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

ABSTRACT: 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.

SUBMITTER: Xie W

PROVIDER: S-EPMC6876085 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Xie Wanze W Jensen Sarah K G SKG Wade Mark M Kumar Swapna S Westerlund Alissa A Kakon Shahria H SH Haque Rashidul R Petri William A WA Nelson Charles A CA

BMC medicine 20191125 1

<h4>Background</h4>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 ( ...[more]

PMID: 31760950

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Project description:BACKGROUND:Prenatal cocaine exposure (PCE) is linked to addiction and obesity vulnerability. Neural responses to stressful and appetitive cues in adolescents with PCE versus those without have been differentially linked to substance-use initiation. However, no prior studies have assessed cue-reactivity responses among PCE adolescents using a connectivity-based approach. METHODS:Twenty-two PCE and 22 non-prenatally drug-exposed (NDE) age-, sex-, IQ- and BMI-matched adolescents participated in individualized guided imagery with appetitive (favorite-food), stressful and neutral-relaxing cue scripts during functional magnetic resonance imaging. Subjective favorite-food craving scores were collected before and after script exposure. A data-driven voxel-wise intrinsic connectivity distribution analysis was used to identify between-group differences and examine relationships with craving scores. RESULTS:A group-by-cue interaction effect identified a parietal lobe cluster where PCE versus NDE adolescents showed less connectivity during stressful and more connectivity during neutral-relaxing conditions. Follow-up seed-based connectivity analyses revealed that, among PCE adolescents, the parietal seed was positively connected to inferior parietal and sensory areas and negatively connected to corticolimbic during both stress and neutral-relaxing conditions. For NDE, greater parietal connectivity to parietal, cingulate and sensory areas and lesser parietal connectivity to medial prefrontal areas were found during stress compared to neutral-relaxing cueing. Craving scores inversely correlated with corticolimbic connectivity in PCE, but not NDE adolescents, during the favorite-food condition. CONCLUSIONS:Findings from this first data-driven intrinsic connectivity analysis of PCE influences on adolescent brain function indicate differences relating to PCE status and craving. These findings provide insight into the developmental impact of in utero drug exposure.

Project description:BackgroundThe prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction (PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.Methodology/principal findingsWe performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1-24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3-26.9), with a PAF of 59.5%.ConclusionsA significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.

Dataset Information

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

Publications

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

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