森 千里

The increasing exposure to environmental chemicals calls for comprehensive non-targeted analysis to detect unrecognized substances in human samples. We examined human serum samples to classify compounds as endogenous or exogenous using public databases and to explore the relationships between exposure markers and metabolic patterns. Serum samples from 84 pregnant women at 32 weeks gestation were analyzed using LC-QToFMS. Using the PubChemLite for Exposomics database, we annotated and classified 106 compounds (51 endogenous, 55 exogenous). The compound patterns were analyzed using three dimensional reduction methods: Principal Component Analysis (PCA), regularized Generalized Canonical Correlation Analysis (rGCCA), and Uniform Manifold Approximation and Projection (UMAP). OPTICS clustering applied to these methods revealed two distinct clusters, with 89 % of significant compounds overlapping between clusters. The detected exogenous compounds included dietary substances, phthalates, nitrogenous compounds, and parabens. Pathway enrichment analysis showed that chemical exposure was linked to changes in amino acid metabolism, protein and mineral transport, and energy metabolism. While we found associations between exposure and metabolite changes, we could not establish causality. Our approach of analyzing both exogenous and endogenous chemicals from the same dataset using PubChemLite database presents a new method for exposome research, despite limitations in sample size and peak annotation accuracy. These findings contribute to understanding multiple chemical exposures and their metabolic effects in human biomonitoring.

BackgroundParents' educational background is presumed to influence the incidence of vaccine-preventable diseases in children through their decisions about vaccinations and other family lifestyle choices. Regarding voluntary vaccination, a household's economic situation may also be associated with non-vaccination. Therefore, this study investigated the association between parental education and vaccine-preventable diseases (varicella, mumps, influenza [flu], pertussis, measles, and rubella) in children, which currently remains elusive.MethodsWe used datasets from the Japan Environment and Children's Study, which included 104,062 fetal records; our study population comprised 80,930 children up to the age of three years. The associations between parental educational background and children's infectious diseases were examined using binomial logistic regression analysis. The mediating effects of household income, vaccination, and smoking were examined using a path analysis.ResultsFor varicella, mumps, and influenza covered by voluntary vaccination, a higher education level of the father was associated with a lower incidence of infection. The association between mothers' education and children's infection was limited. There were both income-mediated and non-income-mediated pathways between parental education and voluntary vaccination. For pertussis, measles, and rubella, which are covered by routine vaccines, there was no association between parental education and the child's infection.ConclusionAn association between parental education and childhood infections was observed. Additionally, providing financial support for vaccination and communicating the benefits of vaccination in a way that parents at all levels of education can understand will help reduce the incidence of infectious diseases among children.

One-carbon metabolism (OCM) is a complex and interconnected network that undergoes drastic changes during pregnancy. In this study, we investigated the longitudinal distribution of OCM-related metabolites in maternal and cord blood and explored their relationships. Additionally, we conducted cross-sectional analyses to examine the interrelationships among these metabolites. This study included 146 healthy pregnant women who participated in the Chiba Study of Mother and Child Health. Maternal blood samples were collected during early pregnancy, late pregnancy, and delivery, along with cord blood samples. We analyzed 18 OCM-related metabolites in serum using stable isotope dilution liquid chromatography/tandem mass spectrometry. We found that serum S-adenosylmethionine (SAM) concentrations in maternal blood remained stable throughout pregnancy. Conversely, S-adenosylhomocysteine (SAH) concentrations increased, and the total homocysteine/total cysteine ratio significantly increased with advancing gestational age. The betaine/dimethylglycine ratio was negatively correlated with total homocysteine in maternal blood for all sampling periods, and this correlation strengthened with advances in gestational age. Most OCM-related metabolites measured in this study showed significant positive correlations between maternal blood at delivery and cord blood. These findings suggest that maternal OCM status may impact fetal development and indicate the need for comprehensive and longitudinal evaluations of OCM during pregnancy.

Abstract 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.

Volatile organic compounds (VOCs) have been suspected to cause building-related symptoms (BRSs). Although some studies investigated the association between BRSs and VOCs in indoor air, those results were inconsistent. This study investigated the contamination status of VOCs in the indoor air of 154 houses in Japan. Additionally, these samples were grouped by hierarchical clustering analysis based on the VOC composition, and the relationship between a VOC cluster and the BRSs was investigated. The median concentration of the sum of VOCs (ΣVOCs) was 140 μg m-3 (range: 18-3500 μg m-3). The levels of acetaldehyde in four samples and p-dichlorobenzene in one sample exceeded the guideline value. As a result of the hierarchical clustering analysis, the samples in this study were divided into six characteristic clusters based on the VOC composition. The ΣVOCs in cluster 1 were significantly lower than those in other clusters. In cluster 2, acyclic and aromatic hydrocarbons were dominant. Cluster 3 had a relatively high proportion of limonene. In cluster 4, the concentrations and composition ratios of α-pinene were higher than those of other clusters. In cluster 5, p-dichlorobenzene accounted for 42 %-72 % of the total VOCs. Cluster 6 had a relatively high proportion of decamethyl cyclopentasiloxane. This clustering likely depended on the construction of houses and lifestyles. As a result of logistic regression analysis, cluster 5 was associated with the cough symptoms of the BRSs. The results of the present study suggest that investigating the association between VOCs and BRSs is necessary to consider not only total concentrations such as TVOC and ΣVOCs but also VOC composition.

Abstract Background Although the importance of the dynamic intra-individual relationship between mother-to-infant bonding and postpartum depressive symptoms has been widely recognized, the complex interplay between them is not well understood. Furthermore, the potential role of prenatal depressive symptoms and infant temperament in this relationship remains unclear. This study aims to examine the bidirectional influence of mother-to-infant bonding on postpartum depressive symptoms within individuals and to elucidate whether prenatal depressive symptoms and infant temperament would influence deviations from stable individual states. Methods Longitudinal data were collected from 433 women in early pregnancy. Of these, 360 participants completed the main questionnaires measuring impaired mother-to-infant bonding and postpartum depressive symptoms at least once during the postpartum period. Data were collected at early and late pregnancy and several postpartum time points: shortly after birth and at one, four, ten, and 18 months postpartum. We also assessed prenatal depressive symptoms and infant temperament. A random-intercept cross-lagged panel model was used. Results Within-individual variability in mother-to-infant bonding, especially anger and rejection, significantly predicted subsequent postpartum depressive symptoms. However, the inverse relationship was not significant. Additionally, prenatal depressive symptoms and difficult infant temperament were associated with greater within-individual variability in impaired mother-to-infant bonding and postpartum depressive symptoms. Conclusions The present study demonstrated that the within-individual relationship between mother-to-infant bonding and postpartum depressive symptoms is likely non-bidirectional. The significance of the findings is underscored by the potential for interventions aimed at improving mother-to-infant bonding to alleviate postpartum depressive symptoms, suggesting avenues for future research and practice.

Recently, prediction of gestational diabetes mellitus (GDM) using artificial intelligence (AI) from medical records has been reported. We aimed to evaluate GDM-predictive AI-based models using birth cohort data with a wide range of information and to explore factors contributing to GDM development. This investigation was conducted as a part of the Japan Environment and Children's Study. In total, 82,698 pregnant mothers who provided data on lifestyle, anthropometry, and socioeconomic status before pregnancy and the first trimester were included in the study. We employed machine learning methods as AI algorithms, such as random forest (RF), gradient boosting decision tree (GBDT), and support vector machine (SVM), along with logistic regression (LR) as a reference. GBDT displayed the highest accuracy, followed by LR, RF, and SVM. Exploratory analysis of the JECS data revealed that health-related quality of life in early pregnancy and maternal birthweight, which were rarely reported to be associated with GDM, were found along with variables that were reported to be associated with GDM. The results of decision tree-based algorithms, such as GBDT, have shown high accuracy, interpretability, and superiority for predicting GDM using birth cohort data.

Constipation is common in children and can significantly affect quality of life. Prebiotics are reportedly helpful for constipation in adults, but few studies have examined their use in young children. In this study, the effect of 1-kestose (kestose), which has excellent bifidobacterial growth properties, on constipation in kindergarten children (n = 11) was compared with that of maltose (n = 12) in a randomized, double-blind study. Three grams of kestose per day for 8 weeks did not affect stool properties, but significantly increased the number of defecations per week (Median; 3 → 4 times/week, p = 0.017, effect size = 0.53). A significant decrease in Intestinibacter, a trend toward increased bifidobacteria, and a trend toward decreased Clostridium sensu stricto were observed after kestose ingestion, while concentrations of short-chain fatty acids in stools were unchanged.

Semi-volatile organic compounds (SVOCs), such as phthalates and organophosphate flame retardants (OPFRs), are used in plastic products and electrical and electronic applications as plasticisers or flame retardants. There has been a growing concern that exposure to SVOCs can have an adverse impact on human health. Several large-scale epidemiological studies employ the sampling of house dust using household vacuum cleaners as the standard method. However, in this method, house dust samples might be contaminated by flame retardants and plasticisers because of the presence of these chemicals in the plastic materials of cleaners. Therefore, this study aimed to develop a low-cost, easy-to-distribute sampling method to collect house dust using a mop and analyse OPFRs, phthalate esters, and alternative plasticisers in house dust. Our findings show that the proposed mop sampling method can be easily distributable and lower contamination from a sampling tool. Moreover, the proposed house dust sampling method is extremely useful for a large-scale survey such as a cohort study.

type:text [要旨]2022年9月，千葉大学予防医学センターはコロナ禍の中断を経て3年ぶりに海外研修を再開した。「新規感染症とワンヘルス」を研修のテーマとし，本学大学院医学薬学府，看護学研究科等の学生と教職員総勢約27名が参加した。9月20日から23日までスイス・ジュネーブを訪れ，世界保健機関(World Health Organization: WHO)本部の視察にはじまり，全部で7つの国際機関の日本人職員等から各機関の役割や課題等について話を聞いた。9月26日から29日まではドイツ・ベルリンを訪れ，予防医学センターとシャリテ・ベルリン医科大学の共催による日独集中講義，および在ドイツ日本国大使館の支援による日独シンポジウムを開催し，公衆衛生や感染症の専門家による講演や活発なディスカッションが行われた。かつて森鷗外がドイツから日本に取り入れた公衆衛生の歴史を振り返ると共に，現代の脅威である新型コロナウイルス感染症(COVID-19)への各国の取り組みを学び，新規感染症発生の背景にある，人・動物・環境の生態系のバランスと健康を維持するワンヘルス・アプローチの重要性を認識した。参加者が本研修で学んだことを生かし，将来広い視野をもって国際保健の問題に取り組まれることを期待する。

The increase in fetal requirements of long-chain polyunsaturated fatty acids (LCPUFAs) during pregnancy alters maternal fatty acid metabolism, and therefore, fatty acid desaturase (FADS) gene polymorphisms may change blood fatty acid composition or concentration differently during pregnancy. We investigated the relationship between a FADS1 single-nucleotide polymorphism (SNP) and maternal serum LCPUFA levels in Japanese pregnant women during the first and third trimesters and at delivery. Two hundred and fifty-three pregnant women were included, and fatty acid compositions of glycerophospholipids in serum (weight %) and the FADS1 SNP rs174547 (T/C) were analyzed. LCPUFAs, including arachidonic acid (ARA) and docosahexaenoic acid (DHA), significantly decreased from the first to the third trimester of pregnancy. Furthermore, DHA significantly decreased from the third trimester of pregnancy to delivery. At all gestational stages, linoleic acid (LA) and α-linolenic acid were significantly higher with the number of minor FADS1 SNP alleles, whereas γ-linolenic acid and ARA and the ARA/LA ratio were significantly lower. DHA was significantly lower with the number of minor FADS1 SNP alleles only in the third trimester and at delivery, suggesting that genotype effects become more obvious as pregnancy progresses.

The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) is known to regulate the cholinergic ascending anti-inflammatory pathway. We previously reported that Chrna7 knock-out (KO) mice show depression-like behaviors through abnormal composition of gut microbiota and systemic inflammation. Given the role of subdiaphragmatic vagus nerve in gut-microbiota-brain axis, we investigated whether subdiaphragmatic vagotomy (SDV) could affect depression-like behaviors, abnormal composition of gut microbiota, and microbes-derived metabolites in Chrna7 KO mice. SDV blocked depression-like behaviors and reduced expression of synaptic proteins in the medial prefrontal cortex (mPFC) of Chrna7 KO mice. LEfSe (linear discriminant analysis effect size) analysis revealed that the species Lactobacillus sp. BL302, the species Lactobacillus hominis, and the species Lactobacillus reuteri, were identified as potential microbial markers in the KO + SDV group. There were several genus and species altered among the three groups [wild-type (WT) + sham group, KO + sham group, KO + SDV group]. Furthermore, there were several plasma metabolites altered among the three groups. Moreover, there were correlations between relative abundance of several microbiome and behavioral data (or synaptic proteins). Network analysis showed correlations between relative abundance of several microbiome and plasma metabolites (or behavioral data). These data suggest that Chrna7 KO mice produce depression-like behaviors and reduced expression of synaptic proteins in the mPFC through gut-microbiota-brain axis via subdiaphragmatic vagus nerve.

The indoor environment, particularly indoor air quality (IAQ), is significantly associated with building-related symptoms (BRSs) in humans. In our previous studies, we demonstrated a significant relationship between BRSs and indoor chemical concentrations. In Japan, the Ministry of Health, Labor, and Welfare (MHLW) guideline recommends an air quality target of 13 volatile organic compounds (VOCs) and a provisional target of 400 μg/m3 for total VOCs (TVOC). The objective of this study was to determine the relationship between TVOC levels and the risk of BRSs using the Japanese provisional target TVOC level of 400 μg/m3. The relationship between odor intensity and BRSs while the TVOC levels were under 400 μg/m3 was also examined. The study was conducted in a laboratory house (LH) on the campus of Chiba University from 2017-2019. The study included 149 participants who spent 60 minutes in the LH. The participants were asked to evaluate the IAQ of the LH. A significant relationship between the risk of BRSs and the provisional target TVOC level was observed (odds ratio: 2.94, 95% confidence interval: 1.18-7.35). Furthermore, a significant relationship between odor intensity and risk of BRSs in spaces with TVOC levels less than 400 μg/m3 was detected (odds ratio: 6.06, 95% confidence interval: 1.21-30.44). In conclusion, the risk of BRSs is significantly lower in spaces with low TVOC levels and low odor intensity. Reducing the concentration of airborne chemicals and odor intensity may improve IAQ and prevent BRSs.

Abstract The Parenting Stress Index-Short Form (PSI-SF) has been widely employed to assess parenting stress in a number of research and clinical trials. To date, no parenting stress studies in Japan have examined the factor structure, validity, and reliability of the PSI-SF. Therefore, this study aimed to evaluate the psychometric properties of this 19-item version as administered in a national cohort study, the Japan Environment and Children’s Study, to two sample groups of mothers, those with a 1.5-year-old child and those with a 2.5-year-old child (n = 79,282 and 75,831, respectively). We performed exploratory factor analysis to re-examine the appropriate factor structure, confirmatory factor analysis to evaluate goodness of fit, and calculated Cronbach’s α and Pearson’s r coefficients to evaluate internal consistency and reproducibility over time, respectively. The results highlighted that a three-factor structure fit the instrument better than a two-factor structure, yielding better scores for the model fit indices and the α and r coefficients. In addition, the third factor identified in this study was strongly associated with having a relationship with and help from the husband. The findings suggest the importance of using a parenting stress scale with various factors to evaluate mothers’ parenting stress.

The aetiology of building-related symptoms (BRSs) is not well supported by sufficient scientific evidence, and it remains unclear whether BRSs are mediated by psychosocial and personal factors or a genuine physical susceptibility to low-dose chemical exposure. In April 2014, a 40-year-old man consulted the Environmental Medical Clinic at Chiba University complaining of recurring BRSs. Indoor air samples were collected from the patient's house at 11 time points and subjected to chemical analyses. The patient simultaneously completed a questionnaire about his symptoms at the time of the measurements. Statistical examination of the indoor environmental factors and patient survey revealed that the patient's symptoms were highly correlated with the indoor air quality. Additionally, ventilation may have mitigated his BRSs, whereas aerial odour did not trigger symptoms. These findings suggest that exposure to specific airborne chemicals in an indoor environment can cause BRSs, and ventilation may be one of the treatment options to mitigate symptoms. Additional investigations on the adverse impacts of airborne environmental chemicals on human health are necessary to develop effective treatments and establish preventive measures for BRSs, and further improvement of ventilation systems is required to ensure clean indoor air.

BACKGROUND: The association between maternal antibiotic exposure during pregnancy and childhood obesity is still unclear. OBJECTIVES: The study aimed to evaluate the association between prenatal exposure to antibiotics and obesity at age 3 years using data from a large Japanese birth cohort. METHODS: The Japan Environment and Children's Study is a nationwide birth cohort study. In this study, singleton vaginal full-term births were included. Obesity was defined as body mass index ≥95th percentile according to child growth standards. Prenatal antibiotic exposure was defined as antimicrobial agent use during pregnancy and was collected from maternal interviews and medical record transcripts. Logistic regression analysis was performed to evaluate the association of prenatal antibiotic exposure with child obesity at 3 years. RESULTS: In the crude and adjusted models with all children, maternal antibiotic exposure during pregnancy showed a marginal relationship with child obesity at 3 years. In the analyses according to exposure period and sex, exposure to antibiotics during the second/third trimester was significantly associated with obesity at the age of 3 years in female infants, but not in male infants, although the exposure during the first trimester was not in both sexes. CONCLUSION: Maternal antibiotic exposure during mid/late pregnancy may result in child obesity.

Increasing epidemiological evidence shows that the use of cannabis during adolescence could increase the risk for psychosis in adulthood. However, the precise mechanisms underlying long-lasting cannabis-induced risk for psychosis remain unclear. Accumulating evidence suggests the role of gut microbiota in the pathogenesis of psychiatric disorders. Here, we examined whether gut microbiota plays a role in the risk for psychosis of adult after exposure of cannabinoid (CB) receptor agonist WIN55,212-2 during adolescence. Repeated administration of WIN55,212-2 (2 mg/kg/day) during adolescence (P35-P45) significantly increased the expression of Iba1 (ionized calcium-binding adapter molecule 1) in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) of adult mice after administration of lipopolysaccharide (LPS: 0.5 mg/kg). In contrast, there were no changes in blood levels of pro-inflammatory cytokines between the two groups. Although alpha-diversity and beta-diversity of gut microbiota were no differences between the two groups, there were several microbes altered between the two groups. Interestingly, there were significant correlations between the relative abundance of microbiota and Iba1 expression in the mPFC and NAc. Furthermore, there were also significant correlations between the relative abundance of microbiota and several metabolites in the blood. These findings suggest that gut microbiota may play a role in the microglial activation in the mPFC and NAc of adult mice after repeated WIN55,212-2 exposure during adolescence. Therefore, it is likely that gut-microbiota-microglia crosstalk might play a role in increased risk for psychosis in adults with cannabis use during adolescence.

Imiquimod (IMQ) is widely used as animal model of psoriasis, a chronic inflammatory skin disorder. Although topical application of IMQ to back skin causes splenomegaly in mice, how the spleen affects the psoriasis-like phenotype of IMQ-treated mice remains unclear. In this study, we analyzed the cellular composition of spleen and measured metabolites in blood of IMQ-treated mice. We also investigated whether splenectomy influences the degree of skin inflammation and pathology in IMQ-treated mice. Flow cytometry showed that the numbers of CD11b+Ly6c+ neutrophils, Ter119+ proerythroblasts, B220+ B cells, F4/80+ macrophages, and CD11c+ dendritic cells in the spleen were significantly higher in IMQ-treated mice compared to control mice. An untargeted metabolomics analysis of blood identified 14 metabolites, including taurine and 2,6-dihydroxybenzoic acid, whose levels distinguished the two groups. The composition of cells in the spleen and blood metabolites positively correlated with the weight of the spleen. However, splenectomy did not affect IMQ-induced psoriasis-like phenotypes compared with sham-operated mice, although splenectomy increased the expression of interleukin-17A mRNA in the skin of IMQ-treated mice. These data suggest that the spleen does not play a direct role in the development of psoriasis-like phenotype on skin of IMQ-treated mice, though IMQ causes splenomegaly.

Cadaver surgical training (CST), which ensures medical safety by improving the skills of surgeons, is popular overseas. However, training involves ethical issues given the use of cadavers. In 2012, the Japan Surgical Society and the Japanese Association of Anatomists compiled and opened the "Guidelines for Cadaver Dissection in Education and Research of Clinical Medicine (Guideline 2012)" to the public. This has allowed Japan to conduct CST or research under the regulations of Postmortem Examination and Corpse Preservation Act and the Body Donation Act. However, its dissemination has been sluggish. The Clinical Anatomy Lab (CAL), established in 2010 at Chiba University, is a facility for conducting CST and research. In the 11 years since its inception, 250 programs have been implemented. Orthopedics had the most implemented in the clinical field, with 120 (48%), followed by emergency and critical care medicine with 27 (10.8%), and neurological surgery with 27 (10. 8%). Based on the purpose of the training, the most common objective for the programs (approximately 83%) was education. Further, the highest number of programs was recorded in 2018 (34) and participants in 2017 (631). The implementation of CST requires more than just guiding surgeons to a dissection practice room. There are several methods of preserving cadavers to make them suitable for CST. For various surgical simulations, an operating table is more suitable than a dissection table. The current paper provides information on how to implement CST in universities that have so far only worked on anatomy education for medical students.

BACKGROUND: Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches. METHODS: Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children's Study (JECS). Measurements of infant birth size-including body weight, body length, and head and chest circumference-were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR). RESULTS: Of the 103,060 JECS pregnancies, 93,739 mother-infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese-but not mercury-were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect. CONCLUSION: Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention.

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)2D3 to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D3 to 25(OH)D) using data from the Japan Environment and Children's Study at Chiba Regional Center. A total of 297 mother-neonate pairs were analyzed. Using liquid chromatography-tandem mass spectrometry, we measured 25(OH)D2, 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.

Abstract This study aimed to evaluate the association of neonatal transfer with the risk of neurodevelopmental outcomes at 3 years of age. Data were obtained from the Japan Environment and Children’s Study. A general population of 103,060 pregnancies with 104,062 fetuses was enrolled in the study in 15 Regional Centers between January 2011 and March 2014. Live-born singletons at various gestational ages, including term infants, without congenital anomalies who were followed up until 3 years were included. Neurodevelopmental impairment was assessed using the Ages and Stages Questionnaire, third edition (ASQ-3) at 3 years of age. Logistic regression was used to estimate the adjusted risk and 95% confidence interval (CI) for newborns with neonatal transfer. Socioeconomic and perinatal factors were included as potential confounders in the analysis. Among 83,855 live-born singletons without congenital anomalies, 65,710 children were studied. Among them, 2780 (4.2%) were transferred in the neonatal period. After adjustment for potential confounders, the incidence of neurodevelopmental impairment (scores below the cut-off value of all 5 domains in the ASQ-3) was higher in children with neonatal transfer compared with those without neonatal transfer (communication: 6.5% vs 3.5%, OR 1.42, 95% CI 1.19–1.70; gross motor: 7.6% vs 4.0%, OR 1.26, 95% CI 1.07–1.49; fine motor: 11.3% vs 7.1%, OR 1.19, 95% CI 1.03–1.36; problem solving: 10.8% vs 6.8%, OR 1.29, 95% CI 1.12–1.48; and personal-social: 6.2% vs 2.9%, OR 1.52, 95% CI 1.26–1.83).    Conclusion: Neonatal transfer was associated with a higher risk of neurodevelopmental impairment at 3 years of age.<table><tbody><tr><td colspan="2">What is Known:• Neonatal transfer after birth in preterm infants is associated with adverse short-term outcomes.• Long-term outcomes of outborn infants with neonatal transfer in the general population remain unclear.</td> </tr><tr><td colspan="2">What is New:• This study suggests that neonatal transfer at birth is associated with an increased risk of neurodevelopmental impairment.• Efforts for referring high-risk pregnant women to higher level centers may reduce the incidence of neonatal transfer, leading to improved neurological outcomes in the general population.</td> </tr></tbody></table>

BACKGROUND: Manganese (Mn) is an essential trace metal and a neurotoxicant. Adverse effects of Mn exposure on the neurodevelopment of children have been reported. However, there is limited information on the effects of maternal exposure during pregnancy. OBJECTIVES: We aimed to investigate the association between maternal and cord blood Mn levels and neurodevelopment in children aged between 6 months and 3 years using data from a Japanese nationwide birth cohort study. METHODS: We used the data of 63,767 mother-child pairs with maternal blood Mn measurements recorded during the second and third trimester and of 3,787 mother-child pairs with cord blood Mn measurements. Neurodevelopment was assessed using the Japanese version of the Ages and Stages Questionnaires, third edition (J-ASQ-3), which was completed by parents or guardians at 6 months, 1 year, 1.5 years, 2 years, 2.5 years, and 3 years of age. RESULTS: The median maternal and cord blood Mn levels were 15.2 and 44.5 ng/g, respectively. After adjusting for covariates, both maternal and cord blood Mn levels were negatively associated with J-ASQ-3 scores. Maternal blood Mn levels were negatively associated with gross motor function scores at all ages except for that at 1.5 years (adjusted β: -0.55 to -1.23 for a two-fold increase in maternal Mn levels). The risk of developmental delay (score below the cut-off) in gross motor function increased at the same time points (adjusted odds ratio: 1.08 to 1.13). In the subgroup, cord blood Mn levels were negatively associated with gross motor function scores at 1, 2, and 2.5 years (adjusted β: -1.84 to -3.27). DISCUSSION: Maternal blood Mn levels during pregnancy and cord blood Mn levels were negatively associated with neurodevelopment in children up to 3 years of age. Excessive maternal and fetal exposure to Mn may have adverse effects on neuromotor function in children.

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography-electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels.

Maternal exposure to polychlorinated biphenyls (PCBs) during pregnancy is associated with a low birth weight; however, the congener-specific effects of PCB congeners are not well defined. In this study, we used maternal serum samples from the Chiba Study of Mother and Child Health (C-MACH) cohort, collected at 32 weeks of gestational age, to analyze the effects of PCB congener exposure on birth weight by examining the relationship between newborn birth weight and individual PCB congener levels in maternal serum (n = 291). The median total PCB level in the serum of mothers of male and female newborns at approximately 32 weeks of gestation was 39 and 37 ng g−1 lipid wt, respectively. The effect of the total PCB levels and the effects of PCB congener mixtures were analyzed using a linear regression model and a generalized weighted quantile sum regression model (gWQS). The birth weight of newborns was significantly associated with maternal exposure to PCB mixtures in the gWQS model. The results suggest that exposure to PCB mixtures results in low newborn birth weight. However, specific impacts of individual PCB congeners could not be related to newborn birth weight.

Abstract Purpose This study aimed to investigate neurodevelopment in children conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with several types of embryo transfers. Methods We analyzed data for 77 928 children and their mothers included in a Japanese birth cohort study. Among the included children, 4071 were conceived via IVF, while 1542 were conceived via ICSI. Neurodevelopmental delay at the age of 3 years was assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition. Results In the crude model, the odds ratios for developmental delay in 1–4 domains were higher among children conceived via IVF, ICSI, and non‐ART (ovulatory induction or intrauterine insemination) than in spontaneously conceived children. After adjusting for parental background factors and the child's sex, there were no differences in the risk of developmental delay when comparing singletons conceived by IVF, ICSI, or non‐ART and those conceived spontaneously. Higher odds ratios for developmental delay in one domain were observed in singleton girls conceived via IVF when compared with those who were spontaneously conceived. Conclusion Most cases of developmental delay may be associated with multiple pregnancies and factors related to infertility, such as parental age, irrespective of the use of ART.

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.

In recent years, there has been an increase in the number of problems associated with neurodevelopmental disorders in children, and there has been a growing interest in the relationship between environmental chemicals and children's health. The objective of this study was to examine whether an association exists between occupational or environmental prenatal maternal exposure to volatile organic compounds and the risk of neurodevelopmental disorders in children using Japanese translations of the Ages & Stages Questionnaires, Third Edition (J-ASQ-3). An increase in the risk of neurodevelopmental delay in 12-month-old children associated with maternal exposure to formalin or formaldehyde was identified in terms of problem-solving (odds ratio (OR): 1.76, 95% confidence interval (CI): 0.99-3.12) and personal-social skills (OR: 3.32, 95% CI: 1.46-7.55). It is not clear whether or not this tendency is reversible, and whether it is observed past 12 months of age. Further research and a preventive approach are needed. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The relationship between chemical concentrations in indoor air and the human sense of comfort and relaxation have been reported. We investigated the effect of the sum of volatile organic compounds (ΣVOCs; sum of 79 VOCs) on the level of relaxation in two laboratory houses with almost identical interior and exterior appearances. The electroencephalogram (EEG) was monitored to evaluate the degree of personal relaxation objectively. The experiments were conducted in laboratory houses (LH) A and B with lower and higher levels of ΣVOCs, respectively. A total of 168 healthy volunteers participated, who each performed the task for 20 min, followed by a 10-min break, and EEG was measured during the break. Simultaneously as subjective evaluations, the participants were asked to fill a questionnaire regarding the intensity of odor and preference for the air quality in each LH. The subjective evaluation showed a significant association between ΣVOCs and participants' relaxation (OR: 2.86, 95%CI: 1.24-6.61), and the objective evaluation indicated that the participants were more relaxed in the LH with lower levels of ΣVOCs than that with higher levels (OR: 3.03, 95%CI: 1.23-7.50). Therefore, the reduction of ΣVOCs and odors in indoor air would have an effect, which is the promotion of relaxation.

Background: Hypertensive disorders of pregnancy (HDP) are one of the most common medical conditions that women encounter during pregnancy. Whether or not hypertensive disorders of pregnancy (HDP) are associated with allergic conditions in the offspring is unclear. This study used data from a large Japanese birth cohort to investigate whether HDP contributes to the development of allergic conditions in the offspring at 3 years. We also assessed the effect of blood pressure at different pregnancy trimesters on children's allergies. Methods: We obtained data from the Japan Environment and Children's Study (JECS), which included 104 062 fetal records. After data selection, we analyzed 77 505 mother–child pairs, using logistic regression models to examine the relationships between HDP or the mother's blood pressure and their children's allergic conditions. In addition, we also evaluated the effect of HDP during pregnancy on allergies with a propensity score matched dataset, using a logistic regression model that predicts the conditional probability of whether a mother belonged to the HDP or non-HDP group. Results: Among the 77 505 mothers eligible for analysis, 2334 (3.0%) had HDP. Percentages of women with hypertension were 1.7% in early gestation, 1.0% in mid-gestation, and 1.6% in late gestation. After adjusting for multiple potential confounders, HDP contributed nothing to allergy development in offspring. Children born to women with hypertension were no more likely than those without to have allergic conditions at 3 years of age. The propensity score matched dataset showed similar findings. Conclusion: HDP and high blood pressure during pregnancy are apparently not risk factors for developing allergy in offspring. This information may help clinicians in counseling women who suffered HDP during pregnancy.

kkPeople's living environments and lifestyles have drastically changed with the times. It is necessary to reassess risk factors associated with changes in social conditions to prevent sick building syndrome (SBS). This study aimed to determine the association between the onset of SBS and participant characteristics, social and residential environments, and lifestyle. An online nationwide questionnaire survey involving 4996 participants was conducted. The risk factors for SBS were examined using logistic regression analyses. The main risk factors for SBS were female sex (odds ratio [OR] = 1.20, confidence interval [CI] = 1.01-1.42) and young age (OR = 2.42, CI = 1.55-3.78). Other risk factors included having a medical history of allergies and mental illness (OR = 1.75, CI = 1.34-2.29), special housing specifications for the indoor environment (OR = 0.77, CI = 0.63-0.95), smoking indoors (OR = 1.25, CI = 1.00-1.55), and others. Women, young individuals, and those with a history of diseases, such as allergies and mental illness, had an increased risk of SBS, indicating that such individuals need to pay attention to chemical exposure. The study results indicate the possibility of preventing SBS by the careful selection of indoor environments and lifestyle.

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in mid-pregnancy are associated with small- (SGA) or large- (LGA) for-gestational-age independent of pre-pregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: To prospectively investigate the association between maternal TC in mid-pregnancy and SGA or LGA. DESIGN AND SETTING: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. PARTICIPANTS: A total of 37,449 non-diabetic, non-hypertensive mothers with singleton birth at term without congenital abnormalities. OUTCOME MEASURES: Birth weight for the gestational age <10 percentile and ≥90 percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7±4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, pre-pregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and Study Areas, one standard deviation decrement of maternal TC was linearly associated with SGA [odds ratio (OR): 95% confidence intervals (CI) = 1.20: 1.15-1.25]. In contrast, one standard deviation increment of maternal TC was linearly associated with LGA [OR: 95% CI = 1.13: 1.09-1.16]. Associations did not differ according to pre-pregnancy BMI and gestational weight gain (p for interaction>0.20). CONCLUSION: Maternal TC levels in mid-pregnancy were associated with SGA or LGA in Japanese. Maternal TC in mid-pregnancy may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

Chemokine (C-C motif) ligand 17 (CCL17) is a pro-allergic factor: high CCL17 levels in cord blood (CB) precede later allergic predisposition. Short-chain fatty acid (SCFA) treatment during pregnancy has been shown to protect mouse pups against allergic diseases. The maternal microbial metabolome during pregnancy may affect fetal allergic immune responses. We therefore examined the associations between CB CCL17 and gut SCFA levels in healthy pregnant Japanese women. CB CCL17 serum levels at birth, and maternal non-specific IgE levels in maternal sera at 32 weeks of gestation were measured. Maternal stool samples were collected at 12 (n = 59) and 32 (n = 58) weeks of gestation for gut microbiota analysis, based on barcoded 16S rRNA sequencing and metabolite levels. The CB CCL17 levels correlated negatively with butyrate concentrations and positively with isobutyrate at 12 weeks; CB CCL17 correlated positively with valerate and lactate at 32 weeks. Similarly, butyrate levels correlated negatively with maternal non-specific IgE levels, whereas the lactate concentration correlated positively with IgE levels. At 32 weeks, the Shannon diversity index (SDI) of Firmicutes and Proteobacteria correlated negatively with CB CCL17 levels, while those of the total microbiota correlated positively with the CB CCL17 levels. These metabolites may alter fetal immune responses. This study provides the first link between maternal metabolites during pregnancy and the risk of allergic diseases in human offspring.

医師、歯科医師、パラメディカル(コ・メディカル)を含むすべての医療従事者にとって、人体の構造を学ぶ解剖学は重要な学問である。パラメディカルの学生にとって、解剖見学実習は人体構造を学ぶ上で有益であるが、一般的にはその機会は制限されている。ここで、物事に関する興味・関心は教育における重要な変数であり、例えば興味・関心と成績の間には正の相関があることが報告されている。本研究では、解剖見学実習に参加した看護師、鍼灸師、薬剤師、理学療法士・作業療法士、栄養士、救急救命士の各養成校の学生に対してアンケート調査を実施し、人体の解剖学的構造において特に興味・関心を有する部位の調査を行った。2013年7月から2016年3月の間に、千葉大学医学部において解剖見学実習に参加したパラメディカル学生878人を調査対象とした。解析結果は、1)特に学生にとって興味のある器官系は神経系(6領域全て)、循環器系(看護師、鍼灸師、薬剤師、栄養士、救急救命士)、消化器系(看護師、薬剤師、栄養士、救急救命士)、骨筋系(鍼灸師および理学療法士・作業療法士)であったこと、2)これらの器官系について、特に興味のある器官系構成要素は各専門領域間で異なっていたこと、3)神経系と循環器系は、看護領域の専門学校学生1年生と2年生の両方にとって、特に興味のある器官系であったこと、4)両器官系において特に興味のある器官系構成要素は1年生と2年生の間で異なり、しかしながら「脳」は神経系において両学年にとって特に興味のある器官系要素であったことを示した。これらの各パラメディカル領域における学生の興味・関心の違いは、今後、各領域の専門性に特化した解剖学の教育方法を構築していくにあたり、重要な知見となるものと思われる。(著者抄録)

To conduct a long-term birth cohort study that includes genetic analysis, it is crucial to understand the attitudes of participants to genetic analysis and then take appropriate approaches for addressing their ambiguous and negative attitudes. This study aimed to explore participants' attitudes toward genetic analysis and associated background factors among mothers who were enrolled in a large Japanese birth cohort. A questionnaire was sent to participants' households, and the responses of 1762 mothers (34.0%) were used for the study. The majority of mothers recognized genetic analysis for themselves and their children and sharing of genetic data as beneficial. A low knowledge level of genomic terminology was associated with ambiguous attitudes toward genetic analysis and data sharing. Education level was positively associated with the recognition of the benefits of genetic analysis. Concern about handling genetic information was associated with the unacceptability of data sharing. Trust was associated with the approval of genetic analysis. Most mothers preferred that genetic analysis results be returned. These findings suggest the need for multiple efforts to maximize participants' acceptance of genetic analysis, such as utilizing an educational approach to encourage familiarity with genetics/genomics, optimizing explanations for different educational levels, and explicitly disclosing the handling policy for genetic information.

BACKGROUND: The ulnar collateral ligament complex, particularly the anterior oblique ligament (AOL), is mainly a static stabilizer controlling valgus. Various studies have been conducted on the kinematics of elbow joints after ligament cutting; however, no biomechanical studies have measured the tension applied to the ligament. Finite element modeling (FEM) is a very useful tool for biomechanical evaluation of the elbow. However, an accurate FEM of elbow joints cannot be developed without information on the potential tension of ligaments applied during the flexion and extension of elbow joints. We believe that FEM of the elbow joint could be obtained by measuring the material properties and potential tension of the ligament applied during the flexion and extension of the elbow joint. This study aimed to measure the potential tension and material properties of the ligament during the flexion and extension of the elbow, by identifying the relation between ligament length and tension using mechanical testing. METHODS: We included 10 elbows harvested from 7 fresh-frozen cadavers. The average age of the cadavers was 83.7 ± 5.65 years, and the samples included 8 elbows from 6 male cadavers and 2 elbows from 1 female cadaver. We measured the ligament length at each elbow angle by changing the elbow joint from 0° to 120° in 15° intervals. Thereafter, we extracted the AOL and divided into an anterior band (AB) and a posterior band (PB) and performed a mechanical test to calculate ligament stress. RESULTS: The ligament length of the AB gradually decreased as the flexion angle increased. Conversely, the ligament length of the PB gradually increased as the flexion angle increased. AB and PB lengths were approximately the same between 60° and 75°. The average ligament tension and stress of the AB gradually increased with elbow extension. In contrast, the average ligament tension and stress of the PB gradually increased with elbow flexion. The tension and stress of the AB and PB were balanced around the elbow joint at 60°. CONCLUSION: The AB was tenser on elbow extension, and the PB was tenser following elbow flexion. Also, the angle at which the AOL stress was equalized was 60°, suggesting that ∼60° is the angle at which the AOL is unlikely to be damaged.