Genetic Risk, Lifestyle Adherence, and Risk of Developing Hyperuricaemia in a Japanese Population.

OBJECTIVE: To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. METHODS: This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. RESULTS: Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61-12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736-0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751-0.819 for lifestyle and PRS; p = 0.07). CONCLUSION: : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.

A fine-scale genetic map of the Japanese population.

Genetic maps are fundamental resources for linkage and association studies. A fine-scale genetic map can be constructed by inferring historical recombination events from the genome-wide structure of linkage disequilibrium-a non-random association of alleles among loci-by using population-scale sequencing data. We constructed a fine-scale genetic map and identified recombination hotspots from 10 092 551 bi-allelic high-quality autosomal markers segregating among 150 unrelated Japanese individuals whose genotypes were determined by high-coverage (30×) whole-genome sequencing, and the genotype quality was carefully controlled by using their parents' and offspring's genotypes. The pedigree information was also utilized for haplotype phasing. The resulting genome-wide recombination rate profiles were concordant with those of the worldwide population on a broad scale, and the resolution was much improved. We identified 9487 recombination hotspots and confirmed the enrichment of previously known motifs in the hotspots. Moreover, we demonstrated that the Japanese genetic map improved the haplotype phasing and genotype imputation accuracy for the Japanese population. The construction of a population-specific genetic map will help make genetics research more accurate.

Medication use before and during pregnancy in Japan: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: To elucidate the status of medication use among pregnant women in Japan, by means of a multigenerational genome and birth cohort study: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). METHODS: Questionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (from July 2013 to March 2017) around 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed medication use over three periods: (1) 12 months prior to pregnancy diagnosis, (2) the period between pregnancy diagnosis and around week 12 of pregnancy, and (3) post around week 12 of pregnancy. RESULTS: In total, 19,297 women were included in the analysis. The proportion of pregnant women using medications was 49.0% prior to pregnancy diagnosis, 52.1% from diagnosis to week 12, and 58.4% post week 12 of pregnancy. The most frequently prescribed medications were loxoprofen sodium hydrate (5.5%) prior to pregnancy diagnosis, magnesium oxide (5.9%) from diagnosis to week 12, and ritodrine hydrochloride (10.5%) post week 12 of pregnancy. The number of women who used suspected teratogenic medications during early pregnancy was 96 prior to pregnancy diagnosis, 48 from diagnosis to week 12, and 54 post week 12 of pregnancy. CONCLUSION: We found that ~ 50% of the pregnant women used medications before and during pregnancy and some took potential teratogenic medications during pregnancy. In birth genomic cohort study, it is expected that investigations into the safety and effectiveness of medications used during pregnancy will advance.

The Use of Japanese Traditional (Kampo) Medicines Before and During Pregnancy in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: Japanese traditional (Kampo) medicines are often used for pregnant women in Japan. However, no comprehensive studies have been conducted regarding the self-reported use of these medicines during pregnancy. This study investigated the use of Kampo medicines during pregnancy in Japan using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). METHODS: Questionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (July 2013 to March 2017) at approximately 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed Kampo medicines use over three periods: (1) 12 months before pregnancy diagnosis, (2) the period between pregnancy diagnosis and around Week 12 of pregnancy and (3) from around Week 12 of pregnancy. RESULTS: In total, 19 220 women were included in the analysis. The proportions using prescribed Kampo medicines were 4.1% before pregnancy diagnosis, 4.5% from diagnosis to Week 12% and 4.5% after Week 12 of pregnancy. The most frequently prescribed Kampo medicines were tokishakuyakusan (1.0%) before pregnancy diagnosis, shoseiryuto (1.3%) from diagnosis to Week 12 and shoseiryuto (1.5%) Post-week 12. Sixty of the pregnant women used Kampo medicines containing crude drugs, which should be administered cautiously during pregnancy. CONCLUSION: The proportion of Kampo medicines use before and during pregnancy was 4%-5%. Some pregnant women used Kampo medicines containing crude drugs that should be administered cautiously during pregnancy. Further research is required to determine the safety of Kampo medicines during pregnancy.

Hypertensive disorders of pregnancy, neonatal outcomes and offspring developmental delay in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

INTRODUCTION: Developmental delay at an early age indicates the probability of continued problems after school age. Hypertensive disorders of pregnancy (HDP) are associated with developmental delays in offspring, with inconsistent outcomes. Neonatal outcomes vary according to HDP exposure and are relevant to development in later years. Here we aimed to clarify the relationship between HDP and developmental delay in offspring and whether neonatal outcomes mediate this association. MATERIAL AND METHODS: We used data from 5934 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study conducted in Japan between July 2013 and March 2017. The Ages and Stages Questionnaires, third edition, at 24 and 42 months of age, measured developmental delay in five areas. We performed multivariate quasi-Poisson regression and causal mediation analysis by neonatal outcomes. RESULTS: At 24 months of age, compared to offspring born from normotensive mothers, offspring born from HDP-affected mothers were more likely to experience developmental delay (risk ratio [RR] 1.29, 95% confidence interval [CI]: 1.09-1.52) in the areas of communication (RR 1.21, 95% CI: 1.00-1.45) and personal-social (RR 1.15, 95% CI: 1.03-1.28). This association was mediated by neonatal outcomes: preterm birth, neonatal asphyxia, NICU admission, and neonatal small head circumference. No association was observed between HDP and developmental delay at 42 months of age. CONCLUSIONS: Exposure to HDP during fetal life is associated with offspring developmental delay. This association is partly mediated by neonatal outcomes.

Prospective associations of screen time at age 2 with specific behavioral subscales at age 3: a cohort study.

BACKGROUND: We aim to discover which, if any, of the subscales of internalizing and externalizing behavioral problems at age 3 are still associated with screen time (ST) at age 2 after adjusting for behavioral problems scores at age 2. METHODS: This study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Information was gathered prospectively, with 7207 mother-child pairs included in the analysis. Children's ST was categorized in hours a day at age 2 (<1, 1-<2, 2-<4, ≥4). We assessed children's behavioral problems using the Child Behavior Checklist for Ages 1½-5 (CBCL) at ages 2 and 3. 'Having behavioral problems' was defined by them being within a clinical range for internalizing behaviors (withdrawn, somatic complaints, anxious/depressed and emotionally reactive) and externalizing behaviors (attention problems and aggressive behaviors) at age 3. Continuous scores on each of the behavioral problem scales at age 2 were used as covariates. RESULTS: Greater ST for children at age 2 was associated with specific subscales for emotionally reactive and aggressive behaviors at age 3. CONCLUSIONS: This study found that ST is prospectively associated with some behavioral scales but not others.

Association of physiological factors with grip and leg extension strength: tohoku medical megabank community-based cohort study.

BACKGROUND: Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. METHODS: We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. RESULTS: Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. CONCLUSIONS: Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.

Skin health survey on atopic dermatitis among Japanese children: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Precise skin phenotypic data are indispensable in accurately diagnosing atopic dermatitis (AD). Therefore, this study examined the interobserver concordance for AD and non-AD diagnoses between two dermatologists. AD prevalence determined by the self-reported physician diagnoses and the diagnoses determined from the United Kingdom (UK) diagnostic criteria were compared with the diagnoses made by the two dermatologists, using data from a skin health survey. METHODS: This study included 1,638 children that participated in the skin health survey, which was part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. AD was assessed using dermatologist assessments, self-reported physician diagnoses, and the UK diagnostic criteria. The concordance for diagnoses was evaluated using kappa. The sensitivity and specificity of the self-reported physician diagnoses and the UK diagnostic criteria were calculated by comparing them with the two dermatologists' diagnoses. RESULTS: Among the 1,638 children, 393 (24.0 %), 194 (11.9 %), and 597 (37.2 %) were diagnosed with AD by the two dermatologists, physicians, and the UK diagnostic criteria, respectively. The kappa (95 % CI) of the interobserver concordance for AD or non-AD diagnoses between the two dermatologists was 0.78 (0.75-0.81). The sensitivity and specificity of the self-reported physician diagnoses were 26.7 % and 94.1 %, respectively. The sensitivity and specificity of the UK diagnostic criteria were 85.0 % and 82.4 %, respectively. CONCLUSIONS: Interobserver concordance for AD or non-AD diagnoses between the two dermatologists was substantial. Self-reported physician diagnoses exhibited low sensitivity that potentially indicated underdiagnosis of AD, whereas the UK diagnostic criteria might overdiagnose AD.

Association between frequency of breakfast intake before and during pregnancy and developmental delays in children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

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.

[Posttraumatic growth after the Fukushima nuclear disaster: Examination of free descriptions among Fukushima residents].

Objectives　Posttraumatic growth (PTG) refers to a positive psychological transformation experienced as a result of struggling with a major life crisis or traumatic event. In recent times, PTG has been used as a form of psychological support for those who have experienced trauma. In this study, we classified the free descriptions of PTG in Fukushima residents who experienced the Great East Japan Earthquake (GEJE). We examined the relationship between basic characteristics and PTG clusters, and between "recovery from radiation anxiety" and PTG clusters.Methods　A mail survey was conducted in August 2016 among 2,000 Fukushima residents, aged 20-79 years. We asked the participants for a free description of the specific content of their PTG. We also asked about their age, gender, and education, as well as about radiation anxiety immediately after the GEJE and at the time of the survey. Participants were divided into the following groups: "no anxiety," "recovered from anxiety," and "unrecovered from anxiety". The PTG free descriptions were classified into eight categories, including five dimensions based on the Posttraumatic Growth Inventory (Tedeschi & Calhoun, 1996) ("relating to others," "new possibilities," "personal strength," "spiritual change," and "appreciation of life") and three categories created according to Nishino et al. (2013) ("increased awareness of disaster prevention," "renewed recognition of nuclear-related issues," and "critical examination of information from authorities").Results　Of the 916 collected responses, data from 786 responses with no missing values were analyzed. Among women and young people, the proportion of those who answered "relating to others" and "appreciation of life" was high. For those with higher education, the proportion of those who answered "relating to others," "renewed recognition of nuclear issues," "critical examination of information from authorities," "personal strength," "spiritual change," and "appreciation of life" was high. In the "recovered from anxiety" group, the proportion of those who answered "renewed recognition of nuclear issues" was high.Conclusion　In assessing PTG, women and young people were more likely to report that they felt closely connected to family or friends, as well as to the community, and that they were grateful for their daily lives. Those with higher education tended to recognize that they have come to critically examine information provided by the national government, electric power companies, and national newspapers; they felt mental strength and growth after the earthquake. Those who recovered from radiation anxiety were more likely to report forming a heightened awareness of issues relating to nuclear power plants and energy.

Risk Factors for Problem Drinking among Evacuees in Fukushima following the Great East Japan Earthquake: The Fukushima Health Management Survey.

Many studies have consistently reported the bidirectional relationship between problem drinking and psychological distress following a disaster, but the risk factors of problem drinking following a disaster remain unclear. In this study, we therefore aimed to explore the risk factors associated with the incidence of problem drinking among evacuees after the Great East Japan Earthquake of March 11, 2011. We used the data for evacuees of the Fukushima Daiichi nuclear power plant accident, obtained from the Mental Health and Lifestyle Survey. A total of 12,490 individuals from 13 municipalities, which included the evacuation order areas after the accident, completed surveys between 2012 and 2013. The CAGE (Cutting down, Annoyed by criticism, Guilty feeling, and Eye-opener) questionnaire was used to screen the participants for alcohol dependence, and a score ≥ 2 indicated problem drinking. Logistic regression models were applied to investigate the possible predictors of problem drinking. The results showed that insufficient sleep and heavy drinking (≥ 4 drinks per day) were significant risk factors for the incidence of problem drinking in both men and women. Additional risk factors included family financial issues due to the disaster and trauma symptoms among men and a diagnosed history of mental illness among women. Other remaining variables were not significantly associated with problem drinking. The present study is the first to identify the risk factors for problem drinking following a compound disaster. Our findings could be used to develop a primary intervention program to improve evacuees' health and lives following a disaster.

Efficacy of group intervention involving physical activity on subjective well-being of elderly returnees after evacuation following the Great East Japan Earthquake.

AIM: In general, physically activity contributes to better subjective well-being (SWB) in the elderly. However, the physical activity level of older people who experienced relocation after the Great East Japan Earthquake has been reported to be low, possibly leading to low SWB. This study aimed to examine the efficacy of group intervention involving physical activity on SWB among older returnees after the Great East Japan Earthquake. METHODS: The participants were randomly allocated to an intervention group (4 men, 10 women) or a control group (7 women). Participants in the intervention group attended a series of weekly classes over eight weeks to encourage daily physical activity, whereas participants in the control group received no intervention. SWB, the primary outcome, was assessed by the World Health Organization Five Well-Being Index. RESULTS: Median variation in the World Health Organization Five Well-Being Index scores at 3 months from the baseline in the intervention and control groups was -1.0 and -2.0 points, respectively; the difference was borderline significant (P = 0.06). There was no significant difference between the groups in the median of variation in muscle strength (P = 0.79) or mobility (P = 0.77) at 3 months. CONCLUSION: The intervention might prevent deterioration in participants' SWB. Further studies involving older returnees with poor physical activity and/or sedentary lifestyle may be beneficial for health promotion in the area.

Delayed increase in male suicide rates in tsunami disaster-stricken areas following the great east japan earthquake: a three-year follow-up study in Miyagi Prefecture.

Devastating natural disasters and their aftermath are known to cause psychological distress. However, little information is available regarding suicide rates following tsunami disasters that destroy regional social services and networks. The aim of the present study was to determine whether the tsunami disaster following the Great East Japan Earthquake in March 2011 has influenced suicide rates. The study period was from March 2009 to February 2014. Tsunami disaster-stricken areas were defined as the 16 municipalities facing the Pacific Ocean in Miyagi Prefecture. Inland areas were defined as other municipalities in Miyagi that were damaged by the earthquake. Suicide rates in the tsunami disaster-stricken areas were compared to national averages, using a time-series analysis and the Poisson distribution test. In tsunami disaster-stricken areas, male suicide rates were significantly lower than the national average during the initial post-disaster period and began to increase after two years. Likewise, male suicide rates in the inland areas decreased for seven months, and then increased to exceed the national average. In contrast, female post-disaster suicide rates did not change in both areas compared to the national average. Importantly, the male suicide rates in the inland areas started to increase earlier compared to the tsunami-stricken areas, which may reflect the relative deficiency of mental healthcare services in the inland areas. Considering the present status that many survivors from the tsunami disaster still live in temporary housing and face various challenges to rebuild their lives, we should continue intensive, long-term mental healthcare services in the tsunami-stricken areas.

Changes in suicide rates in disaster-stricken areas following the Great East Japan Earthquake and their effect on economic factors: an ecological study.

OBJECTIVE: Devastating disasters may increase suicide rates due to mental distress. Previous domestic studies have reported decreased suicide rates among men following disasters. Few reports are available regarding factors associated with disasters, making it difficult to discuss how these events affect suicide rates. This study aimed to observe changes in suicide rates in disaster-stricken and neighboring areas following the Great East Japan Earthquake, and examine associations between suicide rates and economic factors. METHODS: Monthly suicide rates were observed from March 2009 to February 2013, during which time the earthquake occurred on March, 2011. Data were included from disaster-stricken (Iwate, Miyagi, and Fukushima Prefectures) and neighboring (control: Aomori, Akita, and Yamagata Prefectures) areas. The association between changes in suicide rates and economic variables was evaluated based on the number of bankruptcy cases and ratio of effective job offers. RESULTS: In disaster-stricken areas, post-disaster male suicide rates decreased during the 24 months following the earthquake. This trend differed relative to control areas. Female suicide rates increased during the first seven months. Multiple regression analysis showed that bankruptcy cases (ß = 0.386, p = 0.038) and ratio of effective job offers (ß = -0.445, p = 0.018) were only significantly associated with male post-disaster suicide rates in control areas. CONCLUSION: Post-disaster suicide rates differed by gender following the earthquake. Our findings suggest that considering gender differences might be important for developing future post-disaster suicide prevention measures. This ecological study revealed that increasing effective job offers and decreasing bankruptcy cases can affect protectively male suicide rates in control areas.

Risk of Major Congenital Malformations Associated with the Use of Japanese Traditional (Kampo) Medicine Containing Ephedra During the First Trimester of Pregnancy.

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.

Combination of taking neuropsychiatric medications and psychological distress in pregnant women, with behavioral problems in children at 2 years of age: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

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.

How Healthy Lifestyle Habits Have Interacted with SARS-CoV-2 Infection and the Effectiveness of COVID-19 Vaccinations: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Introduction: To examine the interaction between lifestyle habits and the COVID-19 vaccinations for preventing SARS-CoV-2 infection, we analyzed 11,016 adult participants registered in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Methods: Lifestyle variables, including regular exercise, smoking and drinking habits, sleep status, body mass index, and daily breakfast consumption, were assessed from 2014 to 2019 using baseline questionnaires. Information on SARS-CoV-2 infection and the COVID-19 vaccination were also collected from March 2020 to May 2023. The study period was divided into two in the postvaccination phase: the first period (the beginning of the vaccination program) and the second period (the fourth shot onward). Results: In the Cox proportional-hazards model analysis, the five-time vaccinations group showed a significantly lower risk of SARS-CoV-2 infection adjusted age, sex, underlying health condition, and lifestyle variables (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.76-0.86). Logistic regression analysis revealed that a higher number of vaccinations was significantly associated with a low risk of SARS-CoV-2 infection regardless of lifestyle habits (three times in the first period: odds ratio [OR] 0.19, 95% CI 0.15-0.24; five times in the second period: OR 0.07, 95% CI 0.05-0.11 vs. none). Regarding lifestyle habits, the risk reduction in those who had sleep satisfaction (OR 0.12, 95% CI 0.08-0.18) was slightly larger than in those who had sleep dissatisfaction (OR 0.23, 95% CI 0.17-0.32) in the group with the highest number of vaccinations in the first period; however, this interaction was hardly confirmed in the second period when the number of infected cases significantly increased. Conclusions: Our findings indicated that a higher number of COVID-19 vaccinations was associated with reduced risk of SARS-CoV-2 infection; otherwise, we may need to understand the advantages and limitations of a healthy lifestyle for preventing infection depending on the situation with vaccinations and infection spreading.

Identifying critical age and gender-based metabolomic shifts in a Japanese population of the Tohoku Medical Megabank cohort.

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.