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To examine whether patterns, such as the timings of onset or recovery from sleep disturbance, are associated with later developmental problems, including autism spectrum disorder (ASD). Mothers participating in the Japan Environment and Children's Study with a child aged 3 years were included in the analyses. Children were assessed for short sleep and frequent awakenings at 1 month, 6 months, and 1 year of age. Developmental problems were evaluated at 3 years of age based on ASD diagnosis and developmental delay, using the Japanese translation of the Ages and Stages Questionnaire (ASQ) 3rd edition. Sleep disturbance patterns were classified by onset age, and developmental problem risks were examined based on onset/recovery ages. Among 63,418 mother-infant dyads, 0.4% of infants were later diagnosed with ASD, and 14.4% had abnormal scores on any ASQ domains. The later the onset of short sleep, the lower the risk of abnormal ASQ scores (RR of short sleep onset at 1 year: 1.41; 6 months: 1.52; 1 month: 1.57). The earlier the infants recovered from short sleep persistence, the lower the risk of developmental delay (RR of remittance of sleep problems identified at 1 month by 6 months: 1.07; 1 year: 1.31; not before 1 year: 1.57). Although not all patterns were significant, later short sleep onset and earlier recovery were associated with lower ASD risk. These findings may have significant implications for future interventions in infant development., (© 2024. The Author(s).)

Objectives: Concerns have been raised regarding the impact of the COVID-19 pandemic on alcohol consumption patterns, which can have implications for public health. In this descriptive study, we aimed to show the change in the frequency and amount of alcohol consumption in Japan before and during the COVID-19 pandemic periods., Methods: We analyzed data from annual health checkups among Japanese workers from April 2018 to March 2021. Changes in the frequency (daily, occasionally, rarely/never) and amount per one-time (4 categories by Japanese alcohol unit) of alcohol consumed among 331 200 participants were summarized by sex as 1-year changes in the periods before (fiscal year [FY] 2018 to FY 2019) and during (FY 2019 to FY 2020) the COVID-19 pandemic., Results: Among daily drinkers and rarely/never drinkers, overall, 1-year changes in the frequency of alcohol consumption during the pandemic were mostly consistent with changes before the pandemic, for both sexes. The number of occasional drinkers who drank less frequently a year later increased during the pandemic compared with before the pandemic (from 9.6% to 11.6% among men and from 12.9% to 16.5% among women); however, occasional drinkers who drank more frequently showed a small increase. Collectively, both men and women showed a slight decrease in both the frequency and amount of alcohol consumption during the pandemic among occasional drinkers., Conclusions: No major shifts in alcohol consumption habits occurred during the pandemic in our study population. Occasional drinkers tended to drink less during the pandemic, suggesting that initial concerns about increased alcohol consumption owing to the pandemic were unfounded., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)

Background: To our knowledge, the association of maternal exposure to metallic elements with weight trajectory pattern from the neonatal period has not been investigated., Objectives: The goals of this study were to identify infant growth trajectories in weight in the first 3 y of life and to determine the associations of maternal blood levels of lead, cadmium, mercury, selenium, and manganese with growth trajectory., Methods: This longitudinal study, part of the Japan Environment and Children Study, enrolled 103,099 pregnant women at 15 Regional Centres across Japan between 2011 and 2014. Lead, cadmium, mercury, selenium, and manganese levels were measured in blood samples collected in the second (14-27 wk gestational age) or third trimester ( ≥ 28 wk ). Growth trajectory of 99,014 children was followed until age 3 y. Raw weight values were transformed to age- and sex-specific weight standard deviation (SD) scores, and latent-class group-based trajectory models were estimated to determine weight trajectories. Associations between maternal metallic element levels and weight trajectory were examined using multinomial logistic regression models after confounder adjustment., Results: We identified 5 trajectory patterns based on weight SD score: 4.74% of infants were classified in Group I, very small to small; 31.26% in Group II, moderately small; 21.91% in Group III, moderately small to moderately large; 28.06% in Group IV, moderately large to normal; and 14.03% in Group V, moderately large to large. On multinomial logistic regression, higher maternal lead and selenium levels tended to be associated with increased odds ratios (ORs) of poor weight SD score trajectories (Groups I and II), in comparison with Group III. Higher levels of mercury were associated with decreased ORs, whereas higher levels of manganese were associated with increased ORs of "moderately large" trajectories (Groups IV and V)., Discussion: Maternal lead, mercury, selenium, and manganese blood levels affect infant growth trajectory pattern in the first 3 y of life. https://doi.org/10.1289/EHP10321.

Several longitudinal studies have examined associations between renal dysfunction and hearing impairment. Here, we explored the longitudinal association between estimated glomerular filtration rate (eGFR) and hearing impairment among the working-age population in Japan. Participants were 88,425 males and 38,722 females aged 20-59 years, without hearing impairment at baseline (2013), who attended Japanese occupational annual health check-ups from 2013 to 2020 fiscal year. eGFR was categorized into four groups (eGFR upper half of ≥90, lower half of ≥90 (reference), 60-89, and <60 mL/min/1.73 m 2 ). Low- and high-frequency hearing impairment were assessed using data from pure-tone audiometric testing. A Cox proportional hazards model was applied to estimate hazard ratio (HR) values for hearing impairment. Low eGFR did not increase the risk of low- or high-frequency hearing impairment. For males, multivariable-adjusted HR of high-frequency hearing impairment was 1.16 (95% confidence interval, 1.01-1.34) for the upper half of the ≥90 mL/min/1.73 m 2 ; however, this positive association between high eGFR and high-frequency hearing impairment did not appear to be robust in a number of sensitivity analyses. We conclude that, among the Japanese working-age population, eGFR was not generally associated with hearing impairment in people of either sex.

This study aimed to examine the association between infant sleep quality and temperament in one-month-old infants using a large cohort study data. We used data from the Japan Environment and Children's Study, a cohort study which follows around 100,000 women from pregnancy until their children's development. The mothers were asked about their infants' sleep and temperament using a structured questionnaire. Frequent crying (adjusted odds ratio [AOR]: 1.05, 95% confidence interval [CI]: 1.00-1.10) and intense crying (AOR: 1.19, 95% CI: 1.13-1.25) were positively associated with longer sleep periods during the day than at night. Female infants with longer daytime sleep periods than that at nighttime were more likely to cry frequently (AOR: 1.11, 95% CI: 1.04-1.20). Parous women with infants who had frequent night awakening believed their infants cried more intensely (AOR: 1.17, 95% CI: 1.03-1.31). The study demonstrated a specific association between sleep quality and temperament in one-month-old infants. Based on the results of this study, further sleep intervention studies are required to improve infant temperament., Competing Interests: The authors have declared that no competing interests exist.

Background: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles., Methods: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion., Results: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study., Conclusion: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Background: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study of environmental factors affecting children's health and development. We summarize the complete blood count and chemistry panel statistical data from pregnant women enrolled in JECS., Methods: Statistical data of up to 58,056 mother's sample in their first (gestational age ≤ 13 weeks) and second trimester (22-27 weeks) were calculated., Results: Mean (SD) values in the first trimester were: white blood cell count, 7866 (1906)/μL; red blood cell count, 417 (33) 10 4 /μL; hemoglobin, 12.4 (1.0) g/dL; hematocrit, 37.1 (2.6)%; mean corpuscular volume, 89.2 (4.7) fL; mean corpuscular hemoglobin, 29.8 (1.9) pg; mean corpuscular hemoglobin concentration, 33.3 (0.9)%; platelet count, 24.8 (5.2) 10 4 /μL; HbA1c, 5.26 (0.26)%; total cholesterol, 181 (28) mg/dL; low density lipoprotein cholesterol, 95 (23) mg/dL; high density lipoprotein cholesterol, 73 (13) mg/dL; free cholesterol, 41 (7) mg/dL; triglycerides, 109 (47) mg/dL; total protein, 6.9 (0.4) g/dL; and albumin, 4.1 (0.2) g/dL. Mean values (SD) in the second trimester were: total cholesterol, 246 (38) mg/dL; free cholesterol, 61 (9) mg/dL; triglycerides, 183 (70) mg/dL; total protein, 6.5 (0.4) g/dL; and albumin, 3.6 (0.2) g/dL., Conclusions: These data will be useful for future JECS studies.

Background: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics., Methods: We recruited 3545 mother-child pairs from the Japan Environment and Children's Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders., Results: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52-0.95) and 0.04 (0.03-0.06) μg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (β = -1.4, 95% confidence interval (CI): -2.7, -0.038), DQ in children of mothers who smoked during pregnancy (β = -2.9, 95% CI: -5.7, -0.12), P-M (β = -5.4, 95% CI: -10, -0.67), C-A (β = -6.1, 95% CI: -11, -1.8), L-S (β = -9.0, 95% CI: -13, -4.8) and DQ scores (β = -6.4, 95% CI: -9.6, -3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (β = -6.0., 95% CI: -11, -0.91) in children born to mothers with gestational diabetes., Conclusions: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Exposure to ambient air pollution is associated with maternal and child health. Some air pollutants exhibit similar behavior in the atmosphere, and some interact with each other; thus, comprehensive assessments of individual air pollutants are required. In this study, we developed national-scale monthly models for six air pollutants (NO, NO 2 , SO 2 , O 3 , PM 2.5 , and suspended particulate matter (SPM)) to obtain accurate estimates of pollutant concentrations at 1 km × 1 km resolution from 2010 through 2015 for application to the Japan Environment and Children's Study (JECS), which is a large-scale birth cohort study. We developed our models in the land use regression framework using random forests in conjunction with kriging. We evaluated the model performance via 5-fold location-based cross-validation. We successfully predicted monthly NO (r 2  = 0.65), NO 2 (r 2  = 0.84), O 3 (r 2  = 0.86), PM 2.5 (r 2  = 0.79), and SPM (r 2  = 0.64) concentrations. For SO 2 , a satisfactory model could not be developed (r 2  = 0.45) because of the low SO 2 concentrations in Japan. The performance of our models is comparable to those reported in previous studies at similar temporal and spatial scales. The model predictions in conjunction with the JECS will reveal the critical windows of prenatal and infancy exposure to ambient air pollutants, thus contributing to the development of environmental policies on air pollution., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: We investigated which trimester of exposure to PM2.5 and its components was associated with birth and placental weight, and the fetoplacental weight ratio., Methods: The study included 63,990 women who delivered singleton term births within 23 Tokyo wards between 2013 and 2015. Each day, we collected fine particles on a filter, and analyzed their chemical constituents, including carbons and ions. Trimester-specific exposure to each pollutant was estimated based on the average daily concentrations., Results: Over the third trimester, sulfate exposure tended to be inversely associated with birth weight, and decreased placental weight (difference for highest vs lowest quintile groups = -6.7 g, 95% confidence interval = -12.5 to -0.9). For fetoplacental weight ratio, there was no relationship., Conclusions: Sulfate exposure over the third trimester may reduce birth weight, particularly placental weight., Competing Interests: Michikawa, Takeda, Morokuma, Yamazaki, Nakahara, Yoshino, Sugata, Takami, Saito, Hoshi, Kato, Nitta, and Nishiwaki have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2021 American College of Occupational and Environmental Medicine.)

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), are three reportedly predictive biomarkers that reflect subclinical chronic inflammatory burden. However, how these biomarkers change during pregnancy and its clinical utility among pregnant women have been rarely studied. Among 76,853 singleton pregnancies delivered at 28-41 weeks of gestation that were enrolled in the Japan Environment and Children's Study, we observed the distribution of maternal NLR, PLR, and LMR values from week 0 to week 36 using spline curves, as well as their predictive values for preterm delivery with and without hypertensive disorders in pregnancy, placental abruption and intrauterine growth restriction (collectively termed ischemic placental disease due to their shared pathological and pathophysiological features) for measurements at 8-11 weeks, 12-17 weeks, and 18-21 weeks. NLR and PLR increased, whereas LMR decreased, with increasing gestation. High LMR and low NLR observed at 18-21 weeks, but not at earlier gestations, were associated with higher risk of preterm delivery with IPD (odds ratio 1.80 [95% CI 1.02, 3.19] per log[LMR]; odds ratio 0.49 [95% CI 0.29, 0.82] per log[NLR]). All parameters were not predictive of preterm delivery without IPD. We provide a robust reference curve for maternal blood count parameters NLR, PLR, and LMR by gestational week., (© 2021. The Author(s).)

Exposure to particulate matter (PM) is one of the important risk factors for morbidity and mortality. Although PM concentrations have been assessed using air quality monitoring stations or modelling, few studies have measured indoor PM in large-scale birth cohorts. The Japan Environment and Children's Study (JECS) measured indoor and outdoor air quality in approximately 5000 households when the participating children were aged 1.5 and 3 years. PM was collected using portable pumps for 7 days (total of 24 h), inside and outside each home. Prediction models for indoor PM concentrations were built using data collected at age 1.5 years and post-validated against data collected at age 3 years. Median indoor/outdoor PM 2.5 and PM 10-2.5 concentrations at age 1.5 years [3 years] were 12.9/12.7 [12.5/11.3] μg/m 3 and 5.0/6.3 [5.1/6.1] μg/m 3 , respectively. Random forest regression analysis found that the major predictors of indoor PM 2.5 were indoor PM 10-2.5 , outdoor PM 2.5 , indoor smoking, observable smoke and indoor/outdoor temperature. Indoor PM 2.5 , outdoor PM 10-2.5 , indoor humidity and opening room windows were important predictors of indoor PM 10-2.5 concentrations. Indoor benzene, acetaldehyde, ozone and nitrogen dioxide concentrations were also found to predict indoor PM 2.5 and PM 10-2.5 concentrations, possibly due to the formation of secondary organic aerosols. These findings demonstrate the importance of reducing outdoor PM concentrations, avoiding indoor smoking, using air cleaner in applicable and diminishing sources of VOCs that could form secondary organic aerosols, and the resulting models can be used to predict indoor PM concentrations for the rest of the JECS cohort., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

This study investigated the association of maternal sleep before and during pregnancy with sleeping and developmental problems in 1-year-old infants. We used data from the Japan Environment and Children's Study, which registered 103,062 pregnancies between 2011 and 2014. Participants were asked about their sleep habits prior to and during pregnancy. Follow-up assessments were conducted to evaluate the sleep habits and developmental progress of their children at the age of 1 year. Development during infancy was evaluated using the Ages and Stages Questionnaire (ASQ). Maternal short sleep and late bedtime before and during pregnancy increased occurrence of offspring's sleeping disturbances. For example, infants whose mothers slept for less than 6 h prior to pregnancy tended to be awake for more than 1 h (risk ratio [RR] = 1.49, 95% confidence interval [CI] 1.34-1.66), sleep less than 8 h during the night (RR = 1.60, 95% CI 1.44-1.79), and fall asleep at 22:00 or later (RR = 1.33, 95% CI 1.26-1.40). Only subjective assessments of maternal sleep quality during pregnancy, such as very deep sleep and feeling very good when waking up, were inversely associated with abnormal ASQ scores in 1-year-old infants.

Volatile organic compounds (VOCs) are major indoor air pollutants. Quantification of indoor concentrations of VOCs and identification of factors associated with these concentrations can help manage indoor air quality. This study measured the concentrations of VOCs and inorganic gaseous pollutants in around 5000 households in Japan and utilised a random forest model to estimate these concentrations and identify important determinants. The homes of 5017 randomly selected participants in the Japan Environment and Children's Study (JECS) were visited twice, when the children were aged 1.5 and 3 years. Twelve VOCs and inorganic gaseous pollutants were measured during 7 days by passive samplers. Various factors in these households, including household appliances, building characteristics, cooking styles, use of consumer products, renovation, pets, personal behaviours and ventilation were recorded. A random forest model with recursive feature elimination was utilised to identify factors predictive of VOCs and inorganic gaseous pollutants. Toluene, formaldehyde and acetaldehyde were the dominant indoor VOCs. The 95th percentiles of indoor p-dichlorobenzene concentrations at 1.5 and 3 years were 67 μg/m 3 and 71 μg/m 3 , respectively. Random forest models with coefficients of determination ranging from 0.34 to 0.76 outperformed the traditional linear regression models. Factors associated with indoor VOC and inorganic gaseous pollutant concentrations included their outdoor concentrations, indoor and outdoor temperature and relative humidity, month of the year, hours windows were open, kerosene heater use and times of operation and building age. The results provided basic descriptions of indoor VOCs and inorganic gaseous pollutants in Japan and identified several determinants of these concentrations. These determinants should be considered to maintain indoor air quality. These results can be used in epidemiological assessments of the effects of VOCs and inorganic gaseous pollutants on health in children., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Organophosphate pesticides (OPPs) exhibit neurodevelopmental toxicity. To evaluate the effect of prenatal exposure to OPPs in the Japan Environment and Children's Study, a nationally representative birth cohort study, 4575 maternal urine samples were analysed for six OPP metabolites, i.e., dialkylphosphates (DAPs). This study aimed to investigate predictors of urinary DAPs using machine learning approaches and to assess the cumulative risk based on relative potency factors among Japanese pregnant women. The median creatinine-normalised urinary concentrations (interquartile ranges) of dimethylphosphate, dimethylthiophosphate and diethylphosphate, which had a detection rate of 50% or higher, were 3.53 (1.91-6.78), 4.09 (1.66-10.8) and 3.28 (1.88-5.98) µg/g-creatinine, respectively. Possible predictors of urinary DAP concentrations were the month of urine sampling, consumption of apple and maternal body mass index. When fenitrothion was used as an index chemical for cumulative risk assessment, 0.36% of participants exceeded the lower 95% confidence limit of the benchmark dose 10 ., Competing Interests: The authors declare no conflict of interest.

Clinical guidelines including those set by the US Institute of Medicine, have based optimal gestational weight gain (GWG) on maternal pre-pregnancy body mass index (BMI), but have not considered the role of environmental toxicants such as heavy metals that can disrupt these processes. This study designed to determine optimal GWG ranges in women grouped according to BMI, and to assess whether blood concentrations of heavy metals alter the relationships between GWG and outcomes. A total of 103,060 participants in the Japan Environment and Children's Study recruited between 2011 and 2014 were followed until their children reached 3 years of age. Outcomes included 1 min Apgar score <7, caesarean delivery, childhood obesity, gestational diabetes, pregnancy-induced hypertension, low birth weight, large for gestational age, macrosomia, operative vaginal delivery, postpartum weight retention, preterm birth and small for gestational age. The optimal GWG ranges were determined using multivariate logistic regression models. Stratified analyses were performed to determine optimal GWG ranges according to quartiles of heavy metals. Optimal GWGs for underweight, normal weight and overweight women were found to be 10.0 to <14.0 kg, 6.0 to <12.0 kg and 4.0 to <8.0 kg, respectively. However, the benefits of optimal GWG were attenuated in women exposed to high concentrations of mercury (Hg), lead (Pb) and cadmium (Cd). Despite being within optimal GWG, underweight women with Hg > 5.21 ng/g and overweight women with Hg 3.67-5.21 ng/g, Pb > 7.31 ng/g and Cd > 0.66 ng/g had null effects. Heavy metals can modify the associations between GWG and outcomes, particularly for underweight and overweight women. Because of the complex interactions of environmental toxicants with pre-pregnancy BMI, GWG and adverse outcomes, GWG guidelines should be interpreted cautiously. Environmental toxicants may influence the determination of a clinical guideline., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There is growing evidence of an association between cadmium (Cd) and unfavorable birth outcomes. The effect of Cd exposure on anthropometric measures at birth or small for gestational age (SGA) infants in a large, nationwide Japanese cohort remains to be clarified., Objectives: To analyze the association between maternal blood Cd levels at different sampling times and sex-dependent infant birth size, weight, body length, chest, and head circumferences, in addition to SGA., Methods: Data of 17,584 pregnant women in the Japan Environment and Children's Study were analyzed for anthropometric measurements. For SGA determination, 13,969 cases of vaginal delivery were analyzed after excluding infants born by cesarean section. Maternal blood Cd levels were categorized into quartiles (Q1-Q4), and the Q1 was used as a reference. Multiple linear regression analysis was performed for anthropometric measurements, and multiple logistic regression analysis was used to investigate the association of maternal blood Cd levels with the risk of SGA., Results: Birth weight tended to decrease according to the increase in quartiles of blood Cd levels (15.63 g decrease [95% confidence level (CI): -33.26, 2.01] for Q4). The overall analysis revealed no decreases in body length and head and chest circumference, but subgroup analysis revealed that chest circumference tended to decrease according to the increase in quartiles in the female sex/third-trimester stratification (0.16 cm decrease [95% CI: -0.32, 0.00] for Q4). SGA risk was also higher and paralleled the increase in blood Cd levels associated with the female sex/third-trimester group (Odds Ratio 1.90 [95% CI: 1.23, 2.94] for Q4)., Conclusion: Our results provide further evidence of sex-specific health risks associated with Cd exposure in early life in a large Japanese pregnancy cohort., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The occurrence of anorectal malformations (ARM) is thought to be reduced with sufficient folate intake. However, there is no apparent evidence. We focused on enzyme cofactors for one-carbon metabolism, including folate (vitamin B9), vitamin B6 and vitamin B12, and explored the association between maternal combined intake of these B vitamins and the risk of ARM. Using baseline data from a Japanese nationwide birth cohort study between 2011 and 2014, we analysed data of 89 235 women (mean age at delivery = 31·2 years) who delivered singleton live births without chromosomal anomalies. Information on dietary intake was obtained via a FFQ focused on early pregnancy and used to estimate B vitamin intake. We also collected information on the frequency of folic acid supplement use. ARM occurrence was ascertained from medical records. We identified forty-three cases of ARM diagnosed up to the first month after birth (4·8 per 10 000 live births). In terms of individual intake of the respective B vitamins, high vitamin B6 intake was non-significantly associated with reduced odds of ARM. Compared with women in the low combined B vitamin intake group, the OR of having an infant with ARM was 0·4 (95 % CI 0·2, 1·0) in the high intake group (folate ≥400 μg/d, and upper half of vitamin B6 and/or vitamin B12). In conclusion, our cohort analysis suggested an inverse association between the combined intake of one-carbon metabolism-related B vitamins in early pregnancy and ARM occurrence.

Locomotive syndrome is a condition of reduced mobility, and patients have a high risk of requiring nursing care. In order to investigate the level of awareness of the term "locomotive syndrome" and the factors relating to awareness in a community, awareness of locomotive syndrome was included in a questionnaire survey on health and daily life conducted in Koumi Town (Japan), which was distributed to 3181 eligible residents aged 40 years or older. Information on age, sex, marital status, educational attainment, lifestyle, and social environment was also collected, and the association of awareness with various factors was analyzed with two multivariable Poisson regression models. As a result, awareness among respondents was 44.6%. Awareness was significantly higher among women, those who were 60-79 years old, married, and had received higher education. Additionally, awareness was significantly associated with social factors, especially attendance at regional events within the last one year, in both women and men: the adjusted prevalence ratios (95% confidence intervals) were 1.26 (1.10-1.43) and 1.48 (1.19-1.83), respectively. In conclusion, in addition to strengthen awareness rising campaigns targeting men and for younger people, providing health education at social settings such as regional events may help improve future musculoskeletal health in the elderly., Competing Interests: The authors declare no conflict of interest.

Few studies have assessed the accuracy of self-reported questionnaires to determine smoking habits relative to urinary biomarkers. This study investigated urinary cotinine cut-off concentrations distinguishing active, passive and non-smokers among pregnant women who participated in the Japan Environment and Children's Study, a nationwide birth cohort study. Pregnant participants with measured urinary cotinine concentrations (UCCs) and who completed self-reported questionnaires on smoking status were included ( n = 89,895). The cut-off values (COVs) for active and passive smokers were calculated by fitting mixed normal distribution functions to UCCs. The sensitivity and specificity of the questionnaires were subsequently evaluated. The median (interquartile range) UCC was 0.24 (0.083-0.96) µg/g-creatinine, with the detection rate of 89%. The COV for distinguishing active smokers from passive and non-smokers was 36.8 µg/g-creatinine. When this COV was considered to represent the true condition, the questionnaire had a sensitivity of 0.523, a specificity of 0.998, a positive predictive value (PPV) of 0.967 and a negative predictive value (NPV) of 0.957. The COV for distinguishing passive smokers from non-smokers was 0.31 µg/g-creatinine, with the questionnaire having a sensitivity of 0.222, a specificity of 0.977, a PPV of 0.868 and an NPV of 0.644. As many as 78% of passive smokers might be misclassified as non-smokers.

Abnormal autonomic function may cause false-positive non-reassuring foetal status (fpNRFS) and may also cause sleeping problems after birth. However, an association between fpNRFS and sleeping problems in infants has not been reported. We previously showed an association of NRFS with temperament, including bad mood and frequent crying for long durations in 1-month-old infants. In the present study, we aimed to assess this association in 1-year-old infants. A total of 62,612 single pregnant women were included in the analysis. fpNRFS was identified from medical records. Sleep problems, such as short sleep duration or crying at night, were investigated in 1-year-old infants using a questionnaire for mothers. We used a log-binominal regression model to explore the association of fpNRFS with each sleep problem and to estimate risk ratios (RRs). The number of fpNRFS cases was 2,071, with a frequency of 3.3%. We observed an association of fpNRFS with shorter sleep duration of less than 8 h a night (RR 1.30, 95% confidence intervals [CI] 1.10-1.54), crying at night (RR 1.19, 95% CI 1.03-1.39), and bedtime after 22:00 (RR 1.09, 95% CI 1.00-1.18). fpNRFS may be associated with sleep problems in 1-year-old infants.

This study aimed to investigate the association of maternal sleep before and during pregnancy with preterm birth, infant sleep and temperament at 1 month of age. We used the data of the Japan Environment and Children's Study, a cohort study in Japan, which registered 103,099 pregnancies between 2011 and 2014. Participants were asked about their sleep before and during pregnancy, and the sleep and temperament of their newborns at 1 month of age. Preterm birth data were collected from medical records. Maternal sleep was not associated with preterm birth, but subjective sleep quality during pregnancy was associated with late preterm birth (birth at 34-36 weeks of gestation). For example, participants with extremely light subjective depth of sleep were more likely to experience preterm birth (RR = 1.19; 95% confidence interval [CI] = 1.04-1.35). Maternal sleep both before and during pregnancy seemed to be associated with infant sleep and temperament at 1 month of age. Infants, whose mothers slept for less than 6 hours before pregnancy, tended to cry intensely (RR = 1.15; 95% CI = 1.09-1.20). Maternal sleep problems before and during pregnancy were associated with preterm birth and child sleep problems and temperament.

Background: The effect of knee osteoarthritis, which causes knee pain, on higher-level functional competence (HLFC) is not clear., Objective: To clarify the effect of knee pain on HLFC in older people., Design: Community-based prospective cohort study., Setting: Kurabuchi town, Gumma prefecture, Japan., Subjects: Community-dwelling individuals aged 65 and older., Methods: A total of 808 residents participated to the baseline examinations. The frequency of knee pain, degree of pain and functional impairment resulting from the pain were asked at baseline (2005-2006) via a self-administered questionnaire in Japanese based on an English version of the Western Ontario and McMaster Universities Osteoarthritis Index. Information on HLFC at baseline and during home visits were collected annually until 2014 with the Tokyo Metropolitan Institute of Gerontology Index of Competence. The association between baseline knee pain and HLFC decline was assessed with a Cox proportional hazards model., Results: Two factors, persistent knee pain and severe functional impairment caused by the pain, were significantly associated with future declines in total HLFC, with adjusted hazard ratios (95% confidence intervals) of 1.51 (1.08-2.11) and 1.49 (1.10-2.00). In analysis by subcategory, persistent knee pain had a significant adverse effect on participants' intellectual and social activities, and that severe physical functional impairment also had a significant impact on social activities., Conclusions: The clear association of the frequency of knee pain and resultant functional impairment with future HLFC decline indicates that collecting information about these factors may be useful in identifying older people at high risk of future HLFC decline., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Numerous epidemiological studies have demonstrated that short-term exposure to ambient PM 2.5 increases mortality and morbidity. Investigating the association using hourly ambient PM 2.5 exposure may provide important insights, as current evidence is limited mostly to daily lag term. This study aimed to investigate the hourly association between ambient PM 2.5 concentrations and all-cause emergency ambulance dispatches (EAD) in 11 cities in Japan. We used a time-stratified case-crossover design and examined the hourly lags of ambient PM 2.5 up to 24 h (unconditional distributed lags and moving average lags) using a conditional Poisson regression model. A significant increase in all-cause EAD was observed at lag 0 h [relative risk (RR): 1.0037 (95% CI: 1.0000, 1.0074)] and all moving average lags. The highest RR was observed within the first 6 h (at lag 0-5 h) [RR: 1.0091 (95% CI: 1.0068, 1.0114)], with a slight ascending pattern. This was followed by a descending pattern at lags 0-11, 0-17, and 0-23 h, but significant positive RR was observed even at lag 0-23 h, when the lowest RR was observed [RR: 1.0072 (95% CI: 1.0044, 1.0100)]. Though similar pattern was observed among the elderly, a different pattern was observed among the children (gradually ascending pattern). We conclude that all-cause EAD could be triggered by ambient PM 2.5 exposure with very short lags., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: No previous study has used repeated measures data to examine the associations of dog/cat ownership with wheezing and asthma prevalence among children. This prospective study used repeated measurers analysis to determine whether dog/cat ownership in childhood is an independent risk factor for wheezing and asthma, after adjustment for gestational, socio-economical, and demographical confounders confounders, in Japan., Methods: We conducted a multicenter pilot study of the Japan Environment and Children's Study (JECS) during 2009-2010. Among 440 newborn infants enrolled, 410 (52.8% males) were evaluated for dog/cat ownership in the home and history of wheezing and asthma in five follow-up questionnaire surveys (until age 6 years). Dog/cat ownership during follow-up period was categorized into four groups: 7.6% were long-term dog/cat owners, 5.9% were toddler-age owners, 5.9% were preschool-age owners, and 80.7% were never owners., Results: The prevalence of wheezing during follow-up period increased from 20.8% to 35.4% and the prevalence of asthma increased from 1.3% to 16.3%. A fitted logistic generalized estimating equation models including important confounders showed no significant associations of the interaction between dog and/or cat ownership and follow-up time with the risks of wheezing and asthma. However, the risks of wheezing and asthma were slightly lower for long-term and toddler-age dog/cat owners than for preschool-age and never owners., Conclusions: The present findings suggest that dog and cat ownership from toddler-age does not increase the risks of wheezing and asthma compared with never owners among Japanese children., Competing Interests: The authors have declared that no competing interests exist.

Poly- and perfluoroalkyl substances (PFAS) have been investigated in a number of cohort studies due to concern over their adverse health effects. The aim of this study was to develop a reliable, high throughput and cost-effective analytical method for a broad range of PFAS in human serum. Protein precipitation, automatic solid phase extraction (SPE) pre-treatment and column-switching LC-MS/MS were employed. The optimised and validated method was then used to analyse the levels of 28 PFAS in 339 maternal serum samples from Pilot Study of the Japan Environment and Children's Study. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnA) and perfluorooctane sulphonic acid (PFOS) were detected in all 339 samples at median (range) concentrations of 1.9 (0.46-15), 1.5 (0.32-10), 1.3 (0.25-4.5) and 3.7 (0.43-15) ng/ml, respectively. These levels are comparable to those reported in previous studies using samples collected from various parts of the world. With a few exceptions, the remainder of the PFAS examined had lower detection rates but were found at concentrations similar to those reported in previous studies. The sensitivity and throughput ability of the method developed here are sufficient for its application in a large-scale biomonitoring study., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest with respect to this study and article., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: Out-of-hospital cardiac arrests (OHCAs) are a major public health concern and a leading cause of death worldwide. Exposure to ambient air pollution is associated with increases in morbidity and mortality and has been recognized as a leading contributor to global disease burden., Objective: To examine the association between short-term exposure to particulate matter with a diameter of 2.5 μm or smaller (PM2.5) and the incidence of OHCAs of cardiac origin and with the development of initial cardiac arrest rhythm., Design, Setting, and Participants: This case-control study used data from cases registered between January 1, 2005, and December 31, 2016, in the All-Japan Utstein Registry, a prospective, nationwide, population-based database for OHCAs across all 47 Japanese prefectures. These OHCA cases included patients who had bystander-witnessed OHCAs and for whom emergency medical services responders initiated resuscitation before hospital transfer. A case-crossover design was employed for the study analyses. A prefecture-specific, conditional logistic regression model to estimate odds ratios was applied, and a random-effects meta-analysis was used to obtain prefecture-specific pooled estimates. All analyses were performed from May 7, 2019, to January 23, 2020., Main Outcomes and Measures: The main outcome was the association of short-term PM2.5 exposure with the incidence of bystander-witnessed OHCAs of cardiac origin. The differences in the distribution of initial cardiac arrest rhythm in OHCAs among those with exposure to PM2.5 were also examined., Results: In total, 103 189 OHCAs witnessed by bystanders were included in the final analysis. Among the patients who experienced such OHCAs, the mean (SD) age was 75 (15.5) years, and 62 795 (60.9%) were men. Point estimates of the percentage increase for a 10-μg/m3 increase in PM2.5 at lag0-1 (difference in mean PM2.5 concentrations measured on the case day and 1 day before) demonstrated a statistically significantly higher incidence of OHCA across most of the 47 prefectures, without significant heterogeneity (I2 = 20.1%; P = .12). A stratified analysis found an association between PM2.5 exposure and OHCAs (% increase, 1.6; 95% CI, 0.1%-3.1%). An initial shockable rhythm, such as ventricular fibrillation or pulseless ventricular tachycardia (% increase, 0.6; 95% CI, -2.0% to 3.2%), was not associated with PM2.5 exposure. However, an initial nonshockable rhythm, such as pulseless electrical activity and asystole, was associated with PM2.5 exposure (% increase, 1.4; 95% CI, 0.1%-2.7%)., Conclusions and Relevance: Findings from this study suggest that increased PM2.5 concentration is associated with bystander-witnessed OHCA of cardiac origin that commonly presents with nonshockable rhythm. The results support measures to reduce PM2.5 exposure to prevent OHCAs of cardiac origin.

Exposure to fine particulate matter (PM 2.5 ) is a potential aggravating factor for respiratory and allergic diseases. However, which PM 2.5 sources are associated with such diseases remains unclear. This study aimed to investigate the association of PM 2.5 sources with allergic and respiratory symptoms in schoolchildren. PM 2.5 samples were collected in Fukuoka during the spring in 2014 and 2015. Asian dust was observed in 2014. Ion components, elemental components, and organic components were analyzed. Positive matrix factorization (PMF) was conducted to calculate PM 2.5 concentrations from each source. Mixed logistic regression analysis with a random intercept for each schoolchild was performed to evaluate the association of components and sources with symptoms. Among 2317 schoolchildren, the mean prevalence was 28.9%, 23.6%, 11.2%, and 11.4% for lower respiratory, nasal, ocular, and skin symptoms, respectively. PMF identified the following six PM 2.5 sources "Secondary sulfate and coal combustion", "Secondary nitrate", "Heavy oil combustion", "Sea salt", "Soil" and "Traffic emission". An interquartile range of PM 2.5 mass was associated with nasal (Odds ratios 1.08, 95% confidence interval [1.03, 1.13]), ocular (1.10, [1.04, 1.16]), and skin symptoms (1.13, [1.06, 1.20]). Among the source factors, "Heavy oil combustion" was significantly associated with nasal symptom (1.11, [1.05, 1.18]) while "Sea salt" was associated with nasal (1.06, [1.02, 1.11]) and skin (1.073, [1.01, 1.14]) symptoms. We found "Soil", which might be affected by Asian dust, was associated with ocular (1.07, [1.03, 1.10]) and skin (1.05, [1.01, 1.08]) symptoms. Further studies in other seasons or places are needed to clarify the influence of PM 2.5 sources on children's health., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Vitamin D insufficiency/deficiency is prevalent worldwide. We investigated the effect of vitamin D intake and ultraviolet ray (UV) exposure on serum vitamin D concentration in Japan. A total of 107 healthy adult participants were recruited from Hokkaido (43°N) and Kumamoto (33°N) prefectures. All participants undertook surveys in both summer and winter. Serum 25-hydroxyvitamin D (25(OH)D 3 ) was examined, and vitamin D intake was assessed with a diet history questionnaire. UV exposure was measured with a wearable UV dosimeter. Regression analysis was performed to investigate the relationship between these factors, with covariates such as sun avoidance behavior. The prevalence of vitamin D insufficiency (serum 25(OH)D 3 ; 12 ng/ml (30 nmol/L) ≤ and <20 ng/ml (50 nmol/L))/deficiency (<12 ng/ml) was 47.7% in summer and 82.2% in winter. UV exposure time was short in Kumamoto (the urban area), at 11.6 minutes in summer and 14.9 minutes in winter. In Hokkaido (the rural area), UV exposure time was 58.3 minutes in summer and 22.5 minutes in winter. Vitamin D intake was significantly associated with serum 25(OH)D 3 , and a 1 μg/1000kcal increase in intake was necessary to increase 25(OH)D 3 by 0.88 ng/ml in summer and by 1.7 ng/ml in winter. UV exposure time was significantly associated with serum 25(OH)D 3 in summer, and a 10 min increase in UV exposure time was necessary to increase 25(OH)D 3 by 0.47 ng/ml. Although consideration of personal occupation and lifestyle is necessary, most Japanese may need to increase both vitamin D intake and UV exposure.

Objective: Asian dust is a natural phenomenon in which dust particles are transported from desert areas in China and Mongolia to East Asia. Short-term exposure to Asian dust has been associated with cardiovascular disease through mechanisms such as systemic inflammation. Because inflammation is a potential trigger of placental abruption, exposure may also lead to abruption. We examined whether exposure to Asian dust was associated with abruption., Design: A bi-directional, time-stratified case-crossover design., Setting and Population: From the Japan Perinatal Registry Network database, we identified 3014 patients who delivered singleton births in hospitals in nine Japanese prefectures from 2009 to 2014 with a diagnosis of placental abruption., Methods: Asian dust levels were measured at Light Detection and Ranging monitoring stations, and these measurements were used to define the Asian dust days. As there was no information on the onset day of abruption, we assumed this day was the day before delivery (lag1)., Main Outcome Measures: Placental abruption., Results: During the study period, the Asian dust days ranged from 15 to 71 days, depending on the prefecture. The adjusted odds ratio of placental abruption associated with exposure to Asian dust was 1.4 (95% confidence interval = 1.0, 2.0) for cumulative lags of 1-2 days. Even after adjustment for co-pollutant exposures, this association did not change substantially., Conclusions: In this Japanese multi-area study, exposure to Asian dust was associated with an increased risk of placental abruption., Tweetable Abstract: Exposure to environmental factors such as Asian dust may be a trigger of placental abruption., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Objective: For several observational studies that have reported the factors related to gastroschisis, the target population in these studies was mainly residents of Europe or the US, and there is little data on the Asian population. In this study, we summarised characteristics of Japanese women who delivered infants with gastroschisis, particularly focusing on the pre-pregnancy body mass index (BMI), which was found to be inversely associated with gastroschisis in past studies, because the distribution of BMI is clearly different in Asia and the West., Results: We used data from a nationwide birth cohort study which recruited pregnant women between 2011 and 2014. Among 92,796 women who delivered singleton live births, the frequency of underweight (pre-pregnancy BMI < 18.5 kg/m 2 ) was 16.2%, reference weight (18.5-24.9 kg/m 2 ) 73.1%, and overweight (≥ 25.0 kg/m 2 ) 10.6%. We identified only 9 infants with gastroschisis, 2 of whose women were underweight (frequency of gastroschisis = 0.01%), 5 were in the reference group (0.01%), and 2 were overweight (0.02%). Of these 9 women, none were aged < 20 years, 2 were aged 20-29 years (frequency = 0.01%), and 7 were aged 30-39 years (0.01%). No reduction in the occurrence of gastroschisis was apparent among Japanese women who were overweight before pregnancy.

The pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case-control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011-2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 μg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 μg/d). When we restricted to mothers with a prepregnancy BMI of 18·5-24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.

Background: From around 2012, the use of automated equipment for fine particulate matter (PM 2.5 ) measurement with equivalence to a reference method has become popular nationwide in Japan. This enabled us to perform a national health effect assessment employing PM 2.5 concentrations based on the standardized measurement method. We evaluated the association between non-accidental mortality and short-term exposure to PM 2.5 and coarse particulate matter (PM), with the latter estimated as the difference between suspended particulate matter and PM 2.5 , for the fiscal years 2012-2014., Methods: This was a time-stratified case-crossover study in 100 highly-populated Japanese cities. Mortality data was obtained from the Ministry of Health, Labour and Welfare. City-specific estimates of PM-mortality association were calculated by applying a conditional logistic regression analysis, and combined with a random-effects meta-analysis., Results: The respective averages of daily mean concentration were 14.6 µg/m 3 for PM 2.5 and 6.4 µg/m 3 for coarse PM. A 10 µg/m 3 increase in PM 2.5 concentrations for the average of the day of death and the previous day was associated with an increase of 1.3% (95% confidence interval (CI), 0.9-1.6%) in total non-accidental mortality. For cause-specific mortality, PM 2.5 was positively associated with cardiovascular and respiratory mortality. After adjustment for PM 2.5 , we observed a 1.4% (95% CI, 0.2-2.6%) increase in total mortality with a 10 µg/m 3 increase in coarse PM., Conclusion: The study revealed that short-term exposure to PM 2.5 had adverse effects on total non-accidental, cardiovascular, and respiratory mortality in Japan. Coarse PM exposure also increased the risk of total mortality.

Background: The progression of hyperkyphosis is a significant factor in declining general health. The purpose of this study was to investigate whether muscle strength and/or mobility is associated with the progression of hyperkyphosis in elderly people., Methods: As part of a cohort study of community-dwelling elderly people, handgrip strength and mobility (evaluated with the Timed Up and Go Test: TUG) were assessed at baseline (2005-2006). Kyphosis was also evaluated at baseline and in follow-up examinations 4 years later, with the block method. To exclude the measurement error, the progression of kyphosis was defined as increase of 2 or more blocks. The association of kyphosis progression in each group with handgrip strength and/or mobility was assessed using Poisson regression analysis., Results: Results on 403 participants were available for the final analysis, and kyphosis progression was observed in 53 (13.1%) of them. Multivariable analysis adjusted for sex, age, baseline block number, bone stiffness, TUG performance, or handgrip strength simultaneously revealed that low handgrip strength (<26 kg in men, <18 kg in women) and low mobility (>13.5 seconds) at baseline were both independently associated with kyphosis progression (adjusted risk ratio [95% confidence interval]: 2.11 [1.06-4.20] and 2.48 [1.26-4.89], respectively)., Conclusions: Our study showed that low handgrip strength and low mobility are clearly associated with the progression of kyphosis. Further study is needed on the applicability of these results to preventive measures., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although several genetic and environmental factors have been identified as risk factors of adolescent idiopathic scoliosis (AIS), the influence of dietary intake has not been elucidated. We evaluated the association between AIS and dietary habits among female students. Junior high school girls aged 12 to 15 years in the Tokyo metropolitan area who underwent a second school screening for scoliosis were recruited. AIS was diagnosed by orthopedic surgeons specializing in scoliosis, using standing whole spine radiography. Students with a Cobb angle of ≥15° were classified into the AIS group, and others were considered healthy controls. Dietary assessment was performed using a validated diet history questionnaire. Dietary intakes were categorized into quintiles based on distribution, and crude and multivariable odds ratios and 95% confidence intervals for AIS for each quintile category of dietary variable were calculated, with the lowest quintile category used as a reference. In total, 2431 subjects were included in the analysis, and 47.8% of them were diagnosed with AIS. None of the selected nutrients or food groups was significantly associated with AIS. In conclusion, dietary habits may not be associated with AIS.

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.

Objective: To explore the association between isoflavone intake in early pregnancy (the critical window of masculinisation) and hypospadias. Since oestrogen is likely to contribute to the differentiation of male external genitalia, dietary intake of isoflavone, which has a similar structure to human oestrogen, may be associated with the occurrence of hypospadias. However, there has been little evidence of this association., Materials and Methods: We used data of a nationwide birth cohort study, which recruited women as early in pregnancy as possible throughout Japan between 2011 and 2014. From the response to a self-administered food-frequency questionnaire, the daily intake of genistein (as a representative for isoflavone) was estimated. Information on hypospadias cases that were diagnosed until the first month after birth was obtained from medical records. Odds ratios (ORs) of hypospadias were estimated using a logistic regression model., Results: Among 41,578 mothers, who delivered singleton live male births, the median genistein intake was 15.3 mg/day, and a total of 51 cases of hypospadias were identified. Compared with mothers in the reference group (genistein intake 11th-89th percentiles), those in the low intake group (≤10th percentile) had an elevated risk of their sons having hypospadias (multivariable-adjusted OR = 2.8, 95% confidence interval = 1.4-5.8). Adverse or beneficial effects of genistein on hypospadias were not observed in the high intake group (≥90th percentile) (OR = 0.9, 95% confidence interval = 0.4-2.4)., Conclusion: Low maternal intake of isoflavone in early pregnancy was associated with an elevated risk of hypospadias., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Current evidence suggests that the aetiology of congenital gastrointestinal (GI) tract atresia is multifactorial, and not based solely on genetic factors. However, there are no established modifiable risk factors for congenital GI tract atresia. We used data from a Japanese nationwide birth cohort study launched in 2011, and examined whether fish consumption in early pregnancy was associated with congenital GI tract atresia. We analysed data of 89 495 women (mean age at delivery=31·2 years) who delivered singleton live births without chromosomal anomalies. Based on the results of the FFQ, we estimated the daily intake of fish and n-3 PUFA consumption in early pregnancy. We defined a composite outcome (oesophageal atresia, duodenal atresia, jejunoileal atresia and/or anorectal malformation) as congenital GI tract atresia. In this population, median fish intake was 31·9 g/d, and seventy-four cases of congenital GI tract atresia were identified. Fish consumption in early pregnancy was inversely associated with the composite outcome (multivariable-adjusted OR for the high v. low consumption category=0·5, 95 % CI 0·3, 1·0). For all the specific types of atresia, decreased OR were observed in the high consumption category, although not statistically significant. Reduced atresia occurrence was observed even beyond the US Food and Drug Administration's recommended consumption of no more than 340 g/week. Also, n-3 PUFA-rich fish and n-3 PUFA consumptions tended to be inversely associated with atresia. Fish consumption in early pregnancy may be a preventive factor for congenital GI tract atresia.

This cohort study conducted in Japan showed that severe age-related kyphosis was visually detected. The visual assessment of kyphosis was associated with declines in ADL, suggesting that we can easily identify people at high risk to develop future ADL reduction in the community setting., Purpose: Age-related kyphosis is related with declines in activities of daily living (ADL). Its conventional diagnosis has been made by orthopedic surgeons and trained examiners using specialized equipment such as X-rays. We investigated whether visual classification of kyphosis by laypersons accurately predicted future ADL decline., Methods: This study was part of the Kurabuchi Study, a cohort study of community-dwelling elderly Japanese. Between 2009 and 2010, three layperson raters used reference illustrations to classify 532 participants without ADL decline at study baseline into four categories. Other examiners used conventional methods to assess kyphosis in the same participants: curve ruler, Spinal Mouse, and the block method. ADL decline was defined as the development of dependence according to the Katz Index, admission to a nursing home, or certification of long-term care need., Results: Thirty-five of the participants (6.6%) were classified with the most severe degree of kyphosis at baseline by visual assessment. Interrater agreement was high (Kappa = 0.73) for the most severe group. During 4.5 years of follow-up, 106 participants (19.9%) showed ADL decline. On the basis of visual assessment, the adjusted risk ratio for ADL decline among the participants with the most severe kyphosis was 2.6 (95% CI: 1.4-4.6). Assessments of kyphosis made with the Spinal Mouse also accurately predicted ADL decline., Conclusions: Visual assessment of kyphosis predicted future declines in ADL in this study. Since our method requires no special tools or training, it may be useful for identifying those at high risk of ADL decline.

Previous studies have highlighted the negative effects of PM 2.5 on mortality, expressed in terms of attributable deaths and life years lost. However, there are very few studies assessing the health impacts of air pollution in terms of economic burden/benefits. This study assessed the health impact of two hypothetical interventions among sex- and age-specific risk populations using a robust risk estimation and economic valuation process. We utilized the sex- and age-stratified daily all-cause mortality together with the daily PM 2.5 of the 9 Japanese cities from 2002 to 2008 in estimating the relative risks. The estimated risks were then utilized for the economic valuation of co-benefits/burden with respect to the two hypothetical PM 2.5 -related mitigation scenarios, in comparison to status quo, namely: i) decrease to Japanese standards, and ii) decrease to WHO standards. Impact of these interventions on health were assessed using the following HIA metrics: attributable mortality, attributable years life lost, and environmental health impact. A 10-μg/m 3 increase in PM 2.5 would increase the risk by 0.52% (95% CI: -0.91% to 1.99%) for all-cause mortality, with varying risk estimates per subgroup. High economic burdens were estimated at status quo, with particularly distinct burden difference for age-specific mortality; 0.40 trillion yen (0-64 y.o.) and 1.50 trillion yen (>64 y.o.). If stricter standards, relative to status quo, were to be enforced, i.e. WHO standard, there is a potential to yield economic benefits in the same risk population; 0.26 trillion yen (0-64 y.o.) and 0.98 trillion yen (>64 y.o.). We did not observe any substantial difference with the burden and benefit related to sex-specific mortality. Using the estimated local risk coefficients complemented with the valuation of the risks, policymaking entities will have the opportunity to operate their own HIA to assess the relevant air pollution-related health impacts., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study was to investigate whether non-reassuring foetal status (NRFS) affected an infant's temperament, or if the temperament formed prenatally resulted in an excessive heart rate reaction that was diagnosed as NRFS. We examined the correlation between NRFS and difficulty in holding a baby, and the amount of crying in the one month after birth, which was considered an indicator of the newborn's temperament. We divided the cases with NRFS into positive NRFS and false positive NRFS. NRFS was associated with bad mood, frequent crying for a long duration, and intense crying. After adjustment for other covariates, NRFS was associated with bad mood (odds ratio, OR = 1.15, 95% confidence interval, CI = 1.00-1.33), and intense crying (1.12, 1.02-1.24). In the multi-variable model, positive and false positive NRFS were not clearly associated with neonatal irritability. When stratified by parity, NRFS and false positive NRFS were likely to be positively associated with neonatal irritability in parous women. The clear association between NRFS and intense crying was observed in parous women (multi-variable adjusted OR = 1.46, 95% CI = 1.16-1.83), but not in nulliparae (1.01, 0.91-1.12) (p for effect modification <0.01). Similarly, increased odds of intense crying associated with false positive NRFS were only found in parous women (multi-variable adjusted OR = 1.40, 95% CI = 1.09-1.81) (p for effect modification = 0.03). There was no association observed between positive NRFS and irritability; therefore, NRFS has no effect on an infant's temperament.

Objectives: The aim of this study was to determine whether haemoglobin A1c (HbA1c) level is associated with the incidence of hearing impairment accounting for smoking status and diabetic condition at baseline., Methods: Participants were 131 689 men and 71 286 women aged 30-65 years and free of hearing impairment at baseline (2008) who attended Japanese occupational annual health check-ups from 2008 to 2015. We defined low-frequency hearing impairment at a hearing threshold >30 dB at 1 kHz and high frequency at >40 dB at 4 kHz in the better ear in pure-tone audiometric tests. HbA1c was categorised into seven categories. The association between HbA1c and hearing impairment was assessed using the Cox proportional hazards model., Results: On 5 years mean follow-up, high HbA1c was associated with high-frequency hearing impairment. In non-smokers, HbA1c≥8.0% was associated with high-frequency hearing impairment, with a multivariable HR (95% CI) compared with HbA1c 5.0%-5.4% of 1.46 (1.10 to 1.94) in men and 2.15 (1.13 to 4.10) in women. There was no significant association between HbA1c and hearing impairment in smokers. A J-shaped association between HbA1c and high-frequency hearing impairment was observed for participants with diabetes at baseline. HbA1c was not associated with low-frequency hearing impairment among any participants., Conclusions: HbA1c ≥8.0% of non-smokers and ≥7.3% of participants with diabetes was associated with high-frequency hearing impairment. These findings indicate that appropriate glycaemic control may prevent diabetic-related hearing impairment., Competing Interests: Competing interests: SN is occupational physicians in All Japan Labor Welfare Foundation., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To examine the association between knee pain and function and depressive symptoms in older Japanese adults., Design: Community-based prospective cohort study., Setting: Kurabuchi Town, Gumma Prefecture, Japan., Participants: Individuals aged 65 and older (N = 573; n = 260 men, n = 313 women) without depressive symptoms participated in baseline examinations in 2005 and 2006; 95.6% participated in follow-up interviews (2007-08)., Measurements: Degree of knee pain and functional impairment was assessed at baseline using a self-administered questionnaire in Japanese based on an English version of the Western Ontario and McMaster Universities Osteoarthritis Index. The Geriatric Depression Scale was used to identify depressive symptoms in face-to-face home-visit interviews conducted 2 years later, and the association between knee pain and functional impairment and depressive symptoms was assessed using logistic regression., Results: During the 2-year follow-up, 11.9% of participants developed depressive symptoms, and pain and functional impairment were found to be associated with development of these symptoms. Pain at night while in bed (adjusted odds ratio (aOR) = 2.6, 95% confidence interval (CI) = 1.4-4.9) and difficulty putting on socks (aOR = 3.7, 95% CI: 1.8-7.5), getting into and out of a car (aOR = 3.4, 95% CI = 1.8-6.5), and taking off socks (aOR = 3.1, 95% CI = 1.5-6.5) were found to be most strongly associated with development of depressive symptoms., Conclusion: Examining elderly people's responses to questions about pain at night and difficulties performing daily activities may be an efficient way of identifying those at high risk of developing depressive symptoms., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Fetal heart rate (FHR) monitoring is essential for fetal management during pregnancy and delivery but results in many false-positive diagnoses. Air pollution affects the uterine environment; thus, air pollution may change FHR reactivity. This study assessed the association between exposure to air pollution during pregnancy and FHR monitoring abnormalities using 2005-2010 data from the Japan Perinatal Registry Network database. Participants were 23,782 singleton pregnant women with FHR monitoring, without acidemia or fetal asphyxia. We assessed exposure to air pollutants, including particulate matter (PM), ozone, nitrogen dioxide (NO 2 ), and sulfur dioxide (SO 2 ). In a multi-trimester model, first-trimester PM exposure was associated with false positives in FHR monitoring (odds ratio [OR] per interquartile range (10.7 μg/m 3 ) increase = 1.20; 95% CI: 1.05-1.37), but not second-trimester exposure (OR = 1.05; 95% CI: 0.91-1.21) and third-trimester exposure (OR = 1.06; 95% CI: 0.96-1.17). The association with first-trimester PM exposure persisted after adjustment for exposure to ozone, NO 2 , and SO 2 ; however, ozone, NO 2 , and SO 2 exposure was not associated with false positives in FHR monitoring. First-trimester PM exposure may alter fetal cardiac response and lead to false positives in FHR monitoring.

Background: Ambient air pollution is hypothesized to be a risk factor for hypertensive disorders in pregnancy, one of the major pregnancy complications. Past studies have reported the supporting evidence, however this mainly referred to the Western population, and results from trimester-specific analysis have been varied. In this study, we focused on exposure during the first trimester of pregnancy (placental development stage), and tested the hypothesis among the Japanese population., Methods: We drew on data from the Japan Perinatal Registry Network database, and studied 36,620 singleton pregnant women without medical complications, in western Japan (Kyushu and Okinawa districts) between 2005 and 2010. In addition, data on ozone, suspended particulate matter (SPM), nitrogen dioxide (NO2), and sulfur dioxide (SO2) concentrations were obtained. The nearest monitoring station to the respective birthing hospital was used as a reference point for assigning average concentrations of each pollutant during the first trimester of pregnancy for each woman. The logistic regression model was applied to assess the association between quintiles of each pollutant and hypertensive disorders in pregnancy., Results: Mean concentrations during the first trimester were 41.3 ppb for ozone, 27.4 μg/m(3) for SPM, 11.8 ppb for NO2, and 3.2 ppb for SO2. High exposure to ozone was associated with an increased risk of hypertensive disorders in pregnancy (for highest quintile vs. lowest: odds ratio=1.20, 95% confidence interval=1.01-1.42). With regard to SPM, NO2 and SO2, we did not obtain the results with constant directionality., Conclusions: Ozone exposure during early pregnancy may be a risk factor for hypertensive disorders in pregnancy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Evidence suggests that estrogen plays a preventive role in primary liver cancer development, and it might be thought that isoflavones, which are structurally similar to estrogens and bind to estrogen receptors, are associated with the risk of liver cancer. We investigated this suspected association by measuring plasma concentrations of isoflavones in a nested case-control study of a population-based prospective cohort in Japan., Methods: From 18,628 target participants ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or hepatitis C virus infection at baseline (n = 1,544). Among these, 90 (28 women and 62 men) were newly diagnosed with primary liver cancer from 1993 through 2006; they were matched with 175 controls (54 women and 121 men). Plasma concentrations of isoflavones (genistein, daidzein, glycitein, and equol) were measured using triple quadrupole tandem liquid chromatography-mass spectrometry. The ORs of liver cancer development based on plasma concentrations were estimated with a conditional logistic regression model., Results: Basically, distributions of plasma isoflavone concentrations did not differ between the cases and controls. No statistically significant associations of genistein, daidzein, glycitein, and equol with primary liver cancer risk were found in either women or men., Conclusions: In middle-aged Japanese women and men with hepatitis virus infection, plasma isoflavones were unassociated with the occurrence of primary liver cancer., Impact: The role of isoflavones in liver carcinogenesis merits further study using both biomarkers and data on dietary intake of isoflavones. Cancer Epidemiol Biomarkers Prev; 24(3); 532-7. ©2014 AACR., (©2014 American Association for Cancer Research.)

Background: The Japan Environment and Children's Study (JECS) is an ongoing nationwide birth cohort study launched in January 2011. In this progress report, we present data collected in the first year to summarize selected maternal and infant characteristics., Methods: In the 15 Regional Centers located throughout Japan, the expectant mothers were recruited in early pregnancy at obstetric facilities and/or at local government offices issuing pregnancy journals. Self-administered questionnaires were distributed to the women during their first trimester and then again during the second or third trimester to obtain information on demographic factors, physical and mental health, lifestyle, occupation, environmental exposure, dwelling conditions, and socioeconomic status. Information was obtained from medical records in the first trimester and after delivery on medical history, including gravidity and related complications, parity, maternal anthropometry, and infant physical examinations., Results: We collected data on a total of 9819 expectant mothers (mean age = 31.0 years) who gave birth during 2011. There were 9635 live births. The selected infant characteristics (singleton births, gestational age at birth, sex, birth weight) in the JECS population were similar to those in national survey data on the Japanese general population., Conclusions: Our final birth data will eventually be used to evaluate the national representativeness of the JECS population. We hope the JECS will provide valuable information on the impact of the environment in which our children live on their health and development.

Background: Evidence of an association between fine particulate matter (PM2.5) and morbidity is limited in Asia. We used a case-crossover design to evaluate the association between short-term exposure to PM2.5 and emergency ambulance dispatches (as a proxy of acute health outcomes), and to calculate the extent to which a 10 μg/m(3) decrease in PM2.5 concentrations would reduce the number of ambulance dispatches., Methods: We used data on emergency ambulance dispatches in Fukuoka City, Japan between 2005 and 2010. Emergency ambulance services are publicly funded and cover the entire city. After excluding ambulance dispatches related to external injuries and pregnancy/childbirth, we analysed data on the remaining 176 123 dispatches. We also collected records of daily concentrations of PM2.5 from one ambient air pollution monitoring station. ORs per 10 μg/m(3) increase in PM2.5 were estimated using conditional logistic regression controlled for ambient temperature and relative humidity., Results: During the study period, the average daily concentration of PM2.5 was 20.3 μg/m(3). Exposure to PM2.5 was associated with emergency ambulance dispatches in general (lag0-1; OR=1.008 (95% CI 1.002 to 1.014)) and with dispatches due to respiratory diseases (lag0-1; OR=1.027 (1.007 to 1.048)). No association was observed for dispatches due to cardiovascular diseases. We estimated that a 10 μg/m(3) decrease in PM2.5 concentrations would have led to approximately 260 (estimated range=70-460) fewer ambulance dispatches in Fukuoka for 2012., Conclusions: Providing further evidence on the short-term health effects of PM2.5 exposure, we found that exposure was associated with an increased number of emergency ambulance dispatches. The effect was, however, relatively small., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)