Residential proximity to agricultural pesticide use and cardiovascular disease risk factors among adult Latina women in California's Salinas Valley.

Cardiovascular disease is a leading cause of death worldwide. There is limited evidence that exposure to current-use pesticides may contribute to cardiovascular disease risk. We examined the association between residential proximity to the application of agricultural pesticides and cardiovascular risk factors among 484 adult women in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a cohort based in an agricultural region of California. Outcome assessment was completed between 2010 and 2013. Using participant residential addresses and California's Pesticide Use Reporting database, we estimated agricultural pesticide use within one km of residences during the 2-year period preceding outcome assessment. We used Bayesian Hierarchical Modeling to evaluate associations between exposure to 14 agricultural pesticides and continuous measures of waist circumference, body mass index, and blood pressure. Each 10-fold increase in paraquat application around homes was associated with increased diastolic blood pressure (ß=2.60 mm Hg, 95% Credible Interval (CrI): 0.27-4.89) and each 10-fold increase in glyphosate application was associated with increased pulse pressure (ß=2.26 mm Hg, 95% CrI: 0.09-4.41). No meaningful associations were observed for the other pesticides examined. Our results suggest that paraquat and glyphosate pesticides may affect cardiovascular disease development in women with chronic environmental exposure.

Pregnancy outcomes and vaccine effectiveness during the period of omicron as the variant of concern, INTERCOVID-2022: a multinational, observational study.

BACKGROUND: In 2021, we showed an increased risk associated with COVID-19 in pregnancy. Since then, the SARS-CoV-2 virus has undergone genetic mutations. We aimed to examine the effects on maternal and perinatal outcomes of COVID-19 during pregnancy, and evaluate vaccine effectiveness, when omicron (B.1.1.529) was the variant of concern. METHODS: INTERCOVID-2022 is a large, prospective, observational study, involving 41 hospitals across 18 countries. Each woman with real-time PCR or rapid test, laboratory-confirmed COVID-19 in pregnancy was compared with two unmatched women without a COVID-19 diagnosis who were recruited concomitantly and consecutively in pregnancy or at delivery. Mother and neonate dyads were followed until hospital discharge. Primary outcomes were maternal morbidity and mortality index (MMMI), severe neonatal morbidity index (SNMI), and severe perinatal morbidity and mortality index (SPMMI). Vaccine effectiveness was estimated, adjusted by maternal risk profile. FINDINGS: We enrolled 4618 pregnant women from Nov 27, 2021 (the day after WHO declared omicron a variant of concern), to June 30, 2022: 1545 (33%) women had a COVID-19 diagnosis (median gestation 36·7 weeks [IQR 29·0-38·9]) and 3073 (67%) women, with similar demographic characteristics, did not have a COVID-19 diagnosis. Overall, women with a diagnosis had an increased risk for MMMI (relative risk [RR] 1·16 [95% CI 1·03-1·31]) and SPMMI (RR 1·21 [95% CI 1·00-1·46]). Women with a diagnosis, compared with those without a diagnosis, also had increased risks of SNMI (RR 1·23 [95% CI 0·88-1·71]), although the lower bounds of the 95% CI crossed unity. Unvaccinated women with a COVID-19 diagnosis had a greater risk of MMMI (RR 1·36 [95% CI 1·12-1·65]). Severe COVID-19 symptoms in the total sample increased the risk of severe maternal complications (RR 2·51 [95% CI 1·84-3·43]), perinatal complications (RR 1·84 [95% CI 1·02-3·34]), and referral, intensive care unit (ICU) admission, or death (RR 11·83 [95% CI 6·67-20·97]). Severe COVID-19 symptoms in unvaccinated women increased the risk of MMMI (RR 2·88 [95% CI 2·02-4·12]) and referral, ICU admission, or death (RR 20·82 [95% CI 10·44-41·54]). 2886 (63%) of 4618 total participants had at least a single dose of any vaccine, and 2476 (54%) of 4618 had either complete or booster doses. Vaccine effectiveness (all vaccines combined) for severe complications of COVID-19 for all women with a complete regimen was 48% (95% CI 22-65) and 76% (47-89) after a booster dose. For women with a COVID-19 diagnosis, vaccine effectiveness of all vaccines combined for women with a complete regimen was 74% (95% CI 48-87) and 91% (65-98) after a booster dose. INTERPRETATION: COVID-19 in pregnancy, during the first 6 months of omicron as the variant of concern, was associated with increased risk of severe maternal morbidity and mortality, especially among symptomatic and unvaccinated women. Women with complete or boosted vaccine doses had reduced risk for severe symptoms, complications, and death. Vaccination coverage among pregnant women remains a priority. FUNDING: None.

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.

Maternal exposure to pyrethroid insecticides during pregnancy and respiratory allergy symptoms among children participating in the Venda Health Examination of Mothers, Babies and their Environment (VHEMBE).

BACKGROUND: Pyrethroid insecticides use for indoor residual spraying (IRS) in malaria-endemic areas results in high levels of exposure to local populations. Pyrethroids may cause asthma and respiratory allergies but no prior study has investigated this question in an IRS area. METHODS: We measured maternal urinary concentrations of pyrethroid metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA) in samples collected at delivery from 751 mothers participating in the Venda Health Examination of Mothers, Babies, and their Environment (VHEMBE), a birth cohort study based in Limpopo, South Africa. At 3.5-year and 5-year follow-up visits, caregivers of 647 and 620 children, respectively, were queried about children's respiratory allergy symptoms based on validated instruments. We applied marginal structural models for repeated outcomes to estimate associations between biomarker concentrations and asthma diagnosis as well as respiratory allergy symptoms at ages 3.5 and 5 years. RESULTS: We found that a10-fold increase in maternal urinary cis-DCCA, trans-DCCA and 3-PBA concentrations were associated with more than a doubling in the risk of doctor-diagnosed asthma (cis-DCCA: RR = 2.1, 95% CI = 1.3, 3.3; trans-DCCA: RR = 2.1, 95% CI = 1.1, 3.9; 3-PBA: RR = 2.4, 95% CI = 1.0, 5.8) and an about 80% increase in the risk of wheezing or whistling in the chest (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.0; trans-DCCA: RR = 1.7, 95% CI = 1.1, 2.6; 3-PBA: RR = 1.8, 95% CI = 1.0, 3.3) and suspected asthma (cis-DCCA: RR = 1.8, 95% CI = 1.1, 3.1; trans-DCCA: RR = 1.8, 95% CI = 1.1, 2.8). We also observed that higher concentrations of cis-DBCA and 3-PBA were related to increases in the risks of dry cough at night (RR = 3.5, 95% CI = 1.3, 9.5) and seasonal rhinoconjunctivitis (RR = 2.0, 95% CI = 1.1, 3.9), respectively. CONCLUSION: Maternal exposure to pyrethroids may increase the risk of asthma and other respiratory allergy symptoms among preschool children from an IRS area.

Prenatal and childhood exposure to organophosphate pesticides and functional brain imaging in young adults.

BACKGROUND: Early life exposure to organophosphate (OP) pesticides has been linked with poorer neurodevelopment from infancy to adolescence. In our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) birth cohort, we previously reported that residential proximity to OP use during pregnancy was associated with altered cortical activation using functional near infrared spectroscopy (fNIRS) in a small subset (n = 95) of participants at age 16 years. METHODS: We administered fNIRS to 291 CHAMACOS young adults at the 18-year visit. Using covariate-adjusted regression models, we estimated associations of prenatal and childhood urinary dialkylphosphates (DAPs), non-specific OP metabolites, with cortical activation in the frontal, temporal, and parietal regions of the brain during tasks of executive function and semantic language. RESULTS: There were some suggestive associations for prenatal DAPs with altered activation patterns in both the inferior frontal and inferior parietal lobes of the left hemisphere during a task of cognitive flexibility (ß per ten-fold increase in DAPs = 3.37; 95% CI: -0.02, 6.77 and ß = 3.43; 95% CI: 0.64, 6.22, respectively) and the inferior and superior frontal pole/dorsolateral prefrontal cortex of the right hemisphere during the letter retrieval working memory task (ß = -3.10; 95% CI: -6.43, 0.22 and ß = -3.67; 95% CI: -7.94, 0.59, respectively). We did not observe alterations in cortical activation with prenatal DAPs during a semantic language task or with childhood DAPs during any task. DISCUSSION: We observed associations of prenatal OP concentrations with mild alterations in cortical activation during tasks of executive function. Associations with childhood exposure were null. This is reasonably consistent with studies of prenatal OPs and neuropsychological measures of attention and executive function found in CHAMACOS and other birth cohorts.

Organophosphate pesticide exposure and risk of SARS-CoV-2 infection.

Several studies have reported immune modulation by organophosphate (OP) pesticides, but the relationship between OP exposure and SARS-CoV-2 infection is yet to be studied. We used two different measures of OP pesticide exposure (urinary biomarkers (N = 154) and residential proximity to OP applications (N = 292)) to examine the association of early-childhood and lifetime exposure to OPs and risk of infection of SARS-CoV-2 using antibody data. Our study population consisted of young adults (ages 18-21 years) from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) Study, a longitudinal cohort of families from a California agricultural region. Urinary biomarkers reflected exposure from in utero to age 5 years. Residential proximity reflected exposures between in utero and age 16 years. SARS-CoV-2 antibodies in blood samples collected between June 2022 and January 2023 were detected via two enzyme linked immunosorbent assays, each designed to bind to different SARS-CoV-2 antigens. We performed logistic regression for each measure of pesticide exposure, adjusting for covariates from demographic data and self-reported questionnaire data. We found increased odds of SARS-CoV-2 infection among participants with higher urinary biomarkers of OPs in utero (OR = 1.94, 95% CI: 0.71, 5,58) and from age 0-5 (OR = 1.90, 95% CI: 0.54, 6.95).

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.

Impacts of COVID-19 shelter in place across key life domains among immigrant farmworker Latina mothers and young adults.

OBJECTIVE: Individuals and families from racial and ethnic groups experience social and economic disadvantage making them vulnerable to the disproportionate impact of the COVID-19 pandemic. This study sought to capture the impacts of Shelter in Place (SIP) across key life domains including family life, education, work, mental health, and coping strategies among a sample of Mexican-origin mothers who were currently engaged in agricultural work, or whose spouses were engaged in agricultural work, and young adults who had a parent working in agriculture. METHOD: During the summer of 2020, while California was under SIP orders, we conducted three virtual focus groups using Zoom(r). We recruited focus group participants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), an ongoing, 20-year, longitudinal cohort study of Mexican-origin families in a predominantly agricultural area of California. Three focus groups were conducted with mothers (n = 9), mean age = 48 years, young adult women (n = 8) and young adult men (n = 5), mean age = 18 years, respectively. RESULTS: Mothers reported high levels of stress stemming from fear of Covid-19 infection, work instability and financial concerns, children's schooling, anxiety about an uncertain future, and the demands of caretaking for dependents. Adverse mental health impacts were particularly pronounced among participants experiencing multiple adversities pre-dating the pandemic, including unemployment, single motherhood, and having undocumented family members. For young adults, work instability and varying work hours were also a source of stress because they made it difficult to make decisions about the future, such as whether to attend college or how many classes to take. Families used coping strategies including expressing gratitude, focusing on what's under one's control, familismo, and community engagement to manage mental health challenges during SIP. CONCLUSION: In the event of future pandemics or disasters, particular attention is needed to those who experience unemployment, are undocumented and/or have undocumented family members, and/or are single parents facing economic adversity. During public health emergencies, action at the local, state, and national level is needed to support farmworkers and other vulnerable groups' secondary major stressors stemming from inequities in access to affordable housing, childcare, living wages, healthcare, and other benefits.

Association of Upper Respiratory Streptococcus pneumoniae Colonization With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Adults.

BACKGROUND: Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. RESULTS: Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08-7.75]) and among symptomatic participants (3.38 [1.35-8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00-1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and noncarriers, respectively). CONCLUSIONS: Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.

Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall (total N = 2196), verbal (total N = 2206) and non-verbal cognitive scores (total N = 3300). The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that variation in cord blood DNA methylation at single CpG sites is associated with cognitive skills and further studies are needed to confirm the association at DUSP22.

Associations between prenatal phthalate exposure and childhood epigenetic age acceleration.

BACKGROUND: Phthalates, a group of pervasive endocrine-disrupting chemicals found in plastics and personal care products, have been associated with a wide range of developmental and health outcomes. However, their impact on biomarkers of aging has not been characterized. We tested associations between prenatal exposure to 11 phthalate metabolites on epigenetic aging in children at birth, 7, 9, and 14 years of age. We hypothesized that prenatal phthalate exposure will be associated with epigenetic age acceleration measures at birth and in early childhood, with patterns dependent on sex and timing of DNAm measurement. METHODS: Among 385 mother-child pairs from the CHAMACOS cohort, we measured DNAm at birth, 7, 9, and 14 years of age, and utilized adjusted linear regression to assess the association between prenatal phthalate exposure and Bohlin's Gestational Age Acceleration (GAA) at birth and Intrinsic Epigenetic Age Acceleration (IEAA) throughout childhood. Additionally, quantile g-computation was utilized to assess the effect of the phthalate mixture on GAA at birth and IEAA throughout childhood. RESULTS: We found a negative association between prenatal di (2-ethylhexyl) phthalate (DEHP) exposure and IEAA among males at age 7 (-0.62 years; 95% CI:-1.06 to -0.18), and a marginal negative association between the whole phthalate mixture and GAA among males at birth (-1.54 days, 95% CI: -2.79 to -0.28), while most other associations were nonsignificant. CONCLUSIONS: Our results suggest that prenatal exposure to certain phthalates is associated with epigenetic aging in children. Additionally, our findings suggest that the influence of prenatal exposures on epigenetic age may only manifest during specific periods of child development, and studies relying on DNAm measurements solely from cord blood or single time points may overlook potential relationships.

Dampened psychobiological responses to stress and substance use in adolescence.

Substance use increases throughout adolescence, and earlier substance use may increase risk for poorer health. However, limited research has examined whether stress responses relate to adolescent substance use, especially among adolescents from ethnic minority and high-adversity backgrounds. The present study assessed whether blunted emotional and cortisol responses to stress at age 14 related to substance use by ages 14 and 16, and whether associations varied by poverty status and sex. A sample of 277 Mexican-origin youth (53.19% female; 68.35% below the poverty line) completed a social-evaluative stress task, which was culturally adapted for this population, and provided saliva samples and rated their anger, sadness, and happiness throughout the task. They also reported whether they had ever used alcohol, marijuana, cigarettes, and vaping of nicotine at age 14 and again at age 16. Multilevel models suggested that blunted cortisol reactivity to stress was associated with alcohol use by age 14 and vaping nicotine by age 16 among youth above the poverty line. Also, blunted sadness and happiness reactivity to stress was associated with use of marijuana and alcohol among female adolescents. Blunted stress responses may be a risk factor for substance use among youth above the poverty line and female adolescents.

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.

Prenatal Exposure to Insecticides and Weight Trajectories Among South African Children in the VHEMBE Birth Cohort.

BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides are sprayed inside dwellings for malaria vector control, resulting in high exposure to millions of people, including pregnant women. These chemicals disrupt endocrine function and may affect child growth. To our knowledge, few studies have investigated the potential impact of prenatal exposure to DDT or pyrethroids on growth trajectories. METHODS: We investigated associations between gestational insecticide exposure and child growth trajectories in the Venda Health Examination of Mothers, Babies and their Environment, a birth cohort of 751 children born between 2012 and 2013 in South Africa. Based on child weight measured at follow-up and abstracted from medical records, we modeled weight trajectories from birth to 5 years using SuperImposition, Translation and Rotation, which estimated two child-specific parameters: size (average weight) and tempo (age at peak weight velocity). We estimated associations between peripartum maternal concentrations of serum DDT, dichlorodiphenyldichloroethylene, or urinary pyrethroid metabolites and SuperImposition, Translation and Rotation parameters using marginal structural models. RESULTS: We observed that a 10-fold increase in maternal concentrations of the pyrethroid metabolite trans-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid was associated with a 21g (95% confidence interval = -40, -1.6) smaller size among boys but found no association among girls (Pinteraction = 0.07). Estimates suggested that pyrethroids may be associated with earlier tempo but were imprecise. We observed no association with serum DDT or dichlorodiphenyldichloroethylene. CONCLUSIONS: Inverse associations between pyrethroids and weight trajectory parameters among boys are consistent with hypothesized disruption of androgen pathways and with our previous research in this population, and support the endocrine-disrupting potential of pyrethroids in humans.

Diabetes mellitus, maternal adiposity, and insulin-dependent gestational diabetes are associated with COVID-19 in pregnancy: the INTERCOVID study.

BACKGROUND: Among nonpregnant individuals, diabetes mellitus and high body mass index increase the risk of COVID-19 and its severity. OBJECTIVE: This study aimed to determine whether diabetes mellitus and high body mass index are risk factors for COVID-19 in pregnancy and whether gestational diabetes mellitus is associated with COVID-19 diagnosis. STUDY DESIGN: INTERCOVID was a multinational study conducted between March 2020 and February 2021 in 43 institutions from 18 countries, enrolling 2184 pregnant women aged ≥18 years; a total of 2071 women were included in the analyses. For each woman diagnosed with COVID-19, 2 nondiagnosed women delivering or initiating antenatal care at the same institution were also enrolled. The main exposures were preexisting diabetes mellitus, high body mass index (overweight or obesity was defined as a body mass index ≥25 kg/m2), and gestational diabetes mellitus in pregnancy. The main outcome was a confirmed diagnosis of COVID-19 based on a real-time polymerase chain reaction test, antigen test, antibody test, radiological pulmonary findings, or ≥2 predefined COVID-19 symptoms at any time during pregnancy or delivery. Relationships of exposures and COVID-19 diagnosis were assessed using generalized linear models with a Poisson distribution and log link function, with robust standard errors to account for model misspecification. Furthermore, we conducted sensitivity analyses: (1) restricted to those with a real-time polymerase chain reaction test or an antigen test in the last week of pregnancy, (2) restricted to those with a real-time polymerase chain reaction test or an antigen test during the entire pregnancy, (3) generating values for missing data using multiple imputation, and (4) analyses controlling for month of enrollment. In addition, among women who were diagnosed with COVID-19, we examined whether having gestational diabetes mellitus, diabetes mellitus, or high body mass index increased the risk of having symptomatic vs asymptomatic COVID-19. RESULTS: COVID-19 was associated with preexisting diabetes mellitus (risk ratio, 1.94; 95% confidence interval, 1.55-2.42), overweight or obesity (risk ratio, 1.20; 95% confidence interval, 1.06-1.37), and gestational diabetes mellitus (risk ratio, 1.21; 95% confidence interval, 0.99-1.46). The gestational diabetes mellitus association was specifically among women requiring insulin, whether they were of normal weight (risk ratio, 1.79; 95% confidence interval, 1.06-3.01) or overweight or obese (risk ratio, 1.77; 95% confidence interval, 1.28-2.45). A somewhat stronger association with COVID-19 diagnosis was observed among women with preexisting diabetes mellitus, whether they were of normal weight (risk ratio, 1.93; 95% confidence interval, 1.18-3.17) or overweight or obese (risk ratio, 2.32; 95% confidence interval, 1.82-2.97). When the sample was restricted to those with a real-time polymerase chain reaction test or an antigen test in the week before delivery or during the entire pregnancy, including missing variables using imputation or controlling for month of enrollment, the observed associations were comparable. CONCLUSION: Diabetes mellitus and overweight or obesity were risk factors for COVID-19 diagnosis in pregnancy, and insulin-dependent gestational diabetes mellitus was associated with the disease. Therefore, it is essential that women with these comorbidities are vaccinated.

Breastmilk, Stool, and Meconium: Bacterial Communities in South Africa.

Human milk optimizes gut microbial richness and diversity, and is critical for proper immune development. Research has shown differing microbial composition based on geographic location, providing evidence that diverse biospecimen data is needed when studying human bacterial communities. Yet, limited research describes human milk and infant gut microbial communities in Africa. Our study uses breastmilk, stool, and meconium samples from a South African birth cohort to describe the microbial diversity, identify distinct taxonomic units, and determine correlations between bacterial abundance in breastmilk and stool samples. Mother-infant dyads (N = 20) were identified from a longitudinal birth cohort in the Vhembe district of Limpopo Province, South Africa. Breastmilk, meconium, and stool samples were analyzed using 16S ribosomal RNA sequencing of the V4-V5 gene region using the MiSeq platform for identification and relative quantification of bacterial taxa. A non-metric multidimensional scaling using Bray-Curtis distances of sample Z-scores showed that meconium, stool, and breastmilk microbial communities are distinct with varying genus. Breastmilk was mostly comprised of Streptococcus, Staphylococcus, Veillonella, and Corynebacterium. Stool samples showed the highest levels of Bifidobacterium, Faecalibacterium, Bacteroides, and Streptococcus. Alpha diversity measures found that stool samples have the highest Shannon index score compared to breastmilk and meconium. The abundance of Bifidobacterium (r = 0.57), Blautia (r = 0.59), and Haemophilus (r = 0.69) was correlated (p < 0.1) between breastmilk and stool samples. Despite the importance of breastmilk in seeding the infant gut microbiome, we found evidence of distinct bacterial communities between breastmilk and stool samples from South African mother-infant dyads.

Residential proximity to agricultural pesticide use and risk-taking behaviors in young adults from the CHAMACOS study.

BACKGROUND: Prenatal pesticide exposure has been associated with poorer neurodevelopment during childhood, which could lead to greater risk-taking behaviors and delinquency in adolescence. This association may be augmented by adversity exposure. OBJECTIVES: Evaluate the relationship between prenatal pesticide exposure and risk-taking behavior in young adults at 18-years of age. Assess whether adversity exposure modifies these associations. METHODS: Participants included mother-child dyads (n = 467) enrolled in the Center for the Health Assessment of Mothers and Children Of Salinas (CHAMACOS) study, a longitudinal birth cohort set in the agricultural Salinas Valley of California. We estimated agricultural pesticide use within one km of maternal residences during pregnancy using a geographic information system, residential addresses, and California's Pesticide Use Reporting data. We used Bayesian hierarchical regression to evaluate associations of prenatal exposure to a mixture of 11 neurotoxic pesticides with self-reported police encounters, risk-taking behaviors, and unique types and frequency of delinquent acts. We also evaluated effect modification of these relationships by adversity exposure. RESULTS: We observed generally null associations of neurotoxic pesticide use with risk-taking behaviors. Prenatal residential proximity to chlorpyrifos use was associated with higher risk of a police encounter, a delinquent act, and higher incidence of both unique types of acts committed and total frequency of delinquent acts. Prenatal residential proximity to dimethoate use was associated with a higher incidence of police encounters and methomyl with a higher risk of committing a delinquent act. There were no consistent differences when stratified by the number of adverse childhood experiences. CONCLUSIONS: We observed mostly null associations between prenatal residential proximity to agricultural pesticide use and risk-taking behaviors at age 18, with little evidence of effect modification by childhood adversity. There were suggestive associations for chlorpyrifos use with having any police encounter and with all measures of delinquent acts that warrant confirmation in other studies.

Interactions of agricultural pesticide use near home during pregnancy and adverse childhood experiences on adolescent neurobehavioral development in the CHAMACOS study.

BACKGROUND: Studies have documented independent adverse associations between prenatal and early-life exposure to environmental chemicals and social adversity with child neurodevelopment; however, few have considered these exposures jointly. The objective of this analysis is to examine whether associations of pesticide mixtures and adolescent neurobehavioral development are modified by early-life adversity in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort. METHODS: We used linear mixed effects Bayesian Hierarchical Models (BHM) to examine the joint effect of applications of 11 agricultural pesticides within 1 km of maternal homes during pregnancy and youth-reported Adverse Childhood Experiences (ACEs) with maternal and youth-reported internalizing behaviors, hyperactivity, and attention problems assessed via the Behavior Assessment for Children (BASC) (mean = 50, standard deviation = 10) at ages 16 and 18 years (n = 458). RESULTS: The median (25th-75th percentiles) of ACEs was 1 (0-3); 72.3% of participants had low ACEs (0-2 events) and 27.7% had ACEs (3+ events). Overall, there was little evidence of modification of exposure-outcome associations by ACEs. A two-fold increase in malathion use was associated with increased internalizing behaviors among those with high ACEs from both maternal- (ß = 1.9; 95% Credible Interval (CrI): 0.2, 3.7 for high ACEs vs. ß = -0.1; 95% CrI: 1.2, 0.9 for low ACEs) and youth-report (ß = 2.1; 95% CrI: 0.4, 3.8 for high ACEs vs. ß = 0.2; 95% CrI: 0.8, 1.2 for low ACEs). Applications of malathion and dimethoate were also associated with higher youth-reported hyperactivity and/or inattention among those with high ACEs. CONCLUSION: We observed little evidence of effect modification of agricultural pesticide use near the home during pregnancy and adolescent behavioral problems by child ACEs. Future studies should examine critical windows of susceptibility of exposure to chemical and non-chemical stressors and should consider biomarker-based exposure assessment methods.

Exposure to DDT and DDE and functional neuroimaging in adolescents from the CHAMACOS cohort.

BACKGROUND: Epidemiological studies suggest that exposure to p,p'-dichloro-diphenyl-trichloroethane (p,p'-DDT) is associated with poorer cognitive function in children and adolescents, but the neural mechanisms underlying this association remain unclear. OBJECTIVE: We investigated associations of prenatal and childhood exposure to p,p'-DDT and its metabolite p,p'-dichloro-diphenyl-dichloroethylene (p,p'-DDE) with cortical activation in adolescents using functional near-infrared spectroscopy (fNIRS). METHODS: We administered fNIRS to 95 adolescents from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) aged 15-17 years. We assessed cortical activity in the frontal, temporal, and parietal brain regions while participants completed tasks of executive function, language comprehension, and social cognition. We measured serum p,p'-DDT and -DDE concentrations at age 9 years and then estimated exposure-outcome associations using linear regression models adjusted for sociodemographic characteristics. In secondary analyses, we back-extrapolated prenatal concentrations using prediction models and examined their association with cortical activation. RESULTS: Median (P25-P75) p,p'-DDT and -DDE concentrations in childhood were 1.4 (1-2.3) and 141.5 (75.0-281.3) ng/g lipid, respectively. We found that childhood exposure to p,p'-DDT and -DDE was associated with altered patterns of brain activation during tasks of cognition and executive functions. For example, we observed increased activity in the left frontal lobe during a language comprehension task (ß per 10 ng/g lipid increase of serum p,p'-DDE at age 9 years = 3.4; 95% CI: 0.0, 6.9 in the left inferior frontal lobe; and ß = 4.2; 95% CI: 0.9, 7.5 in the left superior frontal lobe). We found no sex differences in the associations of childhood p,p'-DDT and -DDE concentrations with neural activity. Associations between prenatal p,p'-DDT and p,p'-DDE concentrations and brain activity were similar to those observed for child p,p'-DDT and -DDE concentrations. CONCLUSIONS: Childhood p,p'-DDT and -DDE exposure may impact cortical brain activation, which could be an underlying mechanism for its previously reported associations with poorer cognitive function.

Prenatal exposure to organophosphate pesticides and risk-taking behaviors in early adulthood.

INTRODUCTION: Previous studies show evidence for associations of prenatal exposure to organophosphate (OP) pesticides with poorer childhood neurodevelopment. As children grow older, poorer cognition, executive function, and school performance can give rise to risk-taking behaviors, including substance abuse, delinquency, and violent acts. We investigated whether prenatal OP exposure was associated with these risk-taking behaviors in adolescence and young adulthood in a Mexican American cohort. METHODS: We measured urinary dialkyl phosphates (DAPs), non-specific metabolites of OPs, twice (13 and 26 weeks gestation) in pregnant women recruited in 1999-2000 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort set in a primarily Latino agricultural community in the Salinas Valley, California. We followed up children throughout their childhood and adolescence; at the 18-year visit, adolescent youth (n = 315) completed a computer-based questionnaire which included questions about substance use, risky sexual activity, risky driving, and delinquency and police encounters. We used multivariable models to estimate associations of prenatal total DAPs with these risk-taking behaviors. RESULTS: The prevalence of risk-taking behaviors in CHAMACOS youth ranged from 8.9% for smoking or vaping nicotine to 70.2% for committing a delinquent act. Associations of total prenatal DAPs (geometric mean = 132.4 nmol/L) with risk-taking behavior were generally null and imprecise. Isolated findings included a higher risk for smoking or vaping nicotine within the past 30 days (relative risk [RR] per 10-fold increase in prenatal DAPs = 1.89, 95% CI: 1.00, 3.56) and driving without a license (RR = 1.74, 95% CI: 1.25, 2.42). There were no consistent differences by sex or childhood adversity. DISCUSSION: We did not find clear or consistent evidence for associations of prenatal OP exposure with risk-taking behaviors in adolescence/early adulthood in the CHAMACOS population. Our small sample size may have prevented us from detecting potentially subtle associations of early life OP exposure with these risk-taking behaviors.