Prenatal Exposure to Heavy Metals and Adverse Birth Outcomes: Evidence From an E-Waste Area in China.

Electronic waste that has not been properly treated can lead to environmental contamination including of heavy metals, which can pose risks to human health. Infants, a sensitive group, are highly susceptible to heavy metals exposure. The aim of this study was to investigate the association between prenatal heavy metal exposure and infant birth outcomes in an e-waste recycling area in China. We analyzed cadmium (Cd), chromium (Cr), manganese (Mn), lead (Pb), copper (Cu), and arsenic (As) concentrations in 102 human milk samples collected 4 weeks after delivery. The results showed that 34.3% of participants for Cr, which exceeds the World Health Organization (WHO) guidelines, as well as the mean exposure of Cr exceeded the WHO guidelines. We collected data on the birth weight (BW) and length of infants and analyzed the association between metal concentration in human milk and birth outcomes using multivariable linear regression. We observed a significant negative association between the Cd concentration in maternal milk and BW in female infants (ß = -162.72, 95% CI = -303.16, -22.25). In contrast, heavy metals did not associate with birth outcomes in male infants. In this study, we found that 34.3% of participants in an e-waste recycling area had a Cr concentration that exceeded WHO guidelines, and there was a significant negative association between prenatal exposure to the Cd and infant BW in females. These results suggest that prenatal exposure to heavy metals in e-waste recycling areas may lead to adverse birth outcomes, especially for female infants.

Prenatal and postnatal exposure to heavy metals in PM2.5 and autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders, and its incidence is increasing over time. Although several environmental factors have been suspected to be risk factors for ASD, studies on the effects of airborne heavy metals on newly developed ASD are still limited. We conducted a large birth cohort study of 168,062 live term births in Taichung during 2004-2011 to assess the association of heavy metals in particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) with ASD, and identify sensitive time windows during prenatal and postnatal periods. Heavy metals, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in PM2.5, were estimated using the Weather Research and Forecasting/Chem (WRF/Chem), inserted from the top 75 emission sources for the module. The association between childhood ASD and 4 metals were analyzed from pregnancy to 9 months after birth. The Cox proportional hazard model with a distributed lag nonlinear model (DLNM) was used to estimate the association between heavy metals in PM2.5 and ASD. We identified 666 incident ASD cases in 168,062 participants. A positive association between Hg and ASD was found at 9 months after birth (Hazard Ratio: 1.63; 95% CI: 1.13-2.36). According to the DLNM, there was an increased risk of exposure to Hg during 10-25 weeks after birth, and decreased risk of exposure to Hg during gestational weeks 4-6. Exposure to As and Hg on the risk of ASD were significantly stronger in low birth weight infants (<2500 g) than in those of birth weight ≥2500 g during postnatal period. Postnatal exposure to Hg in PM2.5 may associate with increased ASD incidence. Infants with low birth weight and exposure to As and Hg in PM2.5 are more likely to develop ASD.

Maternal exposure to fine particulate matter and congenital heart defects during preconception and pregnancy period: A cohort-based case-control study in the Taiwan maternal and child health database.

BACKGROUND: Few studies have explored the association between maternal exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) and congenital heart defects occurring before and during pregnancy. We aimed to investigate the association and the critical time windows between the maternal exposure to PM2.5 and congenital heart defects. METHOD: We conducted a cohort-based case-control study of 507,960 participants obtained from the Taiwan Maternal and Child Health Database between 2004 and 2015. We applied satellite-based spatiotemporal models with 1-km resolution to calculate the average PM2.5 concentration during preconception and the specific periods of pregnancy. We also performed conditional logistic regression with distributed lag non-linear models (DLNMs) to assess the effects of weekly average PM2.5 on both congenital heart defects and their isolated subtypes, as well as the concentration-response relationships. RESULTS: In DLNMs, exposure to PM2.5 (per 10 µg/m3) during weeks 7-12 before conception and weeks 3-9 after conception was associated with congenital heart defects. The strongest association at 12 weeks before conception (odds ratio [OR] = 1.026, 95% confidence intervals [CI]: 1.012-1.040) and 7 weeks after conception (OR = 1.024, 95% CI: 1.012-1.036) for every 10 µg/m3 increase in PM2.5 concentration. In modification analysis, strongest associations were observed for low SES. CONCLUSIONS: Our study revealed that exposure to ambient PM2.5 raises the risk of congenital heart defects, particularly among individuals with lower socioeconomic status. Moreover, our findings suggest that preconception exposure to PM2.5 may be a crucial period for the development of congenital heart defects.

A hybrid model for estimating the number concentration of ultrafine particles based on machine learning algorithms in central Taiwan.

Modeling is a cost-effective measure to estimate ultrafine particle (UFP) levels. Previous UFP estimates generally relied on land-use regression with insufficient temporal resolution. We carried out in-situ measurements for UFP in central Taiwan and developed a model incorporating satellite-based measurements, meteorological variables, and land-use data to estimate daily UFP levels at a 1-km resolution. Two sampling campaigns were conducted for measuring hourly UFP concentrations at six sites between 2008-2010 and 2017-2021, respectively, using scanning mobility particle sizers. Three machine learning algorithms, namely random forest, eXtreme gradient boosting (XGBoost), and deep neural network, were used to develop UFP estimation models. The performances were evaluated with a 10-fold cross-validation, temporal, and spatial validation. A total of 1,022 effective sampling days were conducted. The XGBoost model had the best performance with a training coefficient of determination (R2) of 0.99 [normalized root mean square error (nRMSE): 6.52%] and a cross-validation R2 of 0.78 (nRMSE: 31.0%). The ten most important variables were surface pressure, distance to the nearest road, temperature, calendar year, day of the year, NO2, meridional wind, the total length of roads, PM2.5, and zonal wind. The UFP levels were elevated along the main roads across different seasons, suggesting that traffic emission is an important contributor to UFP. This hybrid model outperformed prior land use regression models and thus can provide more accurate estimates of UFP for epidemiological studies.

Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children.

BACKGROUND: Prenatal exposure to multiple heavy metals can interfere with early neurodevelopment, lead to changes in sex hormone concentrations in children, and affect female reproductive health. To date, the influence of prenatal exposure to heavy metals on the endocrine system of children in Chinese electronic waste (e-waste) recycling areas has not been elucidated. METHODS: Four weeks after delivery, 10 mL of human milk was collected for analysis of three heavy metals (lead (Pb), cadmium (Cd), and mercury (Hg)) via inductively coupled plasma mass spectrometry (ICP-MS). Four serum steroid hormones, including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA), were analyzed in 4-year-old children (25 boys and 17 girls). A multiple linear regression (MLR) model was implemented to investigate the association between each individual metal and serum steroid hormone. The exposure-response relationships were explored by generalized additive models (GAMs). Additionally, a Bayesian kernel machine regression (BKMR) model was used to assess the effects of multiple heavy metal exposures on each steroid hormone. RESULTS: The MLR results show a significant positive association between a natural log unit increase in Hg and DHEA levels after adjusting for confounders (ß = 65.50, 95% confidence interval (CI) = 4.37, 126.62). According to the GAM, the univariate exposure-response relationship of Hg on DHEA was almost linear. However, this association was attenuated based on the multiple metal MLR and BKMR results after accounting for multiple heavy metal exposures. SIGNIFICANCE: Prenatal Hg exposure may affect sex hormones in children by affecting DHEA levels. IMPACT STATEMENT: Prenatal maternal exposure to Hg may have long-term effects on the next generation. Hence, regulatory measures to reduce Hg exposure and long-term monitoring of children's health in e-waste areas are needed.

Short-term association of air pollution with lung cancer mortality in Osaka, Japan.

Long-term air pollution exposure has been linked to increased lung cancer mortality. However, little is known about whether day-to-day fluctuations in air pollution levels are in relation to lung cancer mortality, particularly in low-exposure settings. This study aimed to evaluate the short-term associations between air pollution and lung cancer mortality. Daily data on lung cancer mortality, fine particulate matter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and weather conditions were collected from Osaka Prefecture, Japan, from 2010 to 2014. Generalized linear models were combined with quasi-Poisson regression were applied to evaluate the associations between each air pollutant and lung cancer mortality after adjusting for potential confounders. Mean (standard deviation) concentrations of PM2.5, NO2, SO2, and CO were 16.7 (8.6) µg/m3, 36.8 (14.2) µg/m3, 11.1 (4.0) µg/m3, and 0.51 (0.16) mg/m3, respectively. Interquartile range increases in concentrations of PM2.5, NO2, SO2, and CO (2-d moving average) were associated with 2.65% (95% confidence intervals [CIs]: 0.96%-4.37%), 4.28% (95% CIs: 2.24%-6.36%), 3.35% (95% CIs: 1.03%-5.73%), and 4.60% (95% CIs: 2.19%-7.05%) increased risk of lung cancer mortality, respectively. Stratified analyses showed that the associations were strongest in the older population and men. Exposure‒response curves showed a continuously increasing mortality risk from lung cancer with elevation of air pollution levels, without discernible thresholds. In summary, we found evidence of increased lung cancer mortality in relation to short-term elevations in ambient air pollution. These findings may merit further research to better understand this issue.

Prenatal and postnatal exposure to PM2 .5 and the risk of tic disorders.

BACKGROUND: Tic disorders are common neurodevelopmental disorders during childhood. Whether prenatal and postnatal exposure to particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5 ) plays a role in the development of tic disorders remains unexplored. OBJECTIVES: To investigate the association of exposure between PM2.5 during the pregnancy and infancy periods and the risk of tic disorders. METHODS: This birth cohort study recruited singleton live births at term gestations in central Taiwan from the Taiwan Maternal and Child Health Database between 2004 and 2012 and followed up to the end of 2017. New cases of tic disorders were defined using the ICD-9-CM (307.2) and ICD-10-CM (F95), which include all tic spectrum disorders. We assigned daily PM2.5 concentrations derived from a satellite-based model to individuals based on maternal residential addresses at delivery. We fit Cox proportional hazard model and distributed lag non-linear model to estimate the associations between PM2.5 and tic disorders, with hazard ratio (HR) with 95% confidence interval (CI) as the effect measure. RESULTS: Of the 309,376 singleton live births at term gestations, we identified 5902 (1.9%) tic disorder cases. The HR of tic disorders was positively associated with a 10 µg/m3 increase in PM2.5 : during pregnancy HR 1.09, 95% CI 1.04, 1.15 and during infancy HR 1.12, 95% CI 1.06, 1.18. The vulnerable time window for infants with increased risk of tic disorders was 6-52 weeks after birth. We observed a nonlinear relationship between PM2.5 and the risk of tic disorders, with exposure to PM2.5 between 16 and 64 µg/m3 being associated with the risk of tic disorders. The association was restricted to Tourette's disorder group. Infant sex did not modify these associations. CONCLUSIONS: Infants delivered at term and exposed to PM2.5 are associated with an increased risk of tic disorders (6-52 weeks). Further studies are needed to confirm these associations.

Sources, transport, and visibility impact of ambient submicrometer particle number size distributions in an urban area of central Taiwan.

This study applied positive matrix factorization (PMF) to identify the sources of size-resolved submicrometer (10-1000 nm) particles and quantify their contributions to impaired visibility based on the particle number size distributions (PNSDs), aerosol light extinction (bp), air pollutants (PM10, PM2.5, SO2, O3, and NO), and meteorological parameters (temperature, relative humidity, wind speed, wind direction, and ultraviolet index) measured hourly over an urban basin in central Taiwan between 2017 and 2021. The transport of source-specific PNSDs was evaluated with wind and back trajectory analyses. The PMF revealed six sources to the total particle number (TPN), surface (TPS), volume (TPV), and bp. Factor 1 (F1), the key contributor to TPN (35.0 %), represented nucleation (<25 nm) particles associated with fresh traffic emission and secondary new particle formation, which were transported from the west-southwest by stronger winds (>2.2 m s-1). F2 represented the large Aitken (50-100 nm) particles transported regionally via northerly winds, whereas F3 represented large accumulation (300-1000 nm) particles, which showed elevated concentrations under stagnant conditions (<1.1 m s-1). F4 represented small Aitken (25-50 nm) particles arising from the growth and transport of the nucleation particles (F1) via west-southwesterly winds. F5 represented large Aitken particles originating from combustion-related SO2 sources and carried by west-northwesterly winds. F6 represented small accumulation (100-300 nm) particles emitted both by local sources and by the remote SO2 sources found for F5. Overall, large accumulation particles (F3) played the greatest role in determining the TPV (66.4 %) and TPS (34.8 %), and their contribution to bp increased markedly from 17.3 % to 40.7 % as visibility decreased, indicating that TPV and TPS are better metrics than TPN for estimating bp. Furthermore, slow-moving air masses-and therefore stagnant conditions-facilitate the build-up of accumulation mode particles (F3 + F6), resulting in the poorest visibility.

Evaluating postnatal exposure to six heavy metals in a Chinese e-waste recycling area.

This study is the first to assess postnatal exposure to heavy metals using breast milk in an electronic waste (e-waste) recycling area. From January to April 2021, 102 and 97 breastfeeding women were recruited from an e-waste recycling area and a control area, respectively. Four weeks after delivery, medical staff collected 20 mL of breast milk from each participant. The breast milk was tested for six heavy metals (lead, cadmium, chromium, arsenic, copper, and manganese) using inductively coupled plasma mass spectrometry (ICP-MS). The estimated daily intake (EDI) of infants during breastfeeding was calculated to assess the impact of postnatal exposure to heavy metals on infant health. The concentrations of chromium and lead in the breast milk were significantly higher in the e-waste recycling area than in the control area. Chromium concentrations in breast milk was 34.3%, exceeding the permissible limits set by the World Health Organization (WHO), in the e-waste recycling area, which is 16 times higher than that in the control areas. The EDIs of lead and chromium in the e-waste area were twice as those in the control area. This strongly indicates that the potential impact of postnatal exposure to lead and chromium on infant and child health in e-waste recycling areas cannot be ignored. Infants and children in e-waste recycling areas are at risk of long-term exposure to heavy metals. Therefore, ongoing health monitoring is necessary.

PM2.5 exposure and incident attention-deficit/hyperactivity disorder during the prenatal and postnatal periods: A birth cohort study.

Only a few studies have assessed the effects of fine particulate matter (PM2.5) exposure during the prenatal and postnatal periods on the development of attention-deficit/hyperactivity disorder (ADHD). We investigated the association of exposure to PM2.5 during pregnancy and early life with ADHD. This birth cohort consisted of 425,736 singleton live-term births between 2004 and 2015 in Taiwan. Daily PM2.5 concentrations were derived from a 1-km satellite-based estimation model. A time-dependent Cox model was used to assess the effects of PM2.5 on ADHD during the first, second, and third trimesters and from age 1-5 years after birth. The distributed lag nonlinear model was utilized to explore the dose-response relationship. Total 9,294 children were diagnosed with ADHD during the study period. The hazard ratio (HR) of ADHD was significantly associated with a 10 µg/m3 increase in PM2.5 during the first trimester (HR = 1.26; 95% confidence interval [CI]: 1.13-1.40) and increased at PM2.5 over 16 µg/m3. For postnatal periods, the HR of ADHD was significantly associated with increased PM2.5 at the first to third year of life (HR ranged between 1.40 and 1.87). According to the dose-response relationship of exposure to PM2.5 at the third year of life, the HR of ADHD was significantly associated with PM2.5 above 16 µg/m3 and sharply increased as PM2.5 >50 µg/m3. We did not observe a significant modification of sex on the relation between PM2.5 and ADHD. Exposure of pregnant women to PM2.5 above 16 µg/m3 from conception to the early life of their children may increase the risk of ADHD. The government should improve the criteria for air quality control and meet the WHO air quality guidelines to protect pregnant women and children from developing ADHD in the future.

Fine particulate matter measured by satellites predicts the risk of age-related macular degeneration in a longitudinal cohort study.

Although studies have revealed that ambient particulate matter (PM) has detrimental effects on the ocular surface, there have been limited reports detailing the effect of ambient PM on the posterior segment of the eye. A large-scale longitudinal cohort study evaluating the association between fine PM, especially PM2.5, and the retina could elucidate the risk of ambient pollutants for retinal diseases. We investigated the association between PM2.5 and the development of age-related macular degeneration (AMD). We conducted a population-based cohort study of 4,284,128 participants in Taiwan between 2001 and 2011. PM2.5 was continuously measured by satellites and subsequently assigned to each geographic district along with its postcode. A time-dependent Cox proportional-hazard model was used to assess the overall effects of average PM2.5. We used distributed lag non-linear models to evaluate the dose-response relationship between PM2.5 and AMD development. The annual mean of PM2.5 exposure was 34.23 ± 7.17 µg/m3. The PM2.5 concentrations were highest in spring, followed by those in winter, autumn, and summer. Twelve thousand ninety-five new AMD cases were reported during the study period. After adjusting for covariates, the AMD risk increased by 19% (95% confidence interval 1.13-1.25) for a 10 µg/m3 PM2.5 increase. The present study demonstrated that chronic exposure to PM2.5 increases the risk of AMD. Almost half of the Taiwanese live in a polluted area where the PM2.5 levels are higher than the World Health Organization recommended air quality guideline of 10 µg/m3 had a 1.4-fold risk, which significantly increases concern about their visual health and social burden.

Relationship between dioxins and steroid hormone in 6-year-olds: A follow-up study in an e-waste region of China.

We conducted a follow-up observational study on the effects of dioxin exposure on the synthesis of steroid hormones in infants during the perinatal period. The participants included 42 pairs of mothers and infants that were previously studied in 2015. We analyzed four types of steroid hormones including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA) in the serum samples of 6-year-olds and the concentration of dioxins in breast milk. A multivariate linear regression was performed to associate steroid hormones (dependent variables) and dioxins with the body mass index (BMI), sex, age, and residence of participants (independent variables). The results were reported as ß (standardized coefficient) and p-values. We found that dioxins have a significant negative correlation with DHEA and A-dione but no significant relationship with progesterone and testosterone. However, in previous studies, we found that testosterone and progesterone levels were significantly related to dioxins in 4-year-olds. We concluded that dioxins can affect the level of steroid hormones, but their effects fluctuate, and the harm caused by dioxins in children requires further long-term monitoring.

Early life exposure to indoor air pollutants and the risk of neurodevelopmental delays: The Japan Environment and Children's Study.

Air pollution has been associated with childhood neurodevelopment. However, the role of indoor air pollution, especially volatile organic compounds (VOCs), on childhood neurodevelopment has been poorly explored to date. We investigated the association between indoor air pollutants and childhood neurodevelopment in 5,017 randomly selected children from the Japan Environment and Children's Study. When the participants reached 1.5 and 3 years of age, they were followed up with home visits and neurodevelopmental tests using the Ages and Stages Questionnaire (ASQ). At both ages, we collected indoor air samples for 1 week and measured 13 indoor air pollutants: particulate matter with an aerodynamic diameter of ≤2.5 µm, ozone, nitrogen dioxide, sulfur dioxide, and nine VOCs. The associations between air pollutants and ASQ scores were estimated using linear mixed effects models and weighted quantile sum regressions (WQS) at each age separately. Stratified analysis by sex was conducted. Exposure to m,p-xylene at the age of 3 was associated with lower communication, fine motor, and overall ASQ scores (coefficients: -0.18 [99% confidence intervals (CI): -0.35, -0.02], -0.23 [99 %CI: -0.43, -0.03], and - 0.72 [99 %CI: -1.41, -0.04] per 1 µg/m3 increase, respectively). Exposure to o-xylene at the age of 3 was associated with lower communication, gross motor, fine motor, and overall ASQ scores (coefficients: -0.48 [99 %CI: -0.90, -0.07], -0.45 [99 %CI: -0.78, -0.13], -0.65 [99 %CI: -1.14, -0.16], and -2.15 [99 %CI: -3.83, -0.47] per 1 µg/m3 increase, respectively). The WQS index was associated with lower gross motor ASQ scores at the age of 3 (coefficient: -0.27 [95 %CI: -0.51, -0.03] for one-unit WQS index increases), which was attributed to benzene (33.96%), toluene (26.02%), o-xylene (13.62%), and ethylbenzene (9.83%). Stratified analysis showed similar results. Although further investigations are required, our results suggest an association of neurodevelopmental delays with indoor low-level exposure to m,p-xylene and o-xylene in early life.

Urinary Metabolites of Organophosphate Pesticides among Pregnant Women Participating in the Japan Environment and Children's Study (JECS).

Organophosphate pesticides (OPPs) exhibit neurodevelopmental toxicity. To evaluate the effect of prenatal exposure to OPPs in the Japan Environment and Children's Study, a nationally representative birth cohort study, 4575 maternal urine samples were analysed for six OPP metabolites, i.e., dialkylphosphates (DAPs). This study aimed to investigate predictors of urinary DAPs using machine learning approaches and to assess the cumulative risk based on relative potency factors among Japanese pregnant women. The median creatinine-normalised urinary concentrations (interquartile ranges) of dimethylphosphate, dimethylthiophosphate and diethylphosphate, which had a detection rate of 50% or higher, were 3.53 (1.91-6.78), 4.09 (1.66-10.8) and 3.28 (1.88-5.98) µg/g-creatinine, respectively. Possible predictors of urinary DAP concentrations were the month of urine sampling, consumption of apple and maternal body mass index. When fenitrothion was used as an index chemical for cumulative risk assessment, 0.36% of participants exceeded the lower 95% confidence limit of the benchmark dose10.

Cold Spells and Cause-Specific Mortality in 47 Japanese Prefectures: A Systematic Evaluation.

BACKGROUND: Many studies have investigated the devastating health effects of heat waves, but less is known about health risks related to cold spells, despite evidence that extreme cold may contribute to a larger proportion of deaths. OBJECTIVES: We aimed to systematically investigate the association between cold spells and mortality in Japan. METHODS: Daily data for weather conditions and 12 common causes of death during the 1972-2015 cold seasons (November-March) were obtained from 47 Japanese prefectures. Cold spells were defined as ≥2 consecutive days with daily mean temperatures ≤5th percentile for the cold season in each prefecture. Quasi-Poisson regression was combined with a distributed lag model to estimate prefecture-specific associations, and pooled associations at the national level were obtained through random-effects meta-analysis. The potential influence of cold spell characteristics (intensity, duration, and timing in season) on associations between cold spells and mortality was examined using a similar two-stage approach. Temporal trends were investigated using a meta-regression model. RESULTS: A total of 18,139,498 deaths were recorded during study period. Mortality was significantly higher during cold spell days vs. other days for all selected causes of death. Mortality due to age-related physical debilitation was more strongly associated with cold spells than with other causes of death. Associations between cold spells and mortality from all causes and several more specific outcomes were stronger for longer and more intense cold spells and for cold spells earlier in the cold season. However, although all outcomes were positively associated with cold spell duration, findings for cold spell intensity and seasonal timing were heterogeneous across the outcomes. Associations between cold spells and mortality due to cerebrovascular disease, cerebral infarction, and age-related physical debility decreased in magnitude over time, whereas temporal trends were relatively flat for all-cause mortality and other outcomes. DISCUSSION: Our findings may have implications for establishing tailored public health strategies to prevent avoidable cold spell-related health consequences. https://doi.org/10.1289/EHP7109.

Indoor air quality of 5,000 households and its determinants. Part A: Particulate matter (PM2.5 and PM10-2.5) concentrations in the Japan Environment and Children's Study.

Exposure to particulate matter (PM) is one of the important risk factors for morbidity and mortality. Although PM concentrations have been assessed using air quality monitoring stations or modelling, few studies have measured indoor PM in large-scale birth cohorts. The Japan Environment and Children's Study (JECS) measured indoor and outdoor air quality in approximately 5000 households when the participating children were aged 1.5 and 3 years. PM was collected using portable pumps for 7 days (total of 24 h), inside and outside each home. Prediction models for indoor PM concentrations were built using data collected at age 1.5 years and post-validated against data collected at age 3 years. Median indoor/outdoor PM2.5 and PM10-2.5 concentrations at age 1.5 years [3 years] were 12.9/12.7 [12.5/11.3] µg/m3 and 5.0/6.3 [5.1/6.1] µg/m3, respectively. Random forest regression analysis found that the major predictors of indoor PM2.5 were indoor PM10-2.5, outdoor PM2.5, indoor smoking, observable smoke and indoor/outdoor temperature. Indoor PM2.5, outdoor PM10-2.5, indoor humidity and opening room windows were important predictors of indoor PM10-2.5 concentrations. Indoor benzene, acetaldehyde, ozone and nitrogen dioxide concentrations were also found to predict indoor PM2.5 and PM10-2.5 concentrations, possibly due to the formation of secondary organic aerosols. These findings demonstrate the importance of reducing outdoor PM concentrations, avoiding indoor smoking, using air cleaner in applicable and diminishing sources of VOCs that could form secondary organic aerosols, and the resulting models can be used to predict indoor PM concentrations for the rest of the JECS cohort.

Indoor air quality of 5,000 households and its determinants. Part B: Volatile organic compounds and inorganic gaseous pollutants in the Japan Environment and Children's study.

Volatile organic compounds (VOCs) are major indoor air pollutants. Quantification of indoor concentrations of VOCs and identification of factors associated with these concentrations can help manage indoor air quality. This study measured the concentrations of VOCs and inorganic gaseous pollutants in around 5000 households in Japan and utilised a random forest model to estimate these concentrations and identify important determinants. The homes of 5017 randomly selected participants in the Japan Environment and Children's Study (JECS) were visited twice, when the children were aged 1.5 and 3 years. Twelve VOCs and inorganic gaseous pollutants were measured during 7 days by passive samplers. Various factors in these households, including household appliances, building characteristics, cooking styles, use of consumer products, renovation, pets, personal behaviours and ventilation were recorded. A random forest model with recursive feature elimination was utilised to identify factors predictive of VOCs and inorganic gaseous pollutants. Toluene, formaldehyde and acetaldehyde were the dominant indoor VOCs. The 95th percentiles of indoor p-dichlorobenzene concentrations at 1.5 and 3 years were 67 µg/m3 and 71 µg/m3, respectively. Random forest models with coefficients of determination ranging from 0.34 to 0.76 outperformed the traditional linear regression models. Factors associated with indoor VOC and inorganic gaseous pollutant concentrations included their outdoor concentrations, indoor and outdoor temperature and relative humidity, month of the year, hours windows were open, kerosene heater use and times of operation and building age. The results provided basic descriptions of indoor VOCs and inorganic gaseous pollutants in Japan and identified several determinants of these concentrations. These determinants should be considered to maintain indoor air quality. These results can be used in epidemiological assessments of the effects of VOCs and inorganic gaseous pollutants on health in children.

Effect of exposure to fine particulate matter during pregnancy and infancy on paediatric allergic rhinitis.

BACKGROUND: The effect of prenatal and postnatal exposure to fine particulate matter (PM2.5) on the development of allergic rhinitis (AR) is poorly understood. We further identified the vulnerable period for AR development to determine methods to decrease adverse effects. METHODS: We used a large population-based birth cohort of 140 911 singleton live infants in Taichung, Taiwan with a highly temporal-resolution satellite-based hybrid model to evaluate the effects of prenatal and early postnatal exposure on the onset of AR. RESULTS: Among 140 911 children, 47 276 (33.55%) were cases of incident AR. The mean age of the children with AR at initial diagnosis was 2.97±1.78 years. We identified a significant association of AR with an interquartile range (IQR 17.98 µg/m3) increase in PM2.5 from 30 gestational weeks to 52 weeks after birth. The exposure-response relationship revealed that AR had a significant positive association between PM2.5 of 26-76 µg/m3 (adjusted hazard ratios ranged from 1.00 to 1.05). CONCLUSION: Our study provides evidence that both prenatal and postnatal exposures to PM2.5 are associated with later development of AR. The vulnerable time window may be within late gestation and the first year of life. Further study is required to confirm the vulnerable time period of PM2.5 on AR.

Long-term exposure to fine particulate matter and osteoporotic fracture: A case-control study in Taiwan.

Few studies have explored the relationship between long-term exposure to particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5) and osteoporotic fracture, particularly in high PM2.5 level areas. The aim of this study was to assess the association between long-term exposure to PM2.5 and osteoporotic fracture. We performed a matched case-control study of 16,175 participants obtained from a hospital registry during 2005-2014 in Taiwan. A major osteoporotic fracture was defined as a fracture of the spine, hip, proximal humerus, and forearm. We applied satellite-based spatiotemporal models with 1-km resolution to individually calculate the 1-year average PM2.5 concentration before the index date which was defined as the first visit date for the osteoporotic fracture. Logistic regression models with and without potential confounding factors were used to estimate odds ratios (OR) and 95% confidence intervals (CI) between PM2.5 and osteoporotic fracture, whereas a restricted cubic spline model was used to estimate the dose-response relationship. The sample's median age was 44.7 years (interquartile range: 30.7, 63.1 years). We observed that long-term PM2.5 exposure was associated with osteoporotic fracture, the OR was 1.12 (95% CI: 1.03, 1.22) per 10-µg/m3 increase in PM2.5 in women. In the dose-response association, the OR of osteoporotic fracture was significantly increased for PM2.5 exposures more than 41 µg/m3. We did not find a significant association between PM2.5 (per 10-µg/m3 increase) and osteoporotic fracture among overall population (adjusted OR, 1.02 [95% CI, 0.97 to 1.08]) and men (adjusted OR, 0.94 [95% CI, 0.86 to 1.02]). The results of the stratified analysis showed that women were more sensitive to the adverse impact of PM2.5 that were men, and evidence was obtained of sex-based effect modification (P for interaction = 0.002). Our findings suggest that long-term exposure to PM2.5 is associated with osteoporotic fracture, particularly among women.

Exposure to heavy metals modifies optimal gestational weight gain: A large nationally representative cohort of the Japan Environment and Children's Study.

Clinical guidelines including those set by the US Institute of Medicine, have based optimal gestational weight gain (GWG) on maternal pre-pregnancy body mass index (BMI), but have not considered the role of environmental toxicants such as heavy metals that can disrupt these processes. This study designed to determine optimal GWG ranges in women grouped according to BMI, and to assess whether blood concentrations of heavy metals alter the relationships between GWG and outcomes. A total of 103,060 participants in the Japan Environment and Children's Study recruited between 2011 and 2014 were followed until their children reached 3 years of age. Outcomes included 1 min Apgar score <7, caesarean delivery, childhood obesity, gestational diabetes, pregnancy-induced hypertension, low birth weight, large for gestational age, macrosomia, operative vaginal delivery, postpartum weight retention, preterm birth and small for gestational age. The optimal GWG ranges were determined using multivariate logistic regression models. Stratified analyses were performed to determine optimal GWG ranges according to quartiles of heavy metals. Optimal GWGs for underweight, normal weight and overweight women were found to be 10.0 to <14.0 kg, 6.0 to <12.0 kg and 4.0 to <8.0 kg, respectively. However, the benefits of optimal GWG were attenuated in women exposed to high concentrations of mercury (Hg), lead (Pb) and cadmium (Cd). Despite being within optimal GWG, underweight women with Hg > 5.21 ng/g and overweight women with Hg 3.67-5.21 ng/g, Pb > 7.31 ng/g and Cd > 0.66 ng/g had null effects. Heavy metals can modify the associations between GWG and outcomes, particularly for underweight and overweight women. Because of the complex interactions of environmental toxicants with pre-pregnancy BMI, GWG and adverse outcomes, GWG guidelines should be interpreted cautiously. Environmental toxicants may influence the determination of a clinical guideline.