of children growing up in poverty in low- and middle-income countries do not meet their full developmental potentials, which in turn affects their academic performance and future earnings.[1,2,3] The identification of biomarkers that are associated with poor neurodevelopmental outcomes offers a promising approach to shed light on biological mechanisms that underpin the association between early adversity and development
Inflammation triggered by recurrent enteric infections early in life may be the driving force behind elevations in systemic inflammatory markers in these children
We conducted a longitudinal analysis of 422 infants from a cohort of 700 children from the PROVIDE study, an ongoing community-based prospective cohort study of enteric infections and oral polio vaccine outcomes in infants from a slum of Mirpur in Dhaka, Bangladesh
Summary
Hundreds of millions of children growing up in poverty in low- and middle-income countries do not meet their full developmental potentials, which in turn affects their academic performance and future earnings.[1,2,3] The identification of biomarkers that are associated with poor neurodevelopmental outcomes offers a promising approach to shed light on biological mechanisms that underpin the association between early adversity and development. Our group has recently identified for the first time a connection of elevated inflammatory markers in children in lowincome countries with neurodevelopmental outcomes. Enteric infections remain a leading cause of morbidity in young children worldwide who carry a disproportionately large share of the disease burden.[10] In this particular cohort of children, enteric infections are pervasive with children having an average of two different enteropathogens in their stool by 6 weeks of age.[11] As such, inflammation triggered by recurrent enteric infections early in life may be the driving force behind elevations in systemic inflammatory markers in these children
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