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Abstract Background Chronic kidney disease (CKD) contributes to decreased life expectancy. We examined the association between leisure-time physical activity (LTPA), non-leisure-time physical activity (non-LTPA) and kidney function. Methods This was a cross-sectional study including 32 162 community-dwelling adults aged ≥ 20 years from the Tohoku Medical MegaBank community-based cohort study. Kidney function was evaluated using cystatin C-based estimated glomerular filtration rate (eGFR) as well as self-reported LTPA and non-LTPA. CKD was defined as either eGFR decline (≤ 60 mL/min/1.73 m2) or presence of albuminuria (albumin-creatinine ≥ 30 mg/g). The association between domain-specific physical activity and kidney function, and CKD prevalence was examined using multivariable-adjusted ordinary least squares and modified Poisson models. Results The mean eGFR was 98.1 (± 13.2) mL/min/1.73 m2. 3 185 (9.9%) participants were classified as having CKD. The mean LTPA and non-LTPA levels were 2.9 (± 4.2) and 16.6 (± 14.2) METs-hour/day, respectively. For LTPA, in the adjusted model, the quartile groups with higher levels had a higher kidney function (β, 0.36; 95% confidence intervals [CI], [0.06, 0.66]; p = 0.019 for the 2nd quartile, β, 0.82; 95% CI, [0.51, 1.14]; p

Background: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants’ characteristics based on their participation type in the baseline survey. Methods: The second period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the second period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The second period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). Results: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the second period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the second period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. Conclusion: The second period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Past earthquakes have shown that cracking affects post-earthquake functionality and accounted for huge repair costs for reinforced concrete (RC) wall buildings, even though the code-compliant seismic design prevents collapse. Engineers should know the maximum residual flexural crack width and volume of repair material needed for the flexural cracks to determine the damage degree and the repair cost. This paper presents the experimental campaign on four RC slender walls that investigated the effect of confining reinforcement and thickness of the wall on flexural crack parameters under quasi-static reversed cyclic loading. The width of all flexural cracks was measured when reaching each cycle peak drift and when unloading to zero lateral loads. Crack widths at peak and residual states increased with increasing peak drift. Based on the experimental observations, it was found that the maximum residual crack width is obtained as a simple function of the extreme tension fiber elongation of the wall tensile fiber within ±30% error. In addition, this paper outlines methods to calculate the volume of repair material for flexural cracks from the extreme tension fiber elongation of the wall. With the fundamental rules found from the experiment in this paper, it will become possible to obtain the maximum crack width and the volume of repair material from simple numerical analysis tools such as a multi-spring line element model.

Abstract To examine child-parent associations of HCT among Japanese adults and their parents. Factors associated with hematocrit (HCT) were analyzed in 3,574 sons and 7,203 daughters using Pearson’s correlation coefficient and Student’s t-test. Multiple linear regression analysis, adjusted by the factors identified by univariate analyses and by living with parents, was performed on 242 son-parent trios and 587 daughter-parent trios. When a child-parent association was observed in the multiple linear regression analysis, it was validated using the random family method (RFM). In univariate analyses, the son’s HCT was associated with age (correlation coefficient = –0.072), white blood cell (WBC) (0.19), alanine aminotransferase (ALT) (0.20), triglyceride (0.11), and estimated glomerular filtration rate (eGFR) (− 0.087). The daughter’s HCT was associated with WBC (0.014), ALT (0.18), and eGFR (− 0.17). In multiple linear regression analysis, the son’s HCT was associated with the son’s WBC (coefficient = 3.48 × 10–4), the son’s eGFR (0.031), the father’s HCT (0.11), and the mother’s HCT (0.17). RFM confirmed the association between the son’s and father’s HCT (p = 0.0070) and between the son’s and mother’s HCT (p = 0.0011). The daughter’s HCT was associated with WBC (2.6 × 10–4), ALT (0.037), and the mother’s HCT (0.14). RFM confirmed the association between the daughter’s and mother’s HCT (p = 0.00043). Child-parent association of HCT was confirmed between son-father, son–mother, and daughter-mother relationships, and differed depending on the sex of the child and the parents.

This study aimed to evaluate the associations of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels at

Abstract Understanding the physiological changes associated with aging and the associated disease risks is essential to establish biomarkers as indicators of biological aging. This study used the NMR-measured plasma metabolome to calculate age-specific metabolite indices. In doing so, the scope of the study was deliberately simplified to capture general trends and insights into age-related changes in metabolic patterns. In addition, changes in metabolite concentrations with age were examined in detail, with the period from 55–59 to 60–64 years being a period of significant metabolic change, particularly in men, and from 45–49 to 50–54 years in females. These results illustrate the different variations in metabolite concentrations by sex and provide new insights into the relationship between age and metabolic diseases.

ABSTRACT Aims This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). Methods A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at

Background: Various disease prediction models have been developed, capitalizing on the wide use of electronic health records, but environmental factors that are important in the development of noncommunicable diseases are rarely included in the prediction models. Hypertensive disorders of pregnancy are leading causes of maternal morbidity and mortality and are known to cause several serious complications later in life. Objective: This study aims to develop early hypertensive disorders of pregnancy prediction models using comprehensive environmental factors based on self-report questionnaires in early pregnancy. Study Design: We developed machine learning and artificial intelligence models for the early prediction of hypertensive disorders of pregnancy using early pregnancy data from approximately 23,000 pregnancies in the Tohoku Medical Megabank Birth and Three Generation Cohort Study. We clarified the important features for prediction based on regression coefficients or Gini coefficients of the interpretable artificial intelligence models (i.e., logistic regression, random forest and XGBoost models) among our developed models. Results: The performance of the early hypertensive disorders of pregnancy prediction models reached an area under the receiver operating characteristic curve of 0.93, demonstrating that the early hypertensive disorders of pregnancy prediction models developed in this study retain sufficient performance in hypertensive disorders of pregnancy prediction. Among the early prediction models, the best performing model was based on self-reported questionnaire data in early pregnancy (mean of 20.2 gestational weeks at filling) which consist of comprehensive lifestyles. The interpretation of the models reveals that both eating habits were dominantly important for prediction. Conclusion: We have developed high-performance models for early hypertensive disorders of pregnancy prediction using large-scale cohort data from the Tohoku Medical Megabank project. Our study clearly revealed that the use of comprehensive lifestyles from self-report questionnaires led us to predict hypertensive disorders of pregnancy risk at the early stages of pregnancy, which will aid early intervention to reduce the risk of hypertensive disorders of pregnancy.

ABSTRACT Background Epidemiological and economic literature has revealed that low birth weight (LBW) is related to poor health conditions and a broader range of negative socio‐economic outcomes, including academic achievement, income levels, and working status. However, Japanese evidence for labor outcomes is particularly lacking, as is the question of whether the impact of LBW on adulthood worsens when disasters occur. We aimed to reveal the impact on LBW on labor outcomes during the disaster recovery phase. Methods We used a cross‐sectional data set of 4156 national health insurance holders, males aged 40–60 years, from the Miyagi and Iwate prefectures during the earthquake recovery phase. Employing a multinomial probit and logistic model, we estimated the impact of LBW on the employment status, changes in income, and the propensity to face a decline in income with a job change. Results The very low birth weights (VLBWs) have a disadvantage in all labor market outcomes. Compared to the non‐LBWs, the VLBWs were 15.2% less likely to be full‐time/self‐employed and 17.1% more likely to be contingent/temporary/part‐time workers. Moreover, 32.9% are more likely to face a decline in income and approximately 3.7 times more likely to change jobs leading to income decline. The LBWs were likely to face a decline in income by 8.6% and 4.6%, respectively, but no other significant effects were found on other outcomes. Conclusions The effects were apparent for the VLBW, but not so much for the LBW. The effects became larger during the disaster recovery phase, even though the regional economies were boosted.

Abstract Aim To examine the association of the combination of taking neuropsychiatric medications from the onset of pregnancy to mid‐pregnancy and maternal psychological distress at mid‐pregnancy, with children's behavioral problems. Methods Neuropsychiatric medication use from the onset of pregnancy to mid‐pregnancy was defined by the self‐reported name of the neuropsychiatric medication in the questionnaire in early and mid‐pregnancy. Maternal psychological distress was defined by the Kessler Psychological Distress Scale (K6) ≥13 on the questionnaire in mid‐pregnancy. We classified the participants into four categories based on the combination of taking neuropsychiatric medications and psychological distress: “None,” “Medications only,” “K6 ≥ 13 only,” and “Both.” Children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½–5 (CBCL) at 2 years of age. The clinical ranges of the internalizing and externalizing scales of the CBCL were defined as behavioral problems. We conducted a multivariable logistic regression analysis to examine the associations between the four categories of maternal exposure and children's behavioral problems. Results Compared with the “None” category (n = 9873), the “K6 ≥ 13 only” category (n = 308) was statistically significantly associated with internalizing and externalizing problems. In contrast, the “Medications only” (n = 93) and “Both” (n = 22) categories were not statistically significantly associated with internalizing and externalizing problems, although the point estimates of the odds ratio in the “Both” category were relatively high (1.58 for the internalizing problem and 2.50 for the externalizing problem). Conclusion The category of mothers taking neuropsychiatric medications and having no psychological distress during pregnancy was not associated with children's behavioral problems in the present population.

Abstract Background Nausea and vomiting during pregnancy (NVP) and hyperemesis gravidarum (HG), common conditions affecting most pregnant women, are highly heritable and associated with maternal and fetal morbidity. However, the pathologies underlying NVP and HG and their associated loci are scarce. Methods We performed genome-wide association studies (GWAS) of NVP in pregnant women (n = 23,040) who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from July 2013 to March 2017. Participants were divided into discovery (n = 9,464) and replication (n = 10,051) stages based on the platform used for their genotyping. Loci that achieved the genome-wide significance level (p

Abstract Recently, many phenotyping algorithms for high-throughput cohort identification have been developed. Prospective genome cohort studies are critical resources for precision medicine, but there are many hurdles in the precise cohort identification. Consequently, it is important to develop phenotyping algorithms for cohort data collection. Hypertensive disorders of pregnancy (HDP) is a leading cause of maternal morbidity and mortality. In this study, we developed, applied, and validated rule-based phenotyping algorithms of HDP. Two phenotyping algorithms, algorithms 1 and 2, were developed according to American and Japanese guidelines, and applied into 22,452 pregnant women in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank project. To precise cohort identification, we analyzed both structured data (e.g., laboratory and physiological tests) and unstructured clinical notes. The identified subtypes of HDP were validated against reference standards. Algorithms 1 and 2 identified 7.93% and 8.08% of the subjects as having HDP, respectively, along with their HDP subtypes. Our algorithms were high performing with high positive predictive values (0.96 and 0.90 for algorithms 1 and 2, respectively). Overcoming the hurdle of precise cohort identification from large-scale cohort data collection, we achieved both developed and implemented phenotyping algorithms, and precisely identified HDP patients and their subtypes from large-scale cohort data collection.

Whether all obesity-related variants contribute to the onset of obesity or one or a few variants cause obesity in genetically heterogeneous populations remains obscure. Here, we investigated the genetic architecture of obesity by clustering the Japanese and British populations with obesity using obesity-related factors. In Step-1, we conducted a genome-wide association study (GWAS) with body mass index (BMI) as the outcome for eligible participants. In Step-2, we assigned participants with obesity (BMI ≥25 kg/m2) to five clusters based on obesity-related factors. Subsequently, participants from each cluster and those with a BMI

Abstract Background Continued use of tenofovir disoproxil fumarate (TDF), an antiretroviral drug, causes renal function decline and tubular damage in individuals with HIV. While tenofovir alafenamide fumarate (TAF) may have less damaging effects, it causes weight gain and abnormal lipid metabolism. Methods This single-center, retrospective cohort study used medical records from the National Hospital Organization Sendai Medical Center to investigate renal function of Japanese HIV-1-positive individuals who switched from TDF to antiretroviral therapy including TAF by 2017. The endpoints were: estimated glomerular filtration rate (eGFR), urinary β2 microglobulin (Uβ2MG), weight, and lipid metabolism parameters at 288 weeks after switching. Possible correlation between eGFR and Uβ2MG and factors affecting eGFR decline were examined. Results Sixty patients switched from TDF to TAF and continued therapy for 288 weeks. eGFR showed a significant decline after 144 weeks, although it was controlled from the time of change until 96 weeks. In the renal impairment group, the decline was suppressed until week 288. Uβ2MG continued to decrease significantly after 48 weeks. However, the suggested correlation between eGFR and Uβ2MG disappeared when patients switched from TDF to TAF. Weight and lipid metabolic parameters increased significantly at 48 weeks and were maintained. Factors associated with decreased eGFR were: history of acquired immune deficiency syndrome (AIDS) and Uβ2MG. However, considering the odds ratio, the switch from TDF to TAF suppressed the eGFR decline in the group with a history of AIDS, and Uβ2MG had no effect on the eGFR decline. Conclusions Switching from TDF to TAF for the long term slows eGFR decline, decreases Uβ2MG levels, and reduces worsening of renal function. Weight gain and abnormal lipid metabolism may occur in the short term but are controllable.

Abstract Background Schizophrenia is a psychiatric disorder characterized by hallucinations, delusions, and other symptoms. Although treatment guidelines for schizophrenia have been established in Japan, drugs are not recommended for pediatric schizophrenia. Additionally, the temporal trends in prescribing antipsychotics for pediatric patients with schizophrenia are unclear. Therefore, we aimed to clarify the trends in antipsychotic prescriptions for Japanese pediatric outpatients from 2015 to 2022. Methods Administrative data (as of November 2023) of Japanese pediatric outpatients with schizophrenia aged 0–18 years who visited acute-care diagnosis procedure combination hospitals between January 1, 2015, and December 31, 2022, were included in this study. The target drugs for schizophrenia were all indicated for treating schizophrenia and marketed in Japan as of December 2022. Annual prescription trends for antipsychotics during this period were calculated based on their proportions. The Cochran–Armitage trend test was used to evaluate the proportion of prescriptions for each antipsychotic. Results The main drugs prescribed for these patients were aripiprazole and risperidone. Among male patients, the proportion of prescriptions for aripiprazole increased significantly from 21.2% in 2015 to 35.9% in 2022, whereas that for risperidone decreased significantly from 47.9% in 2015 to 36.7% in 2022 (both P

Abstract Background Abnormal behavior after oseltamivir administration has been reported in the media; in 2007, the package insert for oseltamivir phosphate was revised to restrict its administration to individuals aged over 10 years. However, in 2018, the age limitation specified in the package insert was removed. Here, we evaluated the trends in anti-influenza drug prescription and adverse drug reactions (ADRs) reported in pediatric outpatients after revising the oseltamivir package insert as an ecological study. Methods Anti-influenza drug prescriptions for pediatric outpatients with influenza aged 0–19 years were downloaded from the acute Diagnosis Procedure Combination hospital databases using the MDV analyzer®. ADR reports on anti-influenza drug prescription among patients aged 0–20 years in the Japanese Adverse Drug Event Report database were downloaded from the Pharmaceutical and Medical Devices Agency website. Data were collected during the 2016/2017 and 2019/2020 influenza seasons. Results During the influenza epidemic season (January–March), the percentage of oseltamivir prescriptions for patients with influenza aged 10–19 years tripled after the revision of the oseltamivir package insert (9.3% during the 2016/2017 season and 29.2% during the 2019/2020 season); however, reports of abnormal behavior did not increase (two during the 2016/2017 season and none during the 2019/2020 season). Conclusions The number of oseltamivir-related ADR reports among minors over 10 years of age did not increase although the proportion of oseltamivir prescriptions increased after the revision of the oseltamivir package insert.

Abstract Background Japanese traditional (Kampo) medicines containing ephedra may be used to treat colds during pregnancy. There are reports that ephedrine, a component of ephedra, has a risk of teratogenicity; however, the evidence remains equivocal. Objective This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with exposure to Kampo medicines containing ephedra during the first trimester of pregnancy using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). Methods To 23,730 mother–infant pairs who participated in the TMM BirThree Cohort Study from July 2013 to March 2017, questionnaires in early and middle pregnancy were distributed approximately at weeks 12 and 26 of pregnancy, respectively. Infants' risk of MCMs in women who used Kampo medicines containing ephedra or acetaminophen during the first trimester was assessed, and the odds ratios (ORs) were estimated with unadjusted and adjusted analyses. Results Among 20,879 women, acetaminophen and Kampo medicines containing ephedra were used in 665 (3.19%) and 376 (1.80%) women, respectively, in the first trimester. Among the infants born to the mothers who used acetaminophen or Kampo medicine containing ephedra during the first trimester, 11 (1.65%) and 8 (2.13%), respectively, had overall MCMs. OR of overall MCMs was higher in women who used Kampo medicines containing ephedra than in those who used acetaminophen in the first trimester (adjusted OR, 1.45; 95% confidence interval (CIs), 0.57–3.71); however, the difference was not statistically significant. Conclusions In this study, there was no statistically significant association between the use of Kampo medicines containing ephedra during the first trimester of pregnancy and the risk of MCMs. Although some point estimates of ORs exceeded 1.00, the absolute magnitude of any increased risks would be low.

Abstract Background Hospitals in Japan established the healthcare delivery system from FY 2018 to 2021 by acquiring an additional reimbursement for infection prevention (ARIP) of category 1 or 2. However, research on outcomes of ARIP applications related to the practice of hospital pharmacists is scarce. Methods This study assessed the activities performed by hospital pharmacists in hospitals with 100 to 299 beds, using ARIP acquirement as an indicator, using data from an annual questionnaire survey conducted in 2020 by the Japanese Society of Hospital Pharmacists on the status of hospital pharmacy departments. Out of the survey items, this study used those related to hospital functions, number of beds, number of pharmacists, whether the hospital is included in the diagnosis procedure combination (DPC) system, average length of stay, and nature of work being performed in the analysis. The relationship between the number of beds per pharmacist and state of implementation of pharmacist services or the average length of hospital stay was considered uncorrelated when the absolute value of the correlation coefficient was within 0–0.2, whereas the relationship was considered to have a weak, moderate, or strong correlation when the absolute value ranged at 0.2–0.4, 0.4–0.7, or 0.7–1, respectively. Results Responses were received from 3612 (recovery rate: 43.6%) hospitals. Of these, 210 hospitals meeting the criteria for ARIP 1 with 100–299 beds, and 245 hospitals meeting the criteria for ARIP 2 with 100–299 beds, were included in our analysis. There was a significant difference in the number of pharmacists, with a larger number in ARIP 1 hospitals. For the pharmacist services, significant differences were observed, with a more frequency in ARIP 1 hospitals in pharmaceutical management and guidance to pre-hospitalization patients, sterile drug processing of injection drugs and therapeutic drug monitoring. In DPC hospitals with ARIP 1 (173 hospitals) and 2 (105 hospitals), the average number of beds per pharmacist was 21.7 and 24.7, respectively, while the average length of stay was 14.3 and 15.4 d, respectively. Additionally, a weak negative correlation was observed between the number of pharmacist services with “Fairly well” or “Often” and the number of beds per pharmacist for both ARIP 1 (R = -0.207) and ARIP 2 (R = -0.279) DPC hospitals. Furthermore, a weak correlation (R = 0.322) between the average number of beds per pharmacist and the average length of hospital stay was observed for ARIP 2 hospitals. Conclusions Our results suggest that lower beds per pharmacist might lead to improved pharmacist services in 100–299 beds DPC hospitals with ARIP 1 or 2. The promotion of proactive efforts in hospital pharmacist services and fewer beds per pharmacist may relate to shorter hospital stays especially in small and medium-sized hospitals with ARIP 2 when ARIP acquisition was used as an indicator. These findings may help to accelerate the involvement of hospital pharmacists in infection control in the future.

Abstract Background Although an association between maternal nutritional intake and developmental delays in children has been demonstrated, the association of the timing of meal intake and development delays remains unclear. We examined the association between breakfast intake frequency before and during pregnancy and developmental delay in children. Methods Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 7491 answered the required questions and were analyzed. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: daily, and 5–6, 3–4, and 0–2 times/week. Child developmental delays at age 2 and 3.5 years were assessed using the Ages & Stages Questionnaire, Third Edition. Logistic regression models were constructed to examine the association between breakfast intake frequency in pregnant women and developmental delays in children aged 2 and 3.5 years. Results The proportion of pregnant women who had breakfast daily was 78.1% in pre- to early pregnancy, and 82.2% in early to mid-pregnancy. The proportion of children with developmental delays was 14.7% and 13.4% at age 2 and 3.5 years, respectively. Compared with the risk in children of women who had breakfast daily from pre- to early pregnancy, children of women who had breakfast 0–2 times/week had a higher risk of developmental delays at 2 years of age: odds ratio (OR) 1.30, (95% confidence interval [CI], 1.02–1.66). The risk of developmental delays at age 2 years increased in the children of women who had breakfast 0–2 times/week in early to mid- pregnancy: OR 1.75 (95% CI, 1.32–2.32). The risk of developmental delays at age 3.5 years did not increase in the children of women who had breakfast 0–2 times/week from pre- to early and early to mid-pregnancy: OR 1.06 (95% CI, 0.81–1.39 and OR 1.15 (95% CI 0.84–1.57), respectively. Conclusion For women with a low frequency of breakfast intake from pre- to mid-pregnancy there was an association with developmental delays in their children at age 2, but not at 3.5 years.

Abstract Background and Aim There is a scarcity of data on long‐term outcomes in patients with new‐onset ulcerative colitis (UC) in the era of biologics. We aimed to clarify the long‐term prognosis of UC and the clinical practice of prescriptions for UC. Methods We collected 6689 new‐onset UC cases using a medical claim database provided by DeSC Healthcare, Inc. We investigated the surgery‐free, systemic steroid‐free, and molecular targeting drug‐free rates and compared their differences based on UC‐onset age. We used multivariate analysis to identify clinical factors affecting long‐term prognosis and investigated the transition of prescriptions for UC. Results The surgery‐free, systemic steroid‐free, and molecular targeting drug‐free rates at 5 years post‐UC diagnosis were 98.5%, 61.0%, and 88.7%, respectively. Pediatric patients had higher surgery‐free rates compared with elderly patients and non‐pediatric/non‐elderly patients (P = 0.022), whereas the systemic steroid‐free and molecular targeting drug‐free rates were significantly lower (P

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

Abstract Background Low birth weight (LBW) is a leading cause of neonatal morbidity and mortality, and increases various disease risks across life stages. Prediction models of LBW have been developed before, but have limitations including small sample sizes, absence of genetic factors and no stratification of neonate into preterm and term birth groups. In this study, we challenged the development of early prediction models of LBW based on environmental and genetic factors in preterm and term birth groups, and clarified influential variables for LBW prediction. Methods We selected 22,711 neonates, their 21,581 mothers and 8,593 fathers from the Tohoku Medical Megabank Project Birth and Three-Generation cohort study. To establish early prediction models of LBW for preterm birth and term birth groups, we trained AI-based models using genetic and environmental factors of lifestyles. We then clarified influential environmental and genetic factors for predicting LBW in the term and preterm groups. Results We identified 2,327 (10.22%) LBW neonates consisting of 1,077 preterm births and 1,248 term births. Our early prediction models archived the area under curve 0.96 and 0.95 for term LBW and preterm LBW models, respectively. We revealed that environmental factors regarding eating habits and genetic features related to fetal growth were influential for predicting LBW in the term LBW model. On the other hand, we identified that genomic features related to toll-like receptor regulations and infection reactions are influential genetic factors for prediction in the preterm LBW model. Conclusions We developed precise early prediction models of LBW based on lifestyle factors in the term birth group and genetic factors in the preterm birth group. Because of its accuracy and generalisability, our prediction model could contribute to risk assessment of LBW in the early stage of pregnancy and control LBW risk in the term birth group. Our prediction model could also contribute to precise prediction of LBW based on genetic factors in the preterm birth group. We then identified parental genetic and maternal environmental factors during pregnancy influencing LBW prediction, which are major targets for understanding the LBW to address serious burdens on newborns' health throughout life.

Abstract We evaluated the association between maternal prenatal folic acid supplement use/dietary folate intake and cognitive development in 4-year-old offspring (N = 3445) using data from the Japan Environment and Children’s Study. Cognitive development was evaluated using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis revealed that offspring of mothers who started using folic acid supplements pre-conception had a significantly higher language-social developmental quotient (DQ) (partial regression coefficient 1.981, 95% confidence interval 0.091 to 3.872) than offspring of mothers who did not use such supplements at any time throughout their pregnancy (non-users). Offspring of mothers who started using folic acid supplements within 12 weeks of gestation had a significantly higher cognitive-adaptive (1.489, 0.312 to 2.667) and language-social (1.873, 0.586 to 3.159) DQ than offspring of non-users. Regarding daily dietary folate intake from preconception to early pregnancy, multiple regression analysis revealed that there was no significant association with any DQ area in the 200 to

Abstract Objective: The association between high sugar-sweetened beverages (SSB) intake during pregnancy and offspring overweight/obesity has been reported only from Western countries. The objective of this study was to examine the association between SSB intake before and during pregnancy and offspring overweight/obesity among Japanese women. Design: Japanese prospective birth cohort study. Setting: We analysed mother–offspring pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SSB intake during pregnancy was evaluated using the FFQ and classified into three groups: none (0 g/d), medium (195 g/d). Overweight or obesity at 1 year of age in offspring was defined as having a BMI Z-score greater than 2 sd, calculated based on the BMI reference data for Japanese children. Multiple logistic regression analyses were performed to examine the associations between SSB intake before and during pregnancy and offspring overweight/obesity, after adjusting for covariates. Participants: Japanese mother–offspring pairs (n 7114). Results: The overweight/obesity rate of the offspring was 8·8 %. Pregnant women with a high intake of SSB in early to mid-pregnancy had a higher risk of overweight/obesity in their offspring compared with those who did not; the OR was 1·52 (95 % CI (1·09, 2·12)). Conclusions: High SSB intake in early to mid-pregnancy was associated with an increased risk of offspring overweight/obesity at 1 year of age.

Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, the association between infertility treatment and HDP was analyzed. A multiple logistic regression model showed an association between infertility treatment and HDP (odds ratio, 1.34; 95% confidence interval, 1.05–1.72). In vitro fertilization/intracytoplasmic sperm injection were also associated with HDP. Moreover, these associations were observed even among women who were not overweight and did not smoke. The application of infertility treatment should be carefully considered, even among women with low modifiable risk factors.

Abstract Objective In children in a metropolitan area of Tokyo, Japan, behavioral change and influenza infection associated with the frequency of nonpharmaceutical interventions (NPI) was assessed from the 2018–2019 season (Preseason) and the 2020–2021 season (coronavirus disease 2019 [COVID-19] season). Methods We conducted an exclusive survey among children attending preschool, elementary school, and junior high school in the Toda and Warabi regions, Japan, during the 2018–2019 (Preseason, distributed via mail) and 2020–2021 seasons (COVID-19 season, conducted online). The proportion of preventive activities (hand washing, face mask-wearing, and vaccination) was compared in the Preseason with that of the COVID-19 season. The multivariate logistic regression model was further applied to calculate the adjusted odds ratio (AOR) with 95% confidence intervals (CIs) for influenza infection associated with NPI frequency (hand washing and face mask wearing) in each Preseason and COVID-19 season. Results The proportion of vaccinated children who carried out hand washing and face mask wearing was remarkably higher during the COVID-19 season (48.8%) than in the Preseason (18.2%). A significant influenza infection reduction was observed among children who washed hands and wore face masks simultaneously (AOR, 0.87; 95% CI, 0.76–0.99; P = 0.033). Conclusions A strong interest and performance in the intensive measures for the prevention of influenza under the COVID-19 pandemic was demonstrated. Positive association was observed from a combination of NPI, hand washing, and face mask-wearing and influenza infection. This study’s findings could help in activities or preventive measures against influenza and other communicable diseases in children.

Abstract Background Low birth weight is associated with an increased risk of developing chronic diseases in adulthood, with a particularly high incidence in Japan among developed countries. Maternal undernutrition is a risk factor for low birth weight, but the association between the timing of food intake and infant birth weight has not been investigated. This study aimed to examine the association between breakfast intake frequency among Japanese pregnant women and infant birth weight. Methods Of all pregnant women who participated in the Tohoku Medical Megabank Project Three Generation Cohort Study, 16,820 who answered the required questions were included in the analysis. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: every day and 5–6, 3–4, and 0–2 times/week. Multivariate linear regression models were constructed to examine the association between breakfast intake frequency among pregnant women and infant birth weight. Results The percentage of pregnant women who consumed breakfast daily was 74% in the pre- to early pregnancy period and 79% in the early to mid-pregnancy period. The average infant birth weight was 3,071 g. Compared to women who had breakfast daily from pre- to early pregnancy, those who had breakfast 0–2 times/week had lower infant birth weight (β = -38.2, 95% confidence interval [CI]: -56.5, -20.0). Similarly, compared to women who had breakfast daily from early to mid-pregnancy, those who had breakfast 0–2 times/week had lower infant birth weight (β = -41.5, 95% CI: -63.3, -19.6). Conclusions Less frequent breakfast intake before and mid-pregnancy was associated with lower infant birth weight.

Background: The present study analyzed the relation of disaster exposure prior to pregnancy with maternal characteristics and obstetric outcomes. Methods: The participants were 13,148 pregnant women recruited from 2013 to 2017. The women were classified into three groups by the severity of housing damage caused by the Great East Japan Earthquake of 2011: group A, house was not destroyed/did not live in the disaster area; group B, half/part of the house was destroyed; and group C, house was totally/mostly destroyed. Maternal characteristics, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), and gestational weeks were obtained using questionnaires and medical records. Multiple logistic regression analyses were performed to investigate the relation between disaster exposure and maternal characteristics, HDP, and GDM. A structural equation model was applied to investigate the relation of disaster exposure with HDP and gestational weeks. Results: The homes of about 11% of the women were totally/mostly destroyed. For groups B and C compared with those in group A, the adjusted ORs for HDP were 1.04 and 1.26 (P for trend = 0.01), and for GDM were 0.89 and 1.14 (P for trend = 0.9), respectively. Pre-pregnancy body mass index (BMI) mediated 23.2% of the relation between disaster exposure and HDP. Disaster exposure was associated with gestational weeks. Conclusion: Disaster exposure at least 2.5 years before pregnancy was found to be associated with maternal characteristics and the prevalence of HDP. Pre-pregnancy BMI mediated the relation between disaster exposure and the prevalence of HDP, and gestational weeks were reduced through HDP.

Abstract This study aimed to explore the relationship between dietary electrolyte intake and the prevalence of hypertensive disorders of pregnancy (HDP) subtypes. Our analysis included 19 914 pregnant women from the Tohoku Medical Megabank Project Birth and Three‐Generation Cohort Study. A food frequency questionnaire was used to estimate dietary calcium, potassium, sodium, and magnesium intakes. HDP was determined based on the medical records during regular antenatal care. Logistic regression analysis assessed the relationship between dietary electrolytes intake quintiles, and HDP subtypes with adjustment for basic characteristics. Dietary electrolyte intakes were applied for the prediction model. Of the cohort, 547 participants delivered with pre‐eclampsia (PE), 278 with superimposed PE (SP), and 896 with gestational hypertension (GH). PE was associated with low crude calcium intake (odds ratio of the first quintile [623 mg/day] and 95% confidence interval, 1.31 [1.00–1.70]) and P for trend was .02. SP was not associated with any nutritional intake; however, the combined outcome of PE and SP was related to low crude calcium and potassium and energy‐adjusted calcium, potassium, and magnesium intakes (P for trend, .01, .048, .02, .04, and .02, respectively). The same tendency was observed for GH. A prediction model that included crude calcium and potassium intakes performed better than a model without them. In conclusion, low dietary calcium, potassium, and magnesium were associated with higher HDP subtypes prevalence. The prediction model implied that crude calcium and potassium intakes might play a critical role in PE and SP pathogenesis.

We aimed to evaluate the adverse birth outcomes of anticancer drug prescription during pregnancy using a Japanese claims database from 2005 to 2019. We applied validated claims-based algorithms to identify pregnant women with birth outcomes, and evaluated drug prescription during pregnancy. The causal relationship between anticancer drugs and adverse birth outcomes was evaluated using the Council for International Organizations of Medical Sciences Working Group VI criteria. Thirteen women with anticancer drugs prescription during pregnancy were identified (mean age: 34.6 years). Atrial/ventricular septal defect was observed in one infant after exposure to cyclophosphamide and doxorubicin for breast cancer in the second and third trimesters. One woman on several anticancer drugs (cyclophosphamide, cytarabine, daunorubicin, l-asparaginase, methotrexate, nelarabine, and vincristine) for acute lymphoblastic leukemia, one on imatinib for chronic myeloid leukemia, and one on cisplatin and fluorouracil for cervical cancer had miscarriages after exposure in the first trimester. A relationship between those anticancer drugs and miscarriage could not be ruled out, while no relationship was identified regarding the atrial/ventricular septal defect considering the period of exposure and organogenesis. Our results suggest increased risk of miscarriage with the use of several anticancer drugs such as methotrexate, imatinib, cisplatin, and fluorouracil in the first trimester.

Background: While a wide range of predictors of postpartum smoking relapse have been suggested, population-based studies have rarely examined these factors exclusively among women who quit in early pregnancy. Furthermore, workplace secondhand smoke (SHS) exposure has never been examined. Methods: We analyzed data from 10,466 pregnant women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Age, education, parity, breastfeeding, postpartum depression, SHS exposure at home, and SHS exposure at work (not working, working without SHS exposure, working with SHS exposure) were evaluated as possible predictors. Multiple logistic regression analyses were conducted to examine the associations between these factors and smoking relapse by 1 year postpartum among women who quit in early pregnancy. Analyses stratified by SHS exposure at home were also conducted. Results: About one-fourth of early-pregnancy quitters had relapsed into smoking by 1 year postpartum. Lower education, multiparity, not breastfeeding, postpartum depression, and SHS exposure at home were associated with increased risks of smoking relapse. Working with SHS exposure was associated with an increased risk of smoking relapse; the multivariate-adjusted odds ratios of working without SHS exposure and working with SHS exposure compared with not working were 1.14 (95% confidence interval [CI], 0.82–1.59) and 2.18 (95% CI, 1.37–3.46), respectively. The significant association of workplace SHS exposure was observed only among women without SHS exposure at home. Conclusion: SHS exposure at work, as well as education, multiparity, breastfeeding, postpartum depression, and SHS exposure at home were associated with postpartum smoking relapse among early-pregnancy quitters.

Abstract Background Hypertensive disorders of pregnancy (HDP) adversely affect the prognosis of mother and child, and the prognosis depends on the subtype of HDP. Skipping breakfast may be associated with increased blood pressure due to disruption of the circadian clock, but the association with the development of HDP has not been studied. The purpose of this study was to examine the association between skipping breakfast and the development of HDP and HDP subtypes in Japanese pregnant women. Methods Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 18,839 who answered the required questions were included in the analysis. This study had a cross-sectional design. The breakfast intake frequency from pre-pregnancy to early pregnancy was classified into four groups: daily, 5–6 times per week, 3–4 times per week, and 0–2 times per week. HDP was classified into gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and severe preeclampsia (SuPE). Multiple logistic regression analysis and multinomial logistic analysis were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for breakfast intake frequency and development of HDP or HDP subtypes. We performed a stratified analysis based on energy intake. Results Of the participants, 74.3% consumed breakfast daily, and 11.1% developed HDP. Women who consumed breakfast 0–2 times per week had a higher risk of HDP (OR: 1.33, 95% CI: 1.14–1.56), CH (OR: 1.63, 95% CI: 1.21–2.19), and PE (OR: 1.68, 95% CI: 1.27–2.21) than those who consumed breakfast daily. No association was found between skipping breakfast and the risk of developing GH (OR: 1.26, 95% CI: 0.99–1.61) and SuPE (OR: 0.91, 95% CI: 0.55–1.49). Stratified analysis showed that the risk of developing HDP due to skipping breakfast was highest in the group with the highest daily energy intake. Conclusions Skipping breakfast during pre-to early pregnancy is associated with the development of HDP. Further longitudinal studies are required to clarify the causal association between skipping breakfast and HDP.

Abstract Background Childcare facilities are a factor that lowers the established association of mother’s postnatal psychiatric symptoms with children's behavioral problems. However, no studies have considered the prenatal psychiatric symptoms yet. This study examined whether the use of childcare facilities moderates the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years. Methods The present study was based on the data from 23,130 mother–child pairs participating in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. K6 was used to classify maternal psychological distress in early pregnancy and at two years postpartum into four categories: none in both prenatal and postnatal periods (none), only the prenatal period (prenatal only); only the postnatal period (postnatal only); both prenatal and postnatal periods (both). The children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½–5 (CBCL) aged four years. The clinical range of the externalizing, internalizing, and total problem scales of the CBCL was defined as having behavioral problems. To examine whether availing childcare facilities moderates the association between maternal psychological distress and children's behavioral problems, we conducted a stratified analysis based on the use of childcare facilities or not, at two years of age. The interaction term between maternal psychological distress and use of childcare facilities was included as a covariate in the multivariate logistic regression analysis to confirm the p-value for the interaction. Results The prevalence of the clinical ranges of externalizing problems, internalizing problems, and clinical range of total problems were 13.7%, 15.4%, and 5.8%, respectively. The association of maternal psychological distress with a high risk of children's behavioral problems was significant; however, the association between prenatal only psychological distress and externalizing problems in the group that did not use childcare facilities was not significant. Interactions between the use of childcare facilities and maternal psychological distress on behavioral problems in children were not significant. Conclusions Use of childcare facilities did not moderate the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years.

Abstract Background Information sharing among medical professionals is important for providing quality medical care. The purpose of the present study was to elucidate the actual status of information sharing between hospitals and other healthcare delivery facilities by surveying information sharing among the pharmaceutical departments of Japanese hospitals in 2020 conducted by the Japanese Society of Hospital Pharmacists. Methods Responses were received from 3612 (43.6%) of the 8278 target medical institutions between May 2020 and August 2020. Results The proportions of hospitals that shared information with community pharmacies, other hospitals, and long-term nursing homes were 40.6%, 36.4%, and 27.3%, respectively. While tracing reports were the most common tool used by hospitals for information sharing with community pharmacies (54.3%), drug summaries were used for sharing information with other hospitals and long-term nursing homes (77.4% and 78.0%, respectively). The proportion of hospitals sharing information with community pharmacies and other hospitals showed a tendency to increase as the number of hospital beds increased. No relationship could be established between the number of hospital beds and the proportion of hospitals sharing information with long-term nursing homes. Conclusion Information between hospitals and community pharmacies was shared primarily using tracing reports, whereas information between hospitals and other hospitals and long-term nursing homes was primarily shared via drug summaries.

Abstract Background: Previous observational studies have shown similarities in cardiometabolic risk factors between spouses. It is still possible that this result reflects the age similarity of spouses rather than environmental factors of spouses (e.g. cohabitation effect). To clarify the importance of mate cardiometabolic risk factors for similarity of environmental factors, it is necessary to examine whether they are observed in random male-female pairs while maintaining the age of the spousal pairs. This study aimed to determine whether the similarities found between spousal pairs for cardiometabolic risks were also observed between random male-female pairs. Methods: This cross-sectional study included 5,391 spouse pairs from Japan; data were obtained from a large biobank study. For pairings, women of the same age were randomly shuffled to create new male-female pairs of the same age as that of the original spouse pairs. Similarities in cardiometabolic risk factors between the random male-female pairs were analysed using Pearson’s correlation or age-adjusted logistic regression analyses. Results: The mean ages of the men and women were 63.2 and 60.4 years, respectively. Almost all cardiometabolic risk factors similarities were not noted in cardiometabolic risk factors, including the continuous risk factors (anthropometric traits, blood pressure, glycated haemoglobin level, and lipid traits); lifestyle habits (smoking, drinking, and physical activity); or diseases (hypertension, type 2 diabetes mellitus, and metabolic syndrome) between the random male-female pairs. The age-adjusted correlation coefficients ranged from − 0.007 for body mass index to 0.071 for total cholesterol. The age-adjusted odds ratio (95% confidence interval) for current drinkers was 0.94 (0.81 − 1.09); hypertension, 1.07 (0.93 − 1.23); and type 2 diabetes mellitus, 1.08 (0.77 − 1.50). Conclusion: In this study, few similarities in cardiometabolic risk factors were noted among the random male-female pairs. As spouse pairs may share environmental factors, intervention strategies targeting lifestyle habits and preventing lifestyle-related diseases may be effective.

Abstract Background Although small for gestational age (SGA) is a serious problem worldwide, the association of dietary patterns before and during pregnancy with SGA risk is unclear. We evaluated this association among Japanese pregnant women using three methods: reduced rank regression (RRR) and partial least squares (PLS), methods for extracting dietary patterns that can explain the variation of response variables, and principal component analysis (PCA), a method for extracting dietary patterns of the population. Methods Between July 2013 and March 2017, 22,493 pregnant women were recruited to the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a population-based prospective birth cohort study in Japan. Information on dietary intake was obtained using food frequency questionnaires, and dietary patterns were extracted using RRR, PLS, and PCA. Information on birth weight was obtained from obstetric records, and the birth weight SD score and SGA were defined by the method of the Japan Pediatric Society. The associations of dietary patterns with birth weight SD score and SGA risk were investigated using multiple linear regression and multiple logistic regression, respectively. Results A total of 17,728 mother-child pairs were included. The birth weight SD score was 0.15 ± 0.96, and the prevalence of SGA was 6.3%. The dietary patterns extracted by RRR and PLS were similar and characterized by a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages in both pre- to early pregnancy and from early to mid-pregnancy. Higher adoption of the RRR and PLS patterns in both periods was associated with an increased birth weight SD score and lower risk of SGA. In contrast, the PCA1 pattern was not associated with birth weight SD score or SGA risk in either period. Although the PCA2 pattern was associated with increased birth weight SD score from early to mid-pregnancy, no other associations with birth weight SD score or SGA risk were observed. Conclusions The dietary pattern with a high intake of cereals and fruits and a low intake of alcoholic and non-alcoholic beverages before and during pregnancy was associated with a decreased SGA risk in Japan.

IntroductionPerinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep–wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV).MethodsNine HRV indicators (features) and sleep–wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep–wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated—shallow sleep, deep sleep, and the two types of wake conditions—was also tested.Results and DiscussionIn the test for predicting three types of sleep–wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82–0.88) and accuracy (0.78–0.81). The test using four types of sleep–wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep–wake conditions. Among the seven features, “the number of interval differences of successive RR intervals greater than 50 ms (NN50)” and “the proportion dividing NN50 by the total number of RR intervals (pNN50)” were useful to predict sleep–wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of

A fetal growth restriction is related to adverse child outcomes. We investigated risk ratios and population-attributable fractions (PAF) of small-for-gestational-age (SGA) infants in the Japanese population. Among 28,838 infants from five ongoing prospective birth cohort studies under the Japan Birth Cohort Consortium, two-stage individual-participant data meta-analyses were conducted to calculate risk ratios and PAFs for SGA in advanced maternal age, pre-pregnancy underweight, and smoking and alcohol consumption during pregnancy. Risk ratio was calculated using modified Poisson analyses with robust variance and PAF was calculated in each cohort, following common analyses protocols. Then, results from each cohort study were combined by meta-analyses using random-effects models to obtain the overall estimate for the Japanese population. In this meta-analysis, an increased risk (risk ratio, [95% confidence interval of SGA]) was significantly associated with pre-pregnancy underweight (1.72 [1.42–2.09]), gestational weight gain (1.95 [1.61–2.38]), and continued smoking during pregnancy (1.59 [1.01–2.50]). PAF of underweight, inadequate gestational weight gain, and continued smoking during pregnancy was 10.0% [4.6–15.1%], 31.4% [22.1–39.6%], and 3.2% [−4.8–10.5%], respectively. In conclusion, maternal weight status was a major contributor to SGA births in Japan. Improving maternal weight status should be prioritized to prevent fetal growth restriction.

Traditional Japanese (Kampo) medicines containing rhubarb rhizome are prescribed for constipation during pregnancy; however, detailed safety information of their use for pregnant women is lacking. The aim of current study was to clarify the association between prescription Kampo-containing rhubarb rhizome (KRR) in the first trimester of pregnancy and congenital malformations in newborns. Using a large Japanese health insurance claims database, we included pregnant women who enrolled the same health insurance society from 3 months before pregnancy to the delivery date, who gave birth between 2010 and 2019, and those with data related to their infants. Pregnant women who were prescribed magnesium oxide (MgO), commonly used for constipation, during the first trimester of pregnancy and their infants were extracted as controls. Associations between KRR prescribed in the first pregnancy trimester and major congenital malformations (MCM) in the infants were examined using multivariate logistic regression analysis. Of 75,398 infants, 4,607 (6.1%) were diagnosed with MCMs within the first year after birth. Furthermore, 9,852 infants were born to women prescribed MgO, among whom 680 (6.9%) had MCMs; 450 infants were born to women prescribed KRR, among whom 28 (6.2%) had MCMs. Multivariate logistic regression analysis identified no difference in MCM risk between the two types of prescriptions [crude odds ratio (OR) 0.895, 95% confidence interval (CI) 0.606–1.322, adjusted OR 0.889, 95% CI 0.599–1.320]. In conclusion, the risk of MCMs did not differ between those prescribed KRR or MgO in the first trimester of pregnancy.

Abstract This study aimed to construct a prediction model for small-for-gestational-age (SGA) infants in Japan by creating a risk score during pregnancy. A total of 17,073 subjects were included in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study. A multiple logistic regression model was used to construct risk scores during early and mid-gestational periods (11–17 and 18–21 weeks of gestation, respectively). The risk score during early gestation comprised the maternal age, height, body mass index (BMI) during early gestation, parity, assisted reproductive technology (ART) with frozen-thawed embryo transfer (FET), smoking status, blood pressure (BP) during early gestation, and maternal birth weight. The risk score during mid-gestation also consisted of the maternal age, height, BMI during mid-gestation, weight gain, parity, ART with FET, smoking status, BP level during mid-gestation, maternal birth weight, and estimated fetal weight during mid-gestation. The C-statistics of the risk scores during early- and mid-gestation were 0.658 (95% confidence interval [CI]: 0.642–0.675) and 0.725 (95% CI: 0.710–0.740), respectively. In conclusion, the predictive ability of the risk scores during mid-gestation for SGA infants was acceptable and better than that of the risk score during early gestation.

Abstract Personality has been shown to predict postpartum depressive symptoms (PDS) assessed by the Edinburgh Postnatal Depression Scale (EPDS). However, existing studies have not considered the underlying symptom dimensions in the EPDS. We analyzed data from 15,012 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Personality was assessed in middle pregnancy using the short-form Eysenck Personality Questionnaire-Revised. PDS were defined as EPDS score ≥ 9 at 1 month after delivery. The EPDS items were further divided into three dimensions: depressed mood, anxiety, and anhedonia. Multiple analyses were conducted to examine the associations of each personality scale with PDS and three dimensions in the EPDS, adjusting for age, parity, mode of delivery, education, income, and social isolation. The prevalence of PDS assessed by the EPDS at 1 month after delivery was 13.1%. Higher neuroticism scores were associated with PDS (odds ratio [OR], 2.63; 95% confidence interval [CI], 2.48 to 2.79) and all three dimensions (all p

Abstract Background Maternal mental health problems in each of the prenatal period and postnatal period have been demonstrated as possible risk factors for atopic dermatitis (AD) in children. However, the cumulative impacts of maternal psychological distress in the prenatal and postnatal periods on AD in children remain unclear. This study examined the association between cumulative exposure to maternal psychological distress in the prenatal and postnatal periods and the development of AD in children. Methods Data were derived from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. In total, 8377 mother-child pairs in which the child had no AD at the age of 1 year were analyzed. Maternal psychological distress in early pregnancy and 1 year after delivery was defined as a K6 score ≥ 5, and the participants were categorized into four groups: no psychological distress in both the prenatal and postnatal periods; only the prenatal period; only the postnatal period; and both periods. The development of AD was defined as the presence of AD in a 2-year-old child without AD reported at the age of 1 year using the International Study of Asthma and Allergies in Childhood questionnaire. Generalized linear model analyses were conducted to examine the association between maternal psychological distress and the development of AD in children adjusted for age at delivery, educational attainment, smoking status in pregnancy, maternal history of AD, paternal history of AD, parity, maternal body mass index, and child sex. Results Between the ages of 1 and 2 years, 14.0% of children developed AD. Maternal psychological distress in both prenatal and postnatal periods was associated with an increased risk of AD in children compared to no psychological distress in both periods (relative risk (RR), 95% confidence interval (CI): 1.34, 1.20–1.47). Maternal psychological distress in only the postnatal period was associated with an increased risk of AD in children (RR, 95% CI: 1.23, 1.07–1.39), but not in only the prenatal period (RR, 95% CI: 1.14, 0.98–1.30). Conclusions Cumulative exposure to maternal psychological distress in the prenatal and postnatal periods was associated with the development of AD in children.

Background: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study was launched in 2013 to evaluate the complex interactions of genetic and environmental factors in multifactorial diseases. The present study describes the maternal baseline profile and perinatal data of participating mothers and infants. Methods: Expectant mothers living in Miyagi Prefecture were recruited from obstetric facilities or affiliated centers between 2013 and 2017. Three sets of self-administered questionnaires were collected, and the medical records were reviewed to obtain precise information about each antenatal visit and each delivery. Biospecimens, including blood, urine, umbilical cord blood, and breast milk, were collected for the study biobank. The baseline maternal sociodemographic characteristics, results of screening tests, and obstetric outcomes were analyzed according to the maternal age group. Results: A total of 23,406 pregnancies involving 23,730 fetuses resulted in 23,143 live births. Younger maternal participants had a tendency toward a higher incidence of threatened abortion and threatened premature labor, while older age groups exhibited a significantly higher rate of low lying placenta, placenta previa, gestational diabetes, and hypertensive disorders of pregnancy. Conclusions: The present study clearly shows the distribution of maternal baseline characteristics and the range of perinatal outcomes according to maternal age group. This cohort study can provide strategic information for creating breakthroughs in the pathophysiology of perinatal, developmental, and noncommunicable diseases by collaborative data visiting or sharing.

Introduction and Objectives: Patients with non-alcoholic fatty liver disease (NAFLD) are at risk for cardiovascular and chronic kidney diseases. Liver steatosis and fibrosis were assessed using the fatty liver index and fibrosis-4 index, respectively. This study aimed to examine the association between these two parameters in patients with atherosclerosis and chronic kidney disease. Materials and Methods: The two parameters were calculated for 11,867 adults who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Intima-media thickness and estimated glomerular filtration rate were also measured. Logistic regression models were used to estimate the odds ratios (OR). Results: Overall, 4257 (35.9%) and 4733 (39.9%) participants had a higher probability of liver steatosis and fibrosis, respectively. The adjusted OR of higher fatty liver index compared to lower fatty liver index for atherosclerosis and chronic kidney disease were 0.98 (95% confidence interval [CI], 0.77–1.24) and 1.79 (95% CI, 1.19–2.69), and those of higher FIB-4 compared to lower FIB-4 were 1.03 (95% CI, 0.82–1.30) and 0.79 (95% CI, 0.52–1.19) for atherosclerosis and chronic kidney disease, respectively. Conclusions: A higher FLI was associated with CKD independent of other risk factors. Further research is required to identify the causal relationship between liver fat accumulation and CKD.

Background: Secondhand smoke (SHS) from partners is a major source of exposure for non-smoking women. However, epidemiological studies have rarely examined social factors associated with continued and indoor smoking among pregnant women’s partners. Methods: We analyzed data on 6,091 partners of non-smoking pregnant women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Partners’ age, education, income, workplace SHS exposure (almost never or sometimes, almost every day), and pregnant women’s smoking history (never, quit before pregnancy awareness, quit after pregnancy awareness) were used as social factors. Multiple logistic regression analyses were conducted to examine the associations of social factors with partners’ continued smoking and indoor smoking. Results: Among 2,432 smoking partners, 2,237 continued to smoke after pregnancy awareness. Workplace SHS exposure was associated with increased risk of partners’ continued smoking: the odds ratio of workplace SHS exposure almost every day compared with almost never or sometimes was 2.08 (95% confidence interval, 1.52–2.83). Women’s quitting smoking after—but not before—pregnancy awareness was associated with decreased risk of partners’ continued smoking: the odds ratio of women’s quitting after pregnancy awareness compared with never smoking was 0.57 (95% confidence interval, 0.40–0.80). About one-third of partners who continued to smoke did so indoors. Older age, lower education, workplace SHS exposure, and women’s quitting smoking after pregnancy awareness were associated with increased risk of partners’ indoor smoking. Conclusions: Workplace SHS exposure and pregnant women’s smoking history were associated with continued smoking and indoor smoking among partners of non-smoking pregnant women.

Abstract Background Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF. Methods A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of the treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF. Results Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. The factors significantly correlated with the decrease in eGFR at 144 weeks on TAF were eGFR and weight at the start of TAF. Conclusions In this study, it was confirmed that switching to TAF was effective for Japanese HIV-1-positive patients who had been taking TDF for a long period of time and had a reduced eGFR. It was also found that the transition status depended on the eGFR and weight at the time of switch. Since HIV-1-positive patients in Japan are expected to continue taking TAF for a long time, renal function and body weight should be carefully monitored.

Databases: Integrating megadata for disease research A database integrating 1.3 trillion genome cohort data entries from 157,191 individuals in Japan will facilitate research into the gene-environment interactions underlying common diseases. The Tohoku Medical Megabank integrated database called dbTMM was developed by Soichi Ogishima, Masayuki Yamamoto and colleagues at Tohoku University in Japan. It incorporates the genome, metabolome, proteome, clinical, sociodemographic, lifestyle and environmental data from 84,073 adults, and 73,529 pregnant women and their families, including children. Blood and urine samples were collected from participants and analysed, then obtained genome/multiomics data were stored in dbTMM. Users can stratify the entire population into smaller populations based on multiple data variables, including whole genome variants, to search for statistically significant differences that might warrant further research. The dbTMM is expected to help clarify the genes and gene-environment interactions underlying common diseases and improve disease risk prediction.

In Japan, although a mumps vaccination is outside the national universal vaccination program, some local governments have implemented their own program. However, little is known regarding the implementation status and the impact of these programs. In this study, we investigated the impact on the prevention of mumps, after identification of the status of the local government subsidization programs. We identified the implementation status of the subsidization programs using the websites of local governments. We retrieved the number of reported mumps cases from designated sentinel sites through the Surveillance of Infectious Diseases System implemented according to the Infectious Disease Control Law. Using this data, the impact of the subsidization program on prevention of mumps was assessed by comparing the number of mumps cases per site during the 2015–2016 outbreak among the areas categorized by the subsidization status, using a Poisson regression model. As of 2019, 26.2% (456/1,739) of the local governments were considered as having subsidization programs. We retrieved 52,719 mumps cases from 2010 to 2019. The number of mumps cases per sentinel site tended to be low in areas implementing a subsidization program, compared with the no-implementation areas throughout the data collection period. The adjusted model confirmed that the subsidization program implemented between 2010 and 2015 impacted on the number of mumps cases during the 2015–2016 outbreak, with a decrease in the numbers. Further studies with detailed data including vaccination coverage should be conducted.

Abstract The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.