Language：English  

DOI： 10.1111/irv.13221.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s13006-023-00592-y

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2188/jea.JE20230210.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12884-023-06014-5.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/apa.16998

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-023-02851-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/all.15916.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-023-44313-1.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/jcm12185929.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1136/archdischild-2023-325600

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00467-023-06131-5

Language：English   Publishing type：Research paper (scientific journal)  

We measured the association between history of influenza vaccination by age 2 years and influenza virus (IFV) infection at ages 3 and 4 years by relative risk reduction. We also examined the association between history of IFV infection by age 2 years and recurrent IFV infection at age 3 years. This study included 73,666 children from a large Japanese birth cohort. Among children vaccinated never, once or twice when aged under 2 years, 16.0%, 10.8% and 11.3%, respectively, had been infected with IFV by age 3 years, and 19.2%, 14.5% and 16.0%, respectively, by age 4 years. Compared with no history of influenza vaccination, vaccination at ages 1 and/or 2 years reduced the risk of IFV infection at age 3 by 30%-32% and at age 4 by 17%-24%. The relative risk of recurrent IFV infection at ages 3 and 4 years increased in proportion to the number of prior infections by age 2. One-season-prior influenza vaccination history reduced the IFV infection risk at age 3 years by 25%-42%. Influenza vaccination most effectively protected children at age 3 who lacked older sibling(s) and did not attend nursery school. One-season-prior IFV infection increased the relative risk of recurrent infection at age 3 years (1.72-3.33). In conclusion, influenza vaccination-induced protection may partly extend to the next season. Owing to the relative risk reduction by influenza vaccination and the increased relative risk of IFV infection from prior-season infection, annual influenza vaccination is recommended.

DOI： 10.1016/j.ypmed.2023.107599

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.pmedr.2023.102391

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-023-02796-8

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-023-38524-9.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00431-023-05118-6.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-023-02723-x

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.alit.2023.01.003

Language：English   Publishing type：Research paper (scientific journal)  

Although it remains debatable, exogenous oxytocin, commonly used for labour induction and augmentation, reportedly increases risks of neurodevelopment delay, attention-deficit/hyperactivity disorder, and autism spectrum disorder among children prenatally exposed to exogenous oxytocin. However, only few studies have objectively examined exogenous oxytocin's impact on early childhood development through scoring evaluations. This study investigated the association between exogenous oxytocin exposure and neurodevelopment in 3-year-old children using the Ages and Stages Questionnaires, Third Edition. In this nationwide prospective cohort study, we extracted data from 104,062 foetal records regarding exogenous oxytocin use during labour from the Japan Environment and Children's Study. Participants completed questionnaires throughout the pregnancy and postpartum periods. Outcomes comprised the developmental status less than each cut-off value for the five domains of the Ages and Stages Questionnaire, Third Edition. We conducted multivariable logistic regression analyses on the data of 55,400 children after controlling for confounders. Among the 55,400 included women, 19.0% (n = 10,506) used exogenous oxytocin during labour and 81.0% (n = 44,894) did not. Children exposed to exogenous oxytocin showed no significantly increased risk of developmental delay in any domain (communication: odds ratio [OR] 1.04, 95% confidence interval [CI] 0.92-1.16; gross motor: OR 0.97, 95% CI 0.87-1.08; fine motor: OR 1.00, 95% CI 0.92-1.09; problem-solving: OR 1.02, 95% CI 0.94-1.11; personal-social: OR 0.91, 95% CI 0.80-1.03).   Conclusion: Exogenous oxytocin for labour induction did not adversely affect early childhood development. Further studies accounting for the degree of exogenous oxytocin exposure are required to confirm these results. What is Known: • In developed countries, labour is induced in 20-25% of all pregnancies, for which oxytocin is commonly used. • Studies have associated risks of neurodevelopment delay, attention-deficit/hyperactivity disorder, and autism spectrum disorder with exposure to exogenous oxytocin. What is New: • Evaluation with the Ages and Stages Questionnaire, Third Edition, revealed that exogenous oxytocin use did not adversely affect early childhood development. • This prospective study reinforced the lack of evidence of an association between exogenous oxytocin use and early childhood development after adjustment for confounding and rigorous bias elimination.

DOI： 10.1007/s00431-023-05079-w

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fnut.2023.1203669

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English  

DOI： 10.1016/j.reth.2023.05.007

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0276090

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-023-36484-8

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s43856-023-00314-9 Free PMC article

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12887-023-04128-5 Free PMC article

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10157-023-02370-w

Language：English  

DOI： 10.1186/s12884-023-05810-3

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/pai.13956

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.16686

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12602-023-10086-2

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/microorganisms11051246

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.1080/14767058.2023.2209251

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jad.2023.02.088

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12884-023-05578-6

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/pai.13949

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-023-33653-7

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00431-023-04832-5

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/cea.14286

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.stemcr.2023.02.005

Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1589/jpts.35.252

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12887-023-03878-6

Language：English   Publishing type：Research paper (scientific journal)  

The association between maternal pre-pregnancy smoking status and asthma risk is unclear. This study aimed to investigate the association between pre- and post-pregnancy maternal smoking status and bronchial asthma at 3 years of age in a large birth cohort. Data of 75,411 mother-child pairs from the Japan Environment and Children's Study (JECS) were analysed using multivariate logistic regression analysis. Overall, 7.2% of the children had bronchial asthma. The maternal smoking status before childbirth was as follows: Never = 60.0%, Quit before recognising current pregnancy = 24.1%, Quit after finding out about current pregnancy = 12.3%, and Still smoking = 3.6%. Children of mothers who sustained smoking during pregnancy had an increased risk of bronchial asthma at 3 years of age even after adjusting for pre- and postnatal covariates (adjusted odds ratio [aOR] 1.34, 95% confidence interval [CI] 1.15-1.56). Children of mothers who quit before (aOR 1.09, 95% CI 1.02-1.18) or after (aOR 1.11, 95% CI 1.01-1.23) recognising the current pregnancy had an increased risk of bronchial asthma at 3 years of age. Maternal smoking throughout pregnancy and smoking exposure pre-pregnancy or in early pregnancy increases the risk of bronchial asthma in children.

DOI： 10.1038/s41598-023-30304-9

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fgwh.2022.921361

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cch.13107

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/hsr2.1036

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/hsr2.1036

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The current study aimed to assess the association between low maternal protein intake during pregnancy and child developmental delay at age 3 years. METHODS: This research used data obtained from the Japan Environment and Children's Study. In total, we analyzed 77,237 mother-child pairs. Dietary intake was assessed using the Food Frequency Questionnaire. Developmental outcomes at age 3 years were evaluated with the Japanese version of the Ages and Stages Questionnaire, Third Edition. A multivariate logistic regression analysis was performed to assess the association between maternal protein intake during pregnancy and child development delays at age 3 years. RESULTS: Based on the protein-to-total energy intake ratio during early pregnancy, the participants were categorized into three groups: <9.39% (>2 standard deviation below the mean), the severely low protein (SLP) group; 9.39-<13%, the low protein group; and ≥13%, the normal protein group. After adjusting for potential confounding factors, SLP intake was found to be significantly correlated with a higher risk of developmental delay according to the communication, fine motor and problem-solving skill domains. CONCLUSIONS: SLP intake caused by inadequate diet during early pregnancy was associated with a higher risk of child developmental delay at age 3 years. IMPACT: Animal studies have shown that maternal protein restriction during pregnancy and lactation causes abnormal brain development among offspring. Birth cohort studies to date have not assessed the effects of maternal low protein exposure during pregnancy on child development. Severely low protein intake during early pregnancy was associated with a higher risk of child developmental delay at age 3 years. Since nutritional imbalance in early pregnancy affects not only fetal growth but also postnatal neurodevelopment, nutritional management before pregnancy is considered important.

DOI： 10.1038/s41390-022-02435-8

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.alit.2023.01.003

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-022-24359-

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-022-24915-x

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/1346-8138.16686

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/14767058.2022.2130237

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-022-26748-0

Language：English   Publishing type：Research paper (scientific journal)  

The association between endotoxin and allergic rhinitis (AR) is not conclusive. The aim of this study was to determine the association between endotoxin and house dust mite (HDM) allergens in dust, and HDM sensitization and AR among Japanese infants. This study included 4188 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. Dust was collected from children's mattresses at age 18 months and endotoxin and HDM allergen levels were measured. A logistic regression model was used to analyze the association between endotoxin or HDM allergen and the sensitization to HDM (specific-IgE) at age 2 and AR at age 3. The median (interquartile range) endotoxin level was 375.1(186.9-826.5) EU/m2 and the Der 1 (Der p 1 + Der f 1) level was 51.2 (14.8-168.6) ng/m2. There were significant positive associations between endotoxin and HDM sensitization (Der f 1, adjusted odds ratio [aOR] quartile [Q] 4 vs. Q1, 1.44, 95% CI, 1.04-2.00; Der p 1, aOR Q4 vs. Q1, 1.56, 95% CI, 1.12-2.16). There were also significant positive associations between Der 1 exposure and HDM sensitization (Der f 1, aOR Q3 vs. Q1, 1.75, 95% CI, 1.26-2.44; aOR Q4 vs. Q1, 2.98, 95% CI, 2.15-4.13; Der p 1, aOR Q3 vs. Q1, 1.91, 95% CI, 1.37-2.66; aOR Q4 vs. Q1, 2.91, 95% CI, 2.09-4.05). There were, however, no associations between endotoxin or Der 1 and AR. In the population residing mostly in non-farming settings, both endotoxin and HDM allergens in dust were associated with an increased risk of HDM allergen sensitization, but not with AR.

DOI： 10.3390/ijerph192214796

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

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

DOI： 10.1038/s41598-022-23849-8

Other Link： https://www.nature.com/articles/s41598-022-23849-8

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Levels of peanut protein in dust have been reported to be associated with sensitization and allergy to it, so controlling food protein in dust may help prevent food allergy. However, studies of factors associated with egg protein levels in dust are scarce. This study aimed to determine the factors contributing to egg protein levels in dust. METHODS: This cross-sectional study included 159 participants in the Sub-Cohort Study of the Japan Environment and Children's Study in Yamanashi Prefecture at a 6 year follow up. House dust at 6 years was collected and egg protein concentrations were measured for whole egg protein. Household factors, including the maternal frequency of egg consumption, were assessed by questionnaires. A linear regression model was used to analyze the effect of household environmental factors on egg protein in dust. RESULTS: In multivariate analysis, frequent maternal egg consumption (≥5 times a week) was associated with higher egg protein concentrations in house dust (β = 0.96, P = 0.01). The egg protein load was significantly associated with a higher number of cohabitants (≥5, β = 0.85, P = 0.02) in addition to frequent maternal egg consumption. Among the participants, 140 (88.1%) had no egg allergy, 15 (9.4%) were egg tolerant, and 4 (2.5%) had an egg allergy at 6 years old. There was no significant association between the current egg allergy status and egg protein concentrations in dust. CONCLUSIONS: The frequency of maternal egg consumption and the number of inhabitants are contributing factors to egg protein levels in dust.

DOI： 10.1111/ped.15372

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12889-022-13805-6

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMJ  

Background

Disinfectants are widely used in the medical field, particularly recently because of the coronavirus pandemic, which has led to an increase in their use by both medical professionals and the general population. The objective of this study was to examine whether occupational disinfectant use during pregnancy was associated with the development of allergic disease in offspring at 3 years.

Methods

We used data from 78 915 mother/child pairs who participated in the Japan Environment and Children’s Study, which is a prospective birth cohort recruited between January 2011 and March 2014. We examined the associations between maternal disinfectant use during pregnancy and allergic diseases (asthma, eczema and food allergies) in children after adjustment for covariates including maternal postnatal return to work when the child was 1 year old by multivariate logistic regression.

Results

Compared with those who never used disinfectants, participants who used disinfectant every day had a significantly higher risk of asthma in their offspring (adjusted OR 1.18, 95% CI 1.05 to 1.33 for 1–6 times a week; adjusted OR 1.26, 95% CI 1.05 to 1.52 for every day). The associations between disinfectant exposure and eczema were similar to those of asthma (adjusted OR 1.16, 95% CI 1.02 to 1.31 for 1–6 times a week; adjusted OR 1.29, 95% CI 1.06 to 1.57 for every day). We found a significant exposure-dependent relationship (p for trend &lt;0.01). There were no significant associations between disinfectant use and food allergies.

Conclusion

Disinfectant use by pregnant women may be a risk factor for asthma and eczema in offspring. As disinfectants are an effective tool in the prevention of infectious diseases, replication of this study and further research into the mechanisms are warranted.

DOI： 10.1136/oemed-2021-108034

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)   Publisher：公益財団法人 健康・体力づくり事業財団  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-021-01595-3

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)   Publisher：日本発育発達学会  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

This study aimed to evaluate the association of neonatal transfer with the risk of neurodevelopmental outcomes at 3 years of age. Data were obtained from the Japan Environment and Children’s Study. A general population of 103,060 pregnancies with 104,062 fetuses was enrolled in the study in 15 Regional Centers between January 2011 and March 2014. Live-born singletons at various gestational ages, including term infants, without congenital anomalies who were followed up until 3 years were included. Neurodevelopmental impairment was assessed using the Ages and Stages Questionnaire, third edition (ASQ-3) at 3 years of age. Logistic regression was used to estimate the adjusted risk and 95% confidence interval (CI) for newborns with neonatal transfer. Socioeconomic and perinatal factors were included as potential confounders in the analysis. Among 83,855 live-born singletons without congenital anomalies, 65,710 children were studied. Among them, 2780 (4.2%) were transferred in the neonatal period. After adjustment for potential confounders, the incidence of neurodevelopmental impairment (scores below the cut-off value of all 5 domains in the ASQ-3) was higher in children with neonatal transfer compared with those without neonatal transfer (communication: 6.5% vs 3.5%, OR 1.42, 95% CI 1.19–1.70; gross motor: 7.6% vs 4.0%, OR 1.26, 95% CI 1.07–1.49; fine motor: 11.3% vs 7.1%, OR 1.19, 95% CI 1.03–1.36; problem solving: 10.8% vs 6.8%, OR 1.29, 95% CI 1.12–1.48; and personal-social: 6.2% vs 2.9%, OR 1.52, 95% CI 1.26–1.83).

   Conclusion: Neonatal transfer was associated with a higher risk of neurodevelopmental impairment at 3 years of age.<table><tbody><tr><td colspan="2">What is Known:• Neonatal transfer after birth in preterm infants is associated with adverse short-term outcomes.• Long-term outcomes of outborn infants with neonatal transfer in the general population remain unclear.</td> </tr><tr><td colspan="2">What is New:• This study suggests that neonatal transfer at birth is associated with an increased risk of neurodevelopmental impairment.• Efforts for referring high-risk pregnant women to higher level centers may reduce the incidence of neonatal transfer, leading to improved neurological outcomes in the general population.</td> </tr></tbody></table>

DOI： 10.1007/s00431-022-04450-7

Other Link： https://link.springer.com/article/10.1007/s00431-022-04450-7/fulltext.html

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: It is inconclusive whether prenatal negative life events are a risk for the development of allergic diseases in children or whether social capital modifies the association. The objective of this study was to examine whether women's experiences of such events during pregnancy were associated with the development of allergic diseases in their offspring at 3 years old and whether social capital moderated this association. METHODS: We used data from 81,337 mother-child pairs who participated in the Japan Environment and Children's Study. This is a prospective birth cohort recruited between January 2011 and March 2014. We examined the associations between prenatal maternal negative life events (e.g., bereavement, financial, and marital problems) during pregnancy and allergic diseases (asthma, eczema, and food allergies) in children after adjustment for covariates using multivariate logistic regression. We also examined interactions between these life events and social capital, measured as two items, social cohesion and social support. RESULTS: Prenatal negative life events were significantly associated with doctor-diagnosed asthma at 3 years old with a dose-response relationship (one life event vs. none: adjusted odds ratio 1.13, 95% confidence interval [CI]: 1.07-1.20; two life events vs. none: adjusted odds ratio 1.24, 95% CI: 1.13-1.36; three or more life events vs. none: adjusted odds ratio 1.26, 95% CI: 1.10-1.46; p for trend <0.01). Similar results were observed for eczema and food allergies. There were no interactions between life events and social capital. CONCLUSION: Prenatal negative life events may be a risk factor for allergies in children. There was no modification of the effect of these events by social capital.

DOI： 10.1159/000524854

PubMed

Authorship：Last author   Language：English   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/jdi.13723

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdi.13723

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. METHODS: Our analysis used information of 91,049 mother-child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, -1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. RESULTS: Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. CONCLUSION: Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

DOI： 10.1016/j.envres.2021.112470

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s43856-022-00101-y

Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

Aims/Introduction Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is associated with adverse pregnancy outcomes. This study aimed to explore the associations between glycated hemoglobin (HbA1c) levels at the early stage of pregnancy and the GDM risk among non-diabetic women in a nationwide study in Japan. In addition, the relationship between GDM and adverse pregnancy outcomes was also analyzed. Materials and Methods This cohort study (n = 89,799) used data from the Japan Environment and Children's Study. We stratified the participants into four groups according to HbA1c levels at an early stage of pregnancy. We investigated the association of HbA1c at an early stage of pregnancy with the risk of GDM, and of GDM with the risk of some representative adverse pregnancy outcomes, using the multiple logistic regression model with adjustment for potential confounders. Results The adjusted odds ratio for GDM per 0.1 percentage point increase in HbA1c (%) was 1.20. The adjusted odds ratio for developing GDM was significantly increased in women from the HbA1c 5.0-5.4% category. GDM significantly increased the adjusted odds ratio for adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, polyhydramnios and premature birth. Conclusions High-normal HbA1c levels at the early stage of pregnancy are significantly associated with GDM risk in women in Japan. GDM was significantly associated with adverse pregnancy outcomes.

DOI： 10.1111/jdi.13701

Web of Science

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

IMPORTANCE: It is unclear to what extent the duration of screen time in infancy is associated with the subsequent diagnosis of autism spectrum disorder. OBJECTIVE: To examine the association between screen time in infancy and the development of autism spectrum disorder at 3 years of age. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data from mother-child dyads in a large birth cohort in Japan. This study included children born to women recruited between January 2011 and March 2014, and data were analyzed in December 2020. The study was conducted by the Japan Environment and Children's Study Group in collaboration with 15 regional centers across Japan. EXPOSURES: Screen time at 1 year of age. MAIN OUTCOMES AND MEASURES: The outcome variable, children diagnosed with autism spectrum disorder at 3 years of age, was assessed using a questionnaire administered to mothers of the participating children. RESULTS: A total of 84 030 mother-child dyads were analyzed. The prevalence of children with autism spectrum disorder at 3 years of age was 392 per 100 000 (0.4%), and boys were 3 times more likely to have been diagnosed with autism spectrum disorder than were girls. Logistic regression analysis showed that among boys, when "no screen" was the reference, the adjusted odds ratios were as follows: less than 1 hour, odds ratio, 1.38 (95 % CI, 0.71-2.69; P = .35), 1 hour to less than 2 hours, odds ratio, 2.16 (95 % CI, 1.13-4.14; P = .02), 2 hours to less than 4 hours, odds ratio, 3.48 (95% CI, 1.83-6.65; P < .001), and more than 4 hours, odds ratio, 3.02 (95% CI, 1.44-6.34; P = .04). Among girls, however, there was no association between autism spectrum disorder and screen time. CONCLUSIONS AND RELEVANCE: Among boys, longer screen time at 1 year of age was significantly associated with autism spectrum disorder at 3 years of age. With the rapid increase in device usage, it is necessary to review the health effects of screen time on infants and to control excessive screen time.

DOI： 10.1001/jamapediatrics.2021.5778

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/rmb2.12457

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.3389/fnut.2022.812469

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00431-021-04232-7

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: N-3 polyunsaturated fatty acids (n-3 PUFAs), which are an important nutrient for humans, are particularly essential to the growth and development of the central nervous system (CNS) in fetuses and infants. Consequently, sufficient n-3 PUFA intake by mothers during pregnancy is considered to contribute to CNS development in their infants. CNS development is known to be associated with sleep, but no large epidemiological studies have yet confirmed that n-3 PUFA intake during pregnancy is associated with infants' sleep. METHODS: After exclusion and multiple imputation from a dataset comprising 104 065 records from the Japan Environment and Children's Study (JECS), we examined 87 337 mother-child pairs for the association between mothers' fish and n-3 PUFA intakes and risk of their infants sleeping less than 11 h at 1 year of age. RESULTS: Multiple logistic regression analysis with the lowest quintile used as a reference revealed odds ratios for the second through fifth quintiles of 0.81 (95% confidence interval [95% CI] 0.76-0.87), 0.81 (95% CI 0.76-0.87), 0.78 (95% CI 0.72-0.84), and 0.82 (95% CI 0.76-0.88) for fish intake (p for trend < 0.001) and 0.90 (95% CI 0.84-0.97), 0.88 (95% CI 0.81-0.94), 0.88 (95% CI 0.82-0.95), and 0.93 (95% CI 0.86-0.998) for n-3 PUFA intake (p for trend = 0.04). CONCLUSIONS: Low fish intake during pregnancy may increase the risk of infants sleeping less than 11 h at 1 year of age. This relationship may have been mediated by maternal n-3 PUFA intake and infant neurodevelopment, but further evidence from interventional and other studies is needed to determine the appropriate level of fish intake during pregnancy. TRIAL REGISTRATION: The Japan Environment and Children's Study, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035091 (Registration no. UMIN000030786).

DOI： 10.1007/s00394-021-02671-4

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Barley contains abundant soluble beta-glucan fibers, which have established health benefits. In addition, the health benefits conferred by the gut bacteria have attracted considerable interest. However, few studies have focused on the barley consumption and gut bacteria of the Japanese population. In this study, we aimed to identify the relationship between the barley consumption and gut bacteria composition of the Japanese population. METHODS: In total, 236 participants were recruited in Japan, and 94 participants with no complications of diabetes, hypertension, or dyslipidemia were selected for the study. We analyzed fecal samples from the participants, their medical check-up results, and responses to questionnaires about dietary habits. The participants were grouped according to their median barley consumption. Then, we assessed the relative abundance of 50 genera. Characteristic bacteria were evaluated for their relationship with barley consumption by multiple regression analysis, adjusted for disease and dietary habits, in all participants. We also analyzed the networks and clustering of the 20 selected genera. RESULTS: According to the comparison between barley groups, Bifidobacterium, Butyricicoccus, Collinsella, Ruminococcus 2, and Dialister were characteristic candidate bacterias of the group that consumed large amounts of barley (P < 0.05). The relationship between barley consumption and Bifidobacterium remained after adjusting for disease and dietary habits, and that of Butyricicoccus remained after adjusting for disease. Furthermore, network and cluster analyses revealed that barley consumption was directly correlated with Bifidobacterium and Butyricicoccus. CONCLUSIONS: Barley consumption generates changes in the intestinal bacteria of the Japanese population. We found that Bifidobacterium and Butyricicoccus abundance was positively associated with barley consumption.

DOI： 10.1186/s40795-022-00500-3

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12884-021-04347-7

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.orcp.2021.12.003

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.chiabu.2021.105430

Language：English   Publishing type：Research paper (scientific journal)  

Apgar score (AS) is a well-established tool for assessing viability of newborns, and its association with subsequent child development has been suggested. We aimed to assess whether Apgar scores (ASs) ≥ 7 (generally considered normal) are associated with the developmental status at 3 years of age while adjusting for perinatal and socioeconomic confounders. We extracted the data of ASs at 1 and 5 min among participants of the Japan Environment and Children's Study datasets, which were used in this nationwide cohort study. The outcomes comprised developmental status that was less than each cutoff value for the following five domains of the Ages & Stages Questionnaire (Japanese version, 3rd edition): communication, gross and fine motor, problem-solving, and personal-social domains. For this objective, we conducted multivariable logistic regression analyses on the data of 54,716 children. Compared with ASs ≥ 9 at 5 min, the adjusted odds ratios (aOR) for delayed development in children with ASs ≤ 8 were 1.31 (95% confidence interval, 1.11-1.56), 1.20 (1.04-1.38), and 1.16 (1.01-1.34), respectively, for gross and fine motor, and problem-solving domains. Among neonates with ASs ≤ 8 at 1 min, when those with ASs ≤ 8 at 5 min were compared with those with ASs ≥ 9 at 5 min, the aOR for gross motor domain was 1.34 (1.11-1.61).Conclusion: ASs ≤ 8 compared with those ≥ 9 at 5 min, even considering the change of AS from 1 to 5 min, were associated with increased ORs for developmental delay in 3-year-olds. Even ASs that are considered normal might affect the subsequent development. What is Known: • Apgar score is a general tool for evaluating the vitality of newborns. It is also basically measured at 1 minute and 5 minutes after birth and the scores of ≥7 are considered normal. • The Apgar scores at each minute affect clinical findings of neonates after birth and the subsequent long-term development. What is New: • Neonates with Apgar scores of ≤8 at 5 minutes compared with those of ≥9, including the change in Apgar score from 1 minute to 5 minutes, are associated with increased odds ratios for developmental status at 3 years of age adjusting for perinatal and socioeconomic confounders.

DOI： 10.1007/s00431-021-04249-y

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The hygiene hypothesis assumes a low incidence of allergic diseases in families engaging in farming work. However, a few studies have indicated rural life as a potential risk factor for atopic dermatitis (AD). Using a large Japanese birth cohort dataset, we calculated the accumulated incidence of AD in children aged 6 months and 1, 2, and 3 years by family business and the hazard ratio. We adjusted for confounding factors. The father's job was considered the family business. We analysed data on 41,469 father-child pairs at 6 months of age, 40,067 pairs at 1 year, 38,286 pairs at 2 years, and 36,570 pairs at 3 years. We found the highest accumulated incidence of AD among children with fathers engaged in primary industry, with 2.5% at the age of 6 months, 6.6% at 1 year, 12.0% at 2 years, and 15.4% at 3 years. Among primary industry occupations, forestry was associated with the highest incidence of AD across these ages. The hazard ratio of AD was also highest for children whose family business was primary industry. In conclusion, the highest incidence and hazard ratio of AD were observed among children whose fathers worked in primary industry.

DOI： 10.3390/ijerph19031761

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

In this study, we aimed to determine the association of neonatal/post-neonatal hypothyroidism with mother's iodine exposure, especially povidone iodine disinfection, and hysterosalpingography. Participants were mother-child pairs in a Japanese birth cohort (n = 100,286). Risk factors of hypothyroidism were supplement intake, seaweed intake, other daily iodine intake, povidone iodine disinfection at delivery, and maternal history of hysterosalpingography, thyroid disease (Graves' disease and Hashimoto's thyroiditis), and medication (thiamazole and levothyroxine). Congenital hypothyroidism (CH) at age 1 year was assessed using a questionnaire. Transient hypothyroidism was defined as elevated thyroid stimulating hormone level at birth and absence of CH at age 1 year. The incidence of CH at age 1 year per 100 children was 1.1 for those born at 22-30 weeks' gestation, 0.17 following povidone iodine disinfection, and 0.07, 0.95, 0.81, 1.17, and 1.15 with a maternal history of hysterosalpingography, Graves' disease, Hashimoto's thyroiditis, thiamazole use, and levothyroxine use, respectively. Odds ratios (95% confidence intervals) of CH at age 1 year for povidone iodine disinfection, hysterosalpingography history, maternal Graves' disease, and maternal Hashimoto's thyroiditis were 1.13 (0.71-1.79), 0.47 (0.07-3.36), 7.06 (3.70-13.5), and 5.93 (2.90-12.1), respectively. For transient hypothyroidism for povidone iodine disinfection and hysterosalpingography history, these values were 1.99 (1.51-2.62) and 0.63 (0.20-1.96), respectively. Maternal thyroid disease greatly increased neonatal/post-neonatal hypothyroidism risk. Povidone iodine disinfection may increase transient hypothyroidism risk but not the risk at 1 year of age. Hysterosalpingography does not increase hypothyroidism risk from birth to age 1 year.

DOI： 10.1507/endocrj.EJ21-0168

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1210/clinem/dgab618

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Background: Daily toothbrushing prevents early childhood caries, but reinforcement depends on facilitative parenting behaviours. Mother-to-infant bonding, the maternal affection towards the infant, is an environmental factor that strongly influences parenting. Aim: This study examined the association between maternal bonding and children's daily toothbrushing frequency. Design: The sample consisted of 83 954 mother-infant pairs at two years postpartum, derived from the initial sample of JECS (cohort study), which included 104 062 foetuses. Maternal bonding disorders were assessed using the Mother-to-Infant Bonding Scale (MIBS). After multiple imputation for missing data, a multinomial logistic regression analysis was conducted with adjustments for several maternal (eg, age at delivery) and child-related (eg, self-performed toothbrushing) variables. Results: The odds ratio (95% confidence interval) for the association of maternal bonding disorders with the low (once per day) and the very low child toothbrushing frequency (<1 per day) was 1.12 (1.07-1.17) and 1.23 (0.91-1.66), respectively, after covariate adjustments. Furthermore, the univariate general linear model showed that the mean MIBS scores significantly decreased as the daily child toothbrushing frequency increased. Conclusions: The prevalence of maternal bonding disorders at one year postpartum was prospectively associated with a lower frequency of child toothbrushing at two years of age.

DOI： 10.1111/ipd.12791

Scopus

PubMed

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/ina.12931

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ina.12931

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Socioeconomic status has been found to be associated with allergic diseases in children, but results are inconsistent. This study aimed to assess the association between household income and the development of allergic disease in children at 3 years old. METHODS: We used data from 72,180 participants from the Japan Environment and Children's Study, which is a prospective birth cohort study with participants recruited from January 2011 to March 2014. We examined the associations between household income and allergic diseases (asthma, eczema, and food allergies) in children, adjusting for covariates using multivariate logistic regression. RESULTS: The percentages of doctor-diagnosed allergies at 3 years old were 7.5% for asthma, 7.2% for eczema, and 6.2% for food allergies. Children from households with an annual income of <2 million yen (approx. 18,000 USD) had a significantly higher risk of doctor-diagnosed asthma and eczema than those from households with an income of 4-6 million yen. The adjusted odds ratios (aORs) were 1.17 (95% confidence interval [CI] 1.03-1.34) and 1.21 (95% CI 1.06-1.39). Children from households with an income of >6 million yen tended to have an increased risk of food allergies (aOR 1.07, 95% CI 0.98-1.15). CONCLUSION: Low household income was a risk for doctor-diagnosed asthma and eczema, suggesting that public health professionals should recognize low-income groups as vulnerable populations for these conditions.

DOI： 10.1159/000519153

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

The eligibility of COVID-19 vaccines has been expanded to children aged 12 and above in several countries including Japan, and there is a plan to further lower the age. This study aimed to assess factors related to parental COVID-19 vaccine hesitancy. A nationwide internet-based cross-sectional study was conducted between May 25 and June 3, 2021 in Japan. The target population was parents of children aged 3–14 years who resided in Japan, and agreed to answer the online questionnaire. Parental COVID-19 vaccine hesitancy (their intention to vaccinate their child) and related factors were analyzed using logistic regression models. Interaction effects of gender of parents and their level of social relationship satisfaction related to parental vaccine hesitancy was tested using log likelihood ratio test (LRT). Social media as the most trusted information source increased parental vaccine hesitancy compared to those who trusted official information (Adjusted Odds Ratio: aOR 2.80, 95% CI 1.53–5.12). Being a mother and low perceived risk of infection also increased parental vaccine hesitancy compared to father (aOR 2.43, 95% CI 1.57–3.74) and those with higher perceived risk of infection (aOR 1.55, 95% CI 1.04–2.32) respectively. People with lower satisfaction to social relationships tended to be more hesitant to vaccinate their child among mothers in contrast to fathers who showed constant intention to vaccinate their child regardless of the level of satisfaction to social relationship (LRT p = 0.021). Our findings suggest that dissemination of targeted information about COVID-19 vaccine by considering means of communication, gender and people who are isolated during measures of social distancing may help to increase parental vaccine acceptance.

DOI： 10.1371/journal.pone.0261121

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Both maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) influence maternal and pediatric outcomes. We sought to clarify the impact of prepregnancy BMI-specific GWG and its patterns on the risk of low birth weight (LBW) or macrosomia using data from a large nationwide study in Japan. METHODS: This cohort study (n = 98,052) used data from the Japan Environment and Children's Study (JECS). The outcome variables in this study were LBW and macrosomia. We stratified the subjects into groups according to prepregnancy BMI. RESULTS: GWG from pre-pregnancy to the first trimester had a small effect on the risk of LBW and macrosomia. From the first to second trimesters, insufficient GWG was associated with the risk of LBW, and from the second trimester to delivery, a GWG of less than 2 kg was associated with the risk of LBW. These associations were commonly observed in all prepregnancy BMI categories. Irrespective of the GWG from pre-pregnancy to the first trimester, GWG from the first to second trimesters affects LBW and/or macrosomia. Irrespective of the GWG from the first to second trimesters, GWG from the second trimester to delivery affects LBW and/or macrosomia. LBW or macrosomia was associated with the prevalence of a sustained low or high BMI percentile until three years of age, respectively. CONCLUSIONS: The present large national cohort study indicates that the risk of LBW or macrosomia is associated with GWG in women in Japan; the significance of this risk depends on the GWG patterns.

DOI： 10.1038/s41366-021-00947-7

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Maternal smoking during pregnancy is a risk factor for childhood obesity; however, the combined effect of secondhand smoking during pregnancy on children in the early years is unclear. We examined the effects of maternal active and secondhand smoking during pregnancy on childhood obesity in a large population-based cohort. A nested case-control study originating from the Japan Environment and Children's Study was performed. The maternal smoking status was collected via self-administered questionnaires during mid/late pregnancy. Obesity in children was determined based on BMI measured at 3 years of age. In total, 4875 cases and 19,491 controls were included in the analyses. Conditional logistic regression models with a significance level of 5% (two-tailed test) were used to test the association. The proportion of mothers who continued smoking and who were exposed to secondhand smoking daily during pregnancy were 3.9% and 13.0% in cases and 2.9% and 10.8% in controls, respectively. Continuous maternal smoking was associated with increased odds of obesity compared to those who never smoked or quit smoking before the pregnancy (adjusted odds ratio, 1.39; 95% confidence interval, 1.01-1.92). The odds increased further when combined with secondhand smoking. The promotion of non-smoking among family members, in public and workplace could benefit pregnant women and offspring.

DOI： 10.3390/ijerph182312506

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1016/j.scitotenv.2021.148643

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Scarce knowledge is available on the relationship between maternal chemical exposure during pregnancy and foetal deaths. We studied the association of spontaneous abortions and stillbirths with occupational or daily maternal exposure to chemicals commonly used by pregnant women. Data from the Japan Environment and Children's Study (JECS), a nationwide prospective birth cohort study, were used. The participants of the study were asked about the frequency of their use of gasoline, pesticides, hair dye, and chlorine bleach during the first and the second to third trimesters of pregnancy. We investigated the relationship between the frequency of the use of chemicals and foetal death. Of the 104,065 foetuses, 923 (0.91%) were spontaneous abortions and 379 (0.37%) were stillbirths. Any type of exposure during the first trimester was not significantly associated with spontaneous abortions. Nevertheless, a more than weekly occupational use of hair dye from the first to the second/third trimester was significantly associated with stillbirth. The results of this study suggest that the frequent use of hair dye during pregnancy can have severe adverse effects on the foetus. These findings can help pregnant women, especially hairdressers, refrain from the continuous use of hair dyes.

DOI： 10.3390/ijerph182211748

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jid.2021.05.011

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/hsr2.421. eCollection 2021 Dec

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Hair dye use frequently induces allergic contact dermatitis, and on rare occasions induces immunoglobulin E-mediated immediate urticaria, anaphylaxis, and asthma. The effects of hair dye use during pregnancy on offspring have been studied for carcinogenicity, but not for development of allergies. This study aimed to assess the association between hair dye use during pregnancy and allergic disease in children at 3 years old. METHODS: Data of 77,303 participants from the Japan Environment and Children's Study, which is a prospective birth cohort recruited from January 2011 to March 2014, were used. We examined the associations between using hair dye during pregnancy and allergic diseases (food allergy, asthma, atopic dermatitis and allergic rhinitis) in children after adjustment for covariates by multivariable logistic regression. RESULTS: Among mothers who were exposed to hair dye during pregnancy, 50.0% were exposed in hair salons, 21.3% had home use, and 9.5% had occupational exposure. The percentages of doctor-diagnosed allergies at 3 years old were 6.3% for food allergies, 7.7% for asthma, 7.3% for atopic dermatitis, and 4.6% for allergic rhinitis. In univariable analyses, hair dye use at home and occupational exposure was significantly associated with asthma respectively (odds ratio [OR] 1.15, 95% CI 1.07-1.24 for at home; OR 1.18, 95% CI 1.08-1.28 for occupational exposure). Hair dye use at home were significantly associated with doctor-diagnosed allergic rhinitis at 3 years old (OR 1.12, 95% CI 1.02-1.22). After adjustment for covariates, these associations for asthma decreased and were no longer significant (aOR 1.06, 95% CI 0.98-1.14 for at home; aOR 1.09, 95% CI 1.00-1.20 for occupational exposure, p = 0.057), also for allergic rhinitis (aOR 1.07, 95% CI 0.97-1.19). Doctor-diagnosed allergic rhinitis at 3 years old was significantly associated with hair dye use at home in the most frequent use group (aOR for quite often versus never 1.78, 95% CI 1.22-2.60). CONCLUSION: Both home and occupation use of hair dye during pregnancy showed a trend of increased odds of allergic rhinitis and asthma in offspring at 3 years. However, the only association that reached significance was in frequency of use analyses between the highest frequency of home hair dye users and allergic rhinitis.

DOI： 10.1016/j.envres.2021.111530

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/jjns.12437

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The effects of maternal ritodrine hydrochloride administration (MRA) during pregnancy on fetuses and offspring are not entirely clear. The present study aimed to evaluate the association between MRA and childhood wheezing using data from a nationwide Japanese birth cohort study. METHODS: This study analyzed the data of the participants enrolled in the Japan Environment and Children's Study, a nationwide prospective birth cohort study, between 2011 and 2014. Data of women with singleton live births after 22 weeks of gestation were analyzed. The participants were divided according to MRA status. Considering childhood factors affecting the incidence of wheezing, including smoking environment and childhood viral infections, a logistic regression model was used to calculate odds ratios for "wheezing ever," diagnosis of asthma in the last 12 months, and "asthma ever" in women with MRA, with women who did not receive MRA as the reference. Additionally, participants were stratified by term births, and odds ratios for outcomes were calculated using a logistic regression model. RESULTS: A total of 68,123 participants were analyzed. The adjusted odds ratio for wheezing was 1.17 (95% confidence interval, 1.12-1.22). The adjusted odds ratios for the other outcomes did not significantly increase after adjusting for childhood factors. The same tendency was confirmed after excluding women with preterm births. CONCLUSION: MRA was associated with a slightly increased incidence of childhood wheezing up to three years, irrespective of term or preterm birth status. It is important that perinatal physicians consider the potential effects of MRA on the offspring's childhood health.

DOI： 10.1111/pai.13545

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.alit.2021.05.003

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. METHODS: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. RESULTS: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1-10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270-1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341-2.078; asthma: 1-10 cigarettes/day: aOR 1.389, 95% CI 1.087-1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045-2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083-1.256; asthma: aOR 1.258, 95% CI 1.075-1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739-2.317; asthma: aOR 1.995, 95% CI 1.528-2.605). CONCLUSIONS: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.

DOI： 10.1016/j.alit.2021.04.008

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

<title>Abstract</title>We examined the association between maternal air purifier use during pregnancy and neurodevelopmental delay in toddlers by analysing data from 82,457 mother-toddler pairs. Air purifier use was measured using a simple yes/no question. Developmental delays at 1.5, 2.0, 2.5, and 3.0 years were assessed using the Ages and Stages Questionnaire, Third Edition. Generalized additive mixed model analysis with 21 covariates revealed that air purifier use was associated with lower prevalence of developmental delay in all five areas—communication, gross motor, fine motor, problem solving, and personal-social—at all four time points (adjusted risk ratios ranged from 0.827 to 0.927, and only one 95% confidence interval crossed the reference). These findings suggest a negative association between air purifier use during pregnancy and neurodevelopmental delay in toddlers.

Trial registration: UMIN000030786 (15/01/2018).

DOI： 10.1038/s41598-021-98482-y

Other Link： https://www.nature.com/articles/s41598-021-98482-y

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-021-98311-2

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-021-98311-2

Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1016/j.waojou.2021.100581

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.addbeh.2021.106989

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1177/1945892420983646

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

The aim of this study was to explore the association between maternal allergies and preterm birth by different total immunoglobulin E (IgE) levels. Data of 81 791 pregnant women from the Japan Environment and Children's Study, a prospective birth cohort, were used. Maternal allergic diseases, including a history of bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR), were obtained by self-administered questionnaires. Total serum IgE levels were measured at the first trimester and obstetrical outcomes from medical records transcripts were analyzed. The association between maternal allergic disease and obstetric outcome, including threatened abortion, preterm labor, early preterm birth (22-33 weeks), and late preterm birth (34-36 weeks), were examined by logistic regression. Subgroup analyses were performed by IgE level. Maternal BA and AR were associated with an increased risk of threatened abortion and preterm labor, but high total IgE level was associated with a decreased risk of preterm labor. There was little difference in associations between allergic disease and threatened abortion and preterm labor by total IgE levels. Although there was no significant association between allergic disease and preterm birth, if total IgE was high, AR was significantly associated with a decreased risk of early preterm birth (adjusted odds ratio, 0.60; 95% confidence interval 0.43-0.86). There was significant evidence for differences associated with total IgE levels (P-values for the interaction of the effects of AD and AR on early preterm birth were 0.039 and 0.015, respectively). The effect of allergy on preterm birth might differ depending on the total IgE level.

DOI： 10.1111/ped.14635

Web of Science

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The association between a slower physical growth and poorer neurodevelopment has been established in infants born preterm or small for gestational age. However, this association is inconsistent in term-born infants, and detailed investigations in infancy, when intervention is most beneficial for improving outcomes, are lacking. We therefore examined this association separately by sex during the first year of life in term-born infants. METHODS: Using data collected until children reached 12 months old in an ongoing prospective cohort of the Japan Environment and Children's Study, we analyzed 44,264 boys and 42,541 girls with singleton term-birth. The exposure variables were conditional variables that disentangle linear growth from weight gain relative to linear growth, calculated from the length and weight at birth and 4, 7 and 10 months old. Neurodevelopmental delay was identified using the Japanese-translated version of Ages & Stages Questionnaires, third edition. RESULTS: A reduced risk of neurodevelopmental delay at 6 months old was observed in children with a higher birth weight (adjusted relative risks [aRRs]: 0.91 and 0.93, 95 % confidence intervals [95 % CIs]: 0.87-0.96 and 0.88-0.98 in boys and girls, respectively) and increased linear growth between 0 and 4 months old (aRRs: 0.85 and 0.87, 95 % CIs: 0.82-0.88 and 0.83-0.91 in boys and girls, respectively). A reduced risk at 12 months was found in children with an increased linear growth between 0 and 4 months (aRRs: 0.92 and 0.90, 95 % CIs: 0.87-0.98 and 0.84-0.96 in boys and girls, respectively), boys with an increased relative weight gain between 0 and 4 months (aRR: 0.90, 95 % CI: 0.84-0.97), and girls with a higher birth weight (aRR: 0.89, 95 % CI: 0.83-0.96). CONCLUSIONS: These results suggest that a slow physical growth by four months old may be a predictor of neurodevelopmental delay during infancy.

DOI： 10.1186/s12887-021-02815-9

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jpsychires.2021.05.056

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY  

We aimed to determine mortality risk in underweight patients with diabetic nephropathy for microalbuminuria or macroalbuminuria. We analyzed mortality and death-cause data from BioBank Japan, with baseline years 2003-2007. We analyzed mortality rates from all causes and ischemic heart disease, according to body mass index (<18.5, 18.5-21.9, 22-24.9 and >= 25 kg/m(2)). The mean (standard deviation) of patient age, body mass index, and glycated hemoglobin at enrollment was 61.6 years (11.7 years), 25.0 kg/m(2) (4.4 kg/m(2)) and 7.7% (1.5%), respectively. Hazard ratios of all-cause and ischemic heart disease mortality were highest (1.79 [P = 0.0001] and 2.95 [P = 0.027], respectively) in patients with body mass index <18.5 kg/m(2), as compared with body mass index 22-24.9 kg/m(2). All-cause mortality risk for body mass index <18.5 kg/m(2) was similar to that for current smokers (hazard ratio 1.70, P < 0.0001). Underweight could be a predictor of mortality risk in patients with diabetic nephropathy for microalbuminuria or macroalbuminuria.

DOI： 10.1111/jdi.13483

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-020-01274-9

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1038/s41598-021-93101-2

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Postpartum depression is one of the most commonly experienced psychological disorders for women after childbirth, usually occurring within one year. This study aimed to clarify whether women with delivery with anesthesia, including epidural analgesia, spinal-epidural analgesia, and paracervical block, had a decreased risk of postpartum depression after giving birth in Japan. METHODS: The Japan Environment and Children's Study (JECS) was a prospective cohort study that enrolled registered fetal records (n = 104,065) in 15 regions nationwide in Japan. Binomial logistic regression analyses were performed to calculate the adjusted odd ratios (aORs) for the association between mode of delivery with or without anesthesia and postpartum depression at one-, six- and twelve-months after childbirth. RESULTS: At six months after childbirth, vaginal delivery with anesthesia was associated with a higher risk of postpartum depression (aOR: 1.233, 95% confidence interval: 1.079-1.409), compared with vaginal delivery without analgesia. Nevertheless, the risk dropped off one year after delivery. Among the pregnant women who requested delivery with anesthesia, 5.1% had a positive Kessler-6 scale (K6) score for depression before the first trimester (p < 0.001), which was significantly higher than the proportions in the vaginal delivery without analgesia (3.5%). CONCLUSIONS: Our data suggested that the risk of postpartum depression at six months after childbirth tended to be increased after vaginal delivery with anesthesia, compared with vaginal delivery without analgesia. Requests for delivery with anesthesia continue to be relatively uncommon in Japan, and women who make such requests might be more likely to experience postpartum depressive symptoms because of underlying maternal environmental statuses.

DOI： 10.1186/s12884-021-03996-y

PubMed

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.11236/jph.20-114

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-021-01634-z

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: To compare the incidence of atopic dermatitis in children aged from 6 months to 3 years across birth seasons and climate conditions. DESIGN: Cohort study. SETTING: Fifteen regional centres across Japan. PARTICIPANTS: A total of 100 304 children born from 2011 to 2014. EXPOSURE: Birth month, and mean sunshine duration (short/long) and humidity (high/low) in the first 6 months of life. PRIMARY OUTCOME MEASURE: Incidence of atopic dermatitis. RESULTS: The highest incidence of atopic dermatitis was in children born in the months of October to December. The lowest incidence of atopic dermatitis was in the months of April to June and in periods with a long duration of sunshine and high humidity. Low humidity was significantly associated with a higher incidence of atopic dermatitis. However, this significant difference disappeared when the birth season and parental history of allergic disease were considered in multivariate analysis. CONCLUSIONS: In Japan, being born in the late autumn to early winter months is associated with a risk of developing atopic dermatitis until the age of 3 years. Sunshine duration and humidity from birth to 6 months of age are not associated with the incidence of atopic dermatitis.

DOI： 10.1136/bmjopen-2020-047226

PubMed

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：東京大学生命･医療倫理教育研究センター  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Spine Surgery and Related Research  

DOI： 10.22603/ssrr.2020-0032

Language：English   Publishing type：Research paper (scientific journal)  

Kawasaki disease (KD) is an acute systemic vasculitis that mainly affects infants and young children. The etiology of KD has been discussed for several decades; however, no reproducible risk factors have yet been proven. We used the Japan Environment and Children's Study data to explore the association between the causal effects of exposure during the fetal and neonatal periods and KD onset. The Japan Environment and Children's Study, a nationwide birth cohort study, has followed approximately 100,000 children since 2011. We obtained data on exposures and outcomes from the first trimester to 12 months after birth. Finally, we included 90,486 children who were followed for 12 months. Among them, 343 children developed KD. Multivariate logistic regression revealed that insufficient intake of folic acid during pregnancy (odds ratio [OR], 1.37; 95% CI 1.08-1.74), maternal thyroid disease during pregnancy (OR, 2.03; 95% CI 1.04-3.94), and presence of siblings (OR, 1.33; 95% CI 1.06-1.67) were associated with KD onset in infancy. In this study, we identified three exposures as risk factors for KD. Further well-designed studies are needed to confirm a causal relationship between these exposures and KD onset.

DOI： 10.1038/s41598-021-92669-z

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41390-021-01595-3

Language：English   Publishing type：Research paper (scientific journal)  

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.

DOI： 10.1038/s41598-021-91271-7

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/ped.14577

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/ped.14577

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Pregnant women in Japan express various reasons for limiting gestational weight gain (GWG). We aimed to identify and characterise groups where the women share common reasons to limit GWG and to examine how these groups are associated with inappropriate GWG and abnormal foetal size. METHODS: We prospectively studied information from the Japan Environment and Children's Study (JECS) on 92,539 women who gave birth to live singletons from 2011 through 2014. Pregnant women were recruited during early pregnancy. Their reasons for limiting GWG and other information were collected through self-reported questionnaires and medical records. We applied latent class analysis to group the women based on their reported reasons. We used multinomial logistic regression to compare the risks of inappropriate (inadequate and excessive) GWG and abnormal foetal size (determined by new-born weight for gestational age) between the identified groups. RESULTS: We identified three groups: Group 1 (76.7%), concerned about delivery and new-born health (health-conscious women); Group 2 (14.5%), concerned about body shape, delivery, and new-born health (body-shape- and health-conscious women); and Group 3 (8.8%), women without strong reasons to limit GWG (women lacking body-shape and health consciousness). Compared with Group 1 members, Group 2 members tended to be younger, have lower pre-pregnancy weight, be unmarried, be nulliparous, have practiced weight loss before pregnancy, and not have chronic medical conditions. Group 3 members tended to be less educated, unmarried, multiparous, smokers, and have a higher prevalence of pre-pregnancy underweight and previous caesarean delivery. Relative to Group 1, Group 2 had a lower unadjusted risk for inadequate GWG (relative risk ratio [RRR] = 0.86, 95% CI: 0.81-0.90) and large-for-gestational-age birth (RRR = 0.91, 95% CI 0.86-0.97), whereas Group 3 had a higher unadjusted risk for excessive GWG (RRR = 1.36, 95% CI: 1.29-1.43) and small-for-gestational-age (SGA) births (RRR = 1.15, 95% CI: 1.05-1.25). CONCLUSIONS: In this Japanese nationwide birth cohort study, pregnant women who were less conscious about body shape and health had complex risks for excessive GWG and SGA birth. Health care providers should consider a woman's perception of GWG when addressing factors affecting GWG and foetal growth.

DOI： 10.1186/s12884-021-03827-0

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

High serum immunoglobulin E (IgE) levels are associated with cardiovascular events. We aimed to evaluate the association between total IgE levels during the first trimester of pregnancy and pregnancy-induced hypertension (PIH) development in a large Japanese cohort. We analysed data pertaining to singleton primipara pregnancies recorded in the Japan Environment and Children's Study involving births from 2011 to 2014. Serum IgE levels were determined using the immunonephelometric technique. High serum IgE was defined as level ≥ 170 IU/ml. Hypertensive disorders in pregnancy (HDP) were categorized into early onset (Eo) PIH (developed < 34 weeks) or late onset (Lo) PIH (developed ≧ 34 weeks). A multiple logistic regression model was used to estimate the risk of high serum IgE levels on PIH, Eo-PIH, and Lo-PIH. Overall, 32,518 participants were enrolled. The prevalence of total, Eo-, and Lo-PIH was 3.2%, 0.6%, and 2.3%, respectively. Patients with high serum IgE levels had an increased risk of Lo-HDP (adjusted odds ratio [aOR]:1.19, 95% confidence interval 1.01-1.40). No correlation was found with either PIH (total) or Eo-PIH. High serum IgE levels during the first trimester were associated with the risk of Lo-PIH. Our results could influence and shape further research regarding the pathogenesis of Lo hypertension.

DOI： 10.1038/s41598-021-88227-2

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The aim of this study was to investigate the association between maternal physical activity (PA) before and during pregnancy and sleep and developmental problems in 1-year-old infants. We used data from a nationwide cohort study in Japan that registered 103,062 pregnancies between 2011 and 2014. Participants were asked about their PA before and during pregnancy, and the sleep and development of their children at the age of 1 year. Maternal PA was estimated using the International Physical Activity Questionnaire and was expressed in METs per week. We defined scores below the cut-off points of the Ages and Stages Questionnaire (ASQ) as abnormal for infant development. Based on the levels of PA before or during pregnancy, the participants were divided into five groups. In mothers with higher PA levels, the risk ratio for bedtime after 22:00 or abnormal ASQ scores in their 1-years-old infants were lower. These associations were observed for PA before and during pregnancy. Higher levels of maternal PA, both before and during pregnancy, may reduce sleep and developmental problems in infants.

DOI： 10.1038/s41598-021-87612-1

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： BMC Pregnancy Childbirth

Language：English   Publishing type：Research paper (scientific journal)  

DOI： Clinical Epigenetics

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

We calculated the Poisson-regression-adjusted relative risk (RR) of new influenza infection by vaccination, prior infection, and vaccination after prior infection in a large Japanese birth cohort, using data from ≤89,253 children aged 6 months to 3 years. The effectiveness of risk reduction (1 - RR) by vaccination at ages 1.5-3 years was 21%-31%. The RR of new infection after prior infection vs. no prior infection was 2.58-19.3 at age 1-3 years. An analysis of the 1 - RR data stratified by having at least one senior sibling and/or attending nursery school revealed that vaccination reduced the RR by 22%-40%. The 1 - RR of new infection was 21% in 3-year-old children who were vaccinated after prior infection. All these findings are statistically significant. The results consistently indicate that, regardless of having at least one senior sibling, attending nursery school, and/or being previously infected with influenza, infants and toddlers will benefit from influenza vaccination.

DOI： 10.1016/j.vaccine.2021.02.044

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

This research aimed to examine the efficacy of the early initiation of breastfeeding within 1 h of birth, early skin-to-skin contact, and rooming-in for the continuation of exclusive breastfeeding until 6 months postpartum. The research used data from the Japan Environment and Children's Study (JECS), a nationwide government-funded birth cohort study. A total of 80,491 mothers in Japan between January 2011 and March 2014 who succeeded or failed to exclusively breastfeed to 6 months were surveyed in JECS. Multiple logistic regression model was used to analyse the data. The percentage of mothers who succeeded in exclusively breastfeeding to 6 months is 37.4%. Adjusted odds ratios were analysed for all 35 variables. Early initiation of breastfeeding (adjusted odds ratio [AOR]: 1.455 [1.401-1.512]), early skin-to-skin contact (AOR: 1.233 [1.165-1.304]), and rooming-in (AOR: 1.567 [1.454-1.690]) affected continuation of exclusive breastfeeding. Regional social capital (AOR: 1.133 [1.061-1.210]) was also discovered to support the continuation of breastfeeding. In contrast, the most influential inhibiting factors were starting childcare (AOR: 0.126 [0.113-0.141]), smoking during pregnancy (AOR: 0.557 [0.496-0.627]), and obese body type during early pregnancy (AOR: 0.667 [0.627-0.710]).

DOI： 10.1038/s41598-021-85900-4

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

School-based programmes need to be effective, easy for all, easy to perform within a short duration, and inexpensive. However, no studies have reported whether voluntarily and very short-time active play programmes contribute to improved health outcomes. This study aims to describe the GRoup activity, Active Play and Exercise (GRAPE) cluster randomised controlled trial that examined whether active play interventions of very short durations contribute to increasing physical activity (PA) and bone mass among school-aged children. The trial was conducted in 2018 from January to June, and the activity comprised ≥2 children jumping together for approximately 10 s per session, at least five times a day (approximately 1 min/day). School clusters, pair-matched as per school size (total number of children) and region, were randomly allocated to either intervention or wait-list control groups. The primary outcomes comprised objectively measured changes in PA levels (moderate-to-vigorous PA) evaluated using wrist-worn activity trackers from baseline to the one-year follow-up (six-month post-intervention follow-up) and changes in bone mass evaluated using calcaneus quantitative ultrasound parameters. This study could describe the problems and challenges in school-based PA intervention studies and present findings that could make a potentially important contribution to health education and PA promotion.

DOI： 10.3390/ijerph18073351

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Floating toe (FT) is a frequently seen condition in which a toe is inadequately in contact with the ground. Although toes play an important role in stabilizing standing posture and walking, many aspects of the effects of FT on the body remain unclear. To our knowledge, there have been no reports about the relationship between FT and postural stability, especially in children. This study aimed to clarify the prevalence of FT and its relationship with static postural stability in children. Of the 400 children aged 8 years who participated in our cohort study, 396, who were examined for static postural stability, were included in this study. Postural stability and FT were assessed using a foot pressure plate. The sway path length of the center of pressure and the area of the ellipse defined as the size of the area marked by the center of pressure, were measured as an evaluation of static postural stability. We calculated the "floating toe score (FT score: small FT score indicates insufficient ground contact of the toes)" using the image of the plantar footprint obtained at the postural stability measurement. The rate of FT was elevated at more than 90%, and the FT score in the eyes-closed condition was significantly higher than that in the eyes-open condition in both sexes. The FT score significantly correlated with the center of pressure path and area. Our results suggest that ground contact of the toes is not directly related to static postural stability in children, but it may function to stabilize the body when the condition becomes unstable, such as when the eyes are closed.

DOI： 10.1371/journal.pone.0246010

PubMed

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (bulletin of university, research institution)  

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)   Publisher：医学書院  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Early intervention in type 2 diabetes can prevent exacerbation of insulin resistance. More effective interventions can be implemented by early and precise prediction of the change in glycated haemoglobin A1c (HbA1c). Artificial intelligence (AI), which has been introduced into various medical fields, may be useful in predicting changes in HbA1c. However, the inability to explain the predictive factors has been a problem in the use of deep learning, the leading AI technology. Therefore, we applied a highly interpretable AI method, random forest (RF), to large-scale health check-up data and examined whether there was an advantage over a conventional prediction model. RESEARCH DESIGN AND METHODS: This study included a cumulative total of 42 908 subjects not receiving treatment for diabetes with an HbA1c <6.5%. The objective variable was the change in HbA1c in the next year. Each prediction model was created with 51 health-check items and part of their change values from the previous year. We used two analytical methods to compare the predictive powers: RF as a new model and multivariate logistic regression (MLR) as a conventional model. We also created models excluding the change values to determine whether it positively affected the predictions. In addition, variable importance was calculated in the RF analysis, and standard regression coefficients were calculated in the MLR analysis to identify the predictors. RESULTS: The RF model showed a higher predictive power for the change in HbA1c than MLR in all models. The RF model including change values showed the highest predictive power. In the RF prediction model, HbA1c, fasting blood glucose, body weight, alkaline phosphatase and platelet count were factors with high predictive power. CONCLUSIONS: Correct use of the RF method may enable highly accurate risk prediction for the change in HbA1c and may allow the identification of new diabetes risk predictors.

DOI： 10.1136/bmjnph-2020-000200

PubMed

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)   Publisher：診断と治療社  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：(MISC) Research paper  

DOI： 10.3389/fpubh.2021.641882

Language：English   Publishing type：Research paper (scientific journal)  

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

DOI： 10.1038/s41467-020-20851-4

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

A high maternal body mass index (BMI) is associated with increased risks of asphyxia-related neonatal morbidity. We evaluated the association between maternal pre-pregnancy BMI and foetal acidosis while accounting for the mode of delivery. Participants from the Japan Environment and Children's Study with singleton pregnancies after 22 weeks of gestation who gave birth during 2011-2014 were included. The participants (n = 71,799) were categorised into five groups according to the pre-pregnancy BMI: G1 (BMI < 18.5 kg/m2), G2 (18.5 to < 20.0 kg/m2), G3 (20.0 to < 23.0 kg/m2), G4 (23.0 to < 25.0 kg/m2), and G5 (≥ 25.0 kg/m2). Foetal acidosis was defined as umbilical artery pH (UmA-pH) < 7.20 or < 7.10. Multiple logistic regression analyses were used to evaluate the effect of pre-pregnancy BMI on foetal acidosis risk, accounting for the mode of delivery. In Japanese women, pre-pregnancy BMI ≥ 25.0 kg/m2 significantly increased the likelihood of foetal acidosis in newborns delivered vaginally. We found no association between pre-pregnancy BMI and foetal acidosis in newborns delivered via caesarean section. Counselling for body weight control before pregnancy and adequate management and selection of the mode of delivery in pregnant women with a high BMI who are in labour may be essential to avoid foetal acidosis.

DOI： 10.1038/s41598-020-79178-1

PubMed

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)  

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Other article  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

To clarify the physical and mental conditions of children during the coronavirus disease 2019 pandemic and consequent social distancing in relation to the mental condition of their caregivers. This internet-based nationwide cross-sectional study was conducted between April 30 and May 13, 2020. The participants were 1,200 caregivers of children aged 3-14 years. Child health issues were categorized into "at least one" or "none" according to caregivers' perception. Caregivers' mental status was assessed using the Japanese version of the Kessler Psychological Distress Scale-6. The association between caregivers' mental status and child health issues was analyzed using logistic regression models. Among the participants, 289 (24.1%) had moderate and 352 (29.3%) had severe mental distress and 69.8% of children in their care had health issues. The number of caregivers with mental distress was more than double that reported during the 2016 national survey. After adjusting for covariates, child health issues increased among caregivers with moderate mental distress (odds ratio 2.24, 95% confidence interval 1.59-3.16) and severe mental distress (odds ratio 3.05, 95% confidence interval 2.17-4.29) compared with caregivers with no mental distress. The results highlight parents' psychological stress during the pandemic, suggesting the need for adequate parenting support. However, our study did not consider risk factors of caregivers' mental distress such as socioeconomic background. There is an urgent need for further research to identify vulnerable populations and children's needs to develop sustainable social support programs for those affected by the outbreak.

DOI： 10.1371/journal.pone.0243702.

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)   Publisher：医歯薬出版株式会社  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)  

Language：English   Publishing type：Research paper (scientific journal)  

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DOI： 10.1002/edm2.181. 2020.8

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Authorship：Last author   Language：English   Publishing type：(MISC) Introduction and explanation (international conference proceedings)  

DOI： 10.31662/jmaj.2020-0016

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Summary of the papers read (national conference and other science council)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：Japanese   Publisher：(公社)日本産業衛生学会  

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Research paper  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (bulletin of university, research institution)  

Language：English   Publishing type：Research paper (scientific journal)  

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Language：Japanese  

J-GLOBAL

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

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DOI： 10.1016/j.parkreldis.2019.10.026

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Summary of the papers read (national conference and other science council)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：厚生労働統計協会  

Authorship：Lead author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)   Publisher：民事法研究会  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Lead author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 2018 North American Society for Pediatric and Adolescent Gynecology Study Objective: Few studies have investigated the risky health behaviors and psychosocial characteristics of teenage mothers in countries with a low teenage birth rate, like Japan. We examined the differences in maternal prenatal risky health behaviors and psychosocial characteristics, and birth weight of infants between teenage and adult mothers. Design, Setting, Participants, Interventions, and Main Outcome Measures: We identified 1159 teenage (age younger than 20 years) and 73,547 adult mothers (20-34 years) who participated a nationwide birth cohort study between 2011 and 2014. Behavioral and psychosocial characteristics were ascertained using questionnaires during pregnancy. Birth weight of infants was verified through medical records. Univariate and multivariable logistic regression were used to assess the association of teenage motherhood and birth weight of infants with parity, marital status, household income, maternal education, job status, preconception body mass index, gestational weight gain, psychological distress, and smoking status. Results: Teenage mothers were significantly more likely to smoke and have psychological distress and less likely to use alcohol than adult mothers (9.9% vs 4.6%, P < .001; 8.9% vs 3.4%, P < .001; 1.3% vs 2.5%, P < .001, respectively). No association was found between teenage motherhood and low birth weight in infants (odds ratio 0.99; 95% confidence interval, 0.73-1.32). Further, no association was found after adjusting for covariates. Conclusion: A substantially greater number of Japanese teenage mothers smoked and experienced severe psychological distress than adult mothers. Our findings will be useful for future research and for developing effective policies and programs for teenage mothers and their children.

DOI： 10.1016/j.jpag.2018.10.009

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

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.

DOI： 10.1016/j.envint.2019.01.051

Web of Science

Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 2018 The Authors The results of several epidemiological studies have shown a moderate association between postpartum depression (PPD) and mother-infant bonding (MIB); however, associations and changes that longitudinally considered parity were not reported. We investigated the possible association between PPD and MIB at one month after birth, in addition, the changes of these indices by parity. From a dataset comprising 103,099 maternal registrations in The Japan Environment and Children's Study, the present study analyzed complete data on questionnaires for 76,363 women who participated once (cross-sectional group) and 3753 women who participated twice (follow-up subgroup). Edinburgh Postnatal Depression Scale (EPDS) scores and the Mother-to-Infant Bonding Scale-Japan (MIBS-J) scores were obtained one month after delivery. We identified the two factors of the MIBS-J, “lack of maternal feeling (LMF)” and “anxiety about caregiving (AC)” through confirmatory factor analysis. Associations between total EPDS and each factor of MIBS-J were evaluated using multiple regression analyses after adjusting for potential confounders. Total EPDS and both factors (LMF and AC) were positively related in the cross-sectional group (fully adjusted β = 0.26 and 0.39 for LMF and AC, respectively), in the follow-up subgroup at first participation (0.24 and 0.40, respectively) and at the second participation (0.25 and 0.39, respectively). Multiple regression analyses revealed a robust, moderate relationship between postpartum depression and mother-infant bonding. PPD and MIB scores were shown to decrease from the first child to the second in the follow-up subgroup. Consequently, interventions which would increase a mother's child care experience and expertise would prevent PPD and improve MIB.

DOI： 10.1016/j.jpsychires.2018.11.022

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PubMed

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Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 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.

DOI： 10.1007/s00420-018-1367-7

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PubMed

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

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© 2018, The Author(s). Pregnancy intention is reported to be associated with the risk of postpartum depression (PPD), but the impact of feelings toward being pregnant on PPD is unknown. We aimed to examine whether feelings toward being pregnant are associated with PPD at 1 month after childbirth. In our nationwide study between 2011 and 2014 in Japan, we used multivariate logistic regression analyses to examine the associations between pregnancy intention and feelings toward being pregnant with PPD [Edinburgh Postnatal Depression Scale (EPDS score > 9 or > 12)] among Japanese women. Among 92,431 women, 14.0 and 5.4% had PPD with EPDS scores > 9 and > 12, respectively. Compared with women who felt very happy to be pregnant, those whose pregnancy was unintended but happy, unintended and confused, those who felt troubled, and those who felt no emotion toward being pregnant had increased risks of PPD [multivariable odds ratios (95% confidence intervals (CIs)) = 1.17 (1.11–1.22), 1.39 (1.29–1.49), 1.74 (1.42–2.14), and 1.58 (1.22–2.02), respectively, for EPDS score > 9]. Those associations were more evident without antenatal possible mental illness (K6 score < 13). Women whose pregnancy was unintended should be regarded as targets for the early detection and prevention of PPD irrespective of whether they felt happy or confused.

DOI： 10.1007/s00737-018-0938-7

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Language：English   Publishing type：Research paper (scientific journal)  

© 2018 The Author(s). Background: Few studies have examined the association of workhours and shift work (referred to here as "time-related work factors") with dietary behaviors. We aimed to investigate this association, as well as the dietary behaviors among individuals with occupations characterized by time-related work factors. Methods: A cross-sectional study was performed using data from the Japan Environment and Children's Study. The study included 39,315 working men. Dietary behaviors (i.e., skipping breakfast, eating out, eating instant food, overeating, and eating fast) were assessed with a self-reported information from the Food Frequency Questionnaire. Logistic regression analysis was conducted to examine the associations of time-related work factors with dietary behaviors and dietary behavior tendencies among those in occupations characterized by long workhours and/or shift work. Results: Long workhours were associated with high frequencies of skipping breakfast, eating out, eating instant food, overeating, and eating fast. The frequency of having shift work was associated with high frequencies of skipping breakfast, eating out, and eating instant food. Several occupations involving long workhours and/or shift work showed specific dietary behaviors; in some occupations, the level of significance changed after adjusting for time-related work factors in addition to other potential confounding factors. Conclusions: Time-related work factors may help explain workers' dietary behaviors. Long workhours and shift work may lead to poor dietary behaviors. Other factors influenced by occupation itself, such as food environment, may also influence workers' dietary behaviors. Workhours and/or shift work, and these other work factors, should be given attention in workplace health promotion.

DOI： 10.1186/s12199-018-0753-9

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Language：English   Publishing type：Research paper (scientific journal)  

© 2018 The Author(s). Objective: There have been increasing reports on the association between cesarean section (C-section) and the subsequent development of diseases in infants. C-section affects the diversity of microbiota in the infant's gut. In the present study, we investigated the association between infants delivered by C-section and the development of constipation at 1 year old due to altered gut microbiota using data from the Japan Environment and Children's Study (JECS). Results: This cohort study (n = 83,019) used data from JECS, an ongoing cohort study which began in January 2011. Data on bowel movement and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of C-section, and the results were expressed as risk ratios and their respective 95% confidence intervals. Although infants delivered by C-section were of significantly younger gestational age and lesser birth weight than vaginally delivered infants, the frequency of bowel movements was almost similar between the two, independent of the mode of delivery. The prevalence of constipation in the entire infant was 1.37%. No significant differences were observed for C-section in crude and adjusted risk ratios for constipation.

DOI： 10.1186/s13104-018-3990-5

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 2018 Elsevier Ltd There are many psychosocial and biomedical risk factors for postpartum depression (PPD). However, associations between co-resident family members and PPD risk have not been examined. This study investigated whether co-resident family members were associated with risk for PPD during 1 month postpartum among Japanese women, and if these associations were modified by household income and their perceived partner's involvement in childcare. The sample comprised 86,490 women. Data were drawn from the Japan Environment and Children's Study, a large-scale national cohort study started in 2011. Our major predictor was co-resident family members when they registered around the first trimester of the women's pregnancy: partner, parent(s), parent(s)-in-law, or child(ren). The outcome was PPD at 1 month after delivery, assessed by the Edinburgh Postnatal Depression Scale. Adjusted odds ratios (OR) for family members and PPD incidence were calculated using multivariable logistic regression analysis. Subgroup analyses were conducted by household income and perceived partner's involvement in childcare. Adjusted ORs (95% confidence interval) for PPD for those not living with their partner, parent(s), parent(s)-in-law, or child(ren) compared with those who lived with these family members were 1.21 (1.07–1.37), 1.13 (1.03–1.24), 0.91 (0.84–0.98), and 1.42 (1.31–1.53), respectively. The level of perceived partner's involvement in childcare changed the identified association between family member and PPD. We found that “who a pregnant woman lives with” affects the risk of PPD in the first month postpartum, and high levels of perceived partner's involvement in childcare reduced harmful effects/increased protective effect of family members on PPD incidence. These findings suggested that interventions to increase perceived partner's support for childcare may be effective in preventing PPD, regardless of living situation.

DOI： 10.1016/j.socscimed.2018.09.043

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PubMed

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Health personnel must provide continuous support in response to problematic results from health checks of infants and toddlers (hereinafter "infant[s]"). Among this support, it is important for health personnel to provide nutritional guidance to families as a collaborative effort between the staff from multiple disciplines and community organizations. This study aimed to clarify the factors affecting collaboration with community organizations in providing nutritional guidance to families following health checks for infants in Japan. METHODS: The design of this study consisted of a cross-sectional, multilevel survey. A self-administered questionnaire was mailed to all municipalities (1741 towns and cities) in Japan to be completed by the person responsible for nutrition advice. The research was performed in August 2015. We obtained 988 valid responses (response rate of 56.7%). To identify the factors that affect the collaboration with community organizations in providing nutritional guidance, we determined how municipalities responded to infants needing support (five items), how municipalities evaluated health guidance (five items), the number of distributed maternal and child health handbooks, and the number of infants who received follow-up evaluations. RESULTS: The results of multivariate analyses showed that the factors related to successful community collaboration in providing nutritional guidance included holding a multi-professional staff meeting after health checks (post-conference; odds ratio [OR], 2.34; P = 0.001); following up children suspected of having developmental and mental disabilities or delays before entering elementary school (OR, 1.77; P = 0.0004); and considering dental caries data from dental checkups in providing health guidance (OR, 1.56; P = 0.003). CONCLUSIONS: Holding a multi-professional meeting after infant health checks (post-conference) was strongly associated with community collaboration in providing nutritional guidance for infants.

DOI： 10.1186/s12887-018-1292-7

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

© 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.

DOI： 10.1016/j.envres.2018.06.025

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PubMed

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：日本公衆衛生学会  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

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© 2018 The Author(s). Background: Nausea and vomiting during pregnancy (NVP) is considered to be associated with favorable fetal outcomes, such as a decreased risk for spontaneous abortion. However, the relationship between NVP and preterm births remains unknown. This study was conducted to evaluate the association between NVP and the risk of preterm births. Methods: The dataset of a birth cohort study, the Japan Environment and Children's Study (JECS), was retrospectively reviewed. Participants' experience of NVP prior to 12 gestational weeks were evaluated by a questionnaire administered from 22 weeks of pregnancy to 1 month before delivery. NVP responses were elicited against four choices based on which the study population was divided into four subcohorts. Preterm birth was the main study outcome. Logistic regression analysis was used to quantify an association between NVP and risk of preterm birth. Results: Of 96,056 women, 79,460 (82.7%) experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP. Compared to those who did not experience NVP, women with severe NVP had lower odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval (95% CI) 0.74-0.95]. An even lower OR was found among very preterm birth and extremely preterm birth (aOR 0.44, 95% CI 0.29-0.65). Conclusion: An inverse association exists between NVP and preterm births, especially, very preterm births and extremely preterm births.

DOI： 10.1186/s12884-018-1911-1

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

We evaluated the relationship between preconception folic acid supplementation and the occurrence of neural tube defects (NTDs) in offspring, using data from the Japan Environment and Children's Study (a nationwide prospective birth cohort study) database. Of 92 269 participants with single pregnancies, 74 cases (offspring or fetuses) had NTDs, including 32 cases of spina bifida, 24 cases of anencephaly, and 19 cases of encephalocele. A total of 7634 participants (8.27%) used preconception folic acid supplementation, and of these, 621 (0.67%) also took in dietary folic acid at ≥480 μg/day. Multivariate logistic regression analyses demonstrated no association between preconception folic acid supplementation and NTDs in offspring or fetuses (odds ratio [OR] 0.622; 95% confidence interval [CI]: 0.226-1.713). Moreover, the participants who combined preconception folic acid supplement use with dietary folic acid intake ≥480 μg/day demonstrated no incidence of NTDs in offspring or fetuses. Our analysis is limited by the absence of the data on the daily amount of supplementary folic acid intake, requiring careful attention to the interpretation. Additional surveys are required in Japan to resolve those limitations for further comprehensive assessment.

DOI： 10.1111/cga.12293

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

© 2017 The Authors The results of several epidemiological studies and clinical trials investigating the effects of n-3 polyunsaturated fatty acids (PUFAs) on antenatal and postnatal depression remain controversial. We investigated the possible association of dietary intake of fish and n-3 PUFAs with the risks of maternal and paternal psychological distress during pregnancy and of maternal postpartum depression in Japan. From a dataset comprising 104,102 maternal registrations and 52,426 paternal registrations in The Japan Environment and Children's Study, this study analyzed complete data on questionnaires for 75,139, 79,346, and 77,661 women during early pregnancy, mid-late pregnancy, and after pregnancy, respectively, and for 41,506 male partners. Multivariable logistic regression showed reduced risk of psychological distress in the second and third quintiles for fish intake in early pregnancy and in the second to fifth quintile in mid-late pregnancy. No reductions were observed for n-3 PUFA intake in early pregnancy but in the second to fourth quintile in mid-late pregnancy. For postpartum depression, reductions were observed in the second to fourth quintile for fish intake but only in the first quintile for n-3 PUFA intake. As for paternal psychological distress, only the fourth quintile for fish intake showed a significant reduced risk but none were shown for n-3 PUFA intake. In conclusion, fish intake was associated with some reduced risk of psychological distress during pregnancy, even for male partners. The associations were weaker for n-3 PUFA intake than for fish intake.

DOI： 10.1016/j.jpsychires.2017.11.013

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PubMed

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (scientific journal)   Publisher：(一社)日本外来小児科学会  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一財)厚生労働統計協会  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Last author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)   Publisher：公財 健康・体力づくり事業財団  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.09.012

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一財)厚生労働統計協会  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

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Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1136/bmjopen-2016-014684

Language：English   Publishing type：Research paper (scientific journal)  

Background: For elderly patients, posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (TLIF) is usually performed to treat lumbar degenerative diseases. However, some patients exhibit pseudarthrosis following such procedures. The anabolic agent teriparatide is an approved treatment for promoting bone formation in osteoporotic patients. Our multicenter, prospective randomized study assessed the role of once-weekly teriparatide administration on patient outcomes following interbody fusion. Methods: Patients were females who were ≥50 years of age, had a bone mineral density (BMD) of <80% of the sex-matched young adult mean and/or previous spinal compression or femoral fractures, and had lumbar degenerative disease. Patients were randomly allocated to receive either weekly teriparatide, administered subcutaneously starting at week 1, for 6 months postoperatively (the teriparatide arm), or no teriparatide (the control arm). Blinded radiographic evaluations were performed using dynamic radiography and computed tomography (CT) and assessed by modified intention-to-treat analysis and per-protocol analysis. Clinical and neurological symptoms were evaluated using the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOA-BPEQ) and the Oswestry Disability Index (ODI). Results: Seventy-five patients were randomized to treatment, and 66 patients completed treatment. At 4 months postoperatively, bone fusion in the 2 center CT slices was significantly higher in the teriparatide arm compared with the control arm in the age-adjusted modified intention-to-treat analysis and was significantly higher at 6 months in the per-protocol analysis. Radiographic examinations showed no disc-space narrowing and no intervertebral disc instability. JOA-BPEQ and ODI results were improved postoperatively in both treatment arms. Conclusions: Weekly administration of teriparatide promoted bone formation at the surgical fusion site and decreased bone resorption, as indicated by bone metabolic marker results, within the early postoperative period. Our findings suggest that combining lumbar interbody fusion and teriparatide treatment may be an effective option for managing lumbar degenerative disease in elderly patients. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

DOI： 10.2106/JBJS.16.00230

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Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Introduction and explanation (others)   Publisher：公益財団法人 健康・体力づくり事業財団  

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/ijo.2017.6

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1136/bmjgh-2016-000127

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The BioBank Japan (BBJ) Project was launched in 2003 with the aim of providing evidence for the implementation of personalized medicine by constructing a large, patient-based biobank (BBJ). This report describes the study design and profile of BBJ participants who were registered during the first 5-year period of the project. METHODS: The BBJ is a registry of patients diagnosed with any of 47 target common diseases. Patients were enrolled at 12 cooperative medical institutes all over Japan from June 2003 to March 2008. Clinical information was collected annually via interviews and medical record reviews until 2013. We collected DNA from all participants at baseline and collected annual serum samples until 2013. In addition, we followed patients who reported a history of 32 of the 47 target diseases to collect survival data, including cause of death. RESULTS: During the 5-year period, 200,000 participants were registered in the study. The total number of cases was 291,274 at baseline. Baseline data for 199,982 participants (53.1% male) were available for analysis. The average age at entry was 62.7 years for men and 61.5 years for women. Follow-up surveys were performed for participants with any of 32 diseases, and survival time data for 141,612 participants were available for analysis. CONCLUSIONS: The BBJ Project has constructed the infrastructure for genomic research for various common diseases. This clinical information, coupled with genomic data, will provide important clues for the implementation of personalized medicine.

DOI： 10.1016/j.je.2016.12.005

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.003

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.006

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Several studies have evaluated associations between the characteristics of patients with esophageal and gastric cancer and survival, but these associations remain unclear. We described the distribution of demographic and lifestyle factors among patients with esophageal and gastric cancer in Japan, and investigated their potential effects on survival. METHODS: Between 2003 and 2007, 24- to 95-year-old Japanese patients with esophageal and gastric cancer were enrolled in the BioBank Japan Project. The analysis included 365 patients with esophageal squamous cell carcinoma (ESCC) and 1574 patients with gastric cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality were estimated using medical institution-stratified Cox proportional hazards models. RESULTS: During follow-up, 213 patients with ESCC (median follow-up, 4.4 years) and 603 patients with gastric cancer (median follow-up, 6.1 years) died. Among patients with ESCC, the mortality risk was higher in ever drinkers versus never drinkers (multivariable HR = 2.37, 95% CI: 1.24, 4.53). Among patients with gastric cancer, the mortality risk was higher in underweight patients versus patients of normal weight (multivariable HR = 1.66, 95% CI: 1.34, 2.05). Compared to patients with gastric cancer with no physical exercise habit, those who exercised ≥3 times/week had a lower mortality risk (multivariate HR = 0.75, 95% CI = 0.61, 0.93). However, lack of stage in many cases was a limitation. CONCLUSIONS: Among patients with ESCC, alcohol drinkers have a poor prognosis. Patients with gastric cancer who are underweight also have a poor prognosis, whereas patients with physical exercise habits have a good prognosis.

DOI： 10.1016/j.je.2016.12.002

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.004

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Liver cancer is the fifth cause of cancer-related deaths in Japan. The BioBank Japan (BBJ) project included 200,000 patients with 47 diseases and samples; their clinical information can be used for further studies. METHODS: Patients diagnosed with liver cancer (n = 1733; 1316 men, 417 women) were included. Histology, patient characteristics, clinical characteristics, and causes of death were collected. Cumulative and relative survival rates for liver cancer were calculated. RESULTS: Of the 1354 patients with available liver cancer histology, 91.9% had hepatocellular carcinoma (HCC). Compared with the National Health and Nutrition Examination Survey, greater proportions of the male patients in this cohort were daily alcohol consumers (26%), and a greater proportion of the men was overweight/obesity (22%). Although Japan is the only Asian country with a predominance of hepatitis C virus (HCV)-related HCC, the prevalence of HCV infection (44%) was lower than that in a previous study. The 3-, 5-, and 10-year cumulative survival rates were 57%, 47%, and 25% in men, respectively, and 49%, 41%, and 27% in women, respectively. CONCLUSIONS: The present results provide an overview of the patients with liver cancer in the BBJ project. We are planning further analyses combined with various high-throughput 'omics' technologies.

DOI： 10.1016/j.je.2016.12.007

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.010

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.009

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.008

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in Japan. The present study aimed to develop new risk prediction models for long-term risks of all-cause and cardiovascular death in patients with chronic phase CVD. METHODS: Among the subjects registered in the BioBank Japan database, 15,058 patients aged ≥40 years with chronic ischemic CVD (ischemic stroke or myocardial infarction) were divided randomly into a derivation cohort (n = 10,039) and validation cohort (n = 5019). These subjects were followed up for 8.55 years in median. Risk prediction models for all-cause and cardiovascular death were developed using the derivation cohort by Cox proportional hazards regression. Their prediction performances for 5-year risk of mortality were evaluated in the validation cohort. RESULTS: During the follow-up, all-cause and cardiovascular death events were observed in 2962 and 962 patients from the derivation cohort and 1536 and 481 from the validation cohort, respectively. Risk prediction models for all-cause and cardiovascular death were developed from the derivation cohort using ten traditional cardiovascular risk factors, namely, age, sex, CVD subtype, hypertension, diabetes, total cholesterol, body mass index, current smoking, current drinking, and physical activity. These models demonstrated modest discrimination (c-statistics, 0.703 for all-cause death; 0.685 for cardiovascular death) and good calibration (Hosmer-Lemeshow χ2-test, P = 0.17 and 0.15, respectively) in the validation cohort. CONCLUSIONS: We developed and validated risk prediction models of all-cause and cardiovascular death for patients with chronic ischemic CVD. These models would be useful for estimating the long-term risk of mortality in chronic phase CVD.

DOI： 10.1016/j.je.2016.10.007

PubMed

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.014

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.011

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.013

Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.12.012

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.10.005

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.je.2016.03.001

Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：(MISC) Lecture materials etc. (seminar, tutorial, course, lecture and others)   Publisher：神奈川県医師会学校医部会