Placental transcriptome variation associated with season, location, and urinary prenatal pyrethroid metabolites of Thai farm-working women.

Prenatal exposure to pyrethroids is linked to adverse health effects in early life and proper placental function is critical to fetal development. This study explores the impact of prenatal pyrethroid exposure, as well as factors impacting exposure and effect, on the placental transcriptome, to understand pyrethroid exposures' relationship to placental function. The study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) recruited pregnant farm-working women from two agricultural districts in the Chiang Mai province of Thailand between 2017 and 2019. This cohort was predominantly exposed to cypermethrin (type II), alongside pyrethroids such as cyfluthrin (type II) and permethrin (type I). In 253 participants, maternal urinary pyrethroid metabolites, 3-phenoxybenzoic acid (PBA), cis-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (CDCCA), and trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (TDCCA) were measured in early, middle, and late pregnancy and adjusted for urinary creatinine. The placental transcriptome was analyzed using RNA-Seq. Using generalized linear regression, we identified differentially expressed genes (DEGs) associated with the sum of each metabolite across pregnancy, as well as those associated with location of residence and season of birth. Pathway and upstream transcription factor analyses were performed to examine potential mechanisms associated with DEGs. Notably, TDCCA and CDCCA levels peaked in late pregnancy, with significant regional differences, particularly higher levels in the Fang region. Placental gene expression analysis showed no DEGs associated with individual metabolites at FDR<0.05. However, 251 DEGs by location, implicating immune response and oxidative phosphorylation pathways, were identified, while season of birth was associated with 2585 DEGs, over-represented in fibrosis signaling and metabolism pathways. Finally, transcription factor analysis identified 226 and 282 transcription factors associated with location and season, respectively, related to cell proliferation, differentiation, and the immune system. These alterations may have significant implications for fetal development and other pathologic processes, highlighting the importance of monitoring environmental exposures during pregnancy.

Environmental Health Literacy Regarding Fine Particulate Matter and Related Factors Among Village Health Volunteers in Upper Northern Thailand.

OBJECTIVES: Fine particulate matter pollution has emerged as a significant life-threatening issue in Thailand. Recognizing the importance of environmental health literacy (EHL) in disease prevention is crucial for protecting public health. This study investigated EHL levels and aimed to identify associated factors among village health volunteers (VHVs) in the upper northern region of Thailand. METHODS: A cross-sectional study was conducted to collect data from 710 VHVs using the EHL assessment tool developed by the Department of Health, Thailand. RESULTS: The overall EHL score was moderate (mean, 3.28 out of a possible 5.0), with the highest and lowest domain-specific mean score for the ability to make decisions (3.52) and the ability to access (3.03). Multiple linear regression revealed that the factors associated with EHL score were area of residence (urban areas in Chiang Mai: B=0.254; urban areas in Lampang: B=0.274; and rural areas in Lampang: B=0.250 compared to rural areas in Chiang Mai), higher education levels (senior high school: B=0.212; diploma/high vocational certificate: B=0.350; bachelor's degree or above: B=0.528 compared to elementary school or lower), having annual health checkups compared to not having annual health check-ups (B=0.142), monthly family income (B=0.004), and individuals frequently facing air pollution issues around their residence (B=0.199) compared to those who reported no such issues. CONCLUSIONS: The VHVs exhibited moderate EHL associated with residence area, education, health check-ups, family income, and residential air pollution. Considering these factors is vital for enhancing VHVs' EHL through strategic interventions.

Association of prenatal chlorpyrifos exposure with sexually dimorphic differences in anogenital distance among Thai farmworker children.

Organophosphate (OP) insecticides are some of the most abundantly used insecticides, and prenatal exposures have been linked to adverse maternal and child health outcomes. Anogenital distance (AGD) has emerged as an early marker of androgen activity, and later reproductive outcomes, that is sensitive to alteration by environmental chemicals. Here, we examined associations between prenatal exposure to chlorpyrifos, an OP insecticide, with AGD. Pregnant farmworkers were enrolled in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE; N = 104) between 2017 and 2019 in Northern Thailand. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos, were measured in composited urine samples obtained from each trimester of pregnancy. AGD was measured at 12 months of age. Sex-specific adjusted linear regression models were used to examine associations between average and trimester-specific TCPy levels and AGD. In adjusted models for females and males, increasing TCPy was consistently associated with a modest, non-significant reduction in AGD. Across both strata of sex, associations were greatest in magnitude for trimester 3 (females: ß = -2.17, 95 % confidence interval (CI) = -4.99, 0.66; males: ß = -3.02, 95 % CI = -6.39, 0.35). In the SAWASDEE study, prenatal chlorpyrifos exposure was not strongly associated with AGD at 12 months of age.

Unveiling the Aftermath: Exploring Residue Profiles of Insecticides, Herbicides, and Fungicides in Rice Straw, Soils, and Air Post-Mixed Pesticide-Contaminated Biomass Burning.

This study delved into the impact of open biomass burning on the distribution of pesticide and polycyclic aromatic hydrocarbon (PAH) residues across soil, rice straw, total suspended particulates (TSP), particulate matter with aerodynamic diameter ≤ 10 µm (PM10), and aerosols. A combination of herbicides atrazine (ATZ) and diuron (DIU), fungicide carbendazim (CBD), and insecticide chlorpyriphos (CPF) was applied to biomass before burning. Post-burning, the primary soil pesticide shifted from propyzamide (67.6%) to chlorpyriphos (94.8%). Raw straw biomass retained residues from all pesticide groups, with chlorpyriphos notably dominating (79.7%). Ash residue analysis unveiled significant alterations, with elevated concentrations of chlorpyriphos and terbuthylazine, alongside the emergence of atrazine-desethyl and triadimenol. Pre-burning TSP analysis identified 15 pesticides, with linuron as the primary compound (51.8%). Post-burning, all 21 pesticides were detected, showing significant increases in metobromuron, atrazine-desethyl, and cyanazine concentrations. PM10 composition mirrored TSP but exhibited additional compounds and heightened concentrations, particularly for atrazine, linuron, and cyanazine. Aerosol analysis post-burning indicated a substantial 39.2-fold increase in atrazine concentration, accompanied by the presence of sebuthylazine, formothion, and propyzamide. Carcinogenic PAHs exhibited noteworthy post-burning increases, contributing around 90.1 and 86.9% of all detected PAHs in TSP and PM10, respectively. These insights advance understanding of pesticide dynamics in burning processes, crucial for implementing sustainable agricultural practices and safeguarding environmental and human health.

Predictors of executive function among 2 year olds from a Thai birth cohort.

Executive function (EF) is a critical skill for academic achievement. Research on the psychosocial and environmental predictors of EF, particularly among Southeast Asian, agricultural, and low income/rural populations, is limited. Our longitudinal study explored the influence of agricultural environmental, psychosocial, and temperamental factors on children's emerging EF. Three-hundred and nine farm worker women were recruited during the first trimester of pregnancy. We evaluated the effects of prenatal insecticide exposure and psychosocial factors on "cool" (i.e., cognitive: A-not-B task, looking version) and "hot" EF (i.e., affective, response inhibition) measures of emerging EF. Maternal urine samples were collected monthly during pregnancy, composited, and analyzed for dialkylphosphate (DAP) metabolites of organophosphate insecticides. Psychosocial factors included socioeconomic status, maternal psychological factors, and quality of mother-child behavioral interactions. Backward stepwise regressions evaluated predictors of children's EF at 12 (N = 288), 18 (N = 277) and 24 (N = 280) months of age. We observed different predictive models for cool EF, as measured by A-not-B task, vs. hot EF, as measured by response inhibition tasks. Report of housing quality as a surrogate for income was a significant predictor of emerging EF. However, these variables had opposite effects for cool vs. hot EF. More financial resources predicted better cool EF performance but poorer hot EF performance. Qualitative findings indicate that homes with fewer resources were in tribal areas where children must remain close to an adult for safety reasons. This finding suggests that challenging physical environments (e.g., an elevated bamboo home with no electricity or running water), may contribute to development of higher levels of response inhibition through parental socialization methods that emphasize compliance. Children who tended to show more arousal and excitability, and joy reactivity as young infants in the laboratory setting had better cognitive performance. In contrast, maternal emotional availability was a significant predictor of hot EF. As expected, increased maternal exposure to pesticides during pregnancy was associated with worse cognitive performance but was not associated with inhibitory control. Identifying risk factors contributing to the differential developmental pathways of cool and hot EF will inform prevention strategies to promote healthy development in this and other unstudied rural, low income Southeast Asian farming communities.

Health Risk Assessment of Heavy Metals in Indoor Household Dust in Urban and Rural Areas of Chiang Mai and Lamphun Provinces, Thailand.

Indoor exposure to heavy metals poses human health risks worldwide, but study reports from Thailand are still limited, particularly in rural and urban areas. We measured the heavy metals in a hundred indoor household dust samples collected from urban and rural areas in Chiang Mai and Lamphun provinces and found a significantly higher concentration of As in rural areas and Cd in urban areas with industrial activities. The source identification of the heavy metals showed significant enrichment from traffic emissions, paint, smoking, and mixed sources with natural soil. From health risk assessment models, children were more vulnerable to noncarcinogenic risks (HI = 1.45), primarily via ingestion (HQ = 1.39). Lifetime cancer risks (LCRs) due to heavy metal exposure were found in adults (LCR = 5.31 × 10-4) and children (LCR = 9.05 × 10-4). The cancer risks from As were higher in rural areas via ingestion, while Cr and Ni were higher in urban areas via inhalation and ingestion, respectively. This study estimated that approximately 5 out of 10,000 adults and 9 out of 10,000 children among the population may develop cancer in their lifetime from exposure to indoor heavy metals in this region.

Risk Assessment of Heavy Metals in Sediment Samples from the Mae Chaem River, Chiang Mai, Thailand.

Heavy metals are significant environmental pollutants that are recognized as posing a potential health hazard to human beings. We investigated the concentrations of the heavy metals As, Cd, Cr, Cu, Ni, Pb, and Zn in surface sediments collected from the Mae Chaem River in Chiang Mai, Thailand, during the dry season in 2021. The mean concentrations of heavy metals in sediments were, in decreasing order, Zn > Cr > As > Pb > Ni > Cu > Cd. The mean values of As, Cd, Cr, and Cu were determined to be 32.5 ± 18.3, 0.33 ± 0.07, 45.8 ± 11.9, and 21.9 ± 7.42 mg Kg-1, respectively. These levels are higher than their standard levels in Thailand, namely 10.0, 0.16, 45.5, and 21.5 mg Kg-1, respectively. Principal component analysis (PCA) revealed that the primary origins of heavy metal contamination are predominantly attributed to residential settlements and agricultural areas. The hazard quotient (HQ) was used to estimate the non-carcinogenic risk of exposure to heavy-metal-bound surface sediments for both children and adults. The results showed that the HQ values for both groups were less than 1.0 (HQ < 1.0), indicating no risk. Moreover, assessment of the long-term risk for ingestion of toxic metals indicated no risk (<10-6) based on the lifetime cancer risk (LCR). However, the LCR values of As and Cr were 5.3 × 10-6 and 2.5 × 10-6, respectively, demonstrating the most elevated LCR among the hazardous metals in terms of children's exposure. Therefore, it is possible that children living in agricultural areas and participating in activities around the study area may be exposed to elevated concentrations of As and Cr.

Respiratory infections among junior high school students in upper northern Thailand: The role of building dampness and mould, biomass burning and outdoor relative air humidity (RH).

BACKGROUND: Few studies exist on environmental risk factors for respiratory infections in Thai school children. AIM: To study associations between home and outdoor environment and respiratory infections among school children in Northern Thailand in dry and wet season. METHODS: A repeated questionnaire survey among the children (N = 1159). Data on ambient temperature and relative air humidity (RH) and PM10 and ozone was collected from nearby monitoring stations. We used logistic regression to calculate odds ratios (OR). RESULTS: 14.1% had current respiratory infections (last 7 days), 32.1% had any respiratory infection last 3 months, and 26.1% had any respiratory infection last 12 months with antibiotic treatment. Students with diagnosed allergy (7.7%) and diagnosed asthma (4.7%) had more often respiratory infections (ORs 1.40-5.40; p < 0.05). Current respiratory infections were more common in dry (18.1%) than in wet season (10.4%) (p < 0.001) and was associated with indoor mould (OR 2.16; p = 0.024) and outdoor RH (OR 1.34 per 10% RH; p = 0.004.) in the total material. In wet season, mould (OR 2.32; p = 0.016), window pane condensation (OR 1.79; p = 0.050), water leakage (OR 1.82; p = 0.018), environmental tobacco smoke (ETS) (OR 2.34; p = 0.003) and outdoor RH (OR 2.70 per 10% RH; p = 0.01) were risk factors for current respiratory infections. In dry season, mould (OR 2.64; p = 0.004) and outdoor RH (OR 1.34 per 10% RH; p = 0.046) were associated with current respiratory infections. Irrespectively of season, biomass burning inside or outside the home was a risk factor for respiratory infections (ORs 1.32-2.34; p < 0.05). Living in a wooden house decreased the risk of respiratory infections (OR 0.56: p = 0.006). CONCLUSIONS: Dry season, high outdoor RH, household dampness, indoor mould and ETS can increase childhood respiratory infections. Living in a traditional wooden house can reduce respiratory infections, possibly due to better natural ventilation. Smoke from biomass burning can increase childhood respiratory infections in northern Thailand.

Associations between prenatal organophosphate pesticide exposure and placental gene networks.

BACKGROUND: Exposure to organophosphate (OP) pesticides during pregnancy has been linked to deficiencies of neurobehavioral development in childhood; however, the molecular mechanisms underlying this association remain elusive. The placenta plays a crucial role in protecting the fetus from environmental insults and safeguarding proper fetal development including neurodevelopment. The aim of our study is to evaluate changes in the placental transcriptome associated with prenatal OP exposure. METHODS: Pregnant farm workers from two agricultural districts in northern Thailand were recruited for the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. For 254 participants, we measured maternal urinary concentrations of six nonspecific dialkyl phosphates (DAP) metabolites in early, middle, and late pregnancy. In parallel, we profiled the term placental transcriptome from the same participants using RNA-Sequencing and performed Weighted Gene co-expression Network Analysis (WGCNA). Generalized linear regression modeling was used to examine associations of urinary OP metabolites and placental co-expression module eigenvalues. RESULTS: We identified 21 gene co-expression modules in the placenta. From the six DAP metabolites assayed, diethylphosphate (DEP) and diethylthiophosphate (DETP) were detected in more than 70% of the urine samples. Significant associations between DEP at multiple time points and two specific placental gene modules were observed. The 'black' module, enriched in genes involved in epithelial-to-mesenchymal transition (EMT) and hypoxia, was negatively associated with DEP in early (p = 0.034), and late pregnancies (p = 0.016). The 'lightgreen' module, enriched in genes involved in myogenesis and EMT, was negatively associated with DEP in late pregnancy (p = 0.010). We observed 2 hub genes (CELSR1 and PYCR1) of the 'black' module to be negatively associated with DEP in early and late pregnancies. CONCLUSIONS: Our results suggest that prenatal OP exposure may disrupt placental gene networks in a time-dependent manner. Such transcriptomic effects may lead to down-stream changes in placental function that ultimately affect the developing fetus.

Asthma and rhinitis in wet and dry season among students in upper Northern Thailand: the role of building dampness and household air pollution.

We investigated associations between domestic exposure and respiratory health in students inNorthern Thailand in wet and dry season (1159 participants), calculating odds ratios (OR) with 95% confidence intervals (CI) by multilevel logistic regression. Totally 6.0% had wheeze, 23.0% dyspnoea, 4.0% current asthma, 54.6% rhinitis and 31.5% rhinoconjunctivitis. Girls had less wheeze (OR 0.66; 95% CI 0.43-1.00) and current asthma (OR 0.32; 95% CI 0.19-0.54). Water leakage was associated with wheeze (OR 2.35; 95% CI 1.09-5.06), dyspnea (OR 2.00; 95% CI 1.24-3.23) and rhinoconjunctivitis (OR 1.62; 95% CI 1.11-2.38). Mould was associated with rhinitis (OR 1.89; 95% CI 1.06-3.38). Window pane condensation was associated with wheeze (OR 2.60; 95% CI 1.13-5.98) and rhinoconjunctivitis (OR 1.70; 95% CI 1.08-2.67). Biomass burning was associated with wheeze, dyspnoea, rhinitis and rhinoconjunctivitis. In conclusion, household dampness and pollution from domestic biomass burning can increase asthma symptoms and rhinitis symptoms in students in northern Thailand.

Metabolome-wide association study of the relationship between chlorpyrifos exposure and first trimester serum metabolite levels in pregnant Thai farmworkers.

INTRODUCTION: Organophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides. METHODS: This study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels. RESULTS: In the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 µg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide. DISCUSSION: The metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.

Is biomass burning always a dominant contributor of fine aerosols in upper northern Thailand?

Biomass burning (BB) is an important contributor to the air pollution in Southeast Asia (SEA), but the emission sources remain great uncertainty. In this study, PM2.5 samples were collected from an urban (Chiang Mai University, CMU) and a rural (Nong Tao village, NT) site in Chiang Mai, Thailand from February to April (high BB season, HBB) and from June to September (low BB season, LBB) in 2018. Source apportionment of carbonaceous aerosols was carried out by Latin Hypercube Sampling (LHS) method incorporating the radiocarbon (14C) and organic markers (e.g., dehydrated sugars, aromatic acids, etc.). Thereby, carbonaceous aerosols were divided into the fossil-derived elemental carbon (ECf), BB-derived EC (ECbb), fossil-derived primary and secondary organic carbon (POCf, SOCf), BB-derived OC (OCbb) and the remaining OC (OCnf, other). The fractions of ECbb generally prevailed over ECf throughout the year. OCbb was the dominant contributor to total carbon with a clear seasonal trend (65.5 ± 5.8 % at CMU and 79.9 ± 7.6 % at NT in HBB, and 39.1 ± 7.9 % and 42.8 ± 4.6 % in LBB). The distribution of POCf showed a spatial difference with a higher contribution at CMU, while SOCf displayed a temporal variation with a greater fraction in LBB. OCnf, other was originated from biogenic secondary aerosols, cooking emissions and bioaerosols as resolved by the principal component analysis with multiple liner regression model. The OCnf, other contributed within a narrow range of 6.6 %-14.4 %, despite 34.9 ± 7.9 % at NT in LBB. Our results highlight the dominance of BB-derived fractions in carbonaceous aerosols in HBB, and call the attention to the higher production of SOC in LBB.

Estimation of lung cancer deaths attributable to indoor radon exposure in upper northern Thailand.

Radon exposure is the second leading cause of lung cancer, after smoking. In upper northern Thailand (UNT), lung cancer incidence was frequently reported by Thailand National Cancer Institute. Besides smoking, radon exposure may also influence the high lung cancer incidence in this region. Indoor radon concentrations were measured in 192 houses in eight provinces of UNT. Indoor radon concentrations ranged from 11 to 405 Bq m-3 and estimated annual effective dose ranged from 0.44 to 12.18 mSv y-1. There were significant differences in indoor radon concentrations between the houses of lung cancer cases and healthy controls (p = 0.033). We estimated that 26% of lung cancer deaths in males and 28% in females were attributable to indoor radon exposure in this region. Other factors influencing indoor radon levels included house characteristics and ventilation. The open window-to-wall ratio was negatively associated with indoor radon levels (B = -0.69, 95% CI -1.37, -0.02) while the bedroom location in the house and building material showed no association. Indoor radon hence induced the fractal proportion of lung cancer deaths in UNT.

Investigation of Prenatal Pesticide Exposure and Neurodevelopmental Deficits in Northern Thailand: Protocol for a Longitudinal Birth Cohort Study.

BACKGROUND: Prenatal exposure to pesticides has been linked to adverse neurodevelopmental outcomes. Gaps exist in the current literature about the timing and magnitude of exposures that result in these adverse outcomes. OBJECTIVE: The Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) cohort was established to investigate the impact of prenatal exposure to pesticides on early indicators of cognitive and motor skills, inhibitory control, emotion regulation, and memory that have been found to be important in the development of subsequent neurobehavioral and neurodevelopmental diseases. The overarching goal is to find earlier predictors of potential adverse neurologic outcomes in order to enable earlier interventions that could result in better outcome prognoses. METHODS: Recruitment of this prospective, longitudinal birth cohort began in July 2017 and was completed in June 2019 in Chom Thong and Fang, 2 farming districts in Chiang Mai Province in northern Thailand. Follow-up of the study participants is ongoing. During pregnancy, 7 questionnaires were administered. Time-resolved biospecimen samples were collected monthly (for urine) and during each trimester (for blood) during antenatal care visits. Medical records were abstracted. Infants were administered the NICU Network Neurobehavioral Scale (NNNS) test at 1 month of age. A total of 322 mother-child pairs completed the NNNS test. All children will be followed until 3 years of age and undergo a series of neurodevelopmental tests. We will complete several additional exposure related analyses. RESULTS: A total of 1298 women were screened, and of those, 394 (30.35%) women were enrolled. The mean gestational age at enrollment was 9.9 weeks (SD 2.6). Differences in literacy were observed between Chom Thong and Fang participants. In Fang, about 54 of 105 (51.4%) participants reported being able to read in Thai compared to about 206 of 217 (94.9%) participants in Chom Thong. The percentages were comparable for reporting to be able to write in Thai. CONCLUSIONS: This longitudinal birth cohort study will inform risk assessment standards for pregnant women in Thailand and other countries. Building awareness of how insecticide exposure during specific windows of pregnancy affects the neurodevelopmental trajectories of children in developing countries is a specific need recognized by the World Health Organization. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31696.

The relationship between prenatal exposure to organophosphate insecticides and neurodevelopmental integrity of infants at 5-weeks of age.

Introduction: Organophosphate (OP) insecticides are among the most abundantly used insecticides worldwide. Thailand ranked third among 15 Asian countries in its use of pesticides per unit hectare and fourth in annual pesticide use. More than 40% of Thai women of childbearing age work on farms where pesticides are applied. Thus, the potential for pregnant women and their fetuses to be exposed to pesticides is significant. This study investigated the relationship between early, mid, and late pregnancy maternal urine concentrations of OP metabolites and infant neural integrity at 5 weeks of age. Method: We enrolled women employed on farms from two antenatal clinics in the Chiang Mai province of northern Thailand. We collected urine samples monthly during pregnancy, composited them by early, mid and late pregnancy and analyzed the composited samples for dialkylphosphate (DAP) metabolites of OP insecticides. At 5 weeks after birth, nurses certified in use of the NICU Network Neurobehavioral Scale (NNNS) completed the evaluation of 320 healthy infants. We employed generalized linear regression, logistic and Poisson models to determine the association between NNNS outcomes and DAP concentrations. All analyses were adjusted for confounders and included creatinine as an independent variable. Results: We did not observe trimester specific associations between DAP concentrations and NNNS outcomes. Instead, we observed statistically significant inverse associations between NNNS arousal (ß = -0.10; CI: -0.17, -0.002; p = 0.0091) and excitability [0.79 (0.68, 0.92; p = 0.0026)] among participants with higher average prenatal DAP concentrations across pregnancy. We identified 3 NNNS profiles by latent profile analysis. Higher prenatal maternal DAP concentrations were associated with higher odds of being classified in a profile indicative of greater self-regulation and attention, but arousal and excitability scores below the 50th percentile relative to US normative samples [OR = 1.47 (CI: 1.05, 2.06; p = 0.03)]. Similar findings are also observed among infants with prenatal exposure to substances of abuse (e.g., methamphetamine). Discussion: Overall, the associations between prenatal DAP concentrations and NNNS summary scores were not significant. Further evaluations are warranted to determine the implications of low arousal and excitability for neurodevelopmental outcomes of attention and memory and whether these results are transitory or imply inadequate responsivity to stimulation among children as they develop.

Urinary Concentrations of Dialkylphosphate Metabolites of Organophosphate pesticides in the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE).

BACKGROUND: Measurements of urinary dialkyl phosphate (DAP) metabolites are often used to characterize exposures to organophosphate (OP) insecticides; however, some challenges to using urinary DAP metabolites as an exposure measure exist. OP insecticides have short biological half-lives with measurement in a single urine sample typically only reflecting recent exposure within the last few days. Because of the field staff and participant burden of longitudinal sample collection and the high cost of multiple measurements, typically only one or two urine samples have been used to evaluate OP insecticide exposure during pregnancy, which is unlikely to capture an accurate picture of prenatal exposure. METHODS: We recruited pregnant farmworker women in Chom Thong and Fang, two districts of Chiang Mai province in northern Thailand (N = 330) into the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE) from 2017 to 2019. We collected up to 6 serial urine samples per participant during gestation and composited the samples to represent early, mid, and late pregnancy. We measured concentrations of urinary DAP metabolites in the composited urine samples and evaluated the within- and between-participant variability of these levels. We also investigated predictors of OP insecticide exposure. RESULTS: DAP metabolite concentrations in serial composite samples were weakly to moderately correlated. Spearman correlations indicated that composite urine samples were more highly correlated in Fang participants than in Chom Thong participants. The within-person variances (0.064-0.65) exceeded the between-person variances for DETP, DEP, ∑DEAP, DMP, DMTP, ∑DMAP, ∑DAP. The intraclass correlations (ICCs) for the volume-based individual metabolite levels (ng/mL) ranged from 0.10 to 0.66. For ∑DEAP, ∑DMAP, and ∑DAP the ICCs were, 0.47, 0.17, 0.45 respectively. We observed significant differences between participants from Fang compared to those from Chom Thong both in demographic and exposure characteristics. Spearman correlations of composite samples from Fang participants ranged from 0.55 to 0.66 for the ∑DEAP metabolite concentrations in Fang indicating moderate correlation between pregnancy periods. The ICCs were higher for samples from Fang participants, which drove the overall ICCs. CONCLUSIONS: Collecting multiple (∼6) urine samples during pregnancy rather than just 1 or 2 improved our ability to accurately assess exposure during the prenatal period. By compositing the samples, we were able to still obtain trimester-specific information on exposure while keeping the analytic costs and laboratory burden low. This analysis also helped to inform how to best conduct future analyses within the SAWASDEE study. We observed two different exposure profiles in participants in which the concentrations and variability in data were highly linked to the residential location of the participants.

Fractional exhaled nitric oxide (FeNO) in students in Northern Thailand: associations with respiratory symptoms, diagnosed allergy and the home environment.

OBJECTIVE: There are few studies on fractional exhaled nitric oxide (FeNO) among children in subtropical areas. We studied associations between FeNO and respiratory symptoms, reported diagnosed allergies and indoor and outdoor environmental factors in first grade junior high school students (N = 270) in upper northern Thailand. METHODS: Data on demographics, health and home environment were collected by a questionnaire distributed in dry season (February-March 2018). FeNO was measured when the research team visited the school. Daily outdoor pollution data (PM10 and ozone) were collected from the nearest monitoring station 3 days (lag 3) and 7 days (lag 7) before the FeNO measurements. Two-level (student, school) linear mixed models were used to analyze associations, adjusting for gender and family education level. RESULTS: In total, 29.6% had elevated FeNO level (>20 ppb) and 7.8% reported any allergy diagnosed by a doctor. Male gender (p = 0.02), diagnosed allergy (p = 0.001), especially to cat (p = 0.001) and house dust mite (HDM) allergies (p = 0.001) were associated with FeNO. Eye symptoms (p = 0.01), rhinitis symptoms (p = 0.03) and dyspnea (p = 0.05) in the last 3 days were associated with FeNO. Household indoor mold (p = 0.03), gas cooking (p = 0.03) and PM10 (lag 3 and lag 7) were negatively (protective) associated with FeNO. CONCLUSIONS: Diagnosed allergy, especially to cat and HDM, can be associated with increased FeNO. Indoor mold and gas cooking can be associated with lower FeNO. Ocular, nasal and dyspnea symptoms reported by students in dry season in northern Thailand can be associated with FeNO, a biomarker of Th2 driven airway inflammation.

Association between Haematological Parameters and Exposure to a Mixture of Organophosphate and Neonicotinoid Insecticides among Male Farmworkers in Northern Thailand.

Exposure to insecticides may result in various health problems. This study investigated the association between haematological parameters and exposure to a mixture of organophosphate (OP) and neonicotinoid (NEO) insecticides among male farmworkers in Fang district, Chiang Mai province, northern Thailand. Concentrations of urinary dialkylphosphates, non-specific metabolites of OPs, and NEOs and their metabolites and haematological parameters were measured in 143 male farmworkers. The Bayesian kernel machine regression model was employed to evaluate the associations. Exposure to a mixture of insecticides was significantly associated with the mean corpuscular haemoglobin concentration (MCHC) when the concentrations of all the compounds and their metabolites were at the 60th percentile or higher compared with the 50th percentile. Furthermore, exposure to clothianidin (CLO) showed a decreasing association with MCHC when all the other insecticides were at their mean concentrations. CLO was the most likely compound to reduce MCHC, and this was confirmed by sensitivity analysis. These findings suggest that exposure to NEO insecticides, especially CLO, affects the haematological status relating to haemoglobin parameters.

Associations between indoor environment in residential buildings in wet and dry seasons and health of students in upper northern Thailand.

We performed a repeated questionnaire study on home environment and health (six medical symptoms) in 1159 junior high school students (age 12.8 ± 0.7 years) in upper northern Thailand in wet and dry seasons. Data on outdoor temperature, relative humidity (RH), and air pollution were collected from nearest monitoring station. Odds ratios (OR) were calculated by multi-level logistic regression. Most common symptoms were rhinitis (62.5%), headache (49.8%), throat (42.8%), and ocular symptoms (42.5%). Ocular symptoms were more common at lower RH and rhinitis more common in dry season. Water leakage (28.2%), indoor mold (7.1%), mold odor (4.1%), and windowpane condensation (13.6%) were associated with all six symptoms (ORs: 1.3-3.5). Other risk factors included cat keeping, environmental tobacco smoke (ETS), other odor than mold odor, gas cooking, and cooking with biomass fire. Biomass burning inside and outside the home for other reasons than cooking was associated with all six symptoms (ORs: 1.5-2.6). Associations between home environment exposure and rhinitis were stronger in wet season. In conclusion, dampness-related exposure, windowpane condensation, cat keeping, ETS, gas cooking, and biomass burning can impair adolescent health in upper northern Thailand. In subtropical areas, environmental health effects should be investigated in wet and dry seasons.

Exposure to Organophosphate and Neonicotinoid Insecticides and Its Association with Steroid Hormones among Male Reproductive-Age Farmworkers in Northern Thailand.

Several studies indicated organophosphate (OP) and neonicotinoid (NEO) insecticides are endocrine disruptors; however, data are scarce. This cross-sectional study recruited 143 male farmworkers aged 18-40 years in Fang district, Chiang Mai province, northern Thailand. OP exposure was assessed by measuring urinary dialkylphosphate (DAPs) using a gas-chromatography flame photometric detector. Urinary NEOs, their metabolites (NEO/m) and serum steroid hormones were measured using liquid chromatography-tandem mass spectrometry. Characteristics of participants were determined by face-to-face interviews. DAPs and five NEO/m were detected in more than 60% of samples. The concentration of diethylphosphate was highest among DAP metabolites (geometric mean concentration (GM: 23.9 ng/mL) and the concentration of imidacloprid (IMI) was highest among NEO/m (GM: 17.4 ng/mL). Linear regression models showed that the IMI level was positively associated with testosterone, dehydrocorticosterone (DHC) and dehydroepiandrosterone (DHEA) levels. Imidacloprid-olefin and DHEA levels were positively associated. Thiamethoxam (THX) were inversely associated with DHC and deoxycorticosterone levels. Clothianidin (CLO), THX and N-desmethyl-acetamiprid levels were positively associated with the androstenedione level. CLO and THX levels were inversely associated with the cortisone level. In conclusion, the association between NEO insecticides exposure and adrenal androgens, glucocorticoids and mineralocorticoids, suggest potential steroidogenesis activities. Our findings warrant further investigation.