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 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.

Prenatal and Childhood Exposure to Organophosphate Pesticides and Behavior Problems in Adolescents and Young Adults in the CHAMACOS Study.

BACKGROUND: We previously reported associations of prenatal exposure to organophosphate (OP) pesticides with poorer neurodevelopment in early childhood and at school age, including poorer cognitive function and more behavioral problems, in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort study in an agriculture community. OBJECTIVE: We investigated the extent to which early-life exposure to OP pesticides is associated with behavioral problems, including mental health, in youth during adolescence and early adulthood. METHODS: We measured urinary dialkylphosphates (DAPs), nonspecific OP metabolites, in urine samples collected from mothers twice during pregnancy (13 and 26 wk) and at five different times in their children (ages 6 months to 5 y). We assessed maternal report and youth report of externalizing and internalizing behavior problems using the Behavior Assessment System for Children, 2nd edition (BASC-2), when the youth were ages 14, 16, and 18 y. Because there was evidence of nonlinearity, we estimated associations across quartiles of DAPs and modeled repeated outcome measures using generalized estimating equations. RESULTS: There were 335 youths with prenatal maternal DAP measures and 14-. 16-, or 18-y BASC-2 scores. Prenatal maternal DAP concentrations (specific gravity-adjusted median, Q1-Q3=159.4, 78.7-350.4 nmol/L) were associated with higher T-scores (more behavior problems) from maternal report, including more hyperactivity [fourth vs. first quartile of exposure ß=2.32; 95% confidence interval (CI): 0.18, 4.45], aggression (ß=1.90; 95% CI: 0.15, 3.66), attention problems (ß=2.78; 95% CI: 0.26, 5.30), and depression (ß=2.66; 95% CI: 0.08, 5.24). Associations with youth report of externalizing problems were null, and associations with depression were suggestive (fourth vs. first quartile of exposure ß=2.15; 95% CI: -0.36, 4.67). Childhood DAP metabolites were not associated with behavioral problems. DISCUSSION: We found associations of prenatal, but not childhood, urinary DAP concentrations with adolescent/young adult externalizing and internalizing behavior problems. These findings are consistent with prior associations we have reported with neurodevelopmental outcomes measured earlier in childhood in CHAMACOS participants and suggests that prenatal exposure to OP pesticides may have lasting effects on the behavioral health of youth as they mature into adulthood, including their mental health. https://doi.org/10.1289/EHP11380.

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.

Prenatal exposure to organophosphate pesticides and functional neuroimaging in adolescents living in proximity to pesticide application.

We have reported consistent associations of prenatal organophosphate pesticide (OP) exposure with poorer cognitive function and behavior problems in our Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS), a birth cohort of Mexican American youth in California's agricultural Salinas Valley. However, there is little evidence on how OPs affect neural dynamics underlying associations. We used functional near-infrared spectroscopy (fNIRS) to measure cortical activation during tasks of executive function, attention, social cognition, and language comprehension in 95 adolescent CHAMACOS participants. We estimated associations of residential proximity to OP use during pregnancy with cortical activation in frontal, temporal, and parietal regions using multiple regression models, adjusting for sociodemographic characteristics. OP exposure was associated with altered brain activation during tasks of executive function. For example, with a 10-fold increase in total OP pesticide use within 1 km of maternal residence during pregnancy, there was a bilateral decrease in brain activation in the prefrontal cortex during a cognitive flexibility task (ß = -4.74; 95% CI: -8.18, -1.31 and ß = -4.40; 95% CI: -7.96, -0.84 for the left and right hemispheres, respectively). We also found that prenatal OP exposure was associated with sex differences in brain activation during a language comprehension task. This first functional neuroimaging study of prenatal OP exposure suggests that pesticides may impact cortical brain activation, which could underlie previously reported OP-related associations with cognitive and behavioral function. Use of fNIRS in environmental epidemiology offers a practical alternative to neuroimaging technologies and enhances our efforts to assess the impact of chemical exposures on neurodevelopment.

A community-based education programme to reduce insecticide exposure from indoor residual spraying in Limpopo, South Africa.

BACKGROUND: Indoor residual spraying (IRS), the coating of interior walls of houses with insecticides, is common in malaria-endemic areas. While important in malaria control, IRS potentially exposes residents to harmful insecticides. The World Health Organization recommends steps to minimize exposure; however, no programme has focused on educating populations. METHODS: A dramatic presentation and song were developed by study personnel and performed by lay performers in order to spread awareness of the importance of IRS and to minimize insecticide exposure. Performances were staged at 16 sprayed villages in the Vhembe District of Limpopo, South Africa, at which 592 attendees completed short questionnaires before and after the performance about behaviors that might limit insecticide exposure. Overall indices of the attendees' change in knowledge of precautions to take prior to and after spraying to prevent insecticide exposure were analyzed using hierarchical mixed models to assess the effect of the performance on change in participants' knowledge. RESULTS: Approximately half of attendees lived in homes that had been sprayed for malaria and 62% were female. Over 90% thought it better to allow IRS prior to the presentation, but knowledge of proper precautions to prevent exposure was low. The proportion answering correctly about proper distance from home during spraying increased from 49.4% pre-performance to 62.0% post-performance (RR = 1.26, 95% CI = 1.13, 1.41), and the proportion reporting correctly about home re-entry interval after spraying increased from 58.5 to 91.1% (RR = 1.54, 95% CI 1.35, 1.77). Attendees improved in their knowledge about precautions to take prior to and after spraying from mean of 57.9% correct to a mean of 69.7% (ß = 12.1%, 95% CI 10.9, 13.4). Specifically, increased knowledge in closing cupboards, removing food and bedding from the home, covering immoveable items with plastic, and leading animals away from the home prior to spraying were observed, as was increased knowledge in sweeping the floors, proper disposal of dead insects, and discarding dirty washrags after spraying. CONCLUSIONS: A dramatic presentation and song were able to increase the attendees' knowledge of precautions to take prior to and after spraying in order to limit their insecticide exposure resulting from IRS. This approach to community education is promising and deserves additional study.

Associations of Maternal Exposure to Dichlorodiphenyltrichloroethane and Pyrethroids With Birth Outcomes Among Participants in the Venda Health Examination of Mothers, Babies and Their Environment Residing in an Area Sprayed for Malaria Control.

Although effective in controlling malaria, indoor residual spraying results in elevated exposure to insecticides such as dichlorodiphenyltrichloroethane (DDT) and pyrethroids. These chemicals cross the placenta, but no studies have examined their associations with birth outcomes in populations residing in indoor residual spraying areas. We investigated this question in the Venda Health Examination of Mothers, Babies and Their Environment (VHEMBE), a birth cohort study of 751 South African children born between 2012 and 2013. We measured maternal peripartum serum DDT and urine pyrethroid metabolite concentrations and collected data on birth weight, length, head circumference, and duration of gestation. We analyzed the data using marginal structural models with inverse-probability-of-treatment weights, generalized propensity scores, and standard conditional linear regression. Using all 3 analytical methods, p,p'-DDT, o,p'-DDT, and to a lesser extent p,p'-dichlorodiphenyldichloroethylene were related to elevated birth weight, birth length, and head circumference among girls. Changes in gestational duration did not mediate this relationship, suggesting that these exposures accelerate fetal growth, which is consistent with the known estrogenic properties of o,p'-DDT and p,p'-DDT. No associations with pyrethroid metabolites were found. Results suggest that prenatal exposure to DDT is related to elevated birth size. Further studies are needed to elucidate the implications of these findings.

Prenatal polybrominated diphenyl ether exposures and neurodevelopment in U.S. children through 5 years of age: the HOME study.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been widely used as flame retardants in furniture, carpet padding, car seats, and other consumer products during the past three decades. OBJECTIVE: We examined whether in utero exposure to PBDEs is associated with child cognitive function and behavior in a U.S. study sample. METHODS: In a prospective birth cohort, we measured maternal serum concentrations of BDE-47 and other PBDE congeners in 309 women at 16 weeks of gestation during 2003-2006 and followed their children in Cincinnati, Ohio. We measured cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years; intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years; and children's behaviors using the Behavioral Assessment System for Children-2 annually at ages 2-5 years. We used linear mixed models or generalized estimating equations with adjustment for potential confounders to estimate associations between these outcomes and log10-transformed PBDE concentrations. RESULTS: The geometric mean of BDE-47 in maternal serum (20.1 ng/g lipid) was comparable with U.S. adult national reference values. Prenatal BDE-47 was not significantly associated with Bayley Mental or Psychomotor Development Indices at 1-3 years, but a 10-fold increase in prenatal BDE-47 was associated with a 4.5-point decrease (95% CI: -8.8, -0.1) in Full-Scale IQ and a 3.3-point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years. CONCLUSIONS: Prenatal exposure to PBDEs was associated with lower IQ and higher hyperactivity scores in children.

Differences in lung cancer mortality trends from 1986-2012 by radon risk areas in British Columbia, Canada.

Residential exposure to radon gas is associated with increased risk of lung cancer, especially in smokers. Most evidence about the health effects of radon has been derived from meta-analyses on global epidemiologic studies, but administrative data can help public health authorities to explore the local impacts. Eighty health units in British Columbia (BC), Canada, were classified as having low, moderate, or high radon risk using more than 3,800 residential measurements. Vital statistics records were used to identify deaths due to lung cancer and to all natural causes. The annual ratio of lung cancer mortality to all natural mortality was plotted for the 1986-2012 study period for each radon classification. Visualizations were stratified by gender and by smoking prevalence. The overall ratio increased throughout the study period in high radon areas and remained stable in low and moderate radon areas. The increase was most pronounced for females, especially when plots were stratified by smoking prevalence. These limited but interesting findings confirm that radon is one risk factor for lung cancer mortality in BC and that its effects differ across gender and smoking strata. The results would be strengthened by replication, and more rigorous methods are required to assess other contributing factors.

A comparison of two methods for ecologic classification of radon exposure in British Columbia: residential observations and the radon potential map of Canada.

OBJECTIVE: To compare ecologic classification of radon exposure from observed residential concentrations in BC with classifications based on a map that shows geological radon potential, with particular attention to high-smoking populations. METHODS: First, residential radon measurements from four health agencies were used to classify 74 local health areas (LHAs) as low, moderate, or high exposure based on the number of homes with concentrations greater than 200 and 600 Bq/m³. Second, the Zone 1 (high), Zone 2 (elevated), and Zone 3 (guarded) risk categories of the radon potential map of Canada were used to make the same exposure classifications based on the population-weighted area of each zone in each LHA. Agreement was compared and quantified. Average smoking rates in each LHA were used to further assess agreement for smokers, who are a high-risk group. RESULTS: Both methods showed a range of exposure across LHAs. The radon potential map classified more areas as high exposure than the observed radon concentrations, and the methods agreed in 30 of 74 LHAs. The radon potential map identified much of the southern coastal region as high exposure, but 617 of the 621 observed concentrations were ≤200 Bq/m³, and no observations were >600 Bq/m³. An estimated 36% of the BC population and 35% of BC smokers live in the southern coastal region. CONCLUSIONS: The radon potential map of Canada may communicate potential radon risk, but it was not designed for epidemiologic exposure assessment. Overall, the potential map classified 34 LHAs as higher than observed, and 10 LHAs as lower than observed. The potential map should only be used to inform exposure assessment in conjunction with observed radon concentrations.

In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study.

BACKGROUND: California children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals. OBJECTIVE: Here we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort. METHODS: We measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children's attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323). RESULTS: Maternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination-particularly in the nondominant-at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels. CONCLUSIONS: Both prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development.

Prevention of disability in children: elevating the role of environment.

Much public attention and many resources are focused on medical research to identify risk factors and mitigate symptoms of disability for individual children. But this focus will inevitably fail to prevent disabilities. Stephen Rauch and Bruce Lanphear argue for a broader focus on environmental influences that put entire populations at risk. They argue that identifying and eliminating or controlling environmental risk factors that incrementally increase the prevalence of disability is the key to preventing many disorders. Rauch and Lanphear examine emerging evidence that many disabilities of childhood have their roots in the environment--from toxins in air, water, and soil, to the stressors of poverty, to marketing practices that encourage unhealthy choices or discourage healthy ones. They review research on well-known environmental causes of disability, such as exposures to lead, cigarette smoke, and industrial air pollution. They point to new evidence suggesting that chemicals found in commonly used plastics may have subtle but serious effects on child development, and that many disabilities spring from the complex interplay of environmental risk factors and genetic susceptibility. Rauch and Lanphear make a case for turning our attention to societal or population-level interventions that would rely less on medical and genetic technology and more on policies and regulations that would reduce children's exposure to ubiquitous environmental risks. Examples include required testing of new chemicals for developmental toxicity before they are put on the market; zoning regulations that separate residential communities from industrial areas; and restrictions on advertising of unhealthy products, such as tobacco, alcohol, and junk foods, to children. Rauch and Lanphear outline and assess the effectiveness of interventions that could be adopted, and suggest what a healthy modern community might look like. Such interventions, they acknowledge, are likely to be highly controversial, require both long-term investments and shifts in societal thinking, and produce less well-defined outcomes than individual medical treatments. But in the long run, the authors contend, such interventions could prevent many of the disabilities that now afflict millions of children and adults.