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Despite numerous studies, the associations between per- and polyfluoroalkyl substances (PFAS) exposure and various lipid levels in pregnant women remain ambiguous, especially concerning the association with cord blood lipids. This analysis included 20,960 pregnant women enrolled in the Japan Environment and Children's Study, recruited between 2011 and 2014. Non-fasting plasma samples collected before 22 weeks of gestation were examined for PFAS concentrations. Additionally, non-fasting serum samples collected before, at and after 22 weeks of gestation, at birth, and from cord blood were used to measure total cholesterol (TC) and triglycerides (TG). Linear regression models were applied to quantify the association between each PFAS and various lipid metrics. Among the 28 PFAS analyzed, 7 were quantifiable in more than 80% of participants. Of these, 6 PFAS showed positive associations with TC in maternal blood before 22 weeks of gestation, a trend that remained mostly consistent for maternal blood samples in later stages. However, no associations were found with TC levels in cord blood. Regarding TG, 3 PFAS demonstrated a negative association with TG levels in maternal blood before 22 weeks of gestation, with these relationships generally persisting in later stages, while 4 PFAS were positively associated with TG in cord blood. In summary, this study identified associations between PFAS concentrations in maternal blood and lipid levels in both maternal and cord blood, with differing patterns observed between the two., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Inc.)

The relationship between early childhood phthalate exposure and early adiposity rebound is unclear. This study aimed to investigate the association between 1.5- and 3-year phthalate exposure and EAR and overweight/obesity in 7.5-year-old Japanese children. A total of 452 mother-child pairs were enrolled from the Aichi Regional Cohort of the Japan Environment and Children's Study. The children were followed up at birth and at 1.5, 2, 3, 4, 5, 6, and 7.5 years of age for physical examination. Human biomonitoring of 16 urinary metabolites of eight phthalates was performed at 1.5 and 3 years of age. Latent class mixed models, binary logistic regression, and quantile g-computation were performed to identify body mass index (BMI) trajectories and investigate the relationships of single or mixed phthalate exposure with EAR and overweight/obesity. A one-unit increase in log 10 -transformed 3-year-old Σdi(2-ethylhexyl) phthalate (ΣDEHP) exposure levels was significantly associated with 6-year-old BMI in girls. The 1.5-year mono-iso-butyl phthalate and 3-year Σdi-isodecyl phthalate exposure levels were significantly associated with the repeated measures of longitudinal BMIs in girls. Single phthalate exposure showed null associations with EAR or overweight/obesity in the 7.5-year-old children. Σdi-isononyl phthalate, ΣDEHP, and mono-n-butyl phthalate exhibited the highest proportion of partial positive weights of being in the EAR trajectory after confounder adjustment. Phthalate mixture exposure in 1.5- and 3-year-old children was not significantly associated with EAR. Early childhood phthalate exposure was not related to EAR or overweight/obesity in 7.5-year-old Japanese children. However, few phthalates were positively associated with longitudinal BMIs in girls., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Inc.)

Background: Since the 1920s, motor development has been a strong research theme, focusing on infants' acquisition of motor skills, such as turning over and crawling. In the 1980s, a dynamic systems approach began emphasizing children's own motivation, which helped explain individual differences in the emergence of motor skills. However, few studies have examined factors contributing to individual differences in early motor development. In response, we investigated directional associations between temperament and motor development in children aged 6 months to 3 years., Method: The Japan Environment and Children's Study (JECS-A) recruited mothers between January 2011 and March 2014. 2,639 mothers were sent a questionnaire at 6 months, and responses were received from 1,657 of them, with full data for children aged 6 months, 2 years, and 3 years, including from three mothers of twins, were analyzed through structural equation modeling. Question items regarding fine and gross motor activities at each age were selected by pediatric neurologists specializing in developmental disorders. The Japanese version of the Little Developmental Coordination Disorder Questionnaire was administered at 42 months. Temperament was assessed through the parent-reported Behavior Questionnaire (short version) for infants, toddlers, and children. In all three measures, Surgency and Negative Affectivity were extracted, and Effortful Control, a major form of self-regulation, was found from toddlerhood onward, as in previous studies., Results: A path diagram reveals that at 6 months, Surgency and Orienting/Regulation interacted positively with the motor function (respectively, r = .57; r = 40, ps < .001). Up to about 3 years, Effortful Control plays a role in facilitating the motor function, resulting in positive effects on Control During Movement (CDM), General Coordination (GC), and Fine Motor Movement (FMM) (β = 14; β = 30; β = 37, ps < .001). Surgency had a positive effect on CDM and GC (β = 18; β = 06, ps < .001), whereas Negative Affect had a negative influence on FMM and GC (β = -.08; β = -.08, ps < .001)., Conclusion: While Surgency may be a key reactive factor in early motor development, Effortful Control and Movement develop in an interactive manner., Trial Registration: UMIN000030786. Scientific Title: The Japan Environment and Children's Study. Date of disclosure of the study: 2018/01/15. Only questionnaires were administered in the study., (© 2024. The Author(s).)

Background: Although involvement of toddlers in swimming activities has increased recently, information regarding the impact of swimming during toddlerhood on subsequent child motor competence development is scarce. This study aimed to determine how swimming experience, particularly the timing of initiation and the continuity of swimming activities up to the age of 3 years, affects motor competence development., Methods: This prospective cohort study included data on children aged 1.5 and 3 years (100,286 mother-child pairs) from the Japan Environment and Children's Study. The outcomes measured were gross and fine motor function, using the Japanese version of the Ages and Stages Questionnaire (Third edition). We assessed how these functions correlated with the continuous pattern of swimming pool use frequency from age 1 up to 3 years., Results: The group that used a swimming pool once a month or more from age 1-1.5 years but stopped from age 2-3 years showed consistently significant negative associations with gross motor development delay (minimum adjusted odds ratio [aOR]: 0.66, 95% confidence interval [CI]: 0.60-0.73) and fine motor development delay (minimum aOR: 0.66, 95% CI: 0.58-0.76). The group that continued swimming once a month or more from age 1-3 years showed consistently significant negative associations with gross motor development delay (minimum aOR: 0.64, 95% CI: 0.54-0.75) and fine motor development delay (minimum aOR: 0.42, 95% CI: 0.31-0.55)., Conclusions: These results suggest that swimming experience starting around age 1 year is positively associated with gross and fine motor function development. The beneficial impact on gross motor function persisted from age 1-3 years. In contrast, the effects on fine motor function were not evident until age ≥ 2.5 years after starting swimming at approximately age 1 year. These findings underscore the potential benefits of early swimming experiences in enhancing overall motor skills development during early childhood., (© 2024. The Author(s).)

Background and Aims: In the neurobiological theory of attention, the orienting network mainly supports the temperamental regulatory function in infancy, with soothing methods such as visual attention distraction influencing its development. The attention distraction method chosen for soothing is thought to be influenced by maternal sensitivity, which has been found to decrease with poor maternal mental health. We hypothesize that the degree of maternal distress may affect the choice of attention distraction soothing method. Further, individual differences in being soothed by attention distraction will be associated with the temperamental regulation function in infancy/toddlerhood., Method: Structural equation modeling (SEM) was conducted on longitudinal data at 6 and 24 months on a sample ( N  = 1892) drawn from the sub-cohort of the Japan Environment and Children's Study (JECS). Temperament was examined through the short Infant Behavior Questionnaire-Revised (Japanese version) and the Early Childhood Behavior Questionnaire (Japanese version). Distress in caregivers was measured through the Kessler Psychological Distress Scale (Japanese version) at prenatal and 1-year-postnatal stages. Individual differences in using visual distraction soothing methods were also measured using tailor-made items., Results: Postnatal maternal distress at 12 months was negatively related to the tendency to use visual attention distraction as a soothing method (β = -0.06, p  = 0.006) at 24 months. When we applied the subscale of the temperamental regulatory factor in SEM, the more the mothers chose the distraction method for soothing, i.e., the more the toddlers experienced it, the higher their attention shifting scores (β = 0.07, p  = 0.002)., Conclusion: The findings support the view that caregivers' choice of method for distracting offspring's attention from distress may be associated with the development of self-regulation during infancy and toddlerhood., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Background: Although recent in vitro experimental results have raised the question of whether maternal exposure to per- and polyfluoroalkyl substances (PFAS) may be a potential environmental risk factor for chromosomal abnormalities, epidemiological studies investigating these associations are lacking., Objectives: This study examined whether prenatal PFAS exposure is associated with a higher prevalence of chromosomal abnormalities among offspring., Methods: We used data from the Japan Environment and Children's Study, a nationwide birth cohort study, and employed logistic regression models to examine the associations between maternal plasma PFAS concentrations in the first trimester and the diagnosis of chromosomal abnormalities in all births (artificial abortions, miscarriages, stillbirths, and live births) up to 2 years of age. In addition, we examined associations with mixtures of PFAS using multipollutant models., Results: The final sample consisted of 24,724 births with singleton pregnancies, of which 44 confirmed cases of chromosomal abnormalities were identified (prevalence: 17.8/10,000 births). When examined individually, exposure to perfluorononanoic acid (PFNA) and perfluorooctane sulfonic acid (PFOS) showed positive associations with any chromosomal abnormalities with age-adjusted odds ratios of 1.81 (95% CI: 1.26, 2.61) and 2.08 (95% CI: 1.41, 3.07) per doubling in concentration, respectively. These associations remained significant after Bonferroni correction, although they did not reach the adjusted significance threshold in certain sensitivity analyses. Furthermore, the doubling in all PFAS included as a mixture was associated with chromosomal abnormalities, indicating an age-adjusted odds ratio of 2.25 (95% CI: 1.34, 3.80), with PFOS as the predominant contributor, followed by PFNA, perfluoroundecanoic acid (PFUnA), and perfluorooctanoic acid (PFOA)., Discussion: The study findings suggested a potential association between maternal exposure to PFAS, particularly PFOS, and chromosomal abnormalities in offspring. However, the results should be interpreted cautiously, because selection bias arising from the recruitment of women in early pregnancy may explain the associations. https://doi.org/10.1289/EHP13617.

Fungicides undergo rapid metabolism and are excreted in the urine. There are few methods for screening these ubiquitous compounds, which have a high potential for human exposure. High-resolution mass spectrometry (HRMS) is a suitable technique to assess fungicide exposures; however, there is a lack of spectral libraries for fungicide annotation and in particular for downstream metabolites. We created spectral libraries for 32 fungicides for suspect screening. Fungicide standards were administered to mice, and 24-h urine was analyzed using hydrophilic interaction and reversed-phase chromatography coupled to hybrid quadrupole-orbitrap mass spectrometry. Suspect metabolite MS2 spectra for library creation were selected based on the ratio of exposed-to-control mouse urine. MS2 libraries were applied to urine collected from female university students ( n = 73). Several tetraconazole and tebuconazole metabolites were detected in 3% (2/73) of the samples. The creation of comprehensive suspect screening MS2 libraries is a useful tool to detect fungicide exposure for human biomonitoring.

Prior research into the association between prenatal mercury (Hg) exposure and the secondary sex ratio has yielded inconclusive and conflicting results. Notably, no study has used cord blood Hg measurement in this context. Also, the differences in Hg species and the potential modifying role of selenium (Se) on this association remain unexplored. Using data from the Japan Environment and Children's Study, we analyzed mother-child pairs with available data for concentrations of total mercury (THg) and Se in maternal blood during late pregnancy, and THg, inorganic mercury (IHg), methylmercury (MeHg), and Se in cord blood. Logistic regression models were employed to examine the association between Hg and Se biomarkers and the secondary sex ratio. Out of the total sample of 3698 children, 1877 (50.8 %) were male, corresponding to an overall secondary sex ratio of 1.03. After adjusting for maternal age and parity, no significant associations were observed between THg concentrations of maternal blood and the secondary sex ratio. Nevertheless, we identified that two-fold increases in THg, IHg, and MeHg concentrations in cord blood were positively associated with increased odds of having a male child, yielding adjusted odds ratios of 1.13 (95 %CI: 1.04, 1.22), 1.12 (1.03, 1.21), and 1.12 (1.03, 1.22), respectively. When stratified by the median Se concentrations, no apparent differences were detected in the associations between Hg concentrations and the secondary sex ratio. In summary, elevated Hg concentrations in cord blood, but not maternal blood, were associated with an increased probability of male births., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Librarians at a university had planned to check the collection prior to the library renovations that began in 2015. They had previous knowledge of the presence of a light greyish-white powder with an unpleasant odour (hereinafter referred to as 'powder') sprinkled between the pages of antiquarian books in the library archive. The purpose of this study was to identify this powder with the help of experts from both inside and outside the university. The powder was qualitatively analysed using gas chromatography with mass spectrometry after hexane extraction. The powder was examined under a polarised light microscope and a field-emission scanning electron microscope equipped with an energy-dispersive X-ray spectrometer. Benzene hexachloride (BHC) was detected in the powder. Talc was the most abundant particle in the powder. The powder also contained 0.52 wt% asbestos, which belonged to the tremolite-actinolite series. No other types of asbestos were detected. The powder was presumed to be a bulking agent for BHC, and its major constituent was talc. This is the first report on asbestos-containing insecticides.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM)., Objective: To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan., Design: Prospective observational study using data from the Japan Environment and Children's Study (JECS)., Participants: Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded., Main Outcome Measures: Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model., Results: We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07)., Conclusions: The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Teenage pregnancy increases the threat of depression because of its many factors. Pregnancy during young adulthood may also have several risk factors for depression compared to older pregnancies. However, data on depression in young adult pregnancies are lacking. This study investigated the association between teenage and young adult pregnancy and depression. Data from the Japan Environment and Children's study was used as a nationwide multicenter prospective cohort study. A multivariate logistic regression was performed to investigate the association between age groups (14-19, 20-24, 25-29, 30-34, ≥ 35 years) and depression, adjusted for behavioral and sociodemographic characteristics. Depression was assessed using the Kessler Psychological Distress Scale. In total, 96,808 pregnant women responded to the questionnaire. Teenage (14-19 years) and young adult (20-24 years) pregnancy were associated with an increased risk of depression compared to older pregnancy (≥ 35 years) (teenage: OR 4.28, 95% confidence interval, CI [3.24-5.64]; young adult: OR 3.00, 95% CI [2.64-3.41]). After adjusting for covariates, the magnitude of the risk of depression was attenuated. However, teenage and young adult pregnancy remained at a significantly increased risk of depression compared to older pregnancy (teenage: OR 2.38, 95% CI [1.77-3.21]; young adult: OR 2.14, 95% CI [1.87-2.46]). Our findings indicate that teenage and young adults' pregnancy are at an increased risk of depression compared to older pregnancy. These findings suggest prioritizing teenage and young pregnant women for prevention and interventions related to depression., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Catch-up growth issues among children born small for gestational age (SGA) present a substantial public health challenge. Prenatal exposure to heavy metals can cause adverse effects on birth weight. However, comprehensive studies on the accurate assessment of individual blood concentrations of heavy metals and their effect on the failure to achieve catch-up growth remain unavailable. This study aimed to evaluate the effects of uterine exposure to toxic metals cadmium, lead, and mercury and essential trace metals manganese and selenium at low concentrations on the postnatal growth of children born SGA., Methods: Data on newborn birth size and other factors were obtained from the medical record transcripts and self-administered questionnaires of participants in the Japan Environment and Children's Study. The blood concentrations of lead, cadmium, mercury, selenium, and manganese in pregnant women in their second or third trimester were determined by inductively coupled plasma mass spectrometry. These heavy metal concentrations were also assessed in pregnant women's cord blood. Furthermore, the relationship between each heavy metal and height measure/catch-up growth in SGA children aged 4 years was analyzed using linear and logistic regression methods. These models were adjusted for confounders., Results: We studied 4683 mother-child pairings from 103,060 pregnancies included in the Japan Environment and Children's Study. Of these, 278 pairs were also analyzed using cord blood. At 3 and 4 years old, 10.7% and 9.0% of children who were born below the 10th percentile of body weight had height standard deviation scores (SDSs) below 2, respectively. Cord blood cadmium concentrations were associated with the inability to catch up in growth by 3 or 4 years old and the height SDS at 3 years old. In maternal blood, only manganese was positively associated with the height SDS of SGA children aged 2 years; however, it was not significantly associated with catch-up growth in these children., Conclusion: Cadmium exposure is associated with failed catch-up development in SGA children. These new findings could help identify children highly at risk of failing to catch up in growth, and could motivate the elimination of heavy metal (especially cadmium) pollution to improve SGA children's growth., (© 2024. The Author(s).)

Kawasaki disease (KD) is common among pediatric patients and is associated with an increased risk of later cardiovascular complications, though the precise pathophysiology of KD remains unknown. Per- and polyfluoroalkyl substances (PFAS) have gathered notoriety as the causal pathogens of numerous diseases as well as for their immunosuppressive effects. The present epidemiological study aims to assess whether PFAS may affect KD risk. We evaluated research participants included in the ongoing prospective nationwide birth cohort of the Japan Environment and Children's Study (JECS). Among the over 100,000 pregnant women enrolled in the JECS study, 28 types of PFAS were measured in pregnancy in a subset of participants (N = 25,040). The JECS followed their children born between 2011 and 2014 (n total infants = 25,256; n Kawasaki disease infants = 271), up to age four. Among the 28 types of PFAS, those which were detected in >60 % of participants at levels above the method reporting limit (MRL) were eligible for analyses. Multivariable logistic regressions were implemented on the seven eligible PFAS, adjusting for multiple comparison effects. Finally, we conducted Weighted Quantile Sum (WQS) and Bayesian kernel machine regression (BKMR) to assess the effects of the PFAS mixture on KD. Therefore, we ran the BKMR model using kernel mechanical regression equations to examine PFAS exposure and the outcomes of KD. Upon analysis, the adjusted multivariable regression results did not reach statistical significance for the seven eligible substances on KD, while odds ratios were all under 1.0. WQS regression was used to estimate the mixture effect of the seven eligible PFAS, revealing a negative correlation with KD incidence; similarly, BKMR implied an inverse association between the PFAS mixture effect and KD incidence. In conclusion, PFAS exposure was not associated with increased KD incidence., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The effects of early-life exposure to per- and polyfluoroalkyl substances (PFAS) on the onset of asthma in children have been unclear. We examined the association between prenatal PFAS exposure and wheezing and asthma symptoms among 4-year-old children in a total of 17,856 mother-child pairs from the Japan Environment and Children's Study. Maternal first-trimester serum concentrations of six PFAS were used for the exposure assessment. We defined "wheeze ever," "current wheeze," "current symptoms of severe asthma," and "asthma ever" at the age of 4 years by the responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and "doctor-diagnosed asthma" by the response to a corresponding question. Multivariate logistic regression models were used to examine exposure-outcome associations. Our findings revealed that doubling of the PFOA concentration was associated with a reduced occurrence of "wheeze ever," yielding an adjusted odds ratio of 0.94 (95% CI: 0.90-0.98). Also, doubling in the concentrations of PFOA and PFHxS was associated with a decreased prevalence of "asthma ever," with adjusted odds ratios of 0.94 (95% CI: 0.88-1.00) and 0.95 (95% CI: 0.90-0.99), respectively. However, these associations were not significant after applying the Bonferroni correction. The estimated exposure-response curves were nearly linear with a subtle or flat slope. When stratified by the child's sex or the mother's history of asthma, most of the estimated confidence intervals were overlapped between each pair of strata. Regional stratification analysis indicated low-to-moderate heterogeneity in 12 exposure-outcome pairs and moderate-to-high heterogeneity in 9 out of the 30 examined pairs. This study found no clear associations between prenatal PFAS exposure and the prevalence of wheezing and asthma among children at the age of 4 years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Poor oral hygiene, generally manifesting as dental caries, gingivitis, or periodontitis, is a common chronic condition among both children and adults worldwide and has been reportedly associated with hypertension and arterial stiffness mainly in adult patients. However, these associations have not been well-studied in children and adults in the general population. Therefore, we conducted this cross-sectional study to clarify the associations between oral hygiene indices and high blood pressure (BP)/hypertension and arterial stiffness as assessed by the cardio-ankle vascular index (CAVI) in children along with their mothers. The association between maternal oral hygiene and high BP in children was also examined based on the hypothesis that maternal awareness of oral hygiene is related to their children's oral hygiene., Methods: This study was conducted as an Adjunct Study of the Aichi Regional Sub-Cohort of the Japan Environment and Children's Study. Participating children (n = 220, 85-104 months old) and their mothers (n = 217, 29-52 years old) underwent dental/intra-oral examination and BP and CAVI assessment. High BP in children and hypertension in mothers were diagnosed according to corresponding American guidelines. Logistic regression analysis or analysis of covariance was used to examine the associations of poor oral hygiene indices with BP and CAVI., Results: Maternal dental caries ≥1 was associated with their hypertension (adjusted odds ratio [aOR]: 2.72, 95% confidence interval (CI): 1.12-6.61). Maternal dental plaque ≥1/3 was associated with maternal hypertension and children's high BP (aOR, 95% CI: 4.71, 1.33-16.73 and 5.67, 1.22-25.04, respectively). Maximum pocket depth ≥4 mm was associated with children's high BP (aOR: 6.85, 95% CI: 1.24-38.01). No associations were observed between oral hygiene indices and CAVI in children; however, there was a significant association between dental plaque and CAVI in mothers (F = 5.62, p < 0.01)., Conclusions: The small sample size, especially the case number, made it necessary to refrain from drawing unambiguous conclusion. The hypothesis that warrants further investigation based on the present study results is that poor oral hygiene is associated with high BP in children and hypertension and arterial stiffness in mothers, and maternal oral hygiene is associated with high BP in children.

Background: Recent studies have reported the effect of neonicotinoid (NEO) exposures on development in human. However, information about the risk of childhood development delays due to NEO exposures is limited., Objectives: The study aimed to examine the association between NEO exposure and child development up to 4 years of age using data of the Japan Environment and Children's Study., Methods: The study employed urinary NEO and metabolite concentrations in the first and second or third trimesters; the Japanese translation of the Ages and Stages Questionnaire (third edition; J-ASQ-3) scores on developmental delay in five domains, namely communication, gross motor skills, fine motor skills, problem solving, and personal-social characteristics from 6 months to 4 years of age; and self-reported questionnaire data. The associations between urinary NEO concentrations and J-ASQ-3 results were analysed using the treed distributed lag mixture model. A total of 8538 participants were included in statistical analyses., Results: The determination rates of urinary acetamiprid-N-desmethyl (dm-ACE), clothianidin (CLO), dinotefuran (DIN) and thiamethoxam (THX) were greater than 50%. Median urinary dm-ACE, CLO, DIN and THX concentrations were 0.34, 0.14, 0.22 and 0.05 ng/ml, respectively, in samples collected during gestational weeks < 23, and 0.28, 0.12, 0.18 and 0.04 ng/ml, respectively, in those collected during gestational weeks ≥ 23. The binomial scores divided by the cut-off values of the J-ASQ were used in the treed distributed lag mixture model. The highest percentage for a domain with a value less than the cut-off value was 'problem solving' at 6 months of age among all the J-ASQ-3 scores (10.5%). There was no statistically significant association between maternal urinary dm-ACE, CLO, DIN and THX concentrations during pregnancy and the J-ASQ-3 results up to 4 years of age. Objective assessment of child development in different populations may be warranted to confirm our findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Exposure to low doses of neonicotinoid (NEO) insecticides during pregnancy may have a negative impact on the neurodevelopment of children. Biomarkers are frequently used to investigate the exposure and its health effects in environmental epidemiology. In the present study, we aimed to evaluate the utility of urinary biomarkers of NEO exposure by calculating intra-class correlation coefficients (ICCs). Urine samples were collected from 30 pregnant women who were non-smokers and living in a central part of Japan, between 12 and 22 weeks of gestation. We collected first morning voided (FMV) urine and afternoon spot (PM) urine samples on the same day on five occasions within a 2-week period. The urinary concentrations of NEO and their metabolites (NEO/m) were measured by liquid chromatography-tandem mass spectrometry. Normalisation to the specific gravity and creatinine concentration was used in the calculation of ICC. The number of urine samples required to obtain a reliable biomarker estimate of NEO exposure was calculated. The most frequently detected NEO/m was N-desmethyl-acetamiprid (N-dm-ACE), followed by clothianidin (CLO), thiamethoxam (THX) and dinotefuran (DIN), in both FMV and PM urine samples. The ICC calculations showed poor reproducibility for the measurement of CLO and THX concentrations (ICCs ≤0.25) in both FMV and PM urine samples and for DIN (ICC ≤0.29) in the FMV urine samples, and moderate reproducibility was identified for N-dm-ACE (ICC >0.60) in both FMV and PM urine samples and for DIN (ICC >0.40) in the PM urine samples. A minimum of 1-19 spot urine samples per individual was required to provide a reliable biomarker estimate over a 2 week period. These results suggest that pregnant Japanese women are frequently exposed to NEOs, and that, with the exception of urinary N-dm-ACE, a single measurement of urinary NEO concentrations may not be an appropriate method of characterising overall exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

High urinary levels of dialkylphosphates (DAPs), which are common structures of organophosphate pesticides (OPs), have been associated with several adverse health outcomes in human biomonitoring studies. Previous studies have indicated that dietary OP exposure and ingestion of environmentally degraded DAP, which is inactive with acetylcholinesterase, can lead to an increase in urinary DAP levels in the general population. However, the specific food sources contributing to the intake of OPs and DAPs have not been identified. In this study, we analyzed the levels of OPs and preformed DAPs in various food items. DAP levels were markedly high in certain fruits, such as persimmon, apple juice, kiwi, and mandarin. In contrast, only moderate levels of OPs were detected in these foods. Furthermore, the levels of OPs and DAPs were positively associated with vegetables, whereas no such association was observed in fruits. Increased consumption of certain fruits presumably leads to a marked increase in urinary DAP levels in individuals despite limited exposure to OPs, resulting in reduced reliability of urinary DAPs as a marker of OP exposure. Therefore, the possible effects of dietary habits and the resulting intake of preformed DAPs should be considered when interpreting biomonitoring data of urinary DAPs. Additionally, DAP levels in most organic foods were much lower than those in conventional foods, suggesting that the reduction in urinary DAPs by organic diet intervention may be mainly attributed to the reduced intake of preformed DAPs rather than reduced exposure to OPs. Therefore, urinary DAP levels may not be suitable indicators for evaluating ingested OP exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Prenatal exposure to metallic elements may adversely affect early childhood health. However, more evidence is needed as population-based cohort studies are currently limited., Objectives: We aimed to examine the associations between prenatal metallic (mercury, selenium, and manganese) exposure and the risk of allergic diseases in early childhood until three years of age., Methods: The data from 94,794 mother-infant pairs, who participated in the Japan Environment and Children's study, were used in this study. Prenatal metallic element exposure was measured in maternal blood collected during mid-pregnancy. The incidence of atopic dermatitis, food allergies, asthma, and allergic rhinitis during the first three years of life was prospectively investigated using self-reports of physician-diagnosed allergies. A multivariable modified Poisson regression model was used to estimate the cumulative incidence ratio and their 95% confidence intervals of allergic diseases associated with prenatal exposure to mercury, selenium, and manganese. We further evaluated the interaction between mercury and selenium exposures in this association., Results: We confirmed 26,238 cases of childhood allergic diseases: atopic dermatitis, food allergies, asthma, and allergic rhinitis in 9,715 (10.3%), 10,897 (11.5%), and 9,857 (10.4%), 4,630 (4.9%), respectively. No association was found between prenatal mercury or manganese exposure and the risk of allergic diseases. Prenatal selenium exposure was inversely associated with atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases, but not with asthma. These inverse associations were more pronounced for lower mercury exposures than for higher exposures., Conclusions: Our findings suggest that prenatal exposure to selenium may be beneficial for reducing the risk of atopic dermatitis, food allergies, allergic rhinitis, and any allergic diseases in early childhood, especially with lower prenatal mercury exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To provide an overview of the pathogenesis of pneumatosis cystoides intestinalis (PCI) and hypersensitivity syndrome (HS) caused by trichloroethylene (TCE) and the basic research into their toxicity., Subjects and Methods: We reviewed previously published research articles., Results: PCI clustered in Japan in the 1980s is a rare disease characterized by cyst-like distention of gas in the intestinal wall, which can be secondary or primary. No TCE users were found in the former group, whereas approximately 71% of the latter group were TCE users, suggesting the involvement of TCE exposure in primary PCI. However, the pathogenesis was unclear. TCE is metabolized by the drug-metabolizing enzyme CYP2E1, and intermediate immunocomplexes with CYP2E1 may be involved in hepatotoxicity. HS clustered in the southern part of China since early 2000 is a systemic skin-liver disorder involving anti-CYP2E1 autoantibodies and HLA-B*13:01 polymorphisms, with elevated cytokines and reactivation of Human Herpesvirus 6., Discussion and Conclusion: PCI and HS, occupational diseases caused by TCE, were clustered in Japan and southern China, respectively. HS was mediated by immune system disorders and genetic polymorphisms, whereas their relevance to PCI occurrence remained unknown.

Later-borns tend to be shorter than first-borns in childhood and adulthood. However, large-scale prospective studies examining growth during infancy according to birth order are limited. We aimed to investigate the relationship between birth order and growth during the first 4 years of life in a Japanese prospective birth cohort study. A total of 26,249 full-term singleton births were targeted. General linear and multivariable logistic regression models were performed and adjusted for birth weight, parents' heights, maternal age at delivery, gestational weight gain, maternal smoking and alcohol drinking status during pregnancy, household income, breastfeeding status, and Study Areas. The multivariate adjusted mean length Z-scores in "first-borns having no sibling", "first-borns having siblings", "second-borns", and "third-borns or more" were -0.026, -0.013, 0.136, and 0.120 at birth and -0.324, -0.330, -0.466, and -0.569 at 10 months, respectively. Results similar to those at 10 months were observed at 1.5, 3, and 4 years. The adjusted odds ratios (95% confidence intervals) of short stature at 4 years in "first-borns having siblings", "second-borns", and "third-borns or more" were 1.08 (0.84-1.39), 1.36 (1.13-1.62), and 1.50 (1.20-1.88), respectively, versus "first-borns having no sibling". Birth order was significantly associated with postnatal growth and may be a factor predisposing to short stature in early childhood.

Birth cohort studies examining pregnancy and infant outcomes among adolescent and young adult (AYA) cancer survivors have been limited. The present study examined whether AYA cancer affects pregnancy outcomes of survivors and infectious diseases in their infants up to 1 year of age. Pregnant women were recruited for the Japan Environment and Children's Study, a nationwide, large-scale, prospective cohort study. The present study included 103,060 pregnant women and collected questionnaire-based data during the first and second/third trimester, and at 1 month, 6 months and 1 year after delivery. Adverse pregnancy outcomes and infectious diseases in infants up to 1 year of age were compared between AYA cancer survivors and pregnant women without a history of cancer using binominal logistic regression analyses and a multiple imputation method. Of 99,816 participants (3,244 were missing), 1,102 (1.1%) had a cancer history, including 812 participants (0.8%) with a history of cervical cancer. Among cervical cancer survivors, the adjusted (a)ORs were as follows: 3.25 (95% CI, 2.31-4.57; q=0.00) for a preterm birth <34 weeks' gestation; 2.82 (95% CI, 2.31-3.44; q=0.00) for a preterm birth <37 weeks' gestation; and 1.67 (95% CI, 1.36-2.06; q=0.00) for premature rupture of the membrane. Among the other cancer survivors, the aOR for caesarean section was 1.43 (95% CI, 1.10-1.87; q=0.0). Furthermore, lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery increased significantly in cases with a history of cervical cancer (aOR, 1.77; 95% CI, 1.33-2.36; q=0.00). The present study identified the risk of lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery in cervical cancer survivors for the first time. In addition, the frequency of caesarean section increased in all cancer survivors. No risk of congenital anomalies or other infections were found in the total group of cancer survivors., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Nishikawa et al.)

Phthalate exposure monitoring and risk assessment in non-toilet-trained children are rarely reported. This adjunct study of the Japan Environment and Children's Study assessed cumulative health risks in 1.5-year-old toddlers in the Aichi regional subcohort by biomonitoring 16 urinary metabolites of eight phthalate plasticizers. Overnight urine was extracted from toddlers' diapers ( n = 1077), and metabolites were quantified using ultraperformance liquid chromatography coupled with tandem mass spectrometry. The analyses' quality was assured by running quality control samples. The highest geometric mean concentration was found for mono-(2-ethyl-5-carboxypentyl) phthalate, followed by mono-isobutyl phthalate (23 and 21 μg/L, respectively). Di-2-ethylhexyl phthalate (DEHP) and di-butyl phthalate exhibited higher risks [hazard quotient (HQ) > 1] than the cutoff level in a small proportion of toddlers; 8 and 14% of toddlers were at cumulative risk of multiple phthalates beyond the cutoff level [hazard index, (HI) > 1], based on the tolerable daily intake of the European Food Safety Authority and the United States Environmental Protection Agency Reference Dose. HI > 1 for antiandrogenicity in creatinine-unadjusted and -adjusted estimations were exhibited by 36 and 23% of the children, respectively. Thus, identifying exposure sources and mitigating exposure are necessary for risk management. Additionally, continuous exposure assessment and evaluation of health outcomes, especially antiandrogenic effects, are warranted.