RESUMO
Anthropometric indicators, including stunting, underweight, and wasting, have previously been associated with poor neurocognitive outcomes. This link may exist because malnutrition and infection, which are known to affect height and weight, also impact brain structure according to animal models. However, a relationship between anthropometric indicators and brain structural measures has not been tested yet, perhaps because stunting, underweight, and wasting are uncommon in higher-resource settings. Further, with diminished anthropometric growth prevalent in low-resource settings, where biological and psychosocial hazards are most severe, one might expect additional links between measures of poverty, anthropometry, and brain structure. To begin to examine these relationships, we conducted an MRI study in 2-3-month-old infants growing up in the extremely impoverished urban setting of Dhaka, Bangladesh. The sample size was relatively small because the challenges of investigating infant brain structure in a low-resource setting needed to be realized and resolved before introducing a larger cohort. Initially, fifty-four infants underwent T1 sequences using 3T MRI, and resulting structural images were segmented into gray and white matter maps, which were carefully evaluated for accurate tissue labeling by a pediatric neuroradiologist. Gray and white matter volumes from 29 infants (79 â± â10 days-of-age; F/M â= â12/17), whose segmentations were of relatively high quality, were submitted to semi-partial correlation analyses with stunting, underweight, and wasting, which were measured using height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) scores. Positive semi-partial correlations (after adjusting for chronological age and sex and correcting for multiple comparisons) were observed between white matter volume and HAZ and WAZ; however, WHZ was not correlated with any measure of brain volume. No associations were observed between income-to-needs or maternal education and brain volumetric measures, suggesting that measures of poverty were not associated with total brain tissue volume in this sample. Overall, these results provide the first link between diminished anthropometric growth and white matter volume in infancy. Challenges of conducting a developmental neuroimaging study in a low-resource country are also described.
Assuntos
Estatura , Peso Corporal , Desenvolvimento Infantil , Substância Cinzenta/anatomia & histologia , Pobreza , Substância Branca/anatomia & histologia , Bangladesh , Estatura/fisiologia , Peso Corporal/fisiologia , Desenvolvimento Infantil/fisiologia , Estudos Transversais , Feminino , Substância Cinzenta/diagnóstico por imagem , Transtornos do Crescimento/diagnóstico por imagem , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Projetos Piloto , Magreza/diagnóstico por imagem , Síndrome de Emaciação/diagnóstico por imagem , Substância Branca/diagnóstico por imagemRESUMO
BACKGROUND: Event-related potentials (ERP) data are widely used in brain studies that measure brain responses to specific stimuli using electroencephalogram (EEG) with multiple electrodes. Previous ERP data analyses haven't accounted for the structured correlation among observations in ERP data from multiple electrodes, and therefore ignored the electrode-specific information and variation among the electrodes on the scalp. Our objective was to evaluate the impact of early adversity on brain connectivity by identifying risk factors and early-stage biomarkers associated with the ERP responses while properly accounting for structured correlation. METHODS: In this study, we extend a penalized generalized estimating equation (PGEE) method to accommodate structured correlation of ERPs that accounts for electrode-specific data and to enable group selection, such that grouped covariates can be evaluated together for their association with brain development in a birth cohort of urban-dwelling Bangladeshi children. The primary ERP responses of interest in our study are N290 amplitude and the difference in N290 amplitude. RESULTS: The selected early-stage biomarkers associated with the N290 responses are representatives of enteric inflammation (days of diarrhea, MIP1b, retinol binding protein (RBP), Zinc, myeloperoxidase (MPO), calprotectin, and neopterin), systemic inflammation (IL-5, IL-10, ferritin, C Reactive Protein (CRP)), socioeconomic status (household expenditure), maternal health (mother height) and sanitation (water treatment). CONCLUSIONS: Our proposed group penalized GEE estimator with structured correlation matrix can properly model the complex ERP data and simultaneously identify informative biomarkers associated with such brain connectivity. The selected early-stage biomarkers offer a potential explanation for the adversity of neurocognitive development in low-income countries and facilitate early identification of infants at risk, as well as potential pathways for intervention. TRIAL REGISTRATION: The related clinical study was retrospectively registered with https://doi.org/ClinicalTrials.gov , identifier NCT01375647, on June 3, 2011.
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Eletroencefalografia , Potenciais Evocados , Biomarcadores , Encéfalo , Criança , Humanos , Lactente , Projetos de PesquisaRESUMO
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 (Nâ¯=â¯125) and at 6, 18, 40, 53, and 104 weeks for the older (toddler) cohort (Nâ¯=â¯120). Event-related potentials (ERPs) were also recorded separately for the two cohorts: at 6 months for the younger cohort (Nâ¯=â¯48) and at 36 months for the older cohort (Nâ¯=â¯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 (Nâ¯=â¯98) and with Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 48 months for the older cohort (Nâ¯=â¯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.
Assuntos
Atenção/fisiologia , Córtex Cerebral/fisiopatologia , Inflamação/fisiopatologia , Bangladesh , Proteína C-Reativa/metabolismo , Pré-Escolar , Doença Crônica , Potenciais Evocados/fisiologia , Feminino , Humanos , Lactente , MasculinoRESUMO
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.
Assuntos
Cognição , Transtornos do Crescimento/fisiopatologia , Pobreza , Bangladesh , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Feminino , Transtornos do Crescimento/etiologia , Humanos , Lactente , Modelos Lineares , Masculino , Organização Mundial da SaúdeRESUMO
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.
Assuntos
Desenvolvimento Infantil , Saúde Global , Saúde Mental , Bangladesh , Criança , Pré-Escolar , Cognição , Feminino , Humanos , Masculino , Fatores de RiscoRESUMO
Children living in low-resource settings are at risk for failing to reach their developmental potential. While the behavioral outcomes of growing up in such settings are well-known, the neural mechanisms underpinning poor outcomes have not been well elucidated, particularly in the context of low- and middle-income countries. In this study, we measure brain metabolic responses to social and nonsocial stimuli in a cohort of 6- and 36-month-old Bangladeshi children. Study participants in both cohorts lived in an urban slum and were exposed to a broad range of adversity early in life including extreme poverty, malnutrition, recurrent infections, and low maternal education. We observed brain regions that responded selectively to social stimuli in both ages indicating that these specialized brain responses are online from an early age. We additionally show that the magnitude of the socially selective response is related to maternal education, maternal stress, and the caregiving environment. Ultimately our results suggest that a variety of psychosocial hazards have a measurable relationship with the developing social brain.
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Encéfalo/metabolismo , Cognição/fisiologia , Processos Mentais/fisiologia , Pobreza/psicologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Bangladesh , Mapeamento Encefálico , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , MasculinoRESUMO
Childhood poverty has been associated with structural and functional alterations in the developing brain. However, poverty does not alter brain development directly, but acts through associated biological or psychosocial risk factors (e.g. malnutrition, family conflict). Yet few studies have investigated risk factors in the context of infant neurodevelopment, and none have done so in low-resource settings such as Bangladesh, where children are exposed to multiple, severe biological and psychosocial hazards. In this feasibility and pilot study, usable resting-state fMRI data were acquired in infants from extremely poor (n = 16) and (relatively) more affluent (n = 16) families in Dhaka, Bangladesh. Whole-brain intrinsic functional connectivity (iFC) was estimated using bilateral seeds in the amygdala, where iFC has shown susceptibility to early life stress, and in sensory areas, which have exhibited less susceptibility to early life hazards. Biological and psychosocial risk factors were examined for associations with iFC. Three resting-state networks were identified in within-group brain maps: medial temporal/striatal, visual, and auditory networks. Infants from extremely poor families compared with those from more affluent families exhibited greater (i.e. less negative) iFC in precuneus for amygdala seeds; however, no group differences in iFC were observed for sensory area seeds. Height-for-age, a proxy for malnutrition/infection, was not associated with amygdala/precuneus iFC, whereas prenatal family conflict was positively correlated. Findings suggest that it is feasible to conduct infant fMRI studies in low-resource settings. Challenges and practical steps for successful implementations are discussed.
Assuntos
Experiências Adversas da Infância/estatística & dados numéricos , Tonsila do Cerebelo/fisiologia , Mapeamento Encefálico/métodos , Lobo Parietal/fisiologia , Carência Psicossocial , Tonsila do Cerebelo/crescimento & desenvolvimento , Bangladesh , Conflito Familiar/psicologia , Estudos de Viabilidade , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Lobo Parietal/crescimento & desenvolvimento , Projetos Piloto , Pobreza , Gravidez , Fatores de RiscoRESUMO
For more than 20 years, Japanese HEIs have focused on ICT integration as a means to help students develop twenty-first century skills. However, effective ICT integration is only possible if faculty have an awareness of the possibilities of technology and see the value of a student-centered approach to teaching. This study was conducted to assess the current state of these qualities at a specific Japanese HEI for the purpose of facilitating meaningful professional development. A survey covering ICT usage, barriers to its use, and reasons for ICT integration was distributed to all full-time faculty at this institution. Results showed that ICT integration was superficial and indicative of teacher-centered pedagogy. Another key finding was identifying the perception that ICT is seen as more of a tool to increase teacher productivity than to improve student learning outcomes. Major obstacles to ICT integration were identified as a lack of technical support and a lack of professional development. Results indicate that planning for professional development that will lead to meaningful change in practice requires more than just providing support for how and what faculty can do with ICT. Faculty need to see the value of reclassifying their views regarding their role in higher education. Supplementary Information: The online version contains supplementary material available at 10.1007/s43545-022-00454-0.
RESUMO
Studies of infants growing up in high-income countries reveal developmental changes in electroencephalography (EEG) power whereby socioeconomic factors - specifically, low SES and low income - are associated with lower EEG power in infants aged newborn to nine months. In the current paper we explore relationships of spectral EEG power across three regions (frontal, central, and parietal) and four frequency bands (theta, alpha, beta, and gamma) with socioeconomic and psychosocial factors in a cohort of nâ¯=â¯160 6-month-old infants and nâ¯=â¯187 36-month-old children living in Dhaka, Bangladesh. Household wealth is assessed as a multi-dimensional composite score encompassing income, assets, and housing materials. Psychosocial factors include maternal perceived stress and family caregiving activities. Among the 6-month-old infants we do not observe any association of household wealth or psychosocial factors with EEG power. Among the 36-month-old children, we find that household wealth is negatively associated absolute power in the beta and gamma bands across frontal, central, and parietal electrodes. We also find that higher reports of maternal perceived stress are associated with more absolute theta power in frontal and central regions in the 36-month-old children. The finding of a negative relationship of household wealth with beta and gamma power in 36-month-old children differs from findings previously observed in infants in high-income countries. Overall, findings suggest that children's environment continues to influence the development of EEG oscillations and provide support for the utility of EEG to quantify developmental effects of early life experiences on neural functional outcomes in low income countries.
Assuntos
Encéfalo , Bangladesh , Pré-Escolar , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Pobreza , Fatores SocioeconômicosRESUMO
Observational data suggest maternal handwashing with soap prevents neonatal mortality. We tested the impact of a chlorhexidine-based waterless hand cleansing promotion on the behavior of mothers and other household members. In rural Bangladesh in 2014, we randomized consenting pregnant women to chlorhexidine provision and hand cleansing promotion or standard practices. We compared hand cleansing with chlorhexidine or handwashing with soap before baby care, among mothers and household members in the two groups, and measured chlorhexidine use in the intervention arm. Chlorhexidine was observed in the baby's sleep space in 97% of 130 intervention homes, versus soap in 59% of 128 control homes. Hand cleansing before baby care was observed 5.6 times more frequently among mothers in the intervention arm than in the controls (95% CI = 4.0-7.7). Hand cleansing was significantly more frequently observed in the intervention arm among women other than the mother (RR = 10.9) and girls (RR = 37.0). Men and boys in the intervention arm cleansed hands before 29% and 44% of baby care events, respectively, compared with 0% in the control arm. The median number of grams consumed during the neonatal period was 176 (IQR = 95-305 g), about 7.8 g/day (IQR = 4.2-13.8 g). Promotion of waterless chlorhexidine increased hand cleansing behavior among mothers and other household members. Discrepancy between observed use and measured chlorhexidine consumption suggested courtesy bias in structured observations. A waterless hand cleanser may represent one component of the multimodal strategies to prevent neonatal infections in low-resource settings.
Assuntos
Anti-Infecciosos Locais/farmacologia , Clorexidina/farmacologia , Desinfecção das Mãos , Bangladesh , Demografia , Feminino , Mãos , Humanos , Recém-Nascido , Masculino , Mães , Gravidez , SabõesRESUMO
In this paper we explore the relationship between the Visual Evoked Potential (VEP), a component of the electroencephalogram elicited by visual stimuli, and cognitive functions in children growing up in an urban slum in Bangladesh. VEPs in response to pattern-reversing checkerboards were collected in 6 month-old-infants (n = 91) and 36-month-old children (n = 112). We examine variation in the amplitude and latency of the first positive component, the P1, of the VEP in relation to cognitive scores on the Mullen Scales of Early Learning and the Wechsler Preschool and Primary Scale of Intelligence. We also examine whether children's caregiving experiences prior to the neuro-cognitive assessment explain variation in the P1 of the VEP. We find that the P1 amplitude of the VEP is related to concurrent cognitive performance in each respective cohort. We also find that the P1 amplitude at 6 months is prospectively associated with cognitive outcomes at 27 months, and the P1 amplitude at 36 months is prospectively associated with children's IQ at 60 months. We find no associations between caregiving experiences and variation in the P1 of the VEP at 6 months, yet caregiving experience do explain variation in the P1 amplitude at 36 months. Caregiving experiences also explain variation in children's concurrent and prospective cognitive functioning. The VEP may be used as a biomarker to index the neurobiological embedding of early adversity, which in turn may impact children's cognitive functions.
Assuntos
Cognição/fisiologia , Neurônios/fisiologia , Bangladesh , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Potenciais Evocados Visuais , Feminino , Humanos , Lactente , Cuidado do Lactente , Testes de Inteligência , Masculino , Classe SocialRESUMO
In 2009, a common set of questions addressing handwashing behavior was introduced into nationally representative Demographic and Health Surveys (DHS) and Multiple Indicator Cluster Surveys (MICS), providing large amounts of comparable data from numerous countries worldwide. The objective of this analysis is to describe global handwashing patterns using two proxy indicators for handwashing behavior from 51 DHS and MICS surveys conducted in 2010-2013: availability of soap anywhere in the dwelling and access to a handwashing place with soap and water. Data were also examined across geographic regions, wealth quintiles, and rural versus urban settings. We found large disparities for both indicators across regions, and even among countries within the same World Health Organization region. Within countries, households in lower wealth quintiles and in rural areas were less likely to have soap anywhere in the dwelling and at designated handwashing locations than households in higher wealth quintiles and urban areas. In addition, disparities existed among various geographic regions within countries. This analysis demonstrates the need to promote access to handwashing materials and placement at handwashing locations in the dwelling, particularly in poorer, rural areas where children are more vulnerable to handwashing-preventable syndromes such as pneumonia and diarrhea.
Assuntos
Atitude Frente a Saúde , Desinfecção das Mãos , Comportamentos Relacionados com a Saúde , Inquéritos Epidemiológicos , Sabões , Demografia , Geografia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , População Urbana/estatística & dados numéricos , Abastecimento de ÁguaRESUMO
One-quarter of neonatal deaths are attributed to infections. Maternal handwashing with soap may prevent neonatal sepsis. We examined impact of intensive handwashing promotion on handwashing behavior of mothers of neonates. In Matlab, Bangladesh, we randomly allocated pregnant women at 28-32 weeks' gestation to intensive handwashing promotion or control. Behavior change communicators used a participatory approach to motivate maternal handwashing with soap and provided soap and handwashing stations. In the neonatal period, we observed soap and water at handwashing places and, at the end of the neonatal period, we estimated impact on maternal handwashing by structured observation. Among 253 women enrolled, intervention households were between 5.7 and 15.2 times as likely as control households to have soap and water present at the handwashing station in the baby's sleeping area. Intervention mothers washed hands with soap 4.1 times as frequently as controls (95% CI 2.55-6.59); handwashing with soap at recommended times was infrequent in both intervention (9%) and control (2%) groups. Intensively promoting handwashing with soap resulted in increased availability of soap and water at handwashing places, but only a modest increase in maternal handwashing with soap. Novel approaches to motivating handwashing behavior to protect newborns should be developed and evaluated.
Assuntos
Desinfecção das Mãos , Morte Perinatal/prevenção & controle , População Rural , Sabões , Adulto , Bangladesh/epidemiologia , Feminino , Humanos , Recém-Nascido , GravidezRESUMO
Melanocytic lesions, including Spitz nevi (SN), common benign nevi (CBN) and cutaneous metastatic melanoma (CMM), were analyzed for activating mutations in NRAS, HRAS and BRAF oncogenes, which induce cellular proliferation via the MAP kinase pathway. One of 22 (4.5%) SN tested showed an HRAS G61L mutation. Another lesion, a 'halo' SN, showed a BRAF V600E (T1796A) mutation. BRAF V600E mutations were found in two thirds (20/31) of CBN, while a further 19% (6/31) showed NRAS codon 61 mutations. One third of CMM (10/30) had various BRAF mutations of codon 600, and a further 6% (2/31) showed NRAS codon 61 mutations. Seventeen SN tested for loss of heterozygosity (LOH) at 9p and 10q regions, known to be frequently deleted in melanoma, showed LOH at the 9p loci D9S942 and IFNA. A further lesion was found with low-level microsatellite instability at one locus, D10S214. The low rate of RAS-RAF mutations (2/22, 9.1%) observed in SN suggests that these lesions harbor as yet undetected activating mutations in other components of the RAS-RAF-MEK-ERK-MAPK pathway. Germline DNA from members of 111 multiple-case melanoma families, representing a range of known (CDKN2A) and unknown predisposing gene defects, was analyzed for germline BRAF mutations, but none was found.