Date Published: September 07, 2017
Publisher: The American Society of Tropical Medicine and Hygiene
Author(s): Nona M. Jiang, Fahmida Tofail, Jennie Z. Ma, Rashidul Haque, Beth Kirkpatrick, Charles A. Nelson, William A. Petri.
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.
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.1–3 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. In recent years, there has been a particular interest in the association of inflammatory markers with neurodevelopmental outcomes.4–6 The basis behind studying inflammatory markers is rooted in the idea that inflammation is known to be detrimental to the developing brain as shown in both animal and human studies.7–9
The most significant contribution of this study is the validation in an independent cohort of our earlier finding that early life inflammation is associated with lower neurodevelopmental outcomes in a cohort of children growing up in profound adversity.6 We found that higher levels of sCD14 in sera was significantly associated with lower neurodevelopmental outcomes in all four domains tested. We also found in this study that IL-1β was significantly associated with lower cognitive, language, and social emotional development. Similarly, elevated levels of the acute phase reactant CRP were associated with lower developmental outcomes in all domains.