Depression-like phenotypes in mice following common bile duct ligation: Insights into the gut-liver-brain axis via the vagus nerve.

Depression frequently occurs in patients with liver cirrhosis, yet the reasons for this correlation are not fully understood. Dysbiosis of gut microbiota has been implicated in depression through the gut-brain axis via the vagus nerve. This study explored the potential role of the gut-liver-brain axis via the vagus nerve in depression-like phenotypes in mice with liver cirrhosis. These mice underwent common bile duct ligation (CBDL), a method used to stimulate liver cirrhosis. To assess depression-like behaviors, behavioral tests were conducted 10 days following either sham or CBDL surgeries. The mice with CBDL displayed symptoms such as splenomegaly, elevated plasma levels of interleukin-6 and tumor necrosis factor-α, depression-like behaviors, decreased levels of synaptic proteins in the prefrontal cortex (PFC), disrupted gut microbiota balance, and changes in blood metabolites (or lipids). Additionally, there were positive or negative correlations between the relative abundance of microbiome and behavioral data or blood metabolites (or lipids). Significantly, these changes were reversed in CBDL mice by performing a subdiaphragmatic vagotomy. Intriguingly, depression-like phenotypes in mice with CBDL were improved after a single injection of arketamine, a new antidepressant. These results suggest that CBDL-induced depression-like phenotypes in mice are mediated through the gut-liver-brain axis via the subdiaphragmatic vagus nerve, and that arketamine might offer a new treatment approach for depression in liver cirrhosis patients.

Within-individual relationships between mother-to-infant bonding and postpartum depressive symptoms: a longitudinal study.

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.

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

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

Association between maternal blood or cord blood metal concentrations and catch-up growth in children born small for gestational age: an analysis by the Japan environment and children's study.

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.

Teenage and young adult pregnancy and depression: findings from the Japan environment and children's study.

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.

Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress.

3,4-Methylenedioxymethamphetamine (MDMA) is the most widely used illicit substance worldwide. Nevertheless, recent observational studies demonstrated that lifetime MDMA use among U.S. adults was associated with a lower risk of depression and suicide thoughts. We recently reported that the gut-brain axis may contribute to MDMA-induced stress resilience in mice. To further explore this, we investigated the effects of subdiaphragmatic vagotomy (SDV) in modulating the stress resilience effects of MDMA in mice subjected to chronic restrain stress (CRS). Pretreatment with MDMA (10 mg/kg/day for 14 days) blocked anhedonia-like behavior and reduced expression of synaptic proteins and brain-derived neurotrophic factor in the prefrontal cortex (PFC) of CRS-exposed mice. Interestingly, SDV blocked the beneficial effects of MDMA on these alterations in CRS-exposed mice. Analysis of gut microbiome revealed alterations in four measures of α-diversity between the sham + MDMA + CRS group and the SDV + MDMA + CRS group. Moreover, specific microbes differed between the vehicle + CRS group and the MDMA + CRS group, and further differences in microbial composition were observed among all four groups. Untargeted metabolomics analysis showed that SDV prevented the increase in plasma levels of three compounds [lactic acid, 1-(2-hydroxyethyl)-2,2,6-tetramethyl-4-piperidinol, 8-acetyl-7-hydroxyvumaline] observed in the sham + MDMA + CRS group. Interestingly, positive correlations were found between the plasma levels of two of these compounds and the abundance of several microbes across all groups. In conclusion, our data suggest that the gut-brain axis via the subdiaphragmatic vagus nerve might contribute to the stress resilience of MDMA.

Key role of the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve in demyelination of the cuprizone-treated mouse brain.

Multiple sclerosis (MS) is the most common demyelinating disease that attacks the central nervous system. Dietary intake of cuprizone (CPZ) produces demyelination resembling that of patients with MS. Given the role of the vagus nerve in gut-microbiota-brain axis in development of MS, we performed this study to investigate whether subdiaphragmatic vagotomy (SDV) affects demyelination in CPZ-treated mice. SDV significantly ameliorated demyelination and microglial activation in the brain compared with sham-operated CPZ-treated mice. Furthermore, 16S ribosomal RNA analysis revealed that SDV significantly improved the abnormal gut microbiota composition of CPZ-treated mice. An untargeted metabolomic analysis demonstrated that SDV significantly improved abnormal blood levels of metabolites in CPZ-treated mice compared with sham-operated CPZ-treated mice. Notably, there were correlations between demyelination or microglial activation in the brain and the relative abundance of several microbiome populations, suggesting a link between gut microbiota and the brain. There were also correlations between demyelination or microglial activation in the brain and blood levels of metabolites. Together, these data suggest that CPZ produces demyelination in the brain through the gut-microbiota-brain axis via the subdiaphragmatic vagus nerve.

Association Between Smoking and Hypertension in Pregnancy Among Japanese Women: A Meta-analysis of Birth Cohort Studies in the Japan Birth Cohort Consortium (JBiCC) and JECS.

BACKGROUND: Recent literature suggest the effect of maternal smoking on risk of hypertensive disorders in pregnancy (HDP) and preeclampsia may differ by ethnicity; however, studies on Asians are limited. METHODS: We investigated the association of maternal smoking with HDP and preeclampsia using a common analysis protocol to analyze the association in six birth cohorts participating in a Japanese consortium of birth cohorts (JBiCC). Results were compared with-published results from cohorts not included in this consortium, and, where possible, we produced a meta-analysis including these studies. RESULTS: Meta-analysis of four cohort studies including 28,219 participants produced an odds ratio (OR) of 1.24 (95% confidence interval [CI], 0.88-1.87) for the effect of smoking beyond early pregnancy compared to women who did not smoke during pregnancy. These results combined with those from the Japan Environment and Children's Study (JECS) yielded an OR of 1.19 (95% CI, 1.00-1.43, P = 0.056). Meta-analysis results for categories of smoking volume were insignificant, but when combined with JECS yielded an OR of 0.86 (95% CI, 0.65-1.12) for smoking 1-4 cigarettes, 1.25 (95% CI, 0.98-1.60) for smoking 5-9 cigarettes, and 1.27 (95% CI, 1.04-1.54) for smoking 10 or more cigarettes per day. All effects were insignificant for preeclampsia. CONCLUSION: Our results suggest that the protective effects of smoking longer and smoking more on HDP and preeclampsia repeatedly observed among Europeans and North Americans likely do not hold for the Japanese.

Effect of nausea and vomiting during pregnancy on mother-to-infant bonding and the mediation effect of postpartum depression: the Japan Environment and Children's Study.

BACKGROUND: Mother-to-infant bonding (MIB) is critical for the health and well-being of the mother and child. Furthermore, MIB has been shown to boost the social-emotional development of infants, while also giving mothers a sense of happiness in raising their children. Nausea and vomiting during pregnancy (NVP) is a normal complication of pregnancy, occurring in approximately 50-90% of pregnant women in the early stages of pregnancy. Despite widespread knowledge of MIB and postpartum depression, little research attention has been given to the effects of NVP on MIB. This study aimed to investigate the relationship between NVP and MIB and the mediating effects of postpartum depression. METHODS: We analyzed the data of 88,424 infants and 87,658 mothers from the Japan Environment and Children's Study (JECS), which is a government-funded nationwide birth prospective cohort study. The Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) was used to assess MIB, and the Edinburgh Postpartum Depression Scale (EPDS) was utilized to assess postpartum depression. We divided participants into four groups according to a self-reported questionnaire assessing NVP (No NVP, Mild NVP, Moderate NVP, and Severe NVP). MIB disorder was defined as a MIBS-J score ≥ 5. Logistic analysis was performed to evaluate the effect of NVP on MIB disorder at one year after delivery. A mediation analysis was conducted to examine whether postpartum depression mediated the association between NVP and MIBS-J scores. RESULTS: The logistic regression analysis results revealed reduced risks of MIB disorder among mothers with Moderate NVP (adjusted OR 0.93; 95% confidence interval, 0.86-0.99) and Severe NVP (adjusted OR 0.81; 95% confidence interval, 0.74-0.89), compared to those with No NVP. The mediation analysis revealed that NVP positively correlated with MIBS-J score in the indirect effect via postpartum depression, while NVP (Mild NVP, Moderate NVP, and Severe NVP) negatively correlated with MIBS-J score in the direct effect. CONCLUSION: The risks of MIB disorder were reduced in the Moderate NVP and Severe NVP mothers, although NVP inhibited the development of MIB via postpartum depression. The development of effective interventions for postpartum depression is important to improve MIB among mothers with NVP.

Gut-microbiota-brain axis in the vulnerability to psychosis in adulthood after repeated cannabis exposure during adolescence.

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.

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

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

Effect of Neonicotinoid Pesticides on Japanese Water Systems: Review with Focus on Reproductive Toxicity.

Neonicotinoid pesticides (NPs) are neurotoxic substances. They are highly effective as insecticides owing to their water solubility, permeability, and long-lasting activity. These molecules are structurally similar to nicotine and act as nicotinic acetylcholine receptor agonists. The administration of NPs to experimental animals reportedly causes neuromuscular and reproductive disorders. Moreover, recently reported problems caused by NPs include damage to land-dwelling creatures (such as mammals and birds), hydrobiology, and ecosystems. This review summarizes the recent reports on NP concentrations detected in river systems in several Japanese regions. These values were lower than the environmental standard values; however, seasonal variations were observed. Furthermore, reports on NP-induced testicular and ovarian toxicity were examined, revealing that the mechanism of injury is mainly driven by oxidative stress. The use of NPs is declining worldwide, except in Japan; therefore, continuous monitoring remains necessary.

Neurological development in 36-month-old children conceived via assisted reproductive technology: The Japan Environment and Children's Study.

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.

Participant mothers' attitudes toward genetic analysis in a birth cohort study.

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.

Evaluation of anterior oblique ligament tension at the elbow joint angle-a cadaver study.

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.

Differences in rate and medical indication of caesarean section between Germany and Japan.

BACKGROUND: There are growing concerns about the increasing rate of caesarean section (CS) worldwide. Various strategies have been implemented to reduce the proportion of CS to a reasonable level. Most research on medical indications for CS focuses on nationwide evaluations. Comparative research between different countries is sparse. The aim of this study was to evaluate differences in the rate and indications for CS between Japan and Germany in 2012 and 2013. METHODS: Comparison of the overall rate and medical indications for CS in two cohort studies from Germany and Japan. We used data from the German Perinatal Survey and the Japan Environment and Children's Study (JECS). RESULTS: We analyzed data of 1 335 150 participants from the German perinatal survey and of 62 533 participants from JECS and found significant differences between the two countries in CS rate (30.6% vs 20.6%) and main medical indications: cephalopelvic disproportion (3.2% vs 1.3%; OR: 2.4 [95% CI: 2.2-2.6]), fetal distress (7.3% vs 2.3%; OR: 3.4 [95%-CI: 3.2-3.6]), and past uterine surgery/repeat CS (8.4% vs 8.8%; OR: 0.9 [95%-CI: 0.9-1]). CONCLUSION: There are differences in the rate and medical indications for CS between Germany and Japan at the population level. Fetal distress was identified as a medical indication for CS more often Germany than in Japan. Considering the substantial diagnostic uncertainty of electronic fetal monitoring (EFM) as the major indicator for fetal distress, it would seem to be reasonable to rethink CS decision algorithms.

Association between blood manganese level during pregnancy and birth size: The Japan environment and children's study (JECS).

BACKGROUND: Manganese (Mn) is both an essential element and a potential toxicant. Although a few studies have suggested a nonlinear relationship between the maternal whole blood Mn level at delivery and infant birth weight, little is known about the effects of Mn levels during pregnancy on fetal growth, particularly with regard to sex-specific differences. METHODS: In this nationwide birth cohort study, we examined the association of maternal blood Mn level during pregnancy with infant birth weight, length, and head circumference in 16,473 mother-infant pairs. Pregnant women living in 15 regions across Japan were recruited between January 2011 and March 2014. The analysis of birth size (8,484 males and 7,989 females) was conducted using a nonlinear spline, followed by the use of quadratic regression or linear regression models. The analysis of small-for-gestational-age (SGA) (6,962 males and 6,528 females born vaginally) was conducted using multivariate logistic regression. Additionally, subgroup analysis was conducted according to the timing of blood sampling. RESULTS: The median maternal blood Mn level during pregnancy (i.e., 2nd and 3rd trimesters) was 16.2 µg/L (range, 4.3-44.5 µg/L). A positive linear association between the log blood Mn level and head circumference was observed in both male and female infants. However, a nonlinear relationship between the log blood Mn level and birth weight was observed only in male infants, such that the birth weight increased up to a blood Mn level of 18.6 µg/L. In the subgroup analysis stratified by the timing of maternal blood sampling, this nonlinear relationship was obvious only when sampling was performed in the 3rd trimester. Male infants in the lowest blood Mn level quartile (≤ 13.2 µg/L) faced an increased risk of SGA (odds ratio [95% confidence interval] = 1.35 [1.04-1.74]), as did those in the highest blood Mn level quartile (≥ 21.0 µg/L) when sampling was performed during the 3rd trimester (odds ratio [95% confidence interval] = 1.62 [1.10 to 2.39]), compared to those in the third blood Mn level quartile (the category including 18.6 µg/L). No association of blood Mn level with birth weight was observed among female infants, and blood Mn level was not associated with birth length in either male or female infants. CONCLUSION: A low blood Mn level during pregnancy or a high blood Mn level during the 3rd trimester was associated with a lower birth weight and increased risk of SGA in male infants, but not in female infants. A low blood Mn level was found to correlate slightly with a small head circumference among infants of both sexes.

Prevalence and risk factors of pre-sick building syndrome: characteristics of indoor environmental and individual factors.

BACKGROUND: With the aim to prevent sick building syndrome and worsening of allergic symptoms, primarily resulting from the indoor environment, the relationships among people's residential environment in recent years, their lifestyle habits, their awareness, and their symptoms were investigated using an online survey. METHODS: In the survey, respondents experiencing symptoms specific to sick building syndrome, although they were not diagnosed with sick building syndrome, were categorized in the pre-sick building syndrome group. The relationships among individual characteristics, residential environment, and individual awareness were analyzed. RESULTS: Results showed that the prevalence of pre-sick building syndrome was high among young (aged 20-29 years) population of both sexes. In addition, "condensation," "moisture," "musty odors" in the house, and the "use of deodorant and fragrance" were all significantly associated with pre-sick building syndrome. Conversely, there was no significant association with recently built "wooden" houses that are highly airtight and have thermal insulation. CONCLUSIONS: Efficient "ventilation" plans and "ventilation" improvement and air conditioning systems to prevent mold and condensation in rooms are necessary to maintain a good, indoor environment that is beneficial for health. Efforts should also be made to encourage individuals to regularly clean and effectively ventilate their homes.

Association Between Serum Folate Levels and Caffeinated Beverage Consumption in Pregnant Women in Chiba: The Japan Environment and Children's Study.

BACKGROUND: Several studies have reported the adverse effects of caffeine intake during pregnancy on fetal health. However, the effects of caffeine intake from green and oolong teas has not been investigated, despite the considerable consumption of these teas in Japan and the potential inhibitory effects of catechins-chemicals present at relatively high levels in green and oolong teas-on folic acid absorption. The potential associations of serum folate levels with caffeinated beverage consumption and catechin levels remain largely unstudied. The present study aimed to determine these associations in pregnant Japanese women. METHODS: Pregnant women (n = 2,701) not receiving folate supplementation were enrolled at the Chiba Unit Center, a regional site of the Japan Environment and Children's Study (JECS). Serum folate levels were measured using an Access folate assay kit, and nutrient and caffeine intakes were assessed using a self-administered food frequency questionnaire that was previously evaluated in Japanese populations. RESULTS: The low and normal serum folate groups reported caffeine intakes of 42.3 mg/1,000 kcal and 34.4 mg/1,000 kcal, respectively, and tannin intakes of 40.8 mg/1,000 kcal and 36.3 mg/1,000 kcal, respectively. Multiple regression analyses revealed negative associations of serum folate levels with caffeine and tannin intakes and a positive association between serum folate levels and dietary folate intake. CONCLUSIONS: Considering the negative associations of caffeine and tannin levels with serum folate levels, pregnant women should consume caffeinated beverages, such as coffee and green/oolong teas, with caution.