森 千里

[This corrects the article DOI: 10.1016/j.waojou.2019.100065.].

It is well known that the indoor environment, particularly indoor air quality (IAQ), has significant effects on building-related symptoms (BRSs) in humans, such as irritation of mucosal membranes, headaches, and allergies, such as asthma and atopic dermatitis. In 2017, Chiba University launched the "Chemiless Town Project Phase 3" to investigate the relationship between IAQ and human health. Two laboratory houses (LHs) were built on a university campus in which the interiors and exteriors were similar, but the levels of indoor air volatile organic compounds (VOCs) were different. A total of 141 participants evaluated IAQ using their sensory perception. There was a significant relationship between differences in VOC levels and BRSs occurrence (OR: 6.89, 95% CI: 1.40-33.98). It was suggested that people with a medical history of allergies (OR: 5.73, 95% CI: 1.12-29.32) and those with a high sensitivity to chemicals (OR: 8.82, 95% CI: 1.16-67.16) tended to experience BRSs. Thus, when buildings are constructed, people with a history of allergies or with a sensitivity to chemicals may be at high risk to BRSs, and it is important to pay attention to IAQ to prevent BRSs.

This study aimed to describe the distribution of pregnancies with medical and obstetric complications based on the Japan Environment and Children's Study (JECS). We evaluated the distribution of the history of obstetric/gynaecological diseases, the history of obstetric labour complications, pregnancy with medical and surgical complications, and obstetric labour complications in participants in the JECS. Of 100,818 pregnant women with medical record entries after delivery, 15,305 (15.2%) had medical and surgical complications in pregnancy and 46,756 (46.4%) experienced obstetric labour complications. The proportion of pregnancies with heart disease, kidney disease and hepatitis was 0.3%, 0.3% and 0.1%, respectively. Gestational diabetes was diagnosed in 2715 (2.7%) women. The proportion of women with mild and severe gestational hypertension was 2.3% and 1%, respectively. The JECS is the largest birth cohort in Japan. These data will provide useful, basic information for perinatal care in Japan.IMPACT STATEMENT What is already known on this subject? Epidemiological studies have suggested that pre-existing diseases and complications of pregnancy, such as heart disease in pregnancy, gestational hypertension and gestational diabetes, may have implications for pregnancy outcomes, as well as for children's health and development. What the results of this study add? We evaluated the distribution of the history of obstetric/gynaecological diseases, the history of obstetric labour complications, medical and surgical complications in pregnancy, and obstetric labour complications using data from the Japan Environment and Children's Study (JECS).

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 is to evaluate differences in rate and indications for CS between Japan and Germany in 2012 and 2013. METHODS: Comparison of 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 rate and medical indication for CS between Germany and Japan on 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 seems to be reasonable to rethink decision algorithms.

"Total" folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.

Prenatal exposure to mercury in utero causes abnormal foetal growth and adverse outcomes. DNA methylation is currently considered a possible mechanism through which this occurs. However, few studies have investigated the association between prenatal exposure to mercury and DNA methylation in detail. This study aimed to clarify the relationship between prenatal exposure to total mercury (Hg) and DNA methylation and its associations with sex-specific characteristics in male and female offspring. In a birth cohort study known as the Chiba study of Mother and Child Health, the DNA methylation status in cord tissue and Hg concentrations in cord serum were examined. A total of 67 participants (27 males and 40 females) were analysed based on Spearman's correlations, adjusted by a false discovery rate of the sex of each offspring. Only one methylated locus was positively correlated with Hg concentrations in cord serum in male offspring, but not in female offspring, and was annotated to the haloacid dehalogenase-like hydrolase domain-containing protein 1 (HDHD1) gene on chromosome X. This locus was located in the intron of the HDHD1 gene body and is a binding site for the zinc finger protein CCCTC-binding factor. One of the other loci, located in HDHD1, was highly methylated in the group with higher mercury concentrations, and this locus was in the gene body of HDHD1. Our results suggest that prenatal exposure to Hg might affect the epigenetic status of male foetuses.

Herein, the concentrations of formic acid, acetic acid, and ammonia in samples of indoor air for 47 new houses were measured two weeks after completion. The houses were fabricated with light-gauge steel structures. The measurements were performed in living rooms and bedrooms without furniture and outdoors. Air samples were analyzed using ion chromatography. The mean values were 28 (living room), 30 (bedroom), and 20 μg m-3 (outdoor air) for formic acid; 166 (living room), 151 (bedroom), and 51 μg m-3 (outdoor air) for acetic acid; and 73 (living room), 76 (bedroom), and 21 μg m-3 (outdoor air) for ammonia. The total values of the three substances accounted for 39.4-40.7% of the sum of chemical compound values. The analyzed compounds were indicated by two principal components (PC), PC1 (30.1%) and PC2 (9%), with 39.1% total variance. Formic acid, acetic acid, and ammonia were positively aligned with PC1 and negatively aligned with PC2. Factors such as room temperature, aldehydes, and phthalates were positively aligned with PC1 and negatively aligned with PC2. Furthermore, concentrations of formic acid, acetic acid, and ammonia were significantly and positively correlated with room temperature (p < 0.05).

Background Nutritional requirements increase during pregnancy. However, relatively few studies have examined longitudinal changes in dietary intake from periconception to pregnancy. Here, we investigated changes in the intake of food and nutrients, and compliance with dietary reference intakes (DRIs) in pregnant women. Methods The Japan Environment and Children's Study, a nationwide multicenter prospective cohort study, included 30,373 pregnant women who answered a validated food frequency questionnaire repeatedly to assess changes in dietary intake in periconception and pregnancy. Energy-adjusted intakes of food groups and nutrients were described using the density method. The percentage of women not meeting DRIs was calculated. Results Of all foods groups examined, intake of food significantly increased from periconception to pregnancy for dairy products (mean difference 23.5 g/1000 kcal, 95% confidence interval [CI] 22.0-25.0 g/1000 kcal), confectionaries (2.0 g/1000 kcal, 1.8-2.2 g/1000 kcal), and soft drinks (1.3 g/1000 kcal, 0.3-2.3 g/1000 kcal). Of all nutrients examined, intake was significantly increased for calcium (mean difference 27 mg/1000 kcal, 95% CI 25-29 mg/1000 kcal), vitamin A (15 mu gRE/1000 kcal, 13-18 g/1000 kcal), and saturated fat (0.4% energy, 0.4-0.4% energy). The percentage of women not meeting DRIs increased for vitamin B group, vitamin C, saturated fat and salt. Conclusion We found that energy-adjusted intakes of calcium, vitamin A, and saturated fat increased from periconception to pregnancy, while intake of other nutrients did not increase. The percentage of women not meeting DRIs increased for water-soluble vitamins, saturated fat, and salt.

Objectives We examined the socio-demographic and behavioral factors associated with alcohol consumption before and after pregnancy awareness in pregnant women. Methods This cross-sectional study included 91,828 pregnant women in a nationwide Japanese birth cohort study from 2011 to 2014. Alcohol consumption before and after pregnancy awareness, and sociodemographic behavioral characteristics were assessed through self-reported questionnaires. Determinants of alcohol consumption were investigated using logistic regression. Results Prevalence of alcohol consumption before and after pregnancy awareness was 50.0% and 2.8%, respectively. Most women consumed low to moderate levels of alcohol. Before pregnancy awareness, high educational level (odds ratios [OR] 1.11, 95% confidence interval [CI] 1.07 to 1.15), high household income (OR 1.16, 95% CI 1.09 to 1.24), and smoking (OR 1.77, 95% CI 1.65 to 1.90) were significantly associated with increased odds of alcohol consumption. After pregnancy awareness, older age (OR 1.73, 95% CI 1.54 to 1.94) and smoking (OR 5.57, 95% CI 4.88 to 6.37) were significantly associated with increased odds of alcohol consumption, and high education level (OR 0.72, 95% CI 0.64 to 0.81) and high household income (OR 0.75, 95% CI 0.63 to 0.89) were significantly associated with decreased odds of alcohol consumption. Conclusion A half of women consumed alcohol before pregnancy awareness. Guidelines recommend abstinence from alcohol consumption in pregnant women for precaution, although influence of low to moderate levels of prenatal alcohol exposure on the fetus is inconclusive. Social-demographic characteristics differed between women who consumed alcohol before pregnancy awareness and women who continued alcohol after pregnancy awareness.

Background: Although there has been an increase in reports regarding the association between perinatal risk factors and mother-infant bonding, the results have been inconsistent.Methods: This is an ongoing cohort designed study to measure the effect of environmental factors on children's health with the use of data from the Japan Environment and Children's Study. We investigated mother-infant bonding at 1 year old according to parity and mode of delivery.Results: A total of 82,540 participants, including 36,662 primipara mothers and 45,878 multipara mothers, were analyzed in the present study. Exclusive breastfeeding, marriage, and non-working factors were higher in multipara mothers than in primipara mothers. The total Mother-to-Infant Bonding Scale Japanese version (MIBS-J) score was higher (worse) in primipara than multipara (mean total: 1.129 vs. 0.897, p < 0.001). Primipara mothers also had higher anger and rejection scores than multipara mothers. When we analyzed only multipara mothers without any history of previous Cesarean section (CS), MIBS-J scores were higher in Cesarean delivery mothers than vaginal delivery mothers (p = 0.038).Limitations: We used a self-reported bonding measure. Although a self-report measure is convenient and important, an observer rating may be less susceptible to bias in perception. We did not distinguish elective CS from emergency CS, which may have different influences on mother-infant bonding.Conclusions: Primipara mothers showed worse mother-infant bonding than multipara mothers, regardless of mode of delivery. Caesarian delivery itself appears to have little effect on mother-infant bonding.

子どもで近年アレルギーや肥満が増加しているという報告がある。生体に存在する物質でバイオマーカーとなるものにはゲノムや染色体の変異や遺伝子の発現変異などが挙げられる。染色体の末端にあるテロメアと呼ばれるゲノム配列は、ヒトでは(TTAGGG)の繰り返し配列であり、2.5-15kbpからなる。体細胞では細胞分裂をするたびにテロメアの長さが短縮し、細胞は老化し増殖しなくなる。一方で生殖細胞や幹細胞、がん細胞ではテロメアーゼの働きによりテロメアは伸長し、細胞は増殖する。幼児期の飲料とテロメアの長さに関する報告(Janet MW. et al., 2016, 2017)があるが、胎児期におけるPCBとテロメア長に関する報告はまだない。そこで、我々はPCBがテロメア長に与える影響について調査した。 調査対象は千葉大学予防医学センターが行なっている「千葉こども調査」で収集された94組の母子である。テロメア長は臍帯組織から抽出されたゲノムDNAを用いqPCRで評価した(Toki F. et al., 2016)。PCB異性体は母親の末梢血では21異性体で、臍帯血については23異性体でGC-MSを用いて測定した。Spearmanの順位相関係数で解析を行った結果、主要な異性体のPCB74, 118, 153, 138, 187, 170についてはテロメア長とPCB異性体については男女共、男女別でも関連がなかった(P>0.05)。一方で、男女を合わせた解析では臍帯血のPCB99（ng/g -wet）（rho =0.240、P = 0.021）, 女子のみで臍帯血のPCB99（ng/g -wet）（rho =0.279、P = 0.043）については正の相関があった。PCB99についてはC57BL6 マウスの精子形成に関与することが分かっている。今後はさらにサンプル数を増やして調査する予定である。

© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd Aims/Introduction: We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers of participants in the Japan Environment and Children’s Study, a nationwide, multicenter, pregnancy and birth cohort. Materials and Methods: Pregnant women aged 14–50 years were studied in 15 centers across Japan. Clinical information was obtained using self-administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. Results: Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. Glycated hemoglobin, total cholesterol, low-density lipoprotein cholesterol and triglyceride across all the percentiles increased as prepregnancy body mass index increased, whereas high-density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. Glycated hemoglobin was high in participants with type 1 diabetes or type 2 diabetes only, but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high-density lipoprotein cholesterol, whereas participants with dyslipidemia only showed high total cholesterol and low-density lipoprotein cholesterol throughout. Conclusions: Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The Japan Environment and Children’s Study will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies.

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.

There have been no large, nationwide, birth cohort studies in Japan examining the effects of house renovation during pregnancy on congenital abnormality. This study examined the impact of (1) prenatal exposure to house renovation and (2) maternal occupational exposure to organic solvents and/or formaldehyde on the incidence of congenital abnormality. The fixed data of 67,503 singleton births from a large national birth cohort study that commenced in 2011 were used to evaluate the presence of congenital abnormalities and potential confounding factors. We employed multiple logistic regression analysis to search for correlations between maternal exposure to house renovation or organic solvents and/or formaldehyde during pregnancy and such congenital abnormalities as congenital heart disease, cleft lip and/or palate, male genital abnormality, limb defect, and gastrointestinal obstruction. After controlling for potential confounding factors, we observed that house renovation was significantly associated with male genital abnormality (OR 1.81, 95% CI 1.03-3.17, P = 0.04) when stratified by congenital abnormality, with no other remarkable relations to house renovation or occupational use of organic solvents and/or formaldehyde during pregnancy. There were also significant correlations for maternal BMI before pregnancy, history of ovulation induction through medication, maternal diabetes mellitus/gestational diabetes mellitus, and hypertensive disorder of pregnancy with an increased risk of congenital abnormality. In conclusion, this large nationwide survey provides important information on a possible association of house renovation during pregnancy with congenital male genital abnormality which needs confirmation in future studies.

This study aimed to clarify the interannual changes in intimate partner violence against pregnant women after the March 11, 2011 Great East Japan Earthquake in target areas of Miyagi Prefecture that were damaged by the earthquake and tsunami. Because of this disaster, in Miyagi Prefecture, approximately 12,000 people died or went missing, and approximately 238,000 buildings were destroyed. According to the U.S. Geological Survey, the Great East Japan Earthquake is the fourth largest earthquake in the world and the largest in Japan since 1900. The present study was part of the Japan Environment and Children's Study. Data from June 2011 to May 2014 of 79,222 pregnant women were analyzed, calculating the prevalence of physical and mental intimate partner violence in the inland, north coastal, and south coastal areas of Miyagi. These prevalence rates were compared with nationwide rates of intimate partner violence in 2011 using univariate and logistic regression analyses. After the disaster, the incidence of mental intimate partner violence increased in the south coastal area and then improved later (19.4%, 13.1%, and 13.3% for south coastal area, and 13.8%, 13.8%, and 13.1% for nationwide in 2011, 2012, and 2013, respectively). However, in the north coastal area, the incidence of physical intimate partner violence increased after the disaster and then improved later (2.7%, 1.5%, and 1.3% for north coastal area, and 1.4%, 1.3%, and 1.1% for nationwide in 2011, 2012, and 2013, respectively). In the inland area, however, the prevalence of both mental and physical intimate partner violence was consistently higher than nationwide rates after the disaster.

The Japan Environment and Children’s Study (JECS) is a birth-cohort study of 100,000 mother–child dyads that aims to investigate the effect of the environment on child health and development. Mercury (Hg), lead (Pb), cadmium (Cd), manganese (Mn) and selenium (Se) are considered to be important co-exposures when examining the effect of other chemical substances on child development. The levels of these elements in the blood of 20,000 randomly selected mid/late-term pregnant women from the whole JECS cohort were analysed using inductively coupled plasma-mass spectrometry. The median concentrations (interquartile ranges) for Pb, Hg, Cd, Mn and Se were 0.63 (0.51–0.78) µg dl−1, 3.83 (2.70–5.43) µg l−1, 0.70 (0.52–0.95) µg l−1, 16.1 (13.2–19.6) µg l−1 and 178 (165–192) µg l−1, respectively. Hg and Se correlated positively with each other (Spearman’s ρ = 0.287), as did Pb and Cd (ρ = 0.239) and Cd and Mn (ρ = 0.267). The blood Pb levels decreased by 5–10-fold over the past 25 years. The main predictors of the blood levels of each element were fish consumption for Hg, maternal age and non-alcoholic beverage consumption for Pb, maternal age and smoking for Cd, gestational age at sampling for Mn and serum protein levels for Se. These results revealed the historical trends and current predictors of the blood levels of these elements in pregnant Japanese women.

Maternal exposure to polychlorinated biphenyls (PCBs) results in abnormal fetal development, possibly because of epigenetic alterations. However, the association between PCB levels in cord serum with fetal DNA methylation status in cord tissue is unclear. This study aims to identify alterations in DNA methylation in cord tissue potentially associated with PCB levels in cord serum from a birth cohort in Chiba, Japan (male neonates = 32, female neonates = 43). Methylation array analysis identified five sites for female neonates (cg09878117, cg06154002, cg06289566, cg12838902, cg01083397) and one site for male neonates (cg13368805) that demonstrated a change in the methylation degree. This result was validated by pyrosequencing analysis, showing that cg06154002 (tudor domain containing 9: TDRD9) in cord tissue from female neonates is significantly correlated with total PCB levels in cord serum. These results indicate that exposure to PCBs may alter TDRD9 methylation levels, although this hypothesis requires further validation using data obtained from female neonates. However, since the present cohort is small, further studies with larger cohorts are required to obtain more data on the effects of PCB exposure and to identify corresponding biomarkers.

type:text [要旨] 千葉大学では世界を視野に入れ多種多様な考えを理解し，対応できるグローバルな人材育成のため，国際化の推進を行っている。特にヨーロッパにおいてはドイツ連邦共和国の首都であるベルリンのCharit?-Universit?tsmedizin Berlin （シャリテ・ベルリン医科大学）と2010年に5 年間の大学間交流協定を締結して連携活動が始まり，2015年にはさらに2020年まで更新された。2015年にはシャリテ内に千葉大学ジャーマンセンターベルリンオフィスを開設し，両大学長の相互訪問やシンポジウム開催，共同研究の立ち上げなどを進めている。小論では特に最近3 年間の活動を中心に千葉大学とシャリテの共同作業について研究，教育分野などの現状と将来の展望をまとめた。 [SUMMARY] Chiba University is promoting internationalization in order to develop global human resources that can respond to and understand a wide variety of ideas with a view of the world. Especially in Europe, the first agreement was concluded in 2010 with the Charit?-Universit?tsmedizin Berlin, the capital of Germany Federal Republic, and the cooperation activities were carried out. In 2015, the first period of five years ended, and now the second phase（2015 to 2020）is running. In 2015, we established the Chiba University German Center Berlin Office in the Charit? and are working on a more active partnership.This paper summarizes the current activities and future prospects of the joint work of the Chiba University and the Charit? in the field of research and education,especially in the recent two-year activities.

Background: Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta. Methods: We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. Results: The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb. Conclusion: Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

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.

Smoking during pregnancy is a risk factor for various adverse birth outcomes but lowers the risk of preeclampsia. Cardiovascular adaptations might underlie these associations. We examined the association of maternal smoking with the risk of hypertensive disorders of pregnancy (HDP) in a low-risk population-based cohort of 76,303 pregnant women. This study was a part of the Japan Environment and Children's Study. Smoking status was assessed using questionnaires completed by participants. Information about HDP was assessed using questionnaires completed by doctors. Compared with that for women who did not smoke, women who continued smoking >10 cigarettes per day during pregnancy had a significantly higher risk of developing HDP (odds ratio: 1.58, 95% confidence interval: 1.11-2.25). In multivariate analyses with adjustment for possible confounding factors, the association still remained (odds ratio: 1.51, 95% confidence interval: 1.04-2.19). When we regarded the number of cigarettes as a continuous variable, there was a linear association between the number of cigarettes and risk of HDP, with an odds ratio of 1.02 per cigarette per day (95% confidence interval: 1.00-1.04). Smoking a greater number of cigarettes was associated with a higher risk of HDP after adjustment for possible confounding factors. Cigarette smoking cessation may avoid the complications of HDP. Our findings suggest that, in addition to the risk of small-for-gestational-age children, an increased risk of HDP should be considered in the management of pregnant women who smoke cigarettes.

Background: It is necessary to determine whether there are adverse health effects of prenatal exposure to long-term, low levels of mercury and selenium. However, there are limited that reports on the association between mercury levels by selenium levels and birth size. Therefore, we examined whether maternal mercury levels during pregnancy had any effect on infant birth size, and size, and whether selenium levels influenced this relationship.Objectives: To examine the association between mercury and selenium levels during pregnancy with infant birth size.Methods: The Japan Environment and Children's Study is a prospective birth cohort conducted between 2011 and 2014. Total mercury levels and total selenium levels in maternal blood during the second and third tri-mesters were measured using Inductively Coupled Plasma-Mass Spectrometry. Birth weight and small-for-gestational-age were confirmed by medical records. Small-for-gestational-age was defined as birth weight below the 10th percentile according to standard percentile for gender, parity, and gestational age. Multiple linear and logistic regression analyses were used to examine the association between maternal mercury exposure and birth weight or small-for-gestational-age adjusted for confounders (including maternal age and body mass index pregnancy).Results: Overall, 15,444 pregnant women were included in this study. Median (inter-quartile range) of blood mercury and selenium levels were 3.66 (2.59-5.18) ng/g and 170.0 (158.0-183.0) ng/g, respectively. Compared to infants of mothers with the highest blood selenium level, those of mothers with the lowest blood selenium level had neither a significant birth weight increase (9 g, 95% confidence interval: -6, 25) nor a significant odds ratio for small-for-gestational-age (0.903, 95% confidence interval: 0.748, 1.089). Compared to infants of mothers with the lowest blood mercury level, those of mothers with the highest blood mercury level had neither a significant birth weight reduction (-12 g, 95% confidence interval: -27, 4) nor a significant odds ratio for small-for-gestational-age (0.951, 95% confidence interval: 0.786, 1.150). Compared to infants of mothers with the lowest quartile of maternal blood mercury level, all infants of mothers with the highest quartile of maternal blood mercury level had a reduced birth head circumference of 0.073 cm (95% confidence interval: -0.134, -0.011).Conclusions: There was no association between maternal blood mercury levels and small-for-gestational-age and birth weight among 15,444 pregnant women. In a Japanese population, which has a relatively higher blood mercury level than reported in Western population, reduced birth size was not found to be associated with blood mercury levels, with the exception of birth head circumference.

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: To examine the association between elevated blood cadmium (Cd) and lead (Pb) concentrations and increased risk of gestational diabetes mellitus (GDM). Methods: This cross-sectional study included pregnant women (n = 16,955) enrolled in the Japan Environment and Children’s Study. Concentrations of Cd and Pb in blood samples collected at 22–28 weeks’ gestation were measured by inductively coupled plasma mass spectrometry. GDM was diagnosed according to the 2011 Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists criteria. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression analysis. Results: Blood Cd and Pb concentrations were slightly higher among women with GDM than among those without GDM; however, these differences were not statistically significant. Elevated blood Cd and Pb concentrations were not associated with increased GDM risk in the nulliparous group (Cd OR 0.76; 95% CI 0.28–2.08 for high vs low category; Pb OR 2.51; 95% CI 0.72–8.72) or the parous group (Cd OR 0.64; 95% CI 0.29–1.44; Pb OR 0.31; 95% CI 0.04–2.29). Conclusions: This study demonstrates that Cd and Pb exposure, in the range of blood levels observed, has no significant relationship with the development of GDM. Further prospective studies would be valuable to confirm these findings.

Background: Dysmenorrhea influences emotional distress as well as physical suffering in young non-pregnant women. The aim of this study was to assess the potential association between preconception dysmenorrhea and the development of psychological distress during pregnancy.Methods: This study was a part of the Japan Environment and Children's Study (JECS), a nationwide birth cohort study conducted between 2011 and 2014 in Japan. A total of 87,102 pregnant Japanese women with no psychological distress (Kessler 6-item psychological distress scale [K6] score <= 12) in early pregnancy were eligible. Among these, 7626 had mild and 1638 had severe preconception dysmenorrhea. The prevalence and risk of maternal psychological distress (K6 scores <= 13) in the second or third trimester were compared among preconception dysmenorrhea severity groups.Results: A higher percentage of women with mild (2.6%) or severe preconception dysmenorrhea (3.6%) suffered psychological distress during pregnancy compared to that in women without dysmenorrhea (2.1%). A multilevel logistic regression model, adjusting for baseline characteristics and the K6 score at enrollment, showed that the severity of dysmenorrhea was associated with psychological distress (mild dysmenorrhea: adjusted odds ratio [aOR], 1.154; 95% confidence interval [95% CI], 0.980-1.359; and severe dysmenorrhea: aOR, 1.457; 95% CI, 1.087-1.951).Limitations: Information about dysmenorrhea was obtained during early pregnancy. The JECS did not have clear diagnostic criteria for dysmenorrhea.Conclusions: Preconception dysmenorrhea is associated with an elevated incidence of psychological distress during pregnancy. Additionally, expectant mothers with a history of severe dysmenorrhea symptoms before pregnancy have a higher risk of developing psychological distress.

© 2018 Hidetoshi Mezawa et al. Background: The aims of the present report were to estimate the prevalence of congenital anomalies (CAs) among infants in Japan using data from the Japan Environment and Children’s Study (JECS) and to evaluate the validity of CA classification within JECS. Methods: Data on CAs were collected at delivery and at age 1 month from the medical records of 101,825 infants at 15 regional centers. The analyses focused on 61 CAs, selected on the basis of reported associations with environmental exposure. Prevalence per 10,000 pregnancies (including miscarriages, stillbirths, and live births) was stratified according to four reporting patterns (at delivery, at age 1 month, at either, and at both). To evaluate the accuracy of observed CA prevalence, the medical records of 179 cases from a single JECS regional center underwent independent, retrospective re-evaluation. Results: The prevalence of major CAs in four reporting patterns (at delivery, at age 1 month, at either, and at both) was 2.4, 2.6, 3.5, and 1.4 for myelomeningocele=spina bifida; 4.3, 4.2, 5.3, and 3.2 for cleft palate; 18.1, 17.4, 19.5, and 15.1 for cleft lip with or without cleft palate; 73.4, 100.3, 120.8, and 52.8 for congenital heart disease; and 10.5, 14.1, 15.0, and 9.6 for Down’s syndrome, respectively. In the subsample re-evaluation, CA diagnoses were confirmed for 92.7%, 93.3%, 90.5%, and 97.8% of cases in the four reporting patterns (at delivery, at age 1 month, at either, and at both), respectively. Conclusions: The present report generated reliable data concerning the prevalence of major CAs in JECS.

Clinical trials show that protein supplement increases infant size in malnourished populations; however, epidemiological studies in high-income countries have reported mixed results. Although these findings suggest a non-linear relationship between maternal macronutrient intake and fetal growth, this relationship has not been closely examined. We assessed the association between maternal protein intake and fetal growth among 91637 Japanese women with singletons in a nation-wide cohort study using validated FFQ. The respondents answered the FFQ twice, once during early pregnancy (FFQ1; 16.3 (SD 6.0) weeks), and second during mid-pregnancy (FFQ2, 28.1 (SD 4.1) weeks). Daily energy intake and percentage energy from protein, fats and carbohydrates were 7477 (SD 2577) kJ and 13.5 (SD 2.0), 29.5 (SD 6.5) and 55.3 (SD 7.8) %, respectively, for FFQ1, and 7184 (SD 2506) kJ and 13.6 (SD 2.1), 29.8 (SD 66) and 55.3 (SD 7.9) %, respectively, for FFQ2. The average birth weight was 3028 (SD 406) g, and 6350 infants (6.9 %) were small for gestational age (SGA). In both phases of the survey, birth weight was highest and the risk of SGA was lowest when the percentage energy from protein was 12 %, regardless of whether isoenergetic replacement was with fat or carbohydrates. Furthermore, when protein density in the maternal diet was held constant, birth weight was highest when 25 % of energy intake came from fat and 61 % came from carbohydrates during early pregnancy. We found maternal protein intake to have an inverse U-curve relationship with fetal growth. Our results strongly suggest that the effect of protein on birth weight is non-linear, and that a balanced diet fulfilling the minimum requirement for all macronutrients was ideal for avoiding fetal growth restriction.

© 2018 Elsevier Inc. Background: Heavy metals are widely distributed in the environment. Recent reports have demonstrated the risk of preterm birth following heavy metal exposure. Preterm births are classified as early and late, depending on the duration of pregnancy, and are associated with increased risk of congenital illnesses such as heart failure, asthma, etc. Particularly, early preterm births carry a higher risk of mortality; however, the differential effects of heavy metal exposure on early and late preterm births are unknown. Objectives: To analyze the association between maternal whole blood concentrations of heavy metals, such as cadmium (Cd), lead (Pb), mercury (Hg), selenium (Se), and manganese (Mn) that are common toxicants in Japan, and early and late preterm births. Methods: The data of 14,847 pregnant women who were participants of the Japan Environment and Children's Study were used. Data of the self-questionnaire pertaining to the first trimester (T1), second/third trimester (T2), and medical records after delivery were analyzed. We divided preterm birth into two groups: early preterm (22 to < 34 weeks) and late preterm (34 to < 37 weeks). Maternal blood samples for measuring heavy metal concentrations were collected in T2 (pregnancy weeks: 14–39). The participants were classified into four quartiles (Q1–Q4) according to increasing heavy metal levels. Results: The rate of preterm birth was 4.5%. After controlling for confounding factors, such as age, pre-pregnancy body mass index, smoking, partner's smoking, drinking habits, gravidity, parity, number of cesarean deliveries, uterine infections, household income, educational levels, and sex of infant, Cd levels were found, by multivariable logistic regression analysis, to be significantly associated with early preterm birth (p = 0.002), with odds ratio for early preterm birth of 1.91 (95% confidence interval: 1.12–3.27, P = 0.018) in subjects of Q4 compared with in subjects with term birth (≧ 37 weeks). Conclusion: Maternal blood Cd levels during pregnancy are positively associated with the risk of early preterm birth among Japanese women. Identification of the main source of maternal Cd exposure may contribute to the prevention of early preterm births and health maintenance of mothers and their infants in the future.

The prevention of sick building syndrome necessitates the design and construction of buildings that can maintain low concentrations of Volatile Organic Compounds (VOCs). This study aims to determine whether VOC concentrations in a new commercial bank can be reduced through the selection of building materials and monitoring of construction processes. The building was designed and constructed with close attention to the selection of architectural materials and supervision of construction. Twice during construction, indoor air samples were collected and their chemical compositions determined. The Ministry of Health, Labour, and Welfare of Japan (MHLW) guideline concentrations for VOCs were not exceeded for any of the specified chemicals, including toluene, xylem, ethylbenzene, styrene, p-dichlorobenzene, tetradecane, formaldehyde, and acetaldehyde. After construction, the total VOC concentration was 104 mu g/m(3). This value is substantially lower than the target value of 400 mu g/m(3) recommended by the MHLW. Construction of a bank building with low concentrations of indoor chemical substances can be achieved through the proper selection of architectural materials and construction site supervision.

The 7th Study Tour to International Organizations in Geneva was held by the Center for Preventive Medical Sciences, Chiba University from 25th to 27th September 2017. This is a training program which is open not only medical students but also all the graduate students of Chiba University. In this program, we have learned the role of several international organizations such as the World Health Organization (WHO), the Global Fund, International Federation of Red Cross and Red Crescent Societies(IFRC) and International Labor Organization (ILO). We also visited the Permanent Mission of Japan to the International Organizations in Geneva and discussed with officers and staffs of various international organizations. The participated students had an opportunity to deeply understand a range of global issues through lectures and discussions.

© 2017 Takehiro Michikawa et al. Background: The Japan Environment and Children’s Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children’s health and development. We report the baseline profiles of the participating mothers, fathers, and their children. Methods: Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. Results: The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan’s 2013 Vital Statistics Survey. Conclusions: Between 2011 and 2014, we established one of the largest birth cohorts in the world.

© 2018 WIT Press. The relationship between adverse health effects, including sensory irritation and decline in cognitive performance, and the exposure to indoor air pollutants has been considered inconclusive. This is possibly because the occurrence of relevant symptoms seems to largely depend on individual sensitivity and mental state. Therefore, further evaluation of the relationship between indoor environment and its related adverse health effects using subjective and objective data is required. In 2017, two new laboratory houses (LHs) were built on the campus of Chiba University (Japan) as part of a new project called the Chemiless Town Project, phase 3. This project aims to investigate the impact of the indoor environment on physical and mental health and to construct a healthy indoor environment. The interior and exterior appearances of the two LHs appear the same; however, the concentrations of chemicals inside them differ due to the differences in their construction and interior materials. The project commenced in November 2017 and will continue until 2021. In the project, approximately 400 participants will be recruited who will evaluate indoor air using sensory perception. The evaluation will be performed using objective methods, including monitoring brain waves and heart rate variability, and subjective methods, including completing self-reported questionnaires, while staying in each LH. Simultaneously, the indoor air samples of each laboratory will be collected and analysed. In 2017, 17 healthy female and 26 healthy male volunteers participated in the experiment. The median of sum concentrations of volatile organic compounds in the indoor air of each LH were 314 and 1674 μg/m3, respectively. No significant differences were found in terms of degrees of performance and relaxation of participants between the LHs. Additional research and analysis will be conducted with more participants to further examine the relationship between the indoor environment and related health effects.

In this study, we developed a highly sensitive, robust method for determining 12 congeners of two to ten chlorinated polychlorinated biphenyls (PCBs) in serum samples using gas chromatography (GC)-mass spectrometry (MS) operating in selected ion monitoring mode (SIM: m/z 35) with negative ion chemical ionization (NICI), and the results were compared with those from GC coupled with high-resolution MS (HRMS) with electron impact (EI). The recovery rates of the surrogate PCB congeners were 97.2%-112% (coefficient of variation: 5.3%-8.5%), and the method detection limits for PCBs in each matrix obtained by GC-NICI-quadrupole mass spectrometry (qMS) were 1.9-20 pg g(-1) wet wt. The analytical values of the target compounds in the samples analyzed by GC-NICI-qMS and GC-EI-HRMS were comparable (Passing-Bablok regression: R = 0.888-0.967), and the analytical values obtained via GC-NICI-qMS were almost comparable with those of the certified serum samples from National Institute of Standards and Technology (NIST: SRM1957), indicating that GC-NICI-qMS is suitable for the analysis of tetra-to hepta-chlorinated PCBs in serum samples.

Introduction: The extensor pollicis brevis (EPB) tendon normally inserts into the base of the proximal phalanx of the thumb. However, a distal insertion of the EPB tendon into the thumb interphalangeal joint has been reported in refractory cases of de Quervain’s disease. We hypothesized that the EPB tendon is wider beyond the thumb metacarpophalangeal joint in patients with extended EPB. This study aimed to evaluate the relationship between the extensor tendon width and the point of distal insertion of the EPB tendon. Materials and methods: In 45 hands from 18 male and 27 female adult cadavers, the first extensor compartment was dissected and the existence of the intertendinous septum was assessed. The extensor tendon width was measured at the midpoint of the proximal phalanx, and relationships between extended EPB tendon, existence rate of the intertendinous septum, sex, and extensor tendon width were examined. Results: Of 45 cases, intertendinous septum and extended EPB tendon were observed in 37 (82.2%) and 23 (51.1%), respectively. There was no significant difference between the existence rates of both these factors and sex. The mean extensor tendon width in the extended EPB group was significantly greater than in the normal EPB group. The cut-off value of extensor tendon width in the extended EPB group was 7.12 mm. Conclusions: The extensor tendon width was wider in the extended EPB group than in the normal EPB group, suggesting that the differences in the EPB tendon width can be used to identify various anatomical variations in extended EPB.

AIMS/INTRODUCTION: Impaired glucose tolerance (IGT) is a subtype of prediabetes, a condition having high risk for development to diabetes mellitus, but its pathophysiology is not fully understood. In the present study, we examined metabolic changes in IGT by using two types (D-glucose [Glc] and partial hydrolysate of starch [PHS]) of oral glucose tolerance tests (OGTTs), with emphasis on serum incretins and metabolites. MATERIALS AND METHODS: We carried out the two types of OGTT (Glc/OGTT and PHS/OGTT) in 99 young Japanese individuals who had tested either positive (GU+ ; n = 48) or negative (GU- ; n = 51) for glycosuria. After OGTT, they were sub-grouped into five categories: normal glucose tolerance (NGT) in the GU- group (GU- /NGT; n = 49), NGT in the GU+ group (GU+ /NGT; n = 28), IGT (n = 12), diabetes mellitus (n = 1) and renal glycosuria (n = 9). Serum incretin and metabolites of GU- /NGT and IGT were then measured. RESULTS: When the serum insulin level at each time-point during PHS/OGTT was expressed as its ratio relative to Glc/OGTT, it was increased time-dependently in GU- /NGT, but not in IGT. Such an increase in the ratio was also detected of serum incretin levels in GU- /NGT, but not in IGT, suggesting a lack of deceleration of oligosaccharide absorption in IGT. Metabolome analysis showed a difference in the serum levels of two metabolites of unknown function in mammals, methylcysteine and sedoheptulose 1,7-bisphosphate, between GU- /NGT and IGT. CONCLUSIONS: Comparison of PHS/OGTT and Glc/OGTT showed that oligosaccharide absorption was accelerated in IGT. Methylcysteine and sedoheptulose 1,7-bisphosphate could be novel markers for dysregulated glucose metabolism.

解剖学は、ヒトの病状変化や疾患の有無を診る看護師などさまざまな医療専門職の教育で必要とされる基礎科目である。加えて、生物学と共に医療にとって不可欠な基礎科目であり、上記の専門職のための国家試験にも出題される。しかし、人体の基本構造を知るという点で非常に近い高校の生物学の知識の定着が十分でない学生もいる上、生物学を履修せずに物理・化学で受験した学生もおり、その知識には学生間で大きな隔たりがある。筆頭著者は看護師養成大学において、解剖学・生物学の講義を担当してきた。その経験からガニェ9教授事象を参考にして、入学者のレディネスに合わせ、看護師養成大学の実情に合ったカリキュラムと授業を取り入れた。さらに、毎回小テストを行い、補習や個別指導を実施することにより、専門科目に対応できる学力を定着させることが出来た。解剖学の学期末の期末試験の成績では全体平均点87.3(SD11.0、中央値81.0)と高得点であった。ここでは筆者らの解剖学での取り組みを中心に紹介する。(著者抄録)