Abstract
Improving child cognition in impoverished countries is a public health priority. Yet, biological pathways and associated biomarkers of impaired cognition remain poorly understood and largely unknown, respectively. This study aimed to explore and quantify associations between functional plasma protein biomarkers and childhood intellectual test performance. We applied proteomics to quantify proteins in plasma samples of 249 rural Nepalese children, 6–8years of age who, 1year later at 7–9years of age, were administered the Universal Nonverbal Intelligence Test (UNIT). Among 751 plasma proteins quantified, 22 were associated with UNIT scores, passing a false discovery rate threshold of 5.0% (q<0.05). UNIT scores were higher by 2.3–9.2 points for every 50% increase in relative abundance of two insulin-like growth factor binding proteins (IGFBPs), six subclasses of apolipoprotein (Apo) and transthyretin, and lower by 4.0–15.3 points for each 50% increase in relative abundance of 13 proteins predominantly involved in inflammation. Among them, IGFBP-acid labile subunit, orosomucoid 1 (ORM1), Apo C-I, and pyruvate kinase isoenzymes M1/M2 jointly explained 37% of the variance in UNIT scores. After additional adjustment for height-for-age Z-score and household socio-economic status as indicators of long-term nutritional and social stress, associations with 6 proteins involved in inflammation, including ORM1, α-1-antichymotrypsin, reticulocalbin 1, and 3 components of the complement cascade, remained significant (q<0.05). Using untargeted proteomics, stable, constitutive facets of subclinical inflammation were associated with lower developmental test performance in this rural South Asian child population. Plasma proteomics may offer opportunities to identify functional, antecedent biomarkers of child cognitive development.
Highlights
As child survival improves (The United Nations, 2015), attention is turning to assessing and alleviating coexisting burdens of stunted growth and suboptimal cognition among children in low and middle income countries (Black et al, 2013; GranthamMcGregor et al, 2007)
Children had gained some weight and height, their nutritional status remained low and stable over the year with 35% stunted, 43% underweight, and 16% with a low body mass index (BMI) at both visits based on WHO criteria
Twenty-nine percent of children had an elevated plasma alpha-1acid glycoprotein (AGP), suggestive of prolonged inflammation, while 6% had a raised C-reactive protein (CRP), possibly reflecting more acute infection, and a rate that was comparable in magnitude those of lower respiratory infection (2%) and diarrhea (4%) in the past week
Summary
As child survival improves (The United Nations, 2015), attention is turning to assessing and alleviating coexisting burdens of stunted growth and suboptimal cognition among children in low and middle income countries (Black et al, 2013; GranthamMcGregor et al, 2007). Both conditions can be a consequence of undernutrition (Black et al, 2013; Walker et al, 2011) and share complexity and incomplete knowledge of their etiologies, challenging effective prevention (Gale, 2005).
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