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BACKGROUND: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population. METHODS: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile). RESULTS: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation. CONCLUSIONS: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age. IMPACT: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth.
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Lead is an established neurotoxicant, and it has known associations with adverse neurodevelopmental and reproductive outcomes. Exposure to lead at any level is unsafe, and the United States (US) has enacted various federal and state legislations to regulate lead levels in drinking water in K-12 schools and childcare facilities; however, no regulations exist for higher education settings. Upon the discovery of lead in drinking water fixtures in the University of North Carolina at Chapel Hill (UNC-CH) campus, a cross-campus water testing network and sampling plan was developed and deployed. The campaign was based on the US Environmental Protection Agency's (EPA) 3Ts (Training, Testing, and Taking Action) guidance. The seven-month campaign involved 5954 tests on 3825 drinking water fixtures across 265 buildings. A total of 502 (8.43%) tests showed lead above the limit of detection (1 part per billion, ppb), which represented 422 (11.03%) fixtures. Fewer than 1.5% of the tests were above the EPA action level for public water systems (15 ppb). In conclusion, systematic testing of all the fixtures across campus was required to identify localized contamination, and each entity in the cross-campus network undertook necessary roles to generate a successful testing campaign. UNC-CH established preventative measures to test drinking water fixtures every three years, which provide a framework for other higher education institutions in responding to lead contamination.
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Água Potável , Chumbo , Chumbo/análise , Água Potável/análise , Água Potável/química , Universidades , North Carolina , Poluentes Químicos da Água/análise , Humanos , Monitoramento Ambiental , Estados Unidos , United States Environmental Protection AgencyRESUMO
Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipidsâmetabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.
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Fluorocarbonos , Lipídeos , Humanos , Feminino , Gravidez , Lipídeos/sangue , Fluorocarbonos/sangue , Saúde da Criança , Estudos de Coortes , Estudos Transversais , Adulto , Poluentes Ambientais/sangue , Exposição Ambiental , Exposição Materna , CriançaRESUMO
Wildfire events are becoming increasingly common across many areas of the United States, including North Carolina (NC). Wildfires can cause immediate damage to properties, and wildfire smoke conditions can harm the overall health of exposed communities. It is critical to identify communities at increased risk of wildfire events, particularly in areas with that have sociodemographic disparities and low socioeconomic status (SES) that may exacerbate incurred impacts of wildfire events. This study set out to: (1) characterize the distribution of wildfire risk across NC; (2) implement integrative cluster analyses to identify regions that contain communities with increased vulnerability to the impacts of wildfire events due to sociodemographic characteristics; (3) provide summary-level statistics of populations with highest wildfire risk, highlighting SES and housing cost factors; and (4) disseminate wildfire risk information via our online web application, ENVIROSCAN. Wildfire hazard potential (WHP) indices were organized at the census tract-level, and distributions were analyzed for spatial autocorrelation via global and local Moran's tests. Sociodemographic characteristics were analyzed via k-means analysis to identify clusters with distinct SES patterns to characterize regions of similar sociodemographic/socioeconomic disparities. These SES groupings were overlayed with housing and wildfire risk profiles to establish patterns of risk across NC. Resulting geospatial analyses identified areas largely in Southeastern NC with high risk of wildfires that were significantly correlated with neighboring regions with high WHP, highlighting adjacent regions of high risk for future wildfire events. Cluster-based analysis of SES factors resulted in three groups of regions categorized through distinct SES profiling; two of these clusters (Clusters 2 and 3) contained indicators of high SES vulnerability. Cluster 2 contained a higher percentage of younger (<5 years), non-white, Hispanic and/or Latino residents; while Cluster 3 had the highest mean WHP and was characterized by a higher percentage of non-white residents, poverty, and less than a high school education. Counties of particular SES and WHP-combined vulnerability include those with majority non-white residents, tribal communities, and below poverty level households largely located in Southeastern NC. WHP values per census tract were dispersed to the public via the ENVIROSCAN application, alongside other environmentally-relevant data.
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Populações Vulneráveis , Incêndios Florestais , North Carolina/epidemiologia , Humanos , Incêndios Florestais/estatística & dados numéricos , Populações Vulneráveis/estatística & dados numéricos , Fatores Socioeconômicos , Análise por Conglomerados , Justiça SocialRESUMO
OBJECTIVE: To evaluate the association between prenatal maternal health and socioeconomic status (SES) and health-related quality of life (QoL) among 10-year-old children born extremely preterm. DESIGN/ METHODS: Retrospective analysis of the Extremely Low Gestational Age Newborns (ELGAN) Study cohort of infants born < 28 weeks gestational age. QoL was assessed at 10 years of age using the Pediatric Quality of Life Inventory. Multivariate regression models were used for analyses. RESULTS: Of 1198 participants who survived until 10 years of age, 889 (72.2%) were evaluated. Lower maternal age, lack of college education; receipt of public insurance and Supplemental Nutrition Assistance Program (SNAP) were associated with lower QoL scores. Specific maternal health factors were also associated with lower child QoL scores. CONCLUSIONS: Specific, potentially modifiable, maternal health and social factors are associated with lower scores on a measure of parent-reported child QoL across multiple domains for children born extremely preterm.
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Lactente Extremamente Prematuro , Qualidade de Vida , Humanos , Feminino , Masculino , Criança , Estudos Retrospectivos , Recém-Nascido , Idade Materna , Idade Gestacional , Análise Multivariada , Adulto , Classe Social , Saúde Materna , Fatores SocioeconômicosRESUMO
PURPOSE OF REVIEW: We summarize the recent literature investigating exposure to four nonchemical stressors (financial stress, racism, psychosocial stress, and trauma) and DNA methylation, miRNA expression, and mRNA expression. We also highlight the relationships between these epigenetic changes and six critical perinatal outcomes (preterm birth, low birth weight, preeclampsia, gestational diabetes, childhood allergic disease, and childhood neurocognition). RECENT FINDINGS: Multiple studies have found financial stress, psychosocial stress, and trauma to be associated with DNA methylation and/or miRNA and mRNA expression. Fewer studies have investigated the effects of racism. The majority of studies assessed epigenetic or genomic changes in maternal blood, cord blood, or placenta. Several studies included multi-OMIC assessments in which DNA methylation and/or miRNA expression were associated with gene expression. There is strong evidence for the role of epigenetics in driving the health outcomes considered. A total of 22 biomarkers, including numerous HPA axis genes, were identified to be epigenetically altered by both stressors and outcomes. Epigenetic changes related to inflammation, the immune and endocrine systems, and cell growth and survival were highlighted across numerous studies. Maternal exposure to nonchemical stressors is associated with epigenetic and/or genomic changes in a tissue-specific manner among inflammatory, immune, endocrine, and cell growth-related pathways, which may act as mediating pathways to perinatal health outcomes. Future research can test the mediating role of the specific biomarkers identified as linked with both stressors and outcomes. Understanding underlying epigenetic mechanisms altered by nonchemical stressors can provide a better understanding of how chemical and nonchemical exposures interact.
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Metilação de DNA , Epigênese Genética , MicroRNAs , Estresse Psicológico , Humanos , Gravidez , Feminino , Recém-Nascido , Resultado da Gravidez , Nascimento PrematuroRESUMO
OBJECTIVE: To evaluate associations between change in weight z score after neonatal intensive care unit (NICU) discharge and neurodevelopmental outcomes and obesity at 12-48 months of age among individuals born very preterm. STUDY DESIGN: This secondary analysis used data from infants born very preterm participating in the Environmental influences on Child Health Outcomes cohort (n = 1400). Growth during infancy was calculated as change in weight z score between NICU discharge and follow-up at a mean of 27 months of age. Very low weight gain was defined as a change in weight z score <-1.67; very high weight gain was a change in weight z score >1.67. Neurodevelopmental outcomes included the Bayley Scales of Infant and Toddler Development, Child Behavior Checklist 1.5-5 years, and Modified Checklist for Autism in Toddlers. Multivariable linear regression was used to estimate associations between increase in weight z score and neurodevelopmental outcomes. RESULTS: Very low weight gain between NICU discharge and follow-up (experienced by 6.4% of participants) was associated with lower scores on cognitive (adjusted mean difference: -4.26; 95% CI: -8.55, -0.04) and language (adjusted mean difference: -4.80; 95% CI: -9.70, -0.11) assessments. Very high weight gain (experienced by 13.6% of participants) was associated with an increased obesity risk (adjusted relative risk: 6.20; 95% CI: 3.99, 9.66) but not with neurodevelopmental outcomes. CONCLUSIONS: Very high weight gain in the first 12-48 months after NICU discharge was associated with a higher risk of obesity at follow-up; very low weight gain was associated with lower scores on cognitive and language assessments.
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Desenvolvimento Infantil , Aumento de Peso , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Recém-Nascido , Desenvolvimento Infantil/fisiologia , Obesidade Infantil/epidemiologia , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Estudos de Coortes , Seguimentos , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologiaRESUMO
PURPOSE: To evaluate sex differences in autistic traits in youth born extremely preterm (EP; 23-27 weeks) who were later diagnosed with autism spectrum disorder (ASD) at 10-years. METHOD: A longitudinal cohort design from the Extremely Low Gestational Age Newborn Study (ELGAN) followed N = 857 EP infants from birth through 10-years. EP infants later diagnosed with ASD (N = 61, 20 females) participated in the study. Group differences were evaluated via inferential and Bayesian statistics (values > 1 suggest evidence for alternate hypothesis) on ASD screeners (M-CHAT at 2-years, SCQ and SRS-2 at 10-years), and gold-standard diagnostic measures (ADOS-2, ADI-R) at 10-years. RESULTS: Males scored significantly higher than females on measures of Social Affect from the ADOS-2, t(34.27)=-2.20, BF10 = 2.33, and measures of Repetitive and Restricted Behaviors from the ADI-R, t(40.52)=-2.85, BF10 = 5.26. Bayesian estimates suggested marginal evidence for sex differences in Nonverbal Communication, t(30.66)=-1.81, BF10 = 1.25, and Verbal Communication, t(24.64)=-1.89, BF10 = 1.39, from the ADI-R, wherein males scored higher than females. No statistically significant sex differences were identified on any of the ASD screeners at 2 (M-CHAT) or 10 years (SCQ). No significant sex differences were observed on any subscales of the SRS at 10 years. CONCLUSIONS: EP autistic males present with more autistic traits than EP autistic females on gold-standard diagnostic measures of autism at 10-years of age, despite not presenting with higher autistic traits on screeners at either age. These results align with sex differences observed in full-term, autistic youth. These results suggest ASD screeners may under identify autism in EP youth, particularly females.
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Background: Reducing healthcare disparities among children is extremely important given the potential impact of these disparities on long-term health-related quality of life (HRQL). Race and parental socioeconomic status (SES) are associated with child HRQL, but these associations have not been studied in infants born extremely preterm (EP), a population at increased risk for physical, cognitive, and psychosocial impairments. Achieving health equity for infants born EP across their life course requires identifying the impact of racism and SES on HRQL. Objective: We aimed to evaluate the association between self-reported maternal race, SES factors, and HRQL among 10-year-old children born EP. Design/methods: Participants were identified from an ongoing multicenter prospective longitudinal study of Extremely Low Gestational Age Newborns (ELGAN Study), born between 2002 and 2004, and evaluated at 10 years of age using the Pediatric quality of life (QoL) Inventory completed by their parent or guardian, assessing physical, emotional, social, school, and total (composite) QoL domains. Multivariable regression models were used to evaluate the relationship between QoL scores and self-identified maternal race, adjusting for SES factors (education level, marital status, and public insurance). Results: Of 1,198 study participants who were alive at 10 years of age, 863 (72.0%) were evaluated at 10 years of age. Differences in mean 10-year QoL scores across racial groups were observed and were significant on univariate analysis. However, these associations attenuated when adjusted for the marital status, public insurance status, and education status of mothers. A comparison of children with English as the primary language spoken at home vs. any other language revealed a significant difference only in school QoL, in which non-English language was associated with more favorable school QoL scores. Conclusions: Among 10-year-old children born EP, differences in parent-reported QoL were associated with maternal SES factors but not with race. Our results suggest that interventions designed to improve the SES of mothers may enhance the QoL of children born EP. Furthermore, these results underscore that race is a social construct, rather than a biological variable, as we work toward greater equity in care provision.
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BACKGROUND: Bronchopulmonary dysplasia (BPD), a common morbidity among very preterm infants, is associated with chronic disease and neurodevelopmental impairments. A hypothesized mechanism for these outcomes lies in altered glucocorticoid (GC) activity. We hypothesized that BPD and its treatments may result in epigenetic differences in the hypothalamic-pituitary-adrenal (HPA) axis, which is modulated by GC, and could be ascertained using an established GC risk score and DNA methylation (DNAm) of HPA axis genes. METHODS: DNAm was quantified from buccal tissue (ECHO-NOVI) and from neonatal blood spots (ELGAN ECHO) via the EPIC microarray. Prenatal maternal characteristics, pregnancy complication, and neonatal medical complication data were collected from medical record review and maternal interviews. RESULTS: The GC score was not associated with steroid exposure or BPD. However, six HPA genes involved in stress response regulation demonstrated differential methylation with antenatal steroid exposure; two CpGs within FKBP5 and POMC were differentially methylated with BPD severity. These findings were sex-specific in both cohorts; males had greater magnitude of differential methylation within these genes. CONCLUSIONS: These findings suggest that BPD severity and antenatal steroids are associated with DNAm at some HPA genes in very preterm infants and the effects appear to be sex-, tissue-, and age-specific. IMPACT: This study addresses bronchopulmonary dysplasia (BPD), an important health outcome among preterm neonates, and interrogates a commonly studied pathway, the hypothalamic-pituitary-adrenal (HPA) axis. The combination of BPD, the HPA axis, and epigenetic markers has not been previously reported. In this study, we found that BPD itself was not associated with epigenetic responses in the HPA axis in infants born very preterm; however, antenatal treatment with steroids was associated with epigenetic responses.
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The corona virus disease (COVID-19) pandemic disrupted daily life worldwide, and its impact on child well-being remains a major concern. Neighborhood characteristics affect child well-being, but how these associations were affected by the pandemic is not well understood. We analyzed data from 1039 children enrolled in the Environmental influences on Child Health Outcomes Program whose well-being was assessed using the Patient-Reported Outcomes Measurement Information System Global Health questionnaire and linked these data to American Community Survey (ACS) data to evaluate the impacts of neighborhood characteristics on child well-being before and during the pandemic. We estimated the associations between more than 400 ACS variables and child well-being t-scores stratified by race/ethnicity (non-Hispanic white vs. all other races and ethnicities) and the timing of outcome data assessment (pre-vs. during the pandemic). Network graphs were used to visualize the associations between ACS variables and child well-being t-scores. The number of ACS variables associated with well-being t-scores decreased during the pandemic period. Comparing non-Hispanic white with other racial/ethnic groups during the pandemic, different ACS variables were associated with child well-being. Multiple ACS variables representing census tract-level housing conditions and neighborhood racial composition were associated with lower well-being t-scores among non-Hispanic white children during the pandemic, while higher percentage of Hispanic residents and higher percentage of adults working as essential workers in census tracts were associated with lower well-being t-scores among non-white children during the same study period. Our study provides insights into the associations between neighborhood characteristics and child well-being, and how the COVID-19 pandemic affected this relationship.
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COVID-19 , Saúde da Criança , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , COVID-19/epidemiologia , Estudos Transversais , Etnicidade/estatística & dados numéricos , Características da Vizinhança , Pandemias , Estados Unidos/epidemiologia , Grupos Raciais/estatística & dados numéricosRESUMO
There is considerable evidence that prenatal lead exposure is detrimental to child cognitive and socio-emotional development. Further evidence suggests that the effects of prenatal lead on developmental outcomes may be conditional upon exposure to social stressors, such as maternal depression and low socioeconomic status. However, no studies have examined associations between these co-occurring stressors during pregnancy and neonatal brain volumes. Leveraging a sample of 101 mother-infant dyads followed beginning in mid-pregnancy, we examined the main effects of prenatal urinary lead levels on neonatal lateralized brain volumes (left and right hippocampus, amygdala, cerebellum, frontal lobes) and total gray matter. We additionally tested for moderations between lead and depressive symptoms and between lead and family income relative to the federal poverty level (FPL) on the same neurodevelopmental outcomes. Analyses of main effects indicated that prenatal lead was significantly (ps < 0.05) associated with reduced right and left amygdala volumes (ßs = -0.23- -0.20). The testing and probing of cross-product interaction terms using simple slopes indicated that the negative effect of lead on the left amygdala was conditional upon mothers having low depressive symptoms or high income relative to the FPL. We interpret the results in the context of trajectories of prenatal and postnatal brain development and susceptibility to low levels of prenatal lead in the context of other social stressors.
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Depressão , Efeitos Tardios da Exposição Pré-Natal , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Encéfalo , Depressão/complicações , Chumbo/toxicidade , Mães/psicologiaRESUMO
The placenta is a mixture of cell types, which may regulate maternal-fetal transfer of exogenous chemicals or become altered in response to exposures. We leveraged placental DNA methylation to characterize major constituent cell types and applied compositional data analysis to test associations with non-essential metal(loid)s measured in paired umbilical cord tissue (N = 158). Higher proportions of syncytiotrophoblasts were associated with lower arsenic, whereas higher proportions of Hofbauer cells were associated with higher cadmium concentrations in umbilical cords. These findings suggest that placental cellular composition influences amounts of metal(loid)s transferred to the fetus or that prenatal exposures alter the placental cellular makeup.