Validation of Variables for Use in Pediatric Obesity Risk Score Development in Demographically and Racially Diverse United States Cohorts.

OBJECTIVE: To evaluate the performance of childhood obesity prediction models in four independent cohorts in the United States, using previously validated variables obtained easily from medical records as measured in different clinical settings. STUDY DESIGN: Data from four prospective cohorts, Latinx, Eating, and Diabetes; Stress in Pregnancy Study; Project Viva; and Center for the Health Assessment of Mothers and Children of Salinas were used to test childhood obesity risk models and predict childhood obesity by ages 4 through 6, using five clinical variables (maternal age, maternal prepregnancy body mass index, birth weight Z-score, weight-for-age Z-score change, and breastfeeding), derived from a previously validated risk model and as measured in each cohort's clinical setting. Multivariable logistic regression was performed within each cohort, and performance of each model was assessed based on discrimination and predictive accuracy. RESULTS: The risk models performed well across all four cohorts, achieving excellent discrimination. The area under the receiver operator curve was 0.79 for Center for the Health Assessment of Mothers and Children of Salinas and Project Viva, 0.83 for Stress in Pregnancy Study, and 0.86 for Latinx, Eating, and Diabetes. At a 50th percentile threshold, the sensitivity of the models ranged from 12% to 53%, and specificity was ≥ 90%. The negative predictive values were ≥ 80% for all cohorts, and the positive predictive values ranged from 62% to 86%. CONCLUSION: All four risk models performed well in each independent and demographically diverse cohort, demonstrating the utility of these five variables for identifying children at high risk for developing early childhood obesity in the United States.

Pesticide exposure, birth size, and gestational age in the ISA birth cohort, Costa Rica.

Purpose: To examine associations of prenatal biomarkers of pesticide exposure with birth size measures and length of gestation among newborns from the Infants' Environmental Health (ISA) birth cohort, Costa Rica. Methods: We included 386 singleton liveborn newborns with data on birth size measures, length of gestation, and maternal urinary biomarkers of chlorpyrifos, synthetic pyrethroids, mancozeb, pyrimethanil, and 2, 4-D during pregnancy. We associated biomarkers of exposure with birth outcomes using multivariate linear regression and generalized additive models. Results: Concentrations were highest for ethylene thiourea (ETU, metabolite of mancozeb), median = 3.40; p10-90 = 1.90-6.79 µg/L, followed by 3,5,6-trichloro-2-pyridinol (TCP, metabolite of chlorpyrifos) p50 = 1.76 p10-90 = 0.97-4.36 µg/L, and lowest for 2,4-D (p50 = 0.33 p10-90 = 0.18-1.07 µg/L). Among term newborns (≥37 weeks), higher prenatal TCP was associated with lower birth weight and smaller head circumference (e.g., ß per 10-fold-increase) during the second half of pregnancy = -129.6 (95% confidence interval [CI] = -255.8, -3.5) grams, and -0.61 (95% CI = -1.05, -0.17) centimeters, respectively. Also, among term newborns, prenatal 2,4-D was associated with lower birth weight (ß per 10-fold-increase = -125.1; 95% CI = -228.8, -21.5), smaller head circumference (ß = -0.41; 95% CI = -0.78, -0.03), and, during the second half of pregnancy, with shorter body length (ß = -0.58; 95% CI = -1.09, -0.07). Furthermore, ETU was nonlinearly associated with head circumference during the second half of pregnancy. Biomarkers of pyrethroids and pyrimethanil were not associated with birth size, and none of the biomarkers explained the length of gestation. Conclusions: Prenatal exposure to chlorpyrifos and 2,4-D, and, possibly, mancozeb/ETU, may impair fetal growth.

Association of pesticide exposure with neurobehavioral outcomes among avocado farmworkers in Mexico.

BACKGROUND AND AIM: To date, few studies have focused on the health effects of pesticide exposure among avocado farmworkers. We examined the association of exposure to insecticides, fungicides, and herbicides with cognitive and mental health outcomes among these avocado workers from Michoacan, Mexico. MATERIALS AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We collected data on self-reported pesticide use during the 12 months prior to the baseline survey and estimated annual exposure-intensity scores (EIS) using a semi-quantitative exposure algorithm. We calculated specific gravity adjusted average concentrations of 12 insecticide, fungicide, or herbicide metabolites measured in urine samples collected during two study visits (8-10 weeks apart). We assessed participants' cognitive function and psychological distress using the NIH Toolbox Cognition Battery and the Brief Symptom Inventory 18 (BSI-18), respectively. We examined individual associations of EIS and urinary pesticide metabolites with neurobehavioral outcomes using generalized linear regression models. We also implemented Bayesian Weighted Quantile Sum (BWQS) regression to evaluate the association between a pesticide metabolite mixture and neurobehavioral outcomes. RESULTS: In individual models, after adjusting for multiple comparisons, higher concentrations of hydroxy-tebuconazole (OH-TEB, metabolite of fungicide tebuconazole) were associated with higher anxiety (IRR per two-fold increase in concentrations = 1.26, 95% CI:1.08, 1.48) and Global Severity Index (GSI) (IRR = 1.89, 95% CI:1.36, 2.75) scores, whereas higher concentrations of 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) were associated with lower GSI scores (IRR = 0.69, 95% CI: 0.56, 0.85). In BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with higher anxiety (IRR = 1.72, 95% CrI: 1.12, 2.55), depression (IRR = 4.60, 95% CrI: 2.19, 9.43), and GSI (IRR = 1.99, 95% CrI: 1.39, 2.79) scores. OH-TEB and hydroxy-thiabendazole (metabolite of fungicide thiabendazole) combined contributed 54%, 40%, and 54% to the mixture effect in the anxiety symptoms, depression symptoms, and overall psychological distress models, respectively. CONCLUSIONS: We found that exposure to tebuconazole and thiabendazole, fungicides whose effects have been rarely studied in humans, may be associated with increased psychological distress among avocado farmworkers. We also observed that exposure to chlorpyrifos may be associated with decreased psychological distress.

Prenatal current-use pesticide exposure and children's neurodevelopment at one year of age in the Infants' Environmental Health (ISA) birth cohort, Costa Rica.

BACKGROUND: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. OBJECTIVE: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. METHODS: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). RESULTS: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (ßper ten-fold increase = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (ßper ten-fold increase = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (ßper ten-fold increase = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (ßper ten-fold increase = -3.8, 95 % CI = -7.7, 0.1) but not girls (ßper ten-fold increase = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DISCUSSION: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.

Prevalence of SARS-CoV-2 infection and impact of the COVID-19 pandemic in avocado farmworkers from Mexico.

Introduction: The COVID-19 pandemic disproportionately affected farmworkers in the United States and Europe, leading to increased morbidity and mortality. However, little is known about the specific impact of the pandemic on agriculture and food production workers in low- and middle-income countries. This study aimed to investigate the prevalence of SARS-CoV-2 infection and assess the mental health and economic consequences of the COVID-19 pandemic among avocado farmworkers in Michoacan, Mexico. Methods: We conducted a cross-sectional study of adult farmworkers (n = 395) in May 2021. We collected survey data, nasal swabs and saliva samples for SARS-CoV-2 RNA detection, and blood samples for immunoglobulin G (IgG) reactivity measurements. Results: None of the farmworkers tested positive for SARS-CoV-2 RNA. However, among unvaccinated farmworkers (n = 336, 85%), approximately one-third (33%) showed evidence of past infection (positive for IgG against SARS-CoV-2). Unvaccinated farmworkers who lived with other farmworkers (aRR = 1.55; 95% CI: 1.05, 2.05), had ever lived with someone with COVID-19 (aRR = 1.82; 95% CI: 1.22, 2.43), and who had diabetes (aRR = 2.19; 95% CI: 1.53, 2.85) had a higher risk of testing IgG-positive for SARS-CoV-2 infection. In contrast, unvaccinated farmworkers living in more rural areas (outside of Tingambato or Uruapan) (aRR = 0.71; 95% CI: 0.46, 0.96) or cooking with wood-burning stove (aRR = 0.75; 95% CI: 0.55, 0.96) had a lower risk of IgG-positivity. Moreover, 66% of farmworkers reported a negative impact of the pandemic on their lives, 29% reported experiencing food insecurity and difficulty paying bills, and 10% reported depression or anxiety symptoms. Conclusion: The COVID-19 pandemic has significantly affected the mental health and financial well-being of avocado farmworkers. Consequently, the implementation of interventions and prevention efforts, such as providing mental health support and food assistance services, is imperative.

Pesticide exposure and cortical brain activation among farmworkers in Costa Rica.

BACKGROUND: Previous epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. METHODS: We conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3-5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. RESULTS: We found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (ß = -2.3; 95% CI: -3.9, -0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (ß = -3.1; 95% CI: -5.0, -1.2 and -2.3; 95% CI: -4.5, -0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. CONCLUSION: Our findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex - neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.

Childhood Overweight and Obesity and Pubertal Onset Among Mexican-American Boys and Girls in the CHAMACOS Longitudinal Study.

Secular trends in earlier initiation of puberty have been observed in recent decades. One risk factor appears to be increases in adiposity, as measured by body mass index. This trend is particularly notable among Latino populations, who have higher rates of overweight/obesity compared with non-Latino White youth. Previous research has focused primarily on White girls, resulting in data gaps regarding male puberty and among potentially high-risk populations. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined body mass index at age 5 years (2005-2006) and multiple markers of pubertal onset, assessed repeatedly and longitudinally at 7 in-person visits, starting at age 9 and continuing through age 14 (2009-2015), among 336 Mexican Americans in Salinas, California. We observed no associations among boys, but found significantly earlier thelarche in overweight (HR = 1.7, 95% CI: 1.1, 2.7) and obese girls (HR = 1.5, 95% CI: 1.0, 2.4), menarche in overweight girls (HR = 1.6; CI: 1.0, 2.4), and pubarche in obese girls (HR = 1.9; CI: 1.2, 3.0), compared with normal-weight girls. This study examined an understudied population and included key covariates, such as birth weight and early adverse events, which are typically omitted in studies.

Earlier age of sex and substance use initiation is associated with unique hormone profiles during social evaluative threat in Mexican American adolescents.

Latinx adolescents are at a disproportional risk for poor sexual and reproductive health outcomes (STIs, adolescent pregnancy) compared to other ethnic groups. They also report high rates of alcohol and drug use that are similar to non-Hispanic White youth. The hormonal underpinnings of the emergence of sex and substance use behaviors among Latinx adolescents remain understudied however. Pubertal shifts in motivation and reward-seeking in social situations are closely tied to the emergence of risky sexual and substance use behaviors. The experience of developing earlier or later than same age peers may increase stress (cortisol) reactivity during social evaluative situations leading to more risky behavior. Further, testosterone can be responsive to social evaluative threat (SET) and is linked to status-seeking behavior, including risk-taking. The current study sought to unravel the complex relationship between cortisol and testosterone responsivity to social evaluative threat, pubertal status, and the emergence of sex and drug use among US-born Mexican-origin youth growing up in an agricultural community. Mexican American 14-year olds (N = 234, 54% female) from the Center for Health Assessment of Mothers and Children (CHAMACOS) participated in the Trier Social Stress Test. Cortisol and testosterone were assayed from saliva. At 16, youth reported on age at vaginal and oral sex initiation, and alcohol and marijuana use initiation. Hierarchical regressions examined cortisol and testosterone reactivity, and pubertal status within each sex to predict the onset of these risky behaviors. Results indicated that boys who were less developed than their same-aged peers or with lower testosterone reactivity and elevated cortisol reactivity to the TSST reported the earliest sex and substance use initiation. For girls, higher cortisol reactivity predicted earlier alcohol use initiation, and higher testosterone reactivity predicted earlier oral sex. Our results suggests it is important for health care providers to not overlook Latinx boys who may look younger in discussions about mitigating risk. Latinx girls under increased stress may be more likely to try to self-medicate with alcohol, and potentially other drugs.

Deportation Worry, Cardiovascular Disease Risk Factor Trajectories, and Incident Hypertension: A Community-Based Cohort Study.

Background Worry about deportation has been associated with cardiovascular disease risk factors in cross-sectional research. No research has evaluated this association longitudinally or examined the association between deportation worry and incident cardiovascular disease outcomes. Methods and Results We used data from an ongoing community-based cohort of 572 women primarily of Mexican origin. We estimated associations between self-reported deportation worry and: (1) trajectories of blood pressure, body mass index, and waist circumference with linear mixed models, and (2) incident hypertension with Cox proportional hazards models. Nearly half (48%) of women reported "a lot," 24% reported "moderate," and 28% reported "not too much" deportation worry. Higher worry at baseline was associated with nonlinear systolic blood pressure and mean arterial pressure trajectories. For example, compared with not too much worry, a lot of worry was associated with a faster initial increase (ß, interaction with linear year term: 4.10; 95% CI, 1.17-7.03) followed by a faster decrease in systolic blood pressure (ß, interaction with quadratic year term: -0.80; 95% CI, -1.55 to -0.06). There was weak evidence of an association between deportation worry and diastolic blood pressure and no association with body mass index, waist circumference, or pulse pressure trajectories. Among 408 women without baseline hypertension, reporting a lot (hazard ratio, 2.17; 95% CI, 1.15-4.10) and moderate deportation worry (hazard ratio, 2.48; 95% CI, 1.17-4.30) were each associated with greater risk of incident hypertension compared with reporting not too much worry. Conclusions Deportation worry may contribute to widening disparities in some cardiovascular disease risk factors and outcomes over time.

Manganese exposure and working memory-related brain activity in smallholder farmworkers in Costa Rica: Results from a pilot study.

Main sources of manganese (Mn) in the general population are diet and drinking water. Mn is also found in ethylene bisdithiocarbamate (EBDC) fungicides used in agriculture or emitted into the air by ferromanganese plants and welding fumes, which can be additional environmental and occupational sources of exposure. High occupational Mn exposure has been linked with motor, behavioral, and cognitive impairment, but its effects on neural function remain poorly understood. We conducted a functional neuroimaging study in a sample of 48 farmworkers in Zarcero County, Costa Rica, an agricultural region where EBDC fungicides are sprayed. We measured Mn concentrations in farmworkers' toenails (n = 40 farmworkers) and hair (n = 33 farmworkers), and recorded brain activity in the dorsolateral prefrontal cortex during a letter-retrieval working memory task using functional near-infrared spectroscopy (fNIRS). We estimated exposure-outcome associations using multivariable linear regression models adjusted for age and education level. Geometric mean (geometric standard deviation) toenail and hair Mn concentrations were 0.40 µg/g (3.52) and 0.24 µg/g (3.54), respectively. We did not find strong evidence that Mn concentrations were associated with working memory-related brain activity in this sample of farmworkers; we also found null associations between working memory task accuracy and brain activity. However, our small sample size may have limited our ability to detect small effect sizes with statistical precision. Our study demonstrates that fNIRS can be a useful and feasible tool in environmental epidemiology for examining the effects of toxicants, like Mn, on neural function. This may prove to be important for elucidating neuropathological pathways that underlie previously reported associations of elevated Mn exposure with neurotoxic effects.

Age-Related Differences in miRNA Expression in Mexican-American Newborns and Children.

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.

Early-Life Home Environment and Obesity in a Mexican American Birth Cohort: The CHAMACOS Study.

OBJECTIVE: Little is known about the impact of the home environment on biomarkers of obesity, such as adipokines, in children. In this study, we examined the relationship of maternal depressive symptoms and potentially protective social factors, including maternal support and the home learning environment, with body mass index and adipokines. METHODS: Data were obtained from 326 Mexican American participants from the Center for the Health Assessment of Mothers and Children of Salinas cohort. Plasma adipokine levels were assessed in 326 children by enzyme-linked immunoassay at birth or ages 5, 9, or 14 years. Maternal depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale when children were 1, 3.5, 7, and 9 years old; social support was assessed by the Duke-University of North Carolina Questionnaire at ages 1 and 5 years; and home learning environment by the Home Observation for the Measurement of the Environment (HOME) at ages of 6 months and 1, 2, 3.5, 7, 9, and 10.5 years. RESULTS: Age was significantly associated with adiponectin (B = -5.0, SE = 0.2) and leptin (B = 0.01, SE = 0.003) levels. Individual time point analyses identified significant positive associations of HOME scores in childhood with adiponectin at ages 9 years (HOME score; age 3.5 years: B = 0.9, p = .04) and 14 years (HOME score; age 7 years: B = 0.6, p = .02, age 9 years: B = 0.6, p = .05, age 10.5 years: B = 0.5, p = .04). We observed significant relationships of maternal depressive symptoms at age 9 years with adiponectin and body mass index z-score at age 14 years (B = -0.2, p = .003 and B = 0.02, p = .002, resp.), which were confirmed in longitudinal models. CONCLUSIONS: This study adds new evidence that adverse and protective aspects of the home environment could lead to altered obesity status in children.

The role of bicultural adaptation, familism, and family conflict in Mexican American adolescents' cortisol reactivity.

Scarce research has examined stress responsivity among Latino youths, and no studies have focused on the role of acculturation in shaping cortisol stress response in this population. This study assessed Mexican American adolescents' Mexican and Anglo cultural orientations and examined prospective associations between their patterns of bicultural orientation and hypothalamic-pituitary-adrenal cortisol reactivity to an adapted Trier Social Stress Test. The sample included 264 youths from a longitudinal birth cohort study who completed the Trier Social Stress Test and provided saliva samples at age 14. The youths completed assessments of cultural orientation at age 12, and family conflict and familism at age 14. Analyses testing the interactive effects of Anglo and Mexican orientation showed significant associations with cortisol responsivity, including the reactivity slope, peak levels, and recovery, but these associations were not mediated by family conflict nor familism values. Findings revealed that bicultural youth (high on both Anglo and Mexican orientations) showed an expected pattern of high cortisol responsivity, which may be adaptive in the context of a strong acute stressor, whereas individuals endorsing only high levels of Anglo orientation had a blunted cortisol response. Findings are discussed in relation to research on biculturalism and the trade-offs and potential recalibration of a contextually responsive hypothalamic-pituitary-adrenal axis for acculturating adolescents.

PON1 DNA methylation and neurobehavior in Mexican-American children with prenatal organophosphate exposure.

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.

DNA methylation of imprinted genes in Mexican-American newborn children with prenatal phthalate exposure.

AIM: Imprinted genes exhibit expression in a parent-of-origin-dependent manner and are critical for child development. Recent limited evidence suggests that prenatal exposure to phthalates, ubiquitous endocrine disruptors, can affect their epigenetic dysregulation. MATERIALS & METHODS: We quantified DNA methylation of nine imprinted gene differentially methylated regions by pyrosequencing in 296 cord blood DNA samples in a Mexican-American cohort. Fetal exposure was estimated by phthalate metabolite concentrations in maternal urine samples during pregnancy. RESULTS: Several differentially methylated regions of imprinted genes were associated with high molecular weight phthalates. The most consistent, positive, and false discovery rate significant associations were observed for MEG3. CONCLUSION: Phthalate exposure in utero may affect methylation status of imprinted genes in newborn children.

DNA methylation and socioeconomic status in a Mexican-American birth cohort.

Background: Maternal social environmental stressors during pregnancy are associated with adverse birth and child developmental outcomes, and epigenetics has been proposed as a possible mechanism for such relationships. Methods: In a Mexican-American birth cohort of 241 maternal-infant pairs, cord blood samples were measured for repeat element DNA methylation (LINE-1 and Alu). Linear mixed effects regression was used to model associations between indicators of the social environment (low household income and education, neighborhood-level characteristics) and repeat element methylation. Results from a dietary questionnaire were also used to assess the interaction between maternal diet quality and the social environment on markers of repeat element DNA methylation. Results: After adjusting for confounders, living in the most impoverished neighborhoods was associated with higher cord blood LINE-1 methylation (ß = 0.78, 95%CI 0.06, 1.50, p = 0.03). No other neighborhood-, household-, or individual-level socioeconomic indicators were significantly associated with repeat element methylation. We observed a statistical trend showing that positive association between neighborhood poverty and LINE-1 methylation was strongest in cord blood of infants whose mothers reported better diet quality during pregnancy (pinteraction = 0.12). Conclusion: Our findings indicate a small yet unexpected positive association between neighborhood-level poverty during pregnancy and methylation of repetitive element DNA in infant cord blood and that this association is possibly modified by diet quality during pregnancy. However, our null findings for other adverse SES indicators do not provide strong evidence for an adverse association between early-life socioeconomic environment and repeat element DNA methylation in infants.

Prenatal Mancozeb Exposure, Excess Manganese, and Neurodevelopment at 1 Year of Age in the Infants' Environmental Health (ISA) Study.

BACKGROUND: Although growing evidence suggests that early-life excess manganese (Mn) impairs neurodevelopment, data on the neurodevelopmental effects of mancozeb, a fungicide containing Mn, and its main metabolite ethylenethiourea (ETU) are limited. OBJECTIVE: We examined whether prenatal mancozeb exposure and excess Mn were associated with neurodevelopment in 355 1-y-old infants living near banana plantations with frequent aerial mancozeb spraying in Costa Rica. METHODS: We measured urinary ETU, hair Mn, and blood Mn concentrations in samples collected 1-3 times during pregnancy from mothers enrolled in the Infants' Environmental Health (ISA) study. We then assessed neurodevelopment in their 1-y-old infants using the Bayley Scales of Infant and Toddler Development, 3rd edition (BSID-III). We estimated exposure-outcome associations using linear regression models adjusted for maternal education, parity, gestational age at birth, child age, Home Observation for Measurement of the Environment score, and location of neurodevelopmental assessment. RESULTS: Median (P25-P75) urinary ETU, hair Mn, and blood Mn measured during pregnancy were 3.3 µg/L (2.4-4.9; specific gravity-corrected), 1.7 µg/g (0.9-4.1), and 24.0 µg/L (20.3-28.0), respectively. Among girls, higher ETU was associated with lower social-emotional scores [ß per 10-fold increase=-7.4 points (95% CI: -15.2, 0.4)], whereas higher hair Mn was associated with lower cognitive scores [-3.0 (-6.1, 0.1)]. Among boys, higher hair Mn was associated with lower social-emotional scores [-4.6 (-8.5, -0.8)]. We observed null associations for blood Mn, language, and motor outcomes. CONCLUSIONS: Our findings indicate that maternal exposure to mancozeb and excess Mn during pregnancy may have adverse and sex-specific effects on infant neurodevelopment. https://doi.org/10.1289/EHP1955.

Worry About Deportation and Cardiovascular Disease Risk Factors Among Adult Women: The Center for the Health Assessment of Mothers and Children of Salinas Study.

Background: U.S. Latinos report high levels of concern about deportation for themselves or others. No previous research has tested the link between worry about deportation and clinical measures of cardiovascular risk. Purpose: We estimate the associations between worry about deportation and clinically measured cardiovascular risk factors. Methods: Data come from the Center for the Health Assessment of Mothers and Children of Salinas study. The analytic sample includes 545 Mexican-origin women. Results: In multivariable models, reporting a lot of worry about deportation was significantly associated with greater body mass index, greater risk of obesity, larger waist circumference, and higher pulse pressure. Reporting moderate deportation worry was significantly associated with greater risk of overweight and higher systolic blood pressure. Significant associations between worry about deportation and greater body mass index, waist circumference, and pulse pressure, respectively, held after correcting for multiple testing at p < .05. Conclusions: Worry about deportation may be an important cardiovascular risk factor for ethnic minority populations in the USA.

A Modified Trier Social Stress Test for Vulnerable Mexican American Adolescents.

The Trier Social Stress Test (TSST) is a well validated and widely used social stressor that has been shown to induce a 2-4 fold increase in cortisol, the biological output produced by the Hypothalamic-Pituitary-Adrenal (HPA) axis in humans. While studies have explored how modifications to the TSST influence stress responsivity, few studies have created a modified TSST appropriate for vulnerable youth that elicits a significant cortisol stress response. Thus, the current study sought to modify or adjust the TSST in a culturally sensitive way for a vulnerable sample of 14 year-old adolescents. The present study took place within the context of a longitudinal birth cohort study of Mexican American families in California called the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). The CHAMACOS sample was optimal to test the effectiveness of a modified culturally appropriate TSST, as it is comprised of Mexican American youth, who are often excluded from research. These youths also have experienced significant early life adversity. Example modifications included timed prompts, alternative math tasks, use of same-ethnicity peers as confederates, debriefing immediately after the conclusion of the TSST, and using an unknown youth examiner to administer the debrief. Saliva samples were collected at baseline (after a resting phase), and then again at 15, 30, and 45 min post-TSST onset to assess cortisol concentration. A pilot study of 50 participants (50% female) have been analyzed for cortisol reaction to the TSST. Results confirmed that this modified version of the TSST was successful at eliciting a significant cortisol reaction, with a wide range of variability likely due to individual differences. Goals for modifications and ethnicity considerations are discussed. This study provides the foundation for future research to utilize a modified TSST with vulnerable youth.

The relationship between maternal responsivity, socioeconomic status, and resting autonomic nervous system functioning in Mexican American children.

Adversity, such as living in poor socioeconomic conditions during early childhood, can become embedded in children's physiology and deleteriously affect their health later in life. On the other hand, maternal responsivity may have adaptive effects on physiology during early childhood development. The current study tested both the additive and interactive effects of socioeconomic status (SES) and maternal responsivity measured at 1year of age on resting autonomic nervous system (ANS) function and trajectory during the first 5years of life. Participants came from a birth cohort comprised of Mexican-origin families living in California. Children's resting ANS functioning (respiratory sinus arrhythmia; RSA; pre-ejection period; PEP; and heart rate; HR) was collected at 1, 3.5, and 5years of age (N=336) and modeled across time using Hierarchical Linear Modeling. Consistent with hypotheses, results showed that low SES predicted flatter trajectories of resting HR and PEP over early childhood (i.e., patterns of consistently higher heart rate; shorter PEP), whereas children who experienced positive maternal responsivity had steeper trajectories in RSA and PEP over time (i.e., increasing parasympathetic activation; decreasing sympathetic activation). The interaction between SES and maternal responsivity significantly predicted RSA intercept at age 5, such that among children living in low SES environments, high maternal responsivity mitigated the negative effect of poverty and predicted higher resting RSA at 5years of age. Results are consistent with the early life programming theory that suggests that environmental influences become biologically embedded in the physiology of children living in socially disadvantaged contexts, and identify increased maternal responsivity as a developmental mechanism that could offset the deleterious effects of low SES.