Prenatal Maternal Occupation and Child Epigenetic Age Acceleration in an Agricultural Region: NIMHD Social Epigenomics Program.

Importance: Research on fetal epigenetic programming suggests that the intrauterine environment can have long-term effects on offspring disease susceptibility. Objective: To examine the association between prenatal maternal occupation and child epigenetic age acceleration (EAA) among a farmworker community. Design, Setting, and Participants: This cohort study included participants in the Center for the Health Assessment of Mothers and Children of Salinas, a prospective, Latino, prebirth cohort. Pregnant women were recruited from October 1, 1999, to October 1, 2000, from 6 community clinics in California's Salinas Valley agricultural region. Participants were 18 years or older, English or Spanish speaking, Medicaid eligible, and at 20 weeks' gestation or earlier at enrollment. Mother-child pairs who had blood DNA methylation measured at the ages of 7, 9, and 14 years were included. Data were analyzed from July 2021 to November 2023. Exposures: Prenatal maternal occupation was ascertained through study interviews conducted during prenatal visits and shortly after delivery. Main Outcomes and Measures: Child EAA at 7, 9, and 14 years of age was estimated using DNA methylation-based epigenetic age biomarkers. Three EAA measures were calculated: the Horvath EAA, skin and blood EAA, and intrinsic EAA. Linear mixed-effects models were used to estimate longitudinal associations of prenatal maternal occupation and child EAA, adjusting for confounders and prenatal organophosphate pesticide exposure. Results: Analyses included 290 mother-child pairs (mean [SD] maternal age at delivery, 26.5 [5.2] years; 152 [52.4%] female infants); 254 mothers (87.6%) were born in Mexico, 33 (11.4%) in the US, and 3 (1.0%) in other countries; and 179 families (61.7%) were below the federal poverty line during pregnancy. Mothers reported engaging in several types of work during pregnancy, including agricultural fieldwork (90 [31.0%]), other agricultural work (40 [13.8%]), nonagricultural work (53 [18.3%]), or no work (107 [36.9%]). Children whose mothers worked in agricultural fields during pregnancy had a mean of 0.66 (95% CI, 0.17-1.15) years of greater Horvath EAA, 0.62 (95% CI, 0.31-0.94) years of greater skin and blood EAA, and 0.45 (95% CI, 0.07-0.83) years of greater intrinsic EAA compared with children whose mothers did not work during pregnancy. Conclusions and Relevance: In this cohort study, prenatal maternal agricultural fieldwork was associated with accelerated childhood epigenetic aging independent of organophosphate pesticide exposure. Future research on which factors related to agricultural fieldwork accelerate aging in the next generation can inform targeted prevention programs and policies that protect children's health.

Association of pesticide exposure with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico.

BACKGROUND: A growing literature suggests associations between occupational pesticide exposure and respiratory health. In this study, we aimed to examine the association of exposure to insecticides, fungicides, and herbicides, individually and as a mixture, with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico. MATERIAL AND METHODS: We conducted a cross-sectional study of 105 avocado farmworkers between May and August 2021. We quantified 12 insecticide, fungicide, and herbicide metabolites in urine samples collected during two study visits (8-10 weeks apart). We collected survey 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 also assessed respiratory symptoms, including wheezing, chest tightness, wheezing after exercise, and night cough. We used generalized linear regression models to examine associations of individual urinary metabolite concentrations and annual EIS with respiratory health outcomes and rhinitis. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. RESULTS: After adjusting for multiple comparisons, we observed mostly null associations of individual pesticide metabolite concentrations and annual EIS with the outcomes of interest. However, in BWQS analyses, we found evidence of a mixture association of urinary pesticide metabolites with increased odds of night cough (OR: 5.34, 95 % CrI: 1.67, 20.62). Pyrethroid metabolites 3-phenoxybenzoic acid and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid were the main contributors to this association (43 %). CONCLUSIONS: Our findings indicate that exposure to a mixture of pesticides, particularly pyrethroid insecticides, may be associated with night cough in avocado farmworkers.

Childhood exposure to organophosphate pesticides: Functional connectivity and working memory in adolescents.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides is linked with adverse neurodevelopment and brain function in children. However, we have limited knowledge of how these exposures affect functional connectivity, a measure of interaction between brain regions. To address this gap, we examined the association between early life OP pesticide exposure and functional connectivity in adolescents. METHODS: We administered functional near-infrared spectroscopy (fNIRS) to 291 young adults with measured prenatal or childhood dialkylphosphates (DAPs) in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a longitudinal study of women recruited during pregnancy and their offspring. We measured DAPs in urinary samples collected from mothers during pregnancy (13 and 26 weeks) and children in early life (ages 6 months, 1, 2, 3, and 5 years). Youth underwent fNIRS while they performed executive function and semantic language tasks during their 18-year-old visit. We used covariate-adjusted regression models to estimate the associations of prenatal and childhood DAPs with functional connectivity between the frontal, temporal, and parietal regions, and a mediation model to examine the role of functional connectivity in the relationship between DAPs and task performance. RESULTS: We observed null associations of prenatal and childhood DAP concentrations and functional connectivity for the entire sample. However, when we looked for sex differences, we observed an association between childhood DAPs and functional connectivity for the right interior frontal and premotor cortex after correcting for the false discovery rate, among males, but not females. In addition, functional connectivity appeared to mediate an inverse association between DAPs and working memory accuracy among males. CONCLUSION: In CHAMACOS, a secondary analysis showed that adolescent males with elevated childhood OP pesticide exposure may have altered brain regional connectivity. This altered neurofunctional pattern in males may partially mediate working memory impairment associated with childhood DAP exposure.

Prenatal exposure to polybrominated diphenyl ether (PBDE) and child neurodevelopment: The role of breastfeeding duration.

BACKGROUND: Prenatal and early-life exposure to polybrominated diphenyl ethers (PBDEs) is associated with detrimental and irreversible neurodevelopmental health outcomes during childhood. Breastfeeding may be a child's largest sustained exposure to PBDE- potentially exacerbating their risk for adverse neurodevelopment outcomes. However, breastfeeding has also been associated with positive neurodevelopment. Our study investigates if breastfeeding mitigates or exacerbates the known adverse effects of prenatal exposure to PBDEs and child neurodevelopment. METHODS: Participants included 321 mother-infant dyads from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a longitudinal birth cohort in California. PBDE concentrations were measured in maternal serum blood samples collected during pregnancy or at delivery. Using generalized estimated equations (GEE), we estimated associations of PBDE concentrations with children's attention, executive function, and cognitive scores assessed longitudinally between 7 and 12 years of age, stratified by duration of exclusive and complementary breastfeeding. RESULTS: We observed that higher maternal prenatal PBDE concentrations were associated with poorer executive function among children who were complementary breastfed for a shorter duration compared to children breastfed for a longer duration; preservative errors (ß for 10-fold increase in complementary breastfeeding <7 months = -6.6; 95 % Confidence Interval (CI): -11.4, -1.8; ß ≥ 7 months = -5.1; 95 % CI: -10.2, 0.1) and global executive composition (ß for 10-fold increase <7 months = 4.3; 95 % CI: 0.4, 8.2; ß for 10-fold increase ≥7 months = 0.6; 95 % CI: -2.8, 3.9). CONCLUSIONS: Prolonged breastfeeding does not exacerbate but may mitigate some previously observed negative associations of prenatal PBDE exposure and child neurodevelopment.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity. METHODS: We pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth. RESULTS: In comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants. CONCLUSIONS: Phthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

The East Bay Diesel Exposure Project: a biomonitoring study of parents and their children in heavily impacted communities.

BACKGROUND: Diesel exhaust (DE) exposures pose concerns for serious health effects, including asthma and lung cancer, in California communities burdened by multiple stressors. OBJECTIVE: To evaluate DE exposures in disproportionately impacted communities using biomonitoring and compare results for adults and children within and between families. METHODS: We recruited 40 families in the San Francisco East Bay area. Two metabolites of 1-nitropyrene (1-NP), a marker for DE exposures, were measured in urine samples from parent-child pairs. For 25 families, we collected single-day spot urine samples during two sampling rounds separated by an average of four months. For the 15 other families, we collected daily spot urine samples over four consecutive days during the two sampling rounds. We also measured 1-NP in household dust and indoor air. Associations between urinary metabolite levels and participant demographics, season, and 1-NP levels in dust and air were evaluated. RESULTS: At least one 1-NP metabolite was present in 96.6% of the urine samples. Detection frequencies for 1-NP in dust and indoor air were 97% and 74%, respectively. Results from random effect models indicated that levels of the 1-NP metabolite 6-hydroxy-1-nitropyrene (6-OHNP) were significantly higher in parents compared with their children (p-value = 0.005). Urinary 1-NP metabolite levels were generally higher during the fall and winter months. Within-subject variability was higher than between-subject variability (~60% of total variance versus ~40%, respectively), indicating high short-term temporal variability. IMPACT: Biomonitoring, coupled with air monitoring, improves understanding of hyperlocal air pollution impacts. Results from these studies will inform the design of effective exposure mitigation strategies in disproportionately affected communities.