Occurrence of short- and ultra-short chain PFAS in drinking water from Flanders (Belgium) and implications for human exposure.

SHORT: and ultra-short chain perfluoroalkyl substances (S- and US-PFAS) are alternatives for the long-chain PFAS which have been more regulated over time. They are highly mobile in the environment and can easily reach drinking water sources which can become an important human exposure route. Furthermore, there have been growing concerns about the presence of PFAS in Flanders. Because of this, human exposure to S- and US-PFAS through Flemish drinking water was evaluated in this study. For this purpose, the presence of 2 S-PFAS (PFBS and PFBA) and 5 US-PFAS (PFPrS, PFEtS, TFMS, PFPrA and TFA) was investigated in 47 tap water samples, collected from different Flemish provinces, and 16 bottled waters purchased in Flanders. Out of the 7 target PFAS, 4 (PFBA, PFBS, PFPrS and PFEtS) were detected at concentrations above LOQ in tap water. In bottled water, only TFMS was present above its LOQ. PFAS concentrations in all analyzed water samples ranged from <0.7 to 7.3 ng/L for PFBS, <0.03-15.0 ng/L for TFMS and <0.9-12.0 ng/L for PFBA. PFPrS was only detected once above its LOQ, at 0.6 ng/L. No value could be reported for PFPrA due to high procedural blanks resulting in a high LOQ, nor for TFA due to high matrix effect. No significant differences in PFAS concentrations were seen in tap water among different drinking water companies, provinces, nor between the two types of analyzed bottled water (natural mineral water vs spring water). The use of a commercial carbon filter significantly reduced the median concentrations of the studied compounds in tap water. Finally, it was estimated that the presence of S- and US-PFAS in Flemish drinking water does not pose an immediate threat to human health, as concentrations were at least two orders of magnitude below the available guidance values.

Link between Wi-Fi, cordless devices, mobile phone usage patterns, and behavioral problems among Japanese children: A prospective cohort study.

BACKGROUND: With the recent advent of technology, it is important to confirm the health and safety of the youth. This study aimed to prospectively evaluate the relationship between Wi-Fi, cordless phones, and mobile phone usage patterns and behavioral problems. METHODS: This study involved 2465 children aged 8-17 years from the Hokkaido Study on Environment and Children's Health from October 2020 to January 2021, with a follow-up from September 2021 to March 2022. The mother-child dyad provided information on the presence of residential Wi-Fi and cordless phones, cordless phone call duration, and mobile phone usage pattern (duration of calls using mobile network and internet, online audio streaming, online video streaming, and playing online games) via a baseline questionnaire. Based on the scores on Strength and Difficulties Questionnaire at baseline and follow-up, the children were categorized into four groups: normal, persistent, improved, and concurrent. RESULTS: No significant association was found between Wi-Fi, mobile phone calls via mobile networks, and behavioral problems. Cordless phone at home had higher odds for improvement in total difficulty scores, and cordless phone for calling more than 4 min per week had lower odds of persistent problematic prosocial behavior. Longer duration of mobile phone calling via the internet (>40 min/week) had higher odds of concurrent total difficulties. Mobile phone calling via mobile network for <5 min per week had higher odds for improved total difficulty scores. Audio streaming via mobile phones for 60-120 min had lower odds of persistent total difficulties. CONCLUSION: Our results showed sporadic findings between residential RF-EMF indoor sources and mobile phone usage pattern. These observed findings could be affected by residual confounding and chance findings. Ongoing follow-up studies are necessary to further explore this association through detailed exposure assessment and addressing the potential limitations of our study.

HBM4EU E-waste study: Assessing persistent organic pollutants in blood, silicone wristbands, and settled dust among E-waste recycling workers in Europe.

E-waste recycling is an increasingly important activity that contributes to reducing the burden of end-of-life electronic and electrical apparatus and allows for the EU's transition to a circular economy. This study investigated the exposure levels of selected persistent organic pollutants (POPs) in workers from e-waste recycling facilities across Europe. The concentrations of seven polychlorinated biphenyls (PCBs) and eight polybrominated diphenyl ethers (PBDEs) congeners were measured by GC-MS. Workers were categorized into five groups based on the type of e-waste handled and two control groups. Generalized linear models were used to assess the determinants of exposure levels among workers. POPs levels were also assessed in dust and silicone wristbands (SWB) and compared with serum. Four PCB congeners (CB 118, 138, 153, and 180) were frequently detected in serum regardless of worker's category. With the exception of CB 118, all tested PCBs were significantly higher in workers compared to the control group. Controls working in the same company as occupationally exposed (Within control group), also displayed higher levels of serum CB 180 than non-industrial controls with no known exposures to these chemicals (Outwith controls) (p < 0.05). BDE 209 was the most prevalent POP in settled dust (16 µg/g) and SWB (220 ng/WB). Spearman correlation revealed moderate to strong positive correlations between SWB and dust. Increased age and the number of years smoked cigarettes were key determinants for workers exposure. Estimated daily intake through dust ingestion revealed that ΣPCB was higher for both the 50th (0.03 ng/kg bw/day) and 95th (0.09 ng/kg bw/day) percentile exposure scenarios compared to values reported for the general population. This study is one of the first to address the occupational exposure to PCBs and PBDEs in Europe among e-waste workers through biomonitoring combined with analysis of settled dust and SWB. Our findings suggest that e-waste workers may face elevated PCB exposure and that appropriate exposure assessments are needed to establish effective mitigation strategies.

Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study.

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects.

Exposure Trends to the Non-phthalate Plasticizers DEHTP, DINCH, and DEHA in Children from 2012 to 2017: The Hokkaido Study.

Phthalates owing to their endocrine-disrupting effects are regulated in certain products, leading to their replacement with substitutions such as di-2-ethylhexyl terephthalate (DEHTP), 1,2-cyclohexane dicarboxylic acid di(isononyl) ester (DINCH), and di(2-ethylhexyl) adipate (DEHA). However, information on human exposure to these substitutes, especially in susceptible subpopulations such as children, is limited. Thus, we examined the levels and exposure trends of DEHTP, DINCH, and DEHA metabolites in 7 year-old Japanese school children. In total, 180 urine samples collected from 2012 to 2017 were used to quantify 10 DEHTP, DINCH, and DEHA metabolites via isotope dilution liquid chromatography with tandem mass spectrometry. DEHTP and DINCH metabolites were detected in 95.6 and 92.2% of the children, respectively, and DEHA was not detected. This study, annually conducted between 2012 and 2017, revealed a significant (p < 0.05) 5-fold increase in DEHTP metabolites and a 2-fold increase in DINCH metabolites. However, the maximum estimated internal exposures were still below the health-based guidance and toxicological reference values. Exposure levels to DEHTP and DINCH have increased considerably in Japanese school children. DEHA is less relevant. Future studies are warranted to closely monitor the increasing trend in different aged and larger populations and identify the potential health effects and sources contributing to increasing exposure and intervene if necessary.

Reviewing the variability in urinary concentrations of non-persistent organic chemicals: evaluation across classes, sampling strategies and dilution corrections.

Various biomonitoring studies have been carried out to investigate the exposure of populations by measuring non-persistent organic chemicals in urine. To accurately assess the exposure, study designs should be carefully developed to maximise reproducibility and achieve good characterization of the temporal variability. To test these parameters, the intraclass correlation coefficients (ICCs) are calculated from repeated measurements and range from poor (<0.4) to excellent (≥0.75). Several studies have reported ICCs based on diverse study designs, but an overview, including recommendations for future studies, was lacking. Therefore, this review aimed to collect studies describing ICCs of non-persistent organic chemicals, discuss variations due to study design and formulate recommendations for future studies. More than 60 studies were selected, considering various chemical classes: bisphenols, pyrethroids, parabens, phthalates, alternative plasticizers and phosphate flame retardants. The variation in ICCs for an individual chemical was high (e.g. ICC of propyl paraben = 0.28-0.91), showing the large impact of the study design and of the specific exposure sources. The highest ICCs were reported for parabens (median = 0.52), while lowest ICCs were for 3-phenoxybenzoic acid (median = 0.08) and bisphenol A (median = 0.20). Overall, chemicals that had an exposure source with high variation, such as the diet, showed lower ICCs than those with more stable exposure sources, such as indoor materials. Urine correction by specific gravity had an overall positive effect on reducing the variability of ICCs. However, this effect was mostly seen in the adult population, while specific compounds showed less variation with creatinine correction. Single samples might not accurately capture the exposure to most non-persistent organic chemicals, especially when small populations are sampled. Future studies that examine compounds with low ICCs should take adequate measures to improve accuracy, such as correcting dilution with specific gravity or collecting multiple samples for one participant.

Lower Respiratory Tract Infections and Orofacial Clefts: A Prospective Cohort Study From the Japan Environment and Children's Study.

BACKGROUND: Lower respiratory tract infections (LRTIs) are a cause of inpatient and outpatient care among children. Although orofacial clefts seem to be associated with LRTIs, epidemiological studies are scarce on this topic. This study aimed to examine whether infants with orofacial clefts were associated with LRTIs. METHODS: This prospective cohort study used data from the Japan Environment and Children's Study, for which baseline recruitment was conducted during 2011-2014. This study included 81,535 participants. The number of infants with cleft lip and palate (CLP), cleft lip (CL), and cleft palate only (CP) was 67, 49, and 36, respectively. We defined history of LRTIs until 12 months' age reported by their mothers as the dependent variable. Accumulated breastfeeding duration was used as a potential mediator. RESULTS: The incidence proportion of LRTIs among the control group was 6.0%. The incidence proportion among infants with CLP, CL, and CP were 11.9%, 14.3%, and 5.6%, respectively. After adjusting for covariates, compared with the control group, infants with CLP and CL were associated with risk of LRTIs (incidence risk ratio [IRR] of CLP, 2.38; 95% confidence interval [CI], 1.30-4.36 and IRR of CL, 2.73; 95% CI, 1.40-5.33), but not ones with CP (IRR 1.08; 95% CI, 0.28-4.15). Accumulated breastfeeding duration decreased the IRR of CLP only (IRR of CLP, 2.16; 95% CI, 1.19-3.93). CONCLUSION: Infants with orofacial clefts aged 1 year have a potentially high incidence proportion of LRTIs. Accumulated breastfeeding duration might mediate the associations of CLP.

Relations of mold, stove, and fragrance products on childhood wheezing and asthma: A prospective cohort study from the Japan Environment and Children's Study.

This prospective cohort study aimed to examine the associations between mold growth, type of stoves, and fragrance materials and early childhood wheezing and asthma, using data from the Japan Environment and Children's Study. Mold growth at home, usage of kerosene/gas stove, wood stove/fireplace, and air freshener/deodorizer were surveyed using a questionnaire at 1.5-year-old, and childhood wheezing and doctor-diagnosed asthma during the previous year were obtained using a 3-year-old questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between exposure to childhood wheezing and asthma. A total of 60 529 children were included in the analysis. In multivariate analyses, mold growth and wood stove/fireplace had significantly higher odds ratios (ORs) for wheezing (mold growth: 1.13; 95% CI, 1.06-1.22; wood stove/fireplace: 1.23; 95% CI, 1.03-1.46). All four exposures had no significant ORs for childhood doctor-diagnosed asthma; however, in the supplemental analysis of northern regions, wood stove/fireplace had a significantly higher OR for asthma. Mold growth and wood stove/fireplace had significant associations with childhood wheezing in the northern regions. Mold elimination in the dwellings and use of clean heating (no air pollution emissions) should be taken into consideration to prevent and improve childhood wheezing and asthma.

Null Association Between Isolated Orofacial Clefts and Sleep Duration: A Cohort Study From the Japan Environment and Children's Study.

Although children with orofacial clefts have an increased risk for sleep-disordered breathing, no studies have examined the association of sleep duration. Thus, this study aimed to examine associations between orofacial clefts and sleep duration at 1 month, 6 months, 1 year, and 3 years of age in Japan.A cohort study from the Japan Environment and Children's Study.This study consisted of 91 497 children, including ones with isolated cleft lip and palate (n = 69), isolated cleft lip only (n = 48), and isolated cleft palate only (n = 37), for which recruitment was undertaken during 2011 to 2014.Seep durations (hours per day) at 1 month, 6 months, 1 year, and 3 years of age, as reported by their mothers.In the control group, mean sleep durations and standard deviations at 1 month, 6 months, 1 year, and 3 years of age were 15.2 (2.5), 13.6 (1.9), 12.9 (1.6), and 11.6 (1.2) h, respectively. Compared to the control group, linear regression models reported effect sizes and 95% confidence intervals shorter than 1 h for sleep duration of each type of isolated orofacial cleft at each time point.This study suggested null associations between isolated orofacial clefts and sleep duration at 1 month, 6 months, 1 year, and 3 years of age. Children with isolated orofacial clefts had sufficient mean sleep duration.

Prevalence of childhood wheeze and modified DNA methylation at 7 years of age according to maternal folate levels during pregnancy in the Hokkaido Study.

BACKGROUND: A high dose of folic acid during pregnancy may increase the risk of asthma, wheezing, and respiratory disease in childhood. Folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated associations between maternal folate levels during pregnancy and childhood wheezing; furthermore, the study assessed whether maternal folate-modified DNA methylation is related to asthma. Methods Participants in the current study were 6651 mother-child pairs who had complete data on characteristics and who had completed at least one of the International Study of Asthma and Allergies in Childhood questionnaires when the child was 1, 2, 4, and 7 years of age. Moreover, a case-control study to assess DNA methylation at 7 years of age was conducted among 136 children who experienced wheezing and a control group of 139 children with no history of allergies. Results The median of maternal serum was 16.76 nmol/L, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheezing at 2 years age according to maternal folate levels, compared with the lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second, 1.27 [1.05, 1.55]); however, no changes were observed at 1, 4, and 7 years of age. In a case-control study, no association of maternal folate levels with DNA methylation was observed. Conclusion Our results suggest that maternal folate did not affect persistent wheezing in school-aged children, or DNA methylation of gasdermin B, orosomucoid-like 3, and Ikaros family zinc finger 3 at 7 years of age.

Maternal psychological distress, education, household income, and congenital heart defects: a prospective cohort study from the Japan environment and children's study.

BACKGROUND: The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD. METHODS: We conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD. RESULTS: A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050). CONCLUSIONS: The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.

Hokkaido birth cohort study on environment and children's health: cohort profile 2021.

BACKGROUND: The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco. METHODS: The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures. RESULTS: The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies. CONCLUSIONS: Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Between- and within-individual variability of urinary phthalate and alternative plasticizer metabolites in spot, morning void and 24-h pooled urine samples.

Due to international regulations, commonly used phthalates such as di(2-ethylhexyl) phthalate (DEHP) are being replaced by other phthalates, such as di-isononyl phthalate (DINP), and di-isodecyl phthalate (DIDP) and by alternative plasticizers (APs) with similar chemical characteristics, like di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH), di(2-ethylhexyl) terephthalate (DEHTP), or di-(2-ethylhexyl) adipate (DEHA). Urinary concentrations of metabolites are frequently used in the exposure assessment of non-persistent chemicals and for biomonitoring purposes, the intra- and inter-day variability of the metabolites should be known. However, the short-term variability of AP and several phthalate biomarkers has not been investigated yet. In this study, we collected all spot samples from 10 healthy adults for 5 consecutive days and 24h pooled urine on one additional day to investigate the short-term variability of 22 biomarkers of phthalates and APs. Metabolites of DEP, DEHP, DiBP, DnBP, DBzP, DINP and DIDP were found in high detection frequencies, while metabolites of most APs were found in approximately 50% of the samples. The short-term reproducibility of metabolites with diet as primary source (DEHP, DINP, DIDP) was poor (intraclass correlation coefficient - ICC < 0.4), whereas biomarkers of DEP, DnBP, DiBP and BBzP showed good consistency, most likely due to more continuous sources resulting in less between-day variance. ICC values of AP metabolites were similar to those of DEHP, but more studies are required to confirm these findings. Overall, reproducibility improved considerably when values were corrected for urinary dilution and when only morning voids samples were considered. Levels in morning voids samples were consistent for 5 days and comparable to 24-h pooled urine for all metabolites except for OH-MEHTP, sum DINP and sum DIDP, which supports the use of morning voids in human biomonitoring studies.

Biomonitoring and temporal trends of bisphenols exposure in Japanese school children.

The widely used chemical bisphenol A (BPA), applied in various consumer products, has been under scrutiny in the past 20 years due to its widespread detection in humans and potential detrimental effects on human health. Following the implementation of restrictions and phase-out initiatives, BPA has been replaced by other structurally similar bisphenols, which have not yet received the same level of research attention. In this study, we aimed to 1) investigated the internal exposure to seven bisphenols in morning void urine samples (n = 396) from 7-year-old children from Hokkaido, Japan and 2) assess possible time trends in the concentrations of bisphenols between 2012 and 2017. Information on demographic, indoor environment and dietary characteristics of participants were acquired through a self-administered questionnaire. All bisphenols were detected in the study population, with BPA, BPF and BPS showing detection frequencies >50%. Concentrations of bisphenols measured in the Japanese children in our study were generally lower compared to studies worldwide. We found that BPA concentrations decreased significantly over the study time period (average 6.5% per year), whereas BPS rose with 2.8% per year. Levels of BPA and BPF were higher in autumn compared to winter. Higher urinary BPF levels were significantly associated with higher concentrations of the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8-OHdG). BPA and BPF levels were higher in children from families with lower household income. Bisphenol concentrations were significantly influenced by some other personal (e.g. household income), food intake (e.g. vegetables and cow milk) and indoor housing characteristics (e.g. flooring). This is the first study to report longitudinal time trends of bisphenols in Japan. The presented findings imply that further research on bisphenols is warranted in the future to monitor whether these time trends continue.

Combined exposure to phthalate esters and phosphate flame retardants and plasticizers and their associations with wheeze and allergy symptoms among school children.

BACKGROUND: Phthalate esters and phosphate flame retardants and plasticizers (PFRs) are both used as plasticizers and are commonly detected in indoor environments. Although both phthalates and PFRs are known to be associated with children's wheeze and allergic symptoms, there have been no previous studies examining the effects of mixtures of these exposures. OBJECTIVES: To investigate the association between exposure to mixtures of phthalate esters and PFRs, and wheeze and allergic symptoms among school-aged children. METHODS: A total of 128 elementary school-aged children were enrolled. Metabolites of 3 phthalate esters and 7 PFRs were measured in urine samples. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. In the primary model, we created a phthalate ester and PFR mixture exposure index, and estimated odds ratios (ORs) using weighted quantile sum (WQS) regression and quantile g (qg)-computation. The two highest chemicals according to qg-computation weight %s were combined to create a combination high × high exposure estimate, with ORs calculated using the "low × low" exposure group as the reference category. Concentrations of each metabolite were corrected by multiplying this value by the sex- and body size-Standardised creatinine concentration and dividing by the observed creatinine value. All models were adjusted for sex, grade, dampness index and annual house income. RESULTS: The odds ratio of rhinoconjunctivitis for the association between exposure to chemical mixtures according to the WQS index positive models was; OR = 2.60 (95% confidence interval [CI]: 1.38-5.14). However, wheeze and eczema of the WQS index positive model, none of the WQS index negative models or qg-computation result yielded statistically significant results. Combined exposure to the two highest WQS weight %s of "high-high" ΣTCIPP and ΣTPHP was associated with an increased prevalence of rhino-conjunctivitis, OR = 5.78 (1.81-18.43) to the "low × low" group. CONCLUSIONS: Significant associations of mixed exposures to phthalates and PFRs and increased prevalence of rhinoconjunctivitis was found among elementary school-aged children in the WQS positive model. Mixed exposures were not associated with any of allergic symptoms in the WQS negative model or qg-computation approach. However, the combined effects of exposure to two PFRs suggested an additive and/or multiplicative interaction, potentially increasing the prevalence of rhinoconjunctivitis. A further study with a larger sample size is needed to confirm these results.

Lifestyle behaviors and home and school environment in association with sick building syndrome among elementary school children: a cross-sectional study.

BACKGROUND: Sick building syndrome (SBS) refers to the combination of symptoms experienced by occupants of specific building characteristics. This study investigated the associations of children's lifestyle behaviors, allergies, home, and school environment with SBS symptoms. METHODS: A total of 4408 elementary school children living in Sapporo City, Japan participated in this study. SBS was determined on parental answers to MM080 standardized school questionnaires on symptoms that were weekly experienced by these children, and if the symptom is attributed to their home or school environment. The Japanese version of the International Study of Asthma and Allergies in Childhood questionnaire was used to assess wheeze, rhino-conjunctivitis, and eczema. A logistic regression analysis was conducted to evaluate the associations between SBS symptoms and variables by controlling the potential confounders (gender, grade, school, and parental history of allergies). A stepwise backward elimination was conducted to assess independent variables related to SBS. RESULTS: Participants revealed mucosal (6.9%), skin (2.0%), and general (0.8%) symptoms. The presence of one or more allergy was associated with increased mucosal and skin symptoms. Children who skipped breakfast, displayed faddiness (like/dislike of food), had constipation, have insufficient sleep, did not feel refreshed after sleep, and lacked deep sleep showed significantly high odds ratios with SBS symptoms. The stepwise analysis showed faddiness for mucosal symptoms and not feeling refreshed after sleep for mucosal and skin symptoms, whereas constipation and lacking deep sleep for general symptoms were independent variables in increasing the symptoms. We found no significant relationship between SBS in children and schools. Considering children's home, old building, no ventilation, wall-to-wall carpet, and heavy nearby traffic were associated with elevated mucosal symptom, while living in a multifamily home increased general symptoms. Home dampness was an independent variable in increasing all SBS symptoms. CONCLUSIONS: Allergies and lifestyle behaviors were associated with increased SBS in children, including skipping breakfast, displaying faddiness, constipation, insufficient sleep, not feeling refreshed after sleep, and the lack of deep sleep. Further, dampness at home was associated with increase in all SBS symptoms. Lifestyle (e.g., eating and sleeping habits) and home (i.e., dampness) improvements might alleviate SBS symptoms in children.

Dose-dependent associations between prenatal caffeine consumption and small for gestational age, preterm birth, and reduced birthweight in the Japan Environment and Children's Study.

BACKGROUND: Few previous studies have investigated the association between prenatal caffeine intake and birth size (small for gestational age [SGA], preterm birth, and birthweight Z-score) in Japan. OBJECTIVES: We examined the dose-dependency of this association (prenatal caffeine consumption and birth size) as part of the Japan Environment and Children's Study. METHODS: A prospective birth cohort included 94 876 fetuses in Japan. Participants were enrolled between January 2011 and March 2014. Adjusted multiple linear regression and Cox regression models were used to examine the association between prenatal caffeine levels and infant birth size. RESULTS: The median estimated caffeine consumption during pregnancy was 125.5 mg/day, as determined by self-administered questionnaires. There were 7252 SGA infants (7.6%) and 4281 preterm birth infants (4.5%). Compared with infants of mothers whose caffeine consumption during pregnancy was in the lowest quartile (4.2 to <86.4 mg/day), infants of mothers whose caffeine consumption was in the highest quartile 4 (205.5-5080.0 mg/day) were at an increased risk of SGA (relative risk [RR] 1.18, 95% confidence interval [CI] 1.10, 1.27), and at an increased risk of preterm birth at the second trimester of gestation (RR 1.94, 95% CI 1.12, 3.37), with a 0.32-day reduction in gestational age (95% CI -0.52, -0.12) and with a 0.07 reduction in birthweight Z-score observed (95% CI -0.09, -0.05). CONCLUSIONS: Prenatal caffeine consumption was associated with birth size. However, as the association between prenatal caffeine consumption and birth size was likely confounded by unpredicted potential factors, our confidence in the true causality of the association is moderate.

Biomonitoring of organophosphate flame retardants and plasticizers in children: Associations with house dust and housing characteristics in Japan.

Indoor environments contain a wide range of new chemicals such as phosphate flame retardants and plasticizers (PFRs). Despite recent epidemiological evidence suggesting that children might be affected by widespread exposure to PFRs, questions remain about the various exposure pathways to these chemicals. Therefore, the aim of this study was to investigate exposure to PFRs by measuring the concentrations a set of urinary metabolites for schoolchildren from Japan (n = 128) and associating them with house dust concentrations and housing characteristics. Detectable concentrations of both diaryl and dialkyl phosphates (DAPs) and hydroxylated metabolites (HO-PFRs) were found in urine samples of almost all children. 2-Hydroxyethyl bis(2-butoxyethyl) phosphate (BBOEHEP) was the most frequently detected metabolite (98%) followed by 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP, 95%) and tris(chloroethyl) phosphate (TCEP). Next to BBOEHEP, two other metabolites of tris(2-butoxyethyl) phosphate (TBOEP) were also frequently detected. Significant correlations of moderate strength were found between parent compounds detected in high concentrations in house dust (TBOEP, tris(2-chloroisopropyl) phosphate (TCIPP)) and their corresponding metabolites, suggesting that dust is a primary exposure source for these PFRs. Several personal and housing characteristics, such as gender, income, and the use of PVC and ventilation were associated with metabolite concentrations in multivariate linear regression. Overall, this study showed that Japanese schoolchildren are exposed to a wide range of PFRs.

Association between prenatal bisphenol A and phthalate exposures and fetal metabolic related biomarkers: The Hokkaido study on Environment and Children's Health.

Bisphenol A and phthalates are widely detected in human urine, blood, breast milk, and amniotic fluid. Both bisphenol A and phthalates have been suggested as playing a role in obesity epidemics. Exposure to these chemicals during fetal development, and its consequences should be concerning because they can cross the placenta. Thus, this study aimed to assess the association between prenatal exposure to bisphenol A and phthalates, and cord blood metabolic-related biomarkers. Maternal serum was used during the first trimester, to determine prenatal exposure to bisphenol A and phthalates. Levels of metabolic-related biomarkers in the cord blood were also determined. Linear regression models were applied to the 365 participants with both, exposure and biomarker assessments, adjusted for maternal age, pre-pregnancy body mass index, parity, education, and sex of the child. The level of bisphenol A was negatively associated with the leptin level (ß = -0.06, 95% confidence interval [CI]: -0.11, -0.01), but was positively associated with the high-molecular-weight adiponectin level, with marginal significance (ß = 0.03, 95%CI: 0.00, 0.06). The mono-isobutyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP), and summation of MEHP and MECPP to represent DEHP exposure (∑DEHPm) levels were inversely associated with the leptin levels (ß=-0.14, 95%CI: -0.27, -0.01; ß = -0.12, 95%CI: -0.24, 0.00 with marginal significance; ß=0.08, 95%CI: -0.14, -0.03; and ß = -0.09, 95%CI: -0.16, -0.03, respectively). The present study provided some evidence that prenatal exposure to bisphenol A and certain phthalates may modify fetal adiponectin and leptin levels.

The Hokkaido Birth Cohort Study on Environment and Children's Health: cohort profile-updated 2017.

The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.