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™).

Examining the relationship between psychosocial adversity and inhibitory control: an fMRI study of children growing up in extreme poverty.

Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the development of inhibitory control has been based on children in higher resource environments, and little is known how growing up in a low resource setting might exacerbate the link between inhibitory control and health outcomes. In this context we collected fMRI data during a Go/No-Go inhibitory control task and PA variables for 68 children 5 to 7 years of age living in Dhaka, Bangladesh, an area with a high prevalence of PA. The children's mothers completed behavioral questionnaires to assess the child's PA and their own PA. Whole-brain activation underlying inhibitory control was examined using the No-Go versus Go contrast, and associations with PA variables were assessed using whole-brain regressions. Childhood neglect was associated with weaker activation in the right posterior cingulate, whereas greater family conflict, economic stress, and maternal PA factors were associated with greater activation in the left medial frontal gyrus, right superior and middle frontal gyrus, and left cingulate gyrus. These data suggest that neural networks supporting inhibitory control processes may vary as a function of exposure to different types of PA, particularly between those related to threat and deprivation. Furthermore, increased activation in children with greater PA may serve as a compensatory mechanism, allowing them to maintain similar behavioral task performance.

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.

Neural correlates of inhibitory control and associations with cognitive outcomes in Bangladeshi children exposed to early adversities.

There is strong support for the view that children growing up in low-income homes typically evince poorer performance on tests of inhibitory control compared to those growing up in higher income homes. Unfortunately, the vast majority of the work documenting this association has been conducted in high-income countries. It is not yet known whether the mechanisms found to mediate this association would generalize to children in low- and middle-income countries, where the risks of exposure to extreme poverty and a wide range of both biological and psychosocial hazards may be greater. We examined relations among early adversity, neural correlates of inhibitory control, and cognitive outcomes in 154 5-year-old children living in Dhaka, Bangladesh, an area with a high prevalence of poverty. Participants completed a go/no-go task assessing inhibitory control and their behavioral and event-related potential responses were assessed. Cortical source analysis was performed. We collected measures of poverty, malnutrition, maternal mental health, psychosocial adversity, and cognitive skills. Supporting studies in high-income countries, children in this sample exhibited a longer N2 latency and higher P3 amplitude to the no-go versus go condition. Unexpectedly, children had a more pronounced N2 amplitude during go trials than no-go trials. The N2 latency was related to their behavioral accuracy on the go/no-go task. The P3 mean amplitude, behavioral accuracy, and reaction time during the task were all associated with intelligence-quotient (IQ) scores. Children who experienced higher levels of psychosocial adversity had lower accuracy on the task and lower IQ scores.

Small Intestine Bacterial Overgrowth in Bangladeshi Infants Is Associated With Growth Stunting in a Longitudinal Cohort.

INTRODUCTION: Small intestine bacterial overgrowth (SIBO) is common in children from low-income countries and has been cross-sectionally associated with growth stunting. We sought to determine whether SIBO was associated with poor growth and neurodevelopmental in a longitudinal analysis. METHODS: We measured SIBO by glucose hydrogen breath test (GHBT) at 18, 52, 78, and 104 weeks of life in a prospective longitudinal birth cohort of Bangladeshi children. Sociodemographic information and measures of enteric inflammation were analyzed as covariates. Diarrheal samples were tested for enteropathogens using polymerase chain reaction. Regression models were created using standardized mean GHBT area under the H2 curve (AUC) to determine associations with linear growth and cognitive, language, and motor scores on the Bayley-III Scales of Infant and Toddler Development at 2 years. We also investigated associations between GHBT AUC and enteropathogen exposure. RESULTS: A 1-ppm increase in standardized mean GHBT AUC was associated with a 0.01-SD decrease in length-for-age Z score (P = 0.03) and a 0.11-point decrease in Bayley language score (P = 0.05) at 2 years of age in adjusted analysis. Enteroaggregative Escherichia coli, Enteropathogenic Escherichia coli, Giardia, and Enterocytozoon bieneusi were associated with increased GHBT AUC, whereas Clostridium difficile, norovirus GI, sapovirus, rotavirus, and Cryptosporidium were associated with decreased GHBT AUC. None were consistent across all 4 time points. DISCUSSION: SIBO in the first 2 years of life is associated with growth stunting and decreased language ability in Bangladeshi infants and may represent a modifiable risk factor in poor growth and neurodevelopment in low-income countries.

Brain morphometry and diminished physical growth in Bangladeshi children growing up in extreme poverty: A longitudinal study.

Diminished physical growth is a common marker of malnutrition and it affects approximately 200 million children worldwide. Despite its importance and prevalence, it is not clear whether diminished growth relates to brain development and general cognitive ability. Further, diminished growth is more common in areas of extreme poverty, raising the possibility that it may mediate previously shown links between socioeconomic status (SES) and brain structure. To address these gaps, 79 children growing up in an extremely poor, urban area of Bangladesh underwent MRI at age six years. Structural brain images were submitted to Mindboggle software, a Docker-compliant and high-reproducibility tool for tissue segmentation and regional estimations of volume, surface area, cortical thickness, sulcal depth, and mean curvature. Diminished growth predicted brain morphometry and mediated the link between SES and brain morphometry most consistently for subcortical and white matter subcortical volumes. Meanwhile, brain volume in left pallidum and right ventral diencephalon mediated the relationship between diminished growth and full-scale IQ. These findings offer malnutrition as one possible pathway through which SES affects brain development and general cognitive ability in areas of extreme poverty.

Diarrheal Pathogens Associated With Growth and Neurodevelopment.

BACKGROUND: Diarrheal pathogens have been associated with linear growth deficits. The effect of diarrheal pathogens on growth is likely due to inflammation, which also adversely affects neurodevelopment. We hypothesized that diarrheagenic pathogens would be negatively associated with both growth and neurodevelopment. METHODS: We conducted a longitudinal birth cohort study of 250 children with diarrheal surveillance and measured pathogen burden in diarrheal samples using quantitative polymerase chain reaction. Pathogen attributable fraction estimates of diarrhea over the first 2 years of life, corrected for socioeconomic variables, were used to predict both growth and scores on the Bayley-III Scales of Infant and Toddler Development. RESULTS: One hundred eighty children were analyzed for growth and 162 for neurodevelopmental outcomes. Rotavirus, Campylobacter, and Shigella were the leading causes of diarrhea in year 1 while Shigella, Campylobacter, and heat-stable toxin-producing enterotoxigenic Escherichia coli were the leading causes in year 2. Norovirus was the only pathogen associated with length-for-age z score at 24 months and was positively associated (regression coefficient [RC], 0.42 [95% confidence interval {CI}, .04 to .80]). Norovirus (RC, 2.46 [95% CI, .05 to 4.87]) was also positively associated with cognitive scores while sapovirus (RC, -2.64 [95% CI, -4.80 to -.48]) and typical enteropathogenic E. coli (RC, -4.14 [95% CI, -8.02 to -.27]) were inversely associated. No pathogens were associated with language or motor scores. Significant maternal, socioeconomic, and perinatal predictors were identified for both growth and neurodevelopment. CONCLUSIONS: Maternal, prenatal, and socioeconomic factors were common predictors of growth and neurodevelopment. Only a limited number of diarrheal pathogens were associated with these outcomes.