Adverse Child Outcomes Research Articles

Progress in understanding climate change's effects on children and youth.

Climate change remains a major threat to the health and well-being of children globally. This article reviews the myriad health effects of climate change on children throughout their lives and discusses ways in which the general pediatrician can be an advocate for climate solutions. Rising atmospheric temperatures, increased air pollution, and destabilized weather patterns all lead to adverse health outcomes for children and adverse obstetric outcomes. However, the impact of climate change is not evenly distributed. Children living in poverty are more likely to be adversely impacted by the changing climate. Ongoing and emerging research suggests that children are particularly vulnerable to the effects of climate change. The primary care pediatrician is encouraged to see this irrefutable evidence as a call to action for advocacy on behalf of our patients and the planet.

Growing up unequal: Objective and subjective economic disparities and authoritarian parenting

BackgroundAlthough there is evidence of economic disparities in parents' financial and time investments in children, little existing empirical work has considered the disparities in authoritarian parenting, a risk for child maltreatment. Similarly, existing research has largely focused on the role of objective markers of socioeconomic status (SES), although perceived subjective social status (SSS) may be equally powerful in shaping disparities in parenting behaviors. DataThis article draws on 30 years of General Social Survey data to examine the association between objective socioeconomic status and subjective social status and parents' endorsement of authoritarian parenting practices. MethodsWe model the association between parents' SES and SSS and approval of authoritarian parenting practices estimated with odds ratios from logistic regressions and examine parental race as a potential moderator. ResultsWe find that SES and SSS are both associated with increased odds of endorsing authoritarian parenting, that SSS-based disparities are independent of SES, and that white parents' parenting may be more influenced by both SES and SSS than Black parents' parenting. ConclusionsThis work provides evidence that SES not only drives gaps in parental investments in children, but also gaps in their endorsement of authoritarian parenting. This is important because authoritarian parenting is not only directly associated with adverse outcomes for children, but is also associated with an increased risk for child maltreatment. It also expands the existing literature by showing that subjective measures of social status are important and distinct from objective measures of SES, and that these associations vary by race.

Cognitive function and behavioral problems in children born to mothers with preeclampsia: an Indian study

ABSTRACT Studies from high-income countries report associations of preeclampsia (PE) with reduced cognitive function and adverse behavioural outcomes in children. We examined these associations in Indian children aged 5-7 years. Children of mothers with PE (n=74) and without PE (non-PE; n=234) were recruited at delivery at Bharati Hospital, Pune, India. The cognitive performance was assessed using 3 core tests from the Kaufman Assessment Battery and additional tests including Verbal fluency, Kohs block design, and Coding A (from Wechsler Intelligence Scale for Children). The parent-reported Strengths and Difficulties Questionnaire (SDQ) was used to assess children’s behavioral characteristics. Scores were compared between children from PE and non-PE groups, and associations analyzed further using regression models, adjusted for potential confounders. After adjusting for age, sex, socio-economic status and maternal education, children of PE mothers had lower Kohs block design scores (adjusted odds ratio per score category 0.57, [95% CI 0.34-0.96] p=0.034; 0.62 [95%CI (0.36, 1.07), p=0.09 on further adjustment for birth weight and gestation) compared to children of mothers without PE. In the SDQ, there was a lower prevalence of abnormal ‘conduct problem’ scores in PE group than non-PE group (OR=0.33, 95% CI 0.13-0.83, p=0.018, in the fully adjusted model); there were no differences for other behavioral domains. This preliminary study in Indian children suggests that fetal exposure to maternal PE may have an adverse impact on visuo-spatial performance but does not adversely affect behavior. Further studies with larger sample sizes are essential to understand effects of maternal PE on cognitive/behavioral outcomes in children.

Parent priorities for research and communication concerning childhood outcomes following preterm birth.

Background: Children born preterm (before 37 weeks of gestation) are at risk for several adverse childhood outcomes. Parent priorities for research into these outcomes, and preferences for receiving information about these risks, have not previously been established. Here we report the results of an online survey designed to understand parent priorities for research and their preferences for receiving information about childhood outcomes. Methods: An online survey was circulated through social media and was completed by 148 parents of preterm children between the ages of 0 and 12 years from around the United Kingdom (UK). Survey questions were in the form of rating scale, multiple choice, ranking or open-ended free text questions. Descriptive analysis was applied to the quantitative data. Illustrative quotes were extracted from the qualitative free text data and a subset of these questions were analysed using framework analysis. Results: Parent priorities for research centre around identification of factors which can protect against or improve adverse cognitive or developmental outcomes. The majority of parents would prefer for communication to begin within the first year of the child's life. Parents reported a knowledge gap among health visitors, early years educators and schools. Conclusions: In order to align with parent preferences, research should prioritise identification of protective factors and the development of effective interventions to improve outcomes. Training for health visitors and educational professionals could improve the experiences of families and children.

High EVI1 Expression Predicts Adverse Outcomes in Children With De Novo Acute Myeloid Leukemia

BackgroundA high ecotropic viral integration site 1 (EVI1) expression (EVI1 high) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of EVI1 high in pediatric AML. This study aimed to examine the biological and prognostic significance of EVI1 high in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.MethodsA diagnostic assay was developed to determine the relative EVI1 expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for EVI1 high, n = 348 for EVI1 low).ResultsEVI1high was found in 9.0% of all 421 pediatric patients with de novo AML. EVI1 high was predominantly found in acute megakaryoblastic leukemia (FAB M7), MLL rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), CEBPA, NPM1, or C-KIT mutations. In the univariate Cox regression analysis, EVI1 high had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, p = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, EVI1 high was an independent prognostic factor for the OS (HR = 2.447, p = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, EVI1 high was an independent adverse predictor of the OS and EFS of patients with MLL rearrangements (univariate analysis: HR = 9.921 and 7.253, both p < 0.001; multivariate analysis: HR = 7.186 and 7.315, p = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided EVI1 high patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% vs. 50.8%, p = 0.26; 5-year OS: 65.9% vs. 54.8%, p = 0.45).ConclusionIt could be concluded that EVI1 high can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with EVI1 high AML can benefit from HSCT in CR1 needs to be researched further.

COVID-19 Pandemic and Reduced Physical Activity: Is There an Impact on Healthy and Asthmatic Children?

Physical activity (PA) has been seen to improve asthma symptoms, lung function, and quality of life, as well as to reduce airway inflammation and bronchial responsiveness. As a consequence of the COVID-19 pandemic, the minimal amount of PA recommended by the World Health Organization—i.e., about 60 min/day of moderate-to-high intensity—is difficult to achieve for many children, particularly those living in urban areas. Short-term changes in PA because of the COVID-19 pandemic may become habitual, increasing the risk of adverse asthma outcomes in children. Indeed, prolonged home confinement during the COVID-19 pandemic reduces PA levels and increases sedentary behaviors, possibly impairing immune system function and increasing susceptibility to inflammatory diseases. However, there is limited evidence regarding the effects of lockdown due to COVID-19 on PA and sedentary behaviors in asthmatic children. Given that children stay longer indoors, indoor air pollution represents a major issue to consider during home confinement. This narrative review aims to summarize the available evidence about the impact of decreased PA and increased sedentary behaviors on children with asthma during the COVID-19 pandemic. In addition, strategies for supporting PA in children with asthma during the COVID-19 pandemic are suggested, also looking at the issue of indoor air quality.

Iron Deficiency Anemia in Pregnancy.

Anemia is defined as a low red blood cell count, a low hematocrit, or a low hemoglobin concentration. In pregnancy, a hemoglobin concentration of less than 11.0 g/dL in the first trimester and less than 10.5 or 11.0 g/dL in the second or third trimester (depending on the guideline used) is considered anemia. Anemia is the most common hematologic abnormality in pregnancy. Maternal anemia is associated with adverse fetal, neonatal and childhood outcomes, but causality is not established. Maternal anemia increases the likelihood of transfusion at delivery. Besides hemodilution, iron deficiency is the most common cause of anemia in pregnancy. The American College of Obstetricians and Gynecologists recommends screening for anemia with a complete blood count in the first trimester and again at 24 0/7 to 28 6/7 weeks of gestation. Mild anemia, with a hemoglobin of 10.0 g/dL or higher and a mildly low or normal mean corpuscular volume (MCV) is likely iron deficiency anemia. A trial of oral iron can be both diagnostic and therapeutic. Mild anemia with a very low MCV, macrocytic anemia, moderate anemia (hemoglobin 7.0-9.9 g/dL) or severe anemia (hemoglobin 4.0-6.9 g/dL) requires further investigation. Once a diagnosis of iron deficiency anemia is confirmed, first-line treatment is oral iron. New evidence suggests that intermittent dosing is as effective as daily or twice-daily dosing with fewer side effects. For patients with iron deficiency anemia who cannot tolerate, cannot absorb, or do not respond to oral iron, intravenous iron is preferred. With contemporary formulations, allergic reactions are rare.

Parent priorities for research and communication concerning childhood outcomes following preterm birth

Background: Children born preterm (before 37 weeks of gestation) are at risk for several adverse childhood outcomes. Parent priorities for research into these outcomes, and preferences for receiving information about these risks, have not previously been established. Here we report the results of an online survey designed to understand parent priorities for research and their preferences for receiving information about childhood outcomes. Methods: An online survey was circulated through social media and was completed by 148 parents of preterm children between the ages of 0 and 12 years from around the United Kingdom (UK). Survey questions were in the form of rating scale, multiple choice, ranking or open-ended free text questions. Descriptive analysis was applied to the quantitative data. Illustrative quotes were extracted from the qualitative free text data and a subset of these questions were analysed using framework analysis. Results: Parent priorities for research centre around identification of factors which can protect against or improve adverse cognitive or developmental outcomes. The majority of parents would prefer for communication to begin within the first year of the child’s life. Parents reported a knowledge gap among health visitors, early years educators and schools. Conclusions: In order to align with parent preferences, research should prioritise identification of protective factors and the development of effective interventions to improve outcomes. Training for health visitors and educational professionals could improve the experiences of families and children.

Very Preterm Early Motor Repertoire and Neurodevelopmental Outcomes at 8 Years.

Children born very preterm (<32 weeks' gestation) have more neurodevelopmental problems compared with term-born peers. Aberrant fidgety movements (FMs) are associated with adverse motor outcomes in children born very preterm. However, associations of aberrant FMs combined with additional movements and postures to give a motor optimality score-revised (MOS-R) with school-aged cognitive and motor outcomes are unclear. Our aim with this study was to determine those associations. Of 118 infants born <30 weeks' gestation recruited into a randomized controlled trial of early intervention, 97 had a general movements assessment at 3 months' corrected age and were eligible for this study. Early motor repertoire including FMs and MOS-R were scored from videos of infant's spontaneous movement at 3 months' corrected age. At 8 years' corrected age, cognitive and motor performances were evaluated. Associations of early FMs and MOS-R with outcomes at 8 years were determined using linear regression. Seventy-eight (80%) infants with early motor repertoire data had neurodevelopmental assessments at 8 years. A higher MOS-R, and favorable components of the individual subscales of the MOS-R, including the presence of normal FMs, were associated with better performance for general cognition, attention, working memory, executive function and motor function at 8 years; eg, presence of normal FMs was associated with a 21.6 points higher general conceptual ability score (95% confidence interval: 12.8-30.5; P < .001) compared with absent FMs. Favorable early motor repertoire of infants born <30 weeks is strongly associated with improved cognitive and motor performance at 8 years.

WITHDRAWN: Effects of socioeconomic gradient and children’s cognitive development

Many schools raise children with significantly lower levels of academic achievement who flourish in disadvantaged communities. Early in children's lives, even before kindergarten, these educational shortcomings arise and develop through childhood. This research observed some directions that affect cognitive development in early years to 5 years using family socioeconomic position (SEP). In this research, upbringing, fitness, wellbeing, and family relationships are examined and referred to as the early childhood care system. Such factors have been rarely tested in massive datasets together to preclude a systematic scientific study of their position as predictors and effects of adverse child outcomes. The study aims to explore the cognitive development framework (CDF) for early cognizance and shows that several sources have effects: earnings, childcare, the home atmosphere, and the neighborhood of single parenthood. As part of this research, researchers looked at the cognitive development framework (CDF) for early cognizance. They found that several factors impacted, including incomes, daycare, home environment, and neighborhood. The income seems to be a significant independent indicator of the gradient of cognitive growth. The most critical influence is the effect of “length of exposure” and “intensity” based on poverty depth. The whole research enables us to recognize the relative strengths of the most potent health consequences, giving valuable information into how they're being tackled. The CDF enhance outcomes of successful children cognitive development ratio of 97.1%, high-performance analysis ratio of 98.5%, improve reliability ratio of 92.1%, improve probability ratio of 98.7%, knowledge retention ratio of 93.1%, improve learning ability skill ratio of 91.9%, prediction ratio of 98.5%, and enhance critical thinking ratio of 94.2% when compared to research methods. • Enhance critical thinking ratio of 94.2% when compared to research methods • Explores the early cognition cognitive development framework CDF • Socio-economic status in the early to 5 years of family socioeconomic position

Associations between ambient fine particulate matter and child respiratory infection: The role of particulate matter source composition in Dhaka, Bangladesh

Air pollution in the form of fine particulate matter (PM2.5) has been linked to adverse respiratory outcomes in children. However, the magnitude of this association in South Asia and sources of PM2.5 that drive adverse health effects are largely unknown. This study evaluates associations between short-term variation in ambient PM2.5 and incidence of pneumonia and upper respiratory infections among children in Dhaka, Bangladesh. We also perform an exploratory analysis of the PM2.5 source composition that is most strongly associated with health endpoints. We leveraged data from health surveillance of children less than five years of age between 2005 and 2014 in Kamalapur, Bangladesh, including daily physician-confirmed diagnoses of pneumonia and upper respiratory infection. Twice-weekly source-apportioned ambient PM2.5 measurements were obtained for the same period, and Poisson regression adjusted for time-varying covariates was used to estimate lagged associations between ambient PM2.5 and respiratory infection. We use complementary matching and stratification approaches to evaluate whether these associations vary across PM2.5 source composition. Total PM2.5 mass was associated with a modest increase in incidence of pneumonia, with a peak effect size two days after exposure (rate ratio = 1.032; 95% confidence interval = 1.008–1.056). We did not identify a significant association between PM2.5 and upper respiratory infection. Stratified and matching analyses suggested this association was stronger among days when ambient PM2.5 had a higher mass percent associated with brick kiln and fugitive lead emissions.: This study suggests that elevated ambient PM2.5 contributes to increased incidence of child pneumonia in urban Dhaka, and that this relationship varies among days with different source composition of PM2.5.

Diagnostic and treatment intervals are not associated with survival in rhabdomyosarcoma: A Cancer in Young People in Canada study.

Delay in diagnosis and treatment initiation can be associated with adverse outcomes in children with cancer. Diagnostic interval (DI) is defined as the time between the date of first health care contact for symptoms related to cancer to the date of cancer diagnosis, and treatment interval (TI) is defined as interval between the definitive cancer diagnosis and cancer treatment initiation. We aimed to determine the predictors of DI and TI in children with rhabdomyosarcoma (RMS) and their association with event-free survival (EFS) and overall survival (OS). Using the Cancer in Young People in Canada (CYP-C) national population-based database, we conducted a retrospective cohort study of children (0-14.99years) newly diagnosed with RMS between 2001 and 2015 in Canada. Quantile regression was used to assess the predictors of DI and TI, and Cox regression was used to determine if these intervals were associated with EFS and OS. Median DI and TI were 16.5days (interquartile range [IQR] 6.0-38.0) and 5days (IQR 0-12), respectively. DI and TI were not significantly associated with age at diagnosis, sex, race, tumor site, stage or histology, treatment region, distance from treatment center, income quintile or diagnosis year (all p>.05). DI and TI were not associated with EFS (DI: hazard ratio [HR] 1.00, 95% CI 0.96-1.05, p=.871; TI: HR 1.03, 95% CI 1.00-1.05, p=.053) or OS (DI: HR 0.99, 95% CI 0.94-1.05, p=.797; TI: HR 1.02, 95% CI 0.99-1.05, p=.155). In the publicly funded Canadian health care system, DI and TI did not affect the survival of children with RMS.

Trajectories of perinatal depressive symptoms in the context of the COVID-19 pandemic.

This study sought to advance understanding of the potential long‐term consequences of the COVID‐19 pandemic for child development by characterizing trajectories of maternal perinatal depression, a common and significant risk factor for adverse child outcomes. Data came from 393 women (86% White, 8% Latina; mean age = 33.51 years) recruited during pregnancy (n = 247; mean gestational age = 22.94 weeks) or during the first year postpartum (n = 146; mean child age = 4.50 months; 55% female). Rates of depression appear elevated, relative to published reports and to a pre‐pandemic comparison group (N = 155). This study also provides evidence for subgroups of individuals who differ in their depressive symptom trajectories over the perinatal period. Subgroup membership was related to differences in maternal social support, but not to child birth outcomes.

Longitudinal analysis of DNA methylation in relation to gestational perfluoroalkyl substance exposure: An epigenome-wide association study

BACKGROUND AND AIM: Alterations to DNA methylation may underlie the association between gestational exposure to perfluoroalkyl substances (PFAS) and adverse health outcomes in children. However, few studies have examined the association between gestational PFAS exposure and DNA methylation, and no studies have repeated DNA methylation data across childhood. We examined associations between gestational PFAS exposure and repeated measures of offspring peripheral leukocyte DNA methylation among 266 mother-child pairs enrolled in the HOME Study (Cincinnati, OH). METHODS: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers at ~16 weeks gestation. We measured DNA methylation at delivery (cord blood) and age 12 years using the Illumina HumanMethylation EPIC BeadChip. We analyzed the associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using generalized estimating equations. Visit by PFAS interaction terms were used to test the stability of these differences across time. We performed Gene Ontology (GO) enrichment analysis to identify significant biological pathways. RESULTS:A total of 35 loci were significantly associated with PFAS (false discovery rate, q 0.05). Among the 5 loci for PFOS, 10 for PFOA, 7 for PFHxS, and 13 for PFNA (q 0.01), none overlapped. These loci mapped to genes (e.g., AGAP1, HPSE2, HABP2, RNF13, RADIL, and TMEM56) that are associated with cancers, cardiovascular disease, and cognitive function. We found little evidence that associations between PFAS and DNA methylation changed over time. The most significant GO pathways included homophilic cell adhesion, cell-cell adhesion and integral component of plasma membrane. CONCLUSIONS:Using longitudinal data, we identified loci associated with PFAS that have not been reported. Several loci were in genes linked to PFAS-associated health outcomes. Future studies are needed to confirm our findings and examine whether DNA methylation mediates associations between gestational PFAS exposure and offspring health. KEYWORDS: PFAS, Epigenomics, Biomarkers of exposure, Environmental epidemiology

Mixed Metals Exposure and Cognitive Function in Bangladeshi Adolescents

BACKGROUND AND AIM: Over 57 million Bangladeshis face environmental exposure to arsenic (As), cadmium (Cd), manganese (Mn), and lead (Pb). These metals have been linked to adverse neurocognitive outcomes in adults and children, though effects in adolescents are not fully characterized; additionally, previous studies have shown selenium (Se) to have protective effects against these exposures. This study aims to examine the associations between exposure to a metal mixture (As, Cd, Mn, Pb, Se) and the outcome of cognitive function in Bangladeshi adolescents. METHODS: The Metals, Arsenic, & Nutrition in Adolescents Study (MANAS) is a cross-sectional study of 572 Bangladeshi adolescents aged 14-26 years. Venous blood was collected for measurement of As, Cd, Mn, Pb, and Se levels. An abbreviated Cambridge Neuropsychological Test Automated Battery (CANTAB) was administered, with subtests assessing cognitive function tasks. Linear regression models and Bayesian kernel machine regression (BKMR) were employed to examine associations between individual metals, the overall metals mixture, and cognitive function as measured by CABTAB subtests. RESULTS:Linear regression revealed As (B=-2.40) and Mn (B=-5.31) to be negatively associated with Spatial Working Memory (p0.05). Negative associations were seen between Cd and Spatial Recognition Memory (SRM) (B=-2.77, p0.05), and between Pb and Delayed Match to Sample (DMS), a measure of visual recognition and memory (B=-3.67, p0.05). A positive association was seen between Se and Spatial Span Length (B=0.92, p0.05). BKMR showed no overall effect of the metals mixture, but indicated that Pb was negatively associated with DMS and that Cd was negatively associated with SRM. Se was positively associated with Planning, Reaction Time, and Spatial Span. Posterior inclusion probability consistently rated Se as the most important mixture member. CONCLUSIONS:Overall, Se had a protective effect for cognitive outcomes, whereas Mn and As were linked to poorer working memory and Cd and Pb were linked to poorer visual recognition and memory. KEYWORDS: Heavy metals, Mixed metal exposures, Cognitive function, Neurotoxicology, Adolescent cognitive neurotoxicology, Mixtures analysis

Birth Outcomes Associated with Paternal Polybrominated and Polychlorinated Biphenyl Exposure

BACKGROUND AND AIM: In 1973, polybrominated biphenyl (PBB) flame retardant was shipped to Michigan feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds, and is now led by a community-academic partnership. PBB exposure is associated with decreased DNA methylation in sperm regulatory elements controlling imprinted genes, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB), an analogue of PBB. To further understand the impact of paternal exposures on children, we analyzed paternal PBB and PCB levels and premature birth and low birthweight. METHODS: We investigated the outcomes of birthweight and gestational age of offspring whose fathers enrolled in the PBB Registry and provided serum to measure PBB and PCB concentrations. Birth outcomes were determined by linking paternal PBB records to the Michigan vital records. Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks respectively, and paternal PBB and PCB levels were divided into tertiles. Offspring birthweight and gestational age were modeled against paternal PBB and PCB serum concentrations using log-risk regression, adjusting for clustering, paternal health and lifestyle factors, and offspring sex. RESULTS:Elevated PBB and PCB levels are associated with an increased risk of low offspring birthweight, but not preterm birth. Fathers in the middle and upper PBB and PCB tertiles illustrated increased risk ratios (RR) for low offspring birthweight, RR=1.42 (CI=0.93-2.17) and RR=1.47 (CI=1.03-2.10) for PBB, and RR=1.73 (CI=1.12-2.67) and RR=1.42 (CI=0.84-2.41) for PCB respectively. Elevated PBB and PCB levels illustrated no significant increased risk for preterm birth in the middle and upper tertiles. CONCLUSIONS:These findings suggest increased paternal PBB and PCB levels may negatively impact offspring birthweight. KEYWORDS: Endocrine disrupting chemicals, Birth outcomes, Children's environmental health, Community outreach, Environmental epidemiology

Ambient air pollution exposure during pregnancy and cardio-metabolic markers in cord blood: The Healthy Start study

BACKGROUND AND AIM: Prenatal air pollution exposure has been associated with adverse cardiometabolic outcomes in childhood. It is unknown whether evidence of metabolic disruption associated with air pollution may be identified at birth. We estimated associations between maternal residential exposure to air pollution during pregnancy and metabolic and lipid biomarkers in cord blood collected at delivery. METHODS: This study included 812 mother-infant pairs enrolled in the prospective, Colorado-based Healthy Start study (2009-2014). Using inverse-distance-weighted interpolation of data obtained from stationary monitors, we estimated daily particulate matter ≤2.5 micrometers (PM2.5) and ozone (O3) concentrations at participant residences. Daily estimates were averaged by trimester, full pregnancy, and the 7- and 30- days prior to delivery. Outcomes were cord blood concentrations of glucose, insulin, leptin, total and high-density lipoprotein cholesterol, free fatty acids, and triglycerides. Glucose-insulin ratio was calculated as an indirect measure of insulin sensitivity. We used multiple linear regression to estimate associations between PM2.5 and O3 and cord blood metabolic and lipid biomarkers. Covariates included maternal, infant, and meteorological characteristics. RESULTS:Higher O3 exposure, during both recent and longer-term exposure periods during pregnancy, was consistently associated with higher insulin and lower glucose-insulin ratio in cord blood. For example, an interquartile range increase in full pregnancy O3 (6.3 ppb) was associated with a 0.12 log-µIU/ml (95% confidence interval: 0.03, 0.21) increase in cord blood insulin, after adjusting for covariates. There was limited evidence supporting positive associations between PM2.5 and leptin and O3 and total cholesterol. There were inverse associations between PM2.5 and triglycerides, during certain periods of pregnancy. CONCLUSIONS:Prenatal air pollution exposure was associated with cardiometabolic biomarkers in cord blood, most notably for O3 and insulin. Future studies should examine whether these changes persist into childhood and their implications on offspring health. KEYWORDS: prenatal exposure, air pollution, lipids, metabolism, neonate

Association between prenatal metal exposure and respiratory symptoms in childhood

BACKGROUND AND AIM: Arsenic, manganese, and lead have been cross-sectionally associated with adverse respiratory outcomes in childhood but there is limited data on their combined effects starting in utero. Our aim was to examine associations between prenatal lead, arsenic, and manganese exposure and respiratory symptoms in childhood. METHODS: We assessed 637 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) birth cohort in Mexico City. Blood manganese (BMn), arsenic (BAs), and lead (BPb) were measured in mothers at 2nd trimester. Ever wheeze, current wheeze and asthma diagnosis was based on the caregiver’s answers (yes/no) from the International Study of Asthma and Allergies in Childhood (ISAAC) survey applied at 4-5 and 6-7 years old. Covariates included maternal education, maternal asthma status, maternal age at enrollment, child’s sex, and prenatal environmental tobacco smoke exposure. A logistic mixed model regression was generated to simultaneously assess the association between prenatal metals and ever wheeze, current wheeze, and asthma diagnosis longitudinally across both the 4-5 and 6-7 year study visits. RESULTS:The mean ± standard deviation for log-transformed BMn, BPb, and BAs at 2nd trimester were 0.14 µg/dL ± 0.15, 0.48 µg/dL ± 0.27, and -1.11 µg/dL ± 0.19, respectively. In the adjusted model, BPb (Odds Ratio (OR): 1.95, 95% CI: 1.04-3.66) and BAs (OR: 3.44, 95% CI: 1.05-11.34) at 2nd trimester were associated with increased odds of ever wheeze and current wheeze, respectively. BMn at 2nd trimester (OR: 0.05, 95% CI: 0.01-0.27) was negatively associated with current wheeze. CONCLUSIONS:Prenatal exposure to arsenic and lead was associated with higher odds of ever and current wheeze while manganese was negatively associated with odds of current wheeze in childhood. These findings underscore the need to consider prenatal metal exposure, including low levels of exposure, in the study of respiratory diseases. KEYWORDS: Respiratory outcomes, Heavy metals, Allergies, Asthma, Children's environmental health

Predictors of long-term neurodevelopmental outcomes of children born extremely preterm

Children born extremely preterm (<28 weeks’ gestation) are at high risk of a range of adverse neurodevelopmental outcomes in later childhood compared with their peers born at term, including cognitive, motor, and behavioral difficulties. These difficulties can be associated with poorer academic achievement and health outcomes at school age. In this review, we discuss several predictors in the newborn period of early childhood neurodevelopmental outcomes including perinatal risk factors, neuroimaging findings and neurobehavioral assessments, along with social and environmental influences for children born extremely preterm. Given the complexity of predicting long-term outcomes in children born extremely preterm, we recommend multi-disciplinary teams in clinical practice to assist in determining an individual child's risk for adverse long-term outcomes and need for referral to targeted intervention, based upon their risk.

Role of endocrine disrupting chemicals in children's neurodevelopment

Environmental stressors, like endocrine disrupting chemicals (EDC), are considered important contributors to the increased rates of neurodevelopmental dysfunctions. Considering the cumulative research on adverse neurodevelopmental effects associated with prenatal exposure to EDC, the purpose of this study was to review the available limited literature about the effects of postnatal exposure to EDC on child neurodevelopment and behaviour. Despite widespread children's exposure to EDC, there are a limited number of epidemiological studies on the association of this exposure with neurodevelopmental disorders, in particular in the postnatal period. The available research suggests that postnatal EDC exposure is related to adverse neurobehavioral outcomes in children; however the underlying mechanisms of action remain unclear. Timing of exposure is a key factor determining potential neurodevelopmental consequences, hence studying the impact of multiple EDC co-exposure in different vulnerable life periods could guide the identification of sensitive subpopulations. Most of the reviewed studies did not take into account sex differences in the EDC effects on children neurodevelopment. We believe that the inclusion of sex in the study design should be considered as the role of EDC on children neurodevelopment are likely sex-specific and should be taken into consideration when determining susceptibility and potential mechanisms of action.