Multidimensional evaluation of the early emergence of executive function and development in Bangladeshi children using nutritional and psychosocial intervention: A randomized controlled trial protocol.

INTRODUCTION: Reversing malnutrition-induced impairment of cognition and emotional regulation is a critical global gap. We hypothesize that brain-targeted micronutrient supplemented nutritional rehabilitation in children with moderate acute malnutrition, followed by 2 years micronutrient supplementation will impact on the cognition and emotion regulation of these children. METHODS: The primary outcome of this prospective, randomized controlled trial is to study the development of executive functions (EFs) and emotion regulation (ER) in this cohort. Moderate acute malnourished (MAM; WLZ/WHZ <-2 and ≥-3 z-score, and/or 11.5 cm ≤ MUAC < 12.5cm; n = 140)children aged around one year (11m-13m) in Mirpur, Dhaka, Bangladesh will be randomized (1:1) to receive either locally produced Ready to Use Supplementary Food (RUSF) or Enhanced Ready to Use Supplementary Food (E-RUSF) until anthropometric recovery (WLZ/WHZ > -1SD), or for 3 months after enrollment (whichever is earlier). The randomized MAMs groups will be given either Small Quantity Lipid Based Nutrient Supplement (SQLNS) or Enhanced Small Quantity Lipid Based Nutrient Supplement (E-SQLNS), respectively until the end of the 2-year follow up period. Standard psychosocial stimulation will be provided to the MAMs intervention groups. Biological samples will be collected, anthropometric and neurocognitive assessments will be performed at 2 (22m-26m) and 3 (34m-38m) years of age. Two control groups will be recruited: 1), non-malnourished one-year (11m-13m) old children (WLZ/WHZ score>-1SD; n = 70); and 2) three-year (34m-38m) old children (n = 70) with untreated MAM (WHZ <-2 and ≥-3 z-score, and/or 11.5≤MUAC<12.5 cm). The 3-year-old MAM reference group will be assessed once and provided with 2 months of nutritional rehabilitation support (RUSF Nutriset's Plumpy'Sup™).

Association of psychosocial adversity and social information processing in children raised in a low-resource setting: an fNIRS study.

Social cognition skills and socioemotional development are compromised in children growing up in low SES contexts, however, the mechanisms underlying this association remain unknown. Exposure to psychosocial risk factors early in life alters the child's social milieu and in turn, could lead to atypical processing of social stimuli. In this study, we used functional Near Infrared Spectroscopy (fNIRS) to measure cortical responses to a social discrimination task in children raised in a low-resource setting at 6, 24, and 36 months. In addition, we assessed the relation between cortical responses to social and non-social information with psychosocial risk factors assessed using the Childhood Psychosocial Adversity Scale (CPAS). In line with previous findings, we observed specialization to social stimuli in cortical regions in all age groups. In addition, we found that risk factors were associated with social discrimination at 24 months (intimate partner violence and verbal abuse and family conflict) and 36 months (verbal abuse and family conflict and maternal depression) but not at 6 months. Overall, the results show that exposure to psychosocial adversity has more impact on social information processing in toddlerhood than earlier in infancy.

Growth faltering is associated with altered brain functional connectivity and cognitive outcomes in urban Bangladeshi children exposed to early adversity.

BACKGROUND: Stunting affects more than 161 million children worldwide and can compromise cognitive development beginning early in childhood. There is a paucity of research using neuroimaging tools in conjunction with sensitive behavioral assays in low-income settings, which has hindered researchers' ability to explain how stunting impacts brain and behavioral development. We employed high-density EEG to examine associations among children's physical growth, brain functional connectivity (FC), and cognitive development. METHODS: We recruited participants from an urban impoverished neighborhood in Dhaka, Bangladesh. One infant cohort consisted of 92 infants whose height (length) was measured at 3, 4.5, and 6 months; EEG data were collected at 6 months; and cognitive outcomes were assessed using the Mullen Scales of Early Learning at 27 months. A second, older cohort consisted of 118 children whose height was measured at 24, 30, and 36 months; EEG data were collected at 36 months; and Intelligence Quotient (IQ) scores were assessed at 48 months. Height-for-age (HAZ) z-scores were calculated based on the World Health Organization standard. EEG FC in different frequency bands was calculated in the cortical source space. Linear regression and longitudinal path analysis were conducted to test the associations between variables, as well as the indirect effect of child growth on cognitive outcomes via brain FC. RESULTS: In the older cohort, we found that HAZ was negatively related to brain FC in the theta and beta frequency bands, which in turn was negatively related to children's IQ score at 48 months. Longitudinal path analysis showed an indirect effect of HAZ on children's IQ via brain FC in both the theta and beta bands. There were no associations between HAZ and brain FC or cognitive outcomes in the infant cohort. CONCLUSIONS: The association observed between child growth and brain FC may reflect a broad deleterious effect of malnutrition on children's brain development. The mediation effect of FC on the relation between child growth and later IQ provides the first evidence suggesting that brain FC may serve as a neural pathway by which biological adversity impacts cognitive development.

Chronic inflammation is associated with neural responses to faces in bangladeshi children.

BACKGROUND: Early exposure to inflammation in childhood is increasingly recognized as one of the major factors that hinder millions of children worldwide from meeting their full developmental potential. The current study examined the association between systemic inflammation and children's neural responses to facial stimuli and explored if this activity mediated the relation between inflammation and cognitive outcomes. METHOD: Two separate cohorts of children living in an urban slum in Dhaka, Bangladesh who are at high-risk for sustained inflammation were recruited in this study. The concentration of C-reactive protein (CRP) in blood samples served as our index of inflammation. Blood samples were collected once at 18 weeks for the younger (infant) cohort (N = 125) and at 6, 18, 40, 53, and 104 weeks for the older (toddler) cohort (N = 120). Event-related potentials (ERPs) were also recorded separately for the two cohorts: at 6 months for the younger cohort (N = 48) and at 36 months for the older cohort (N = 93), using a face-oddball paradigm in which standard and oddball faces were presented. Cognitive outcomes were evaluated with Mullen Scales of Early Learning (MSEL) at 27 months for the younger cohort (N = 98) and with Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 48 months for the older cohort (N = 124). RESULTS: For the older toddler cohort, the P400 and Nc amplitude differences between the two types of stimuli were found to be associated with the frequency of elevated CRP such that more episodes of elevated CRP corresponded to smaller P400 and Nc differences between the two conditions. In addition, the P400 and Nc differences were both found to mediate the relation between inflammation and performance IQ scores. For the younger infant cohort, the participants showed differentiated N290 response to the two types of stimuli, but no association between the ERP response and CRP concentration was found. CONCLUSIONS: These findings suggest that chronic systemic inflammation has a long-term impact on children's brain functioning and cognitive development. The neural circuitries associated with social attention and recognition memory of faces may be potential pathways by which inflammation exerts its effect on cognitive development.

Cumulative psychosocial risk and early child development: validation and use of the Childhood Psychosocial Adversity Scale in global health research.

BACKGROUND: Evidence suggests that cumulative early psychosocial adversity can influence early child development (ECD). The Childhood Psychosocial Adversity Scale (CPAS) is a novel measure of cumulative risk designed for use in global ECD research. We describe its development and assess validity from its first application in Bangladesh, where it predicts cognitive development scores among young children. METHODS: Items were generated from literature review and qualitatively assessed for local relevance. Two-hundred and eighty-five mother-child dyads from an urban slum of Dhaka completed the CPAS at child ages 18, 24, 48, and/or 60 months. The CPAS was assessed for internal consistency, retest reliability, and convergent, incremental, and predictive validity. RESULTS: The CPAS includes subscales assessing child maltreatment, caregiver mental health, family conflict, domestic violence, and household/community psychosocial risks. In Bangladesh, subscales had good internal consistency (Cronbach's α > 0.70). Full-scale score had good 2-week test-retest reliability (intra-class correlation coefficient = 0.89; F(38,38) = 8.45, p < 0.001). Using multivariate regression, 48-month CPAS score significantly predicted 60-month intelligence quotient, accounting for more variance than socioeconomic status or malnutrition. CONCLUSIONS: The CPAS is a novel tool assessing cumulative childhood psychosocial risk. Evidence supports validity of its use in ECD research in Bangladesh, and ongoing work is applying it in additional countries.