PON1 is a multifunctional enzyme involved in oxidative stress and detoxification of some organophosphate (OP) pesticides. It has been associated with nervous system diseases like Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, and autism. We previously found that PON1 susceptible genotypes were associated with lower IQ scores in children. Epigenetic marks, such as DNA methylation, can regulate gene expression. Yet, data on whether DNA methylation may influence the relationship between PON1 levels and neurobehavior are limited. In this study, we used Illumina 450K and EPIC BeadChip arrays to assess PON1 DNA methylation in blood specimens collected from children (n = 238) at birth (cord blood) and age 7 years and examined their relationship with cognitive outcomes. The Wechsler Intelligence Scale for Children was used to assess Full Scale IQ and four composite measures (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed Indexes) in 7-year-old children. We observed a consistent yet nonsignificant inverse relationship of methylation at several CpG sites close to the PON1 transcription start site with Full Scale IQ and other composite measures of cognition. We also found an inverse relationship between cord blood methylation at cg15887283 with working memory and a positive association of 7-year-old methylation at cg22798737 with processing speed, independent of OP exposure. However, none of the associations remained significant after accounting for multiple comparisons. This study provides some evidence of the role DNA methylation may play in the known relationship between PON1 and neurobehavior in children, however it appears to be only suggestive and warrants additional research.

Epigenetic mechanisms have emerged as an important pathway through which environmental exposures can affect health through the regulation of gene expression without changes in DNA sequence: microRNAs (miRNAs) are short non-coding RNAs that target protein-coding mRNAs, leading to post-transcriptional repression. They are involved in important physiologic processes, but little is known about how miRNA expression may change with age in children. We used an nCounter miRNA assay to assess the expression of 43 miRNAs in buffy coat samples collected from newborns (n = 121) and 7-year-old (n = 142) children. We identified 36 miRNAs that were differentially expressed between newborns and 7-year-olds after controlling for blood cell composition. Using pathway analysis, we found that differentially expressed miRNAs targeted genes enriched for processes related to post-translational modifications, metabolism, and immune response. Our study found that unlike adults, where miRNA expression levels in peripheral blood may decrease with age, expression levels of most miRNAs increased from birth to mid-childhood. This may be reflective of the role miRNAs may play in the highly coordinated mechanisms regulating genes involved in children's development. Furthermore, it will be important to adjust for both age and blood cell composition in future pediatric studies of miRNA expression in blood.

Purpose

Youth are vulnerable to poor mental health outcomes during emerging adulthood. This study examined COVID-19 pandemic effects among young Latino adults and changes in anxiety and depressive symptoms.

Methods

Using data from 309 individuals, predominantly of Mexican origin, we examined anxiety and depressive symptoms (before and during COVID) to determine whether mental health worsened during this period. We also examined associations between specific pandemic-related stressors and mental health. Analyses used paired T-tests and linear regressions. Participant sex was included as a moderator. We corrected for multiple comparisons using the Benjamini-Hochberg method.

Results

During the 2-year time period, depressive symptoms increased while anxiety symptoms decreased. There were no significant stressor by sex interactions; however, exploratory analyses signaled that pandemic-related stressors had stronger mental health effects for young women.

Discussion

Young adults' depressive and anxiety symptoms changed during the pandemic, and pandemic-related stressors were associated with increases in mental health symptoms.

Introduction

Maternal adverse childhood experiences have been linked to a variety of negative health outcomes in young children; however, young adults and, specifically, young adult Latinos have been vastly understudied. This study investigates the intergenerational pathway between maternal adverse childhood experiences and behavioral health outcomes of their young adult children, as mediated through young adults' own adverse childhood experiences and maternal depression.

Methods

Structural equation modeling was used to analyze data (in 2023) from mothers and their young adult children (n=398 dyads) enrolled in the Center for the Health Assessment of Mothers and Children of Salinas cohort, a primarily Latino agricultural sample. Maternal and young adult adverse childhood experiences were self-reported retrospectively during a visit at the age of 18 years (2018-2020). Young adult- and maternal-reported internalizing and maternal-reported externalizing behaviors were assessed at the age of 18 years with the Behavior Assessment for Children, second edition. Maternal depression was assessed during a visit at the age of 9 years (2010-2012) using the Center for Epidemiologic Studies Depression Scale.

Results

Maternal and young adult adverse childhood experiences were weakly but statistically significantly correlated (r=0.22). Maternal adverse childhood experiences were statistically significantly associated with maternal-reported youth internalizing symptoms (β=0.29; 95% CI=0.19, 0.38; p<0.001) and externalizing symptoms (β=0.24; 95% CI=0.14, 0.33; p<0.001) and marginally associated with youth-reported internalizing symptoms (β=0.08; 95% CI= -0.02, 0.18; p=0.13). Youth adverse childhood experiences and maternal depressive symptomatology mediated the associations between maternal adverse childhood experiences and young adult outcomes.

Conclusions

Findings demonstrate the potential impacts of adversity across generations in Latino immigrant families, an understudied population. Understanding the mechanisms and factors associated with these pathways may lead to strategies that prevent poor mental health outcomes in young adults.

Background

Because fine particulate matter [PM, with aerodynamic diameter ≤2.5μm (PM2.5)] is a ubiquitous environmental exposure, small changes in cognition associated with PM2.5 exposure could have great societal costs. Prior studies have demonstrated a relationship between in utero PM2.5 exposure and cognitive development in urban populations, but it is not known whether these effects are similar in rural populations and whether they persist into late childhood.

Objectives

In this study, we tested for associations between prenatal PM2.5 exposure and both full-scale and subscale measures of IQ among a longitudinal cohort at age 10.5 y.

Methods

This analysis used data from 568 children enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort study in California's agricultural Salinas Valley. Exposures were estimated at residential addresses during pregnancy using state of the art, modeled PM2.5 surfaces. IQ testing was performed by bilingual psychometricians in the dominant language of the child.

Results

A 3-μg/m3 higher average PM2.5 over pregnancy was associated with -1.79 full-scale IQ points [95% confidence interval (CI): -2.98, -0.58], with decrements specifically in Working Memory IQ (WMIQ) and Processing Speed IQ (PSIQ) subscales [WMIQ -1.72 (95% CI: -2.98, -0.45) and PSIQ -1.19 (95% CI: -2.54, 0.16)]. Flexible modeling over the course of pregnancy illustrated mid-to-late pregnancy (months 5-7) as particularly susceptible times, with sex differences in the timing of susceptible windows and in which subscales were most affected [Verbal Comprehension IQ (VCIQ) and WMIQ in males; and PSIQ in females].

Discussion

We found that small increases in outdoor PM2.5 exposure in utero were associated with slightly lower IQ in late childhood, robust to many sensitivity analyses. In this cohort there was a larger effect of PM2.5 on childhood IQ than has previously been observed, perhaps due to differences in PM composition or because developmental disruption could alter the cognitive trajectory and thus appear more pronounced as children get older. https://doi.org/10.1289/EHP10812.

The brain's prefrontal cortex directs higher-order cognitive and behavioral processes that are important for attention, working memory, and inhibitory control. We investigated whether gestational exposure to organophosphate (OP) pesticides was associated with these abilities in childhood and early adolescence. Between 1999 and 2000, we enrolled pregnant women in a birth cohort drawn from an agricultural region of California. We measured dialkyl phosphate (DAP) metabolites of OP pesticides in maternal pregnancy urine samples (13 and 26 weeks) and estimated associations with behaviors related to attention-deficit/hyperactivity disorder and executive function, assessed longitudinally; 351 families provided neurodevelopmental outcome data at any point when the child was aged 7-12 years. We assessed function across multiple dimensions (e.g., working memory, attention), methods (e.g., behavior reports, child assessment), and reporters (e.g., mothers, teachers, child self-reports). Higher gestational DAP concentrations were consistently associated with behaviors related to attention-deficit/hyperactivity disorder and executive function. For example, a 10-fold increase in gestational DAP concentration was associated with poorer longitudinally assessed Behavior Rating Inventory of Executive Function scores, as reported by mothers (β = 4.0 (95% confidence interval: 2.1, 5.8); a higher score indicates more problems), and Weschler Intelligence Scale for Children-Fourth Edition Working Memory scores (a 3.8-point reduction; β = -3.8 (95% confidence interval: -6.2, -1.3)). Reducing gestational exposure to OP pesticides through public health policy is an important goal.

Background

Residential proximity to agricultural pesticide use has been associated with neural tube defects and autism, but more subtle outcomes such as cognition have not been studied.

Objectives

We evaluated the relationship between prenatal residential proximity to agricultural use of potentially neurotoxic pesticides and neurodevelopment in 7-year-old children.

Methods

Participants included mothers and children (n=283) living in the agricultural Salinas Valley of California enrolled in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. We estimated agricultural pesticide use within 1 km of maternal residences during pregnancy using a geographic information system, residential location, and California’s comprehensive agricultural Pesticide Use Report data. We used regression models to evaluate prenatal residential proximity to agricultural use of five potentially neurotoxic pesticide groups (organophosphates, carbamates, pyrethroids, neonicotinoids, and manganese fungicides) and five individual organophosphates (acephate, chlorpyrifos, diazinon, malathion, and oxydemeton-methyl) and cognition in 7-year-old children. All models included prenatal urinary dialkyl phosphate metabolite concentrations.

Results

We observed a decrease of 2.2 points [95% confidence interval (CI): −3.9, −0.5] in Full-Scale IQ and 2.9 points (95% CI: −4.4, −1.3) in Verbal Comprehension for each standard deviation increase in toxicity-weighted use of organophosphate pesticides. In separate models, we observed similar decrements in Full-Scale IQ with each standard deviation increase of use for two organophosphates (acephate and oxydemeton-methyl) and three neurotoxic pesticide groups (pyrethroids, neonicotinoids, and manganese fungicides).

Conclusions

This study identified potential relationships between maternal residential proximity to agricultural use of neurotoxic pesticides and poorer neurodevelopment in children. https://doi.org/10.1289/EHP504.

Background

The molecular mechanisms linking environmental exposures to earlier pubertal development are not well characterized. Epigenetics may play an important role, but data on the relationship between epigenetic marks and puberty, particularly in humans, is limited.

Methods

We used pyrosequencing to measure Alu and long interspersed nucleotide elements (LINE-1) methylation in DNA isolated from whole blood samples collected from newborns and 9-y-old children (n = 266). Tanner staging was completed six times between ages 9 and 12 y to determine pubertal status, and hormone levels were measured in 12-y-old boys.

Results

Among girls, we observed a suggestive trend of increased odds of breast and pubic hair development with higher Alu and LINE-1 methylation in 9-y-old blood, respectively. The strongest association identified was an inverse association of LINE-1 methylation in 9-y-old girls with odds of experiencing menarche by age 12 (OR (95% CI): 0.63 (0.46, 0.87); P = 0.005). We observed a consistent inverse relationship for Alu and LINE-1 methylation at 9 y with luteinizing hormone (LH), testosterone and follicle-stimulating hormone levels in boys but it was only significant between LINE-1 and LH.

Conclusion

DNA methylation of Alu and LINE-1 may be involved in puberty initiation and development. This relationship should be confirmed in future studies.

Background

Environmental exposure to endocrine-disrupting chemicals (EDCs), including persistent organic pollutants (POPs), has been hypothesized to increase risk of obesity. Using data from the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined the longitudinal relationship between serum concentrations of a POPs mixture and several obesity measures.

Methods

Concentrations of 17 POPs were measured in serum collected in 2009-2011 from 468 CHAMACOS women. Anthropometry measurements and personal interviews were completed at up to three study visits between 2009 and 2014. We assessed the relationship of serum POPs concentrations with adiposity measures longitudinally using generalized estimating equation (GEE) models. We implemented Bayesian Kernel Machine Regression (BKMR) to elucidate the effects of joint exposure to the POPs mixture.

Results

In GEE models, positive associations with BMI were found for dichlorodiphenyltrichloroethane (Q4 vs Q1: adjusted-β = 3.2 kg/m²; 95%CI 1.5,4.9), β-hexachlorocyclohexane (Q4 vs Q1: adjusted-β = 3.6 kg/m²; 95%CI 2.0,5.2), and PBDE-47 (Q4 vs Q1: adjusted-β = 1.9 kg/m²; 95%CI 0.3,3.5), while PBDE-153 was inversely associated (Q4 vs Q1: adjusted-β = -2.8 kg/m²; 95%CI -4.4,-1.2). BKMR results, while largely consistent with single pollutant models, revealed the shape and direction of the exposure-response relationships, as well as interactions among pollutants within the mixture, that could not be discovered by single-pollutant models.

Conclusion

In summary, we found significant associations of serum POPs with several adiposity measures using both conventional regressions and BKMR. Our results provide support for the chemical obesogen hypothesis, that exposure to EDCs may alter risk for later obesity.

In-utero exposure to endocrine-disrupting compounds, including dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE), has been hypothesized to increase the risk of obesity later in life. We examined the associations of maternal serum concentrations of DDT and DDE during pregnancy with body mass index, obesity, waist circumference, and percentage of body fat in 9-year-old children (n = 261) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal birth cohort study in the Salinas Valley, California (2000-2010). We found associations between prenatal exposure to DDT and DDE and several measures of obesity at 9 years of age in boys but not in girls. For example, among boys, 10-fold increases in prenatal DDT and DDE concentrations were associated with increased odds of becoming overweight or obese (for o,p'-DDT, adjusted odds ratio (OR) = 2.5, 95% confidence interval (CI): 1.0, 6.3; for p,p'-DDT, adjusted OR = 2.1, 95% CI: 1.0, 4.5; and for p,p'-DDE, adjusted OR = 1.97, 95% CI: 0.94, 4.13). The odds ratios for girls were nonsignificant. Results were similar for body mass index z score, waist circumference z score, and odds of increased waist circumference but were less consistent for percentage of body fat. The difference by sex persisted after considering pubertal status. These results provide support for the chemical obesogen hypothesis.