Growth Faltering is Associated With Altered Brain Functional Connectivity and Cognitive Outcomes In Urban Bangladeshi Children Exposed to Early Adversity

1. Height-for-age z-score was negatively associated with brain functional connectivity (FC), with FC serving as a mediating factor between child growth and future intellectual functioning in a sample of impoverished children.

Evidence Rating Level: 2 (Good)

Poverty and early childhood adversity are known risk factors for neurodevelopmental delays and chronic disorders. However, little research has been done on this population using neuroimaging techniques and behavioral assays. The objective of this cohort study was to examine associations between physical growth, brain functional connectivity and cognitive development among children using high-density EEG. The study recruited infants (n = 92) and toddlers (n = 118) living in an urban area of Bangladesh who were born at 34 weeks’ gestation or later, with no history of brain injury or neurological impairments or delays. Socioeconomic status (SES) was assessed via observation and questionnaires, and caregiving was assessed via interviews during EEG assessment. Investigators evaluated height-for-age z-score (HAZ) at three, four, five, and six months (for infant group) and 24, 30, and 36 months (for toddler group). HAZ were averaged across time points due to high correlationsEEG data was collected at six months for infants and 36 months for toddlers. Prevalence of stunting in infants and toddlers, defined as at least two SDs below the population mean, were 16.30% and 33.06%, respectively. Infants were placed into three categories: stunted (n = 39), middle HAZ (n = 39), and high HAZ (n = 40). Cognitive assessment was conducted with the Mullen Scales of Early Learning (MSEL) and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), though these tests are not normed for the Bangladeshi setting and warrant caution in interpretation. For six-month-old infants, average whole-brain FC varied across frequency bands with peaks in theta (mean = 5.68 [1.23]), while the peak for 36-month-old toddlers was found in the alpha band (mean = 7.67 [1.48]). Peak frequency of global FC at 36 months was lower for stunted children than non-stunted toddlers, though no significant associations were discovered. No associations were found with SES, HAZ, or other covariates with whole-brain FC in the infant cohort. For the toddler group, however, 24-36-month HAZ was negatively correlated with theta (β  = -0.267, p = 0.14) and beta FC (β  = -0.298, p = 0.005). Whole-brain FC in these bands were also found to be stronger in stunted than non-stunted children. WPPSI-III scores at 36 months were negatively associated with brain FC in theta (β = -0.179, p = 0.042) and alpha (β = -0.202, p = 0.020) bands, but no associations were found between MSEL scores and FC. The model of theta band was acceptable (χ2(1) = 0.277, p = 0.599; CFI = 1.0; SRMR = 0.009; RMSEA < 0.001) while the model of beta was a poor fit. Longitudinal path analysis determined that HAZ was negatively associated with 36-month FC in beta and theta bands, both of which were also negatively associated with 48-month intellectual functioning. Indirect effects of HAZ on cognitive performance through brain FC in beta (95% CI of standardized estimate 0.03 to 0.13) and theta (95% CI of standardized estimate 0.001 to 0.105). This study is the first to suggest that brain FC may play a critical, mediating role in cognitive impairments resulting from early adversity.

Click to read the study in BMC Medicine

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