Social isolation, characterized by a lack of social connections with family, friends, and others, is associated with adverse health outcomes. However, the genetic contribution to the susceptibility to social isolation remains unclear. This study aimed to identify genetic loci associated with social isolation using the Lubben Social Network Scale (LSNS-6) in a Japanese population. The Tohoku Medical Megabank Community-Based Cohort Study was conducted between 2013 and 2016. The participants were genotyped using the Affymetrix Axiom Japonica Array. The LSNS-6 was used to assess familial and friend ties through six questions and social isolation statuses were defined using the total scale, family subscale, and friend subscale. Genome-wide association studies (GWASs) were conducted using a generalized linear mixed model, adjusting for age, sex, 10 genetic principal components and batch effects. In total, 63,497 participants who completed genotyping and the LSNS-6 were included. The mean age was 59.4 ± 11.9 years, and 41,126 (64.8%) were female. Significant genetic loci were identified in GWASs for the total scale (rs10736933 near ACADSB and HMX3) and friend subscale of LSNS-6 (rs1778366 near LINC02315 and LRFN5). This study provides the first genome-wide evidence of social isolation in the Japanese population, suggesting associations with ACADSB, HMX3, LINC02315, and LRFN5. These findings could enable personalized prevention and intervention for social isolation and related psychiatric disorders.

Abstract <p> Subcortical brain volumes have been extensively mapped by genome-wide association studies (GWASs) in Europeans, but their genetic architecture in East Asians remains unclear. We conducted GWASs on magnetic resonance imaging derived volumes of eight subcortical structures in 9,225 Japanese participants aged 21.6–88.0 years (mean 54.0 ± 15.5 years) from the Tohoku Medical Megabank Brain MRI Study. Genotyping used Japonica Array and volumes were estimated with FreeSurfer. GWASs were performed separately in the discovery ( n  = 7,328) and replication ( n  = 1,897) studies, followed by a meta-analysis. We identified nine significant genome-wide loci in the discovery study, three of which were replicated. Meta-analysis revealed four additional significant loci. We identified three novel variants associated with the volumes of subcortical structures. Previously reported loci in European ancestry studies, including ALPL , SMIM19 , CHRNB3 , DSCAML1 , KTN1 , RPL13AP3 , and DCC , were replicated, leading to the identification of ancestry-specific signals. Functional mapping and expression analyses revealed brain-specific enrichment of genes associated with the caudate and putamen. This first GWAS of subcortical volumes in a Japanese population refines the genetic architecture of these structures and provides insight into mechanisms of brain aging and neuropsychiatric disease. </p>

We aimed to examine the longitudinal and directional associations of children's screen time (ST) with their extensive behavior scales at ages 2, 3, 4, and 5. This study was a part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Information was gathered prospectively, and 7,747 mother-child pairs were included. Analyses using random-intercept cross-lagged panel models were performed for children aged 2, 3, 4, and 5 years. Information on children's ST at ages 2, 3, 4, and 5 was collected from questionnaires completed by caregivers. We assessed children's behavior using the Child Behavior Checklist for Ages 1½-5 at aged 2, 3, 4, and 5 years. This study targeted scores on externalizing behavior and its 2 subscales (aggressive behavior and attention problems), and internalizing behavior and its 4 subscales (withdrawal, somatic complaints, anxious/depressed, and emotional responses). As a result, higher than expected screen time at age 2 was consistently associated with all behavioral scales at age 3. At later ages, specific bidirectional associations were identified for each behavioral scale and age group. These findings may offer preliminary guidance for future discussions on age-appropriate screen use recommendations and family media practices.

PURPOSE: To investigate the distribution of axial length (AL) and the prevalence of long axial length (LAL) in Japanese children and adolescents. STUDY DESIGN: cross-sectional observational study METHODS: We analyzed AL data from 14,482 participants (7,457 boys and 7,025 girls) aged 4-19 in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan. AL was measured using a non-contact optical axis measurement device. We evaluated the distribution of AL in the participants with box plots for age. Segmented regression identified age-related trends and breakpoints. We calculated the age-specific proportions of participants with AL ≥ 24.5 mm and those with AL ≥ 26 mm, defined as LAL, which were considered indicative of suspected myopia. RESULTS: Mean AL increased with age, with a break point at 11.73 years. The slope before the break point was β = 0.27, while the slope after the break point decreased to β = 0.12. Boys showed earlier break point (9.87 years) than girls (15.91 years). Proportions with AL ≥ 24.5mm and ≥26mm began to increase approximately at 8 and 10 years of age respectively, with sex differences noted between ages 7 to 10 years and 10 to 11 years. CONCLUSION: This was the first large-scale AL survey in Japan and revealed the age and sex related distribution of AL and the proportion with LAL among Japanese children and adolescents aged 4 to 19 years.

Small-for-gestational age (SGA) is an important global public health issue because of its increasing prevalence and long-term effects. Maternal smoking is a known risk factor for SGA; however, the effect of grandmaternal smoking on the risk of SGA in grandchildren SGA remains unclear. In this study, we examined whether grandmaternal smoking during pregnancy was associated with small birth weight, length, and head circumference for gestational age. Data were obtained from 23,730 pregnant women and their offspring from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Studies. A total of 1,130 grandmaternal-maternal-child triads were identified. Grandmaternal smoking during pregnancy was defined by the Maternal and Child Health Handbook owned by the mothers at birth mothers when they were born. Birth outcomes of grandchildren were obtained from medical records and converted to SGA using the 10th percentile for weight, length, and head circumference. A multivariate logistic regression and propensity scores were used for the analysis. Prevalence of <10th percentile for birth weight, length, and head circumference in grandmaternal smokers were 10.2%, 2.0%, and 10.2%, respectively. Grandmaternal smoking during pregnancy was associated with the lower grandchild's birth weight (odds ratio (OR) [95% (CI)]: 2.86 [1.05-7.82]) and remained consistent when adjusted by propensity score (OR [95% CI]: 2.87 [1.04-7.92]). Grandmaternal smoking should not be ignored when assessing the SGA risk. Future work should consider the complex mediating relationship between smoking and growth restriction across generations.

ABSTRACT Purpose Vulvovaginal candidiasis is highly prevalent among pregnant women, and its treatment is crucial. However, there is a lack of evidence regarding the risks on fetal outcomes associated with the use of antifungal medications during the first trimester of pregnancy in Japan. This study examined the association between topical antifungal use during the first trimester of pregnancy and the risk of major congenital malformations (MCMs) in infants using a Japanese database. Methods We conducted a cohort study using a pregnancy cohort nested in the JMDC Claims Database from Japan. This dataset included 12 472 women who gave birth between 2010 and 2019 and were diagnosed with vulvovaginal candidiasis. Among the antifungal medications frequently dispensed or prescribed during the first trimester of pregnancy in this cohort, miconazole, oxiconazole, and isoconazole were assessed for the risk of MCMs, using clotrimazole, an antifungal medication with established safety during pregnancy, as a reference. Results Among 12 472 women, the overall prevalence of MCMs was 5.8% ( n  = 249) in women exposed to topical antifungals, while unexposed were 6.2% ( n  = 508). Using propensity score overlap weight (wOR), no increased risk of MCMs in infants was observed in pregnancies exposed to oxiconazole, isoconazole, and miconazole compared to clotrimazole (overlap weighted odds ratio [95% confidence interval]: 0.875 [0.599–1.277], 1.001 [0.611–1.640], and 0.887 [0.497–1.581], respectively). Conclusion There was no significant association between topical antifungal use during the first trimester of pregnancy and the risk of MCMs in infants in Japan.

The placenta plays a crucial role in preeclampsia (PE) pathogenesis, with early onset (EOPE) and late onset (LOPE) presenting with unique manifestations. In this prospective study of 17,709 pregnant Japanese women, the relationship between the PE subtype and birth weight to placental weight ratio (BW/PW ratio) was examined. EOPE was not associated with BW/PW ratio, which was consistent with reduced birth and placental weights. LOPE showed lower BW/PW ratios, indicating potential adaptive hypertrophy of the placenta. These results emphasize the consideration of PE subtypes when utilizing the BW/PW ratio as an index of placental function and to elucidate PE mechanisms.

IMPORTANCE: Exposure to hypertensive disorders of pregnancy (HDP) during the fetal stage has been linked to developmental delays in children. However, the associations between HDP subtypes and longitudinal patterns in child development remain unclear. OBJECTIVE: To investigate the associations of HDP subtypes with child developmental patterns. DESIGN, SETTING, AND PARTICIPANTS: This study used data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study recruiting pregnant individuals in Japan between July 2013 and March 2017. Mother-child pairs were included in the analysis. The data analysis was conducted from November 2023 to February 2024. EXPOSURES: HDP and its subtypes (gestational hypertension and preeclampsia) were identified using an algorithm applied to antenatal visit records. MAIN OUTCOMES AND MEASURES: The latent class trajectory model was applied to child development scores at ages 6, 12, 24, 42, and 48 months to generate patterns in 5 domains (communication, gross motor, fine motor, problem solving, and personal-social). Multinomial Poisson regression analysis calculated the risk ratios (RRs) of different developmental patterns by exposure to any HDP as well as HDP subtypes. A subgroup analysis was performed by preterm birth. RESULTS: Among 14 023 mother-child pairs (maternal mean [SD] age, 32.5 [4.8] years; 6754 [48.2%] female children), 1406 (10.0%) were exposed to HDP. Three patterns were identified in the 5 domains: normal, delay, and catch-up. Point estimates for delays in multiple domains of development were greater for any HDP, preeclampsia, and early-onset preeclampsia, but not all findings were statistically significant. Early-onset preeclampsia was associated with a significantly higher risk of delay pattern in problem solving domain (RR, 2.90; 95% CI, 1.43-5.89; adjusted P = .047), although the risks of delay pattern were not statistically significant in communication (RR, 1.94; 95% CI, 1.14-3.29; adjusted P = .15), gross motor (RR, 2.10; 95% CI, 1.26-3.51; adjusted P = .06), or fine motor (RR, 2.68; 95% CI, 1.26-5.71; adjusted P = .11) domains. In the term-born population, children exposed to preeclampsia and had an RR greater than 1 for the delay pattern in the problem solving domain (RR, 1.67; 95% CI, 1.92-2.74; adjusted P = .60), although this finding was not statistically significant after adjusting for multiple comparisons. CONCLUSIONS AND RELEVANCE: In this cohort study, fetal exposure to early-onset preeclampsia was associated with higher risk of a delayed child developmental pattern in the problem solving domain. The observations were modified by preterm birth. These findings suggest that children exposed to certain HDP subtypes during fetal life require developmental monitoring, especially if they were born preterm.

PURPOSE: Japanese traditional (Kampo) medicines containing ephedra are used to relieve symptoms of the common cold during pregnancy. The risks associated with perinatal outcomes, however, remain unclear. Thus, we evaluated the risk of adverse perinatal outcomes associated with the use of Kampo medicines containing ephedra during pregnancy using data from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). METHODS: Questionnaires were distributed to pregnant women who participated in the TMM BirThree Cohort Study at approximately weeks 12 and 26 of pregnancy. Adverse perinatal outcomes in women who used Kampo medicines containing ephedra or acetaminophen during pregnancy were assessed. Odds ratios (ORs) were estimated using weighted logistic regression analyses. RESULTS: Among 20 083 pregnant women, acetaminophen and Kampo medicines containing ephedra were used by 5.3% and 3.5% of women, respectively. The OR for caesarean section was 0.95 (95% confidence interval [CI], 0.75-1.20), for preterm birth (PTB) was0.99 (95% CI, 0.63-1.55), for low birth weight (LBW) was 1.04 (95% CI, 0.72-1.49), for small for gestational age (SGA) was 0.98 (95% CI, 0.58-1.65), and for low Apgar scores at 5 min was 0.85 (95% CI, 0.25-2.93) in the women who used Kampo medicines containing ephedra during pregnancy. CONCLUSIONS: No statistically significant association was seen between the use of Kampo medicines containing ephedra during pregnancy and an increased risk of needing a caesarean section, PTB, LBW, SGA, or low Apgar scores. Although further research is needed, this study may assist in clinical decision-making.

BACKGROUND: Associations have been suggested between prenatal exposure and allergic diseases in children as well as between respiratory allergies and maternal sleep disorders during pregnancy. PURPOSE: This study aimed to examine the association between maternal sleep disorders during pregnancy and allergic diseases, including respiratory, skin, and ocular allergies, in their children. METHODS: This study was based on the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Sleep disorders during pregnancy were defined as an Athens Insomnia Scale score of ≥6. Allergic diseases in children up to 5 years of age were assessed by maternal selfreport on "bronchial asthma," "atopic dermatitis," "food allergy," and "allergic conjunctivitis/allergic rhinitis/hay fever." Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a Cox proportional hazards model. RESULTS: A total of 11,123 mother-child pairs were included. The mean gestational age at registration was 19.6±7.6 weeks. During pregnancy, 4,115 women (37.0%) experienced sleep disorders. Additionally, 53.7% of the participants had a history of parity, 8.8% worked night shifts, and 0.4% used sleep medications. In the crude models, maternal sleep disorders during pregnancy were associated with all examined allergic diseases in children. After the adjustment for all confounders, the associations remained significant for atopic dermatitis and allergic conjunctivitis/ allergic rhinitis/hay fever (HR [95% CI], 1.09 [0.97-1.23] for bronchial asthma, 1.17 [1.05-1.31] for atopic dermatitis, 1.11 [0.98-1.26] for food allergy, and 1.25 [1.13-1.39] for allergic conjunctivitis/allergic rhinitis/hay fever). CONCLUSION: Maternal sleep disorders during pregnancy were associated with atopic dermatitis as well as allergic conjunctivitis/allergic rhinitis/hay fever in children.

Heritability of cognitive function is estimated to be 50%-80%. Genome-wide association studies (GWASs) have identified multiple cognitive function-associated loci, primarily in the European population. However, those in Asian populations, particularly in individuals of Japanese ancestry, remain limited. Hence, this GWAS aimed to identify cognitive function-associated genetic loci in elderly individuals of Japanese ancestry. Herein, 2571 elderly participants from the Tohoku Medical Megabank Brain Magnetic Resonance Imaging Study were included. Their cognitive function was assessed using the Japanese version of the Mini-Mental State Examination (MMSE), and both binary and continuous MMSE scores were analysed. Genotyping was performed using the Affymetrix Axiom Japonica Array v2, and imputation was conducted with 3.5KJPNv2 and 1KGP3. Statistical analyses were performed using FastGWA-GLMM and FastGWA for binary and continuous MMSE scores, respectively. Although no genome-wide significant loci were identified using binary MMSE values, the following two were detected using continuous MMSE values: rs77877360 (20p12.1) near BANF2 and SNX5 and rs9460729 (6p22.3) near PRL and HDGFL1. Additionally, functional annotation suggested the involvement of these loci in pathways related to cognitive function, including chromatin structure regulation, neuroinflammation, and iron metabolism. Notably, SNX5, identified through chromatin-interaction mapping, has been implicated in neurodegenerative processes, particularly in Parkinson's disease. The findings of this study provide preliminary genome-wide evidence suggesting a genetic predisposition to impaired cognitive function in elderly Japanese individuals.

PURPOSE: To evaluate the risk of major congenital malformations (MCMs) associated with quinolone exposure during the first trimester of pregnancy using a large administrative database in Japan. METHODS: A large claims database was used from January 2005 to November 2019. The dates of pregnancy onset and delivery were estimated using the developed algorithm. MCMs were defined according to the International Classification of Diseases, 10th revision codes. The risk of MCM associated with first-trimester quinolone prescriptions was evaluated in women with infectious diseases diagnosed during the first trimester of pregnancy. We evaluated the overall risk of MCMs in infants, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing women with first-trimester prescriptions of quinolones with those without antibiotic prescriptions, adjusting for covariates with propensity score overlap weights. RESULTS: The prevalence of first-trimester infectious diseases was 51.6% (47 121/91390). Among 47 121 women diagnosed with infectious diseases, 1 320 were prescribed quinolones during their first trimester of pregnancy. The overall prevalence of MCMs was 6.0% (2282/37766) in women unexposed to antibiotics and 5.9% (78/1320) in those exposed to quinolones. The first-trimester prescription of quinolone was not significantly associated with the overall MCM prevalence when overlap-weighted ORs (wOR) were calculated using propensity score overlap weights for covariates (wOR 0.904, 95% CIs 0.684-1.196). CONCLUSIONS: Prescription of quinolones in the first-trimester of pregnancy was not associated with an increased risk of MCMs in infants. Our findings may support clinical decision-making when considering quinolone use during the first-trimester of pregnancy.

ABSTRACT Introduction While social capital can prevent diabetes, these benefits can be heterogeneous with respect to socioeconomic status. We investigated the association between social capital and gestational diabetes mellitus (GDM) while examining effect modification by household income. Materials and Methods We conducted a secondary data analysis using the Tohoku Medical Megabank Project Birth and Three‐Generation Cohort Study carried out between July 2013 and March 2017. Social capital (mutual aid, social trust, informal social control, collective action) and covariates were self‐reported, while GDM diagnosis and other medical and physiological information were obtained from medical records. To assess the association between social capital and GDM, we conducted logistic regression models. We further tested for interactions between social capital and household income as well as stratified the models by income. Results Among 20,339 study participants, 700 (3.4%) were diagnosed with GDM. Multivariable logistic regression models found that social trust and collective action were associated with lower GDM prevalence, even after adjustment of covariates. When stratifying household income, however, social capital was significantly associated with the reduced risks of GDM only among participants with higher household income (OR: 0.90, 95% CI: 0.85–0.97). No significant association was observed among those with lower household income. Conclusions The health benefit of social capital on GDM prevalence was heterogeneous, and the protective effect of social capital on GDM was found only among women with higher household income. The differential impact of social capital on GDM highlights the need for targeted interventions addressing structural health inequities.

AIM: Autism spectrum disorder (ASD) is a neurodevelopmental condition clinically characterized by abnormalities in eye contact during social interactions. Eye-tracking systems have been used to screen individuals with ASD by capturing atypical eye gaze patterns of diagnostic significance, such as reduced duration of eye gaze fixation on social information. However, most prior studies have focused on the screening accuracy of eye-tracking systems in children already diagnosed with ASD, with few longitudinal assessments conducted on a large scale. This large-scale, longitudinal, community-based study aimed to analyze the association between specific neurodevelopmental symptoms and the duration of eye gaze fixation on social information within a community-based setting. METHODS: A longitudinal study involving 2101 participants utilized a generalized linear model (GLM) to examine associations between the duration of eye gaze fixation on social information at age 4 years and subscale scores of the Strengths and Difficulties Questionnaire (SDQ) at ages 6-7. RESULTS: GLM analysis revealed that shorter durations of eye gaze fixation on social information at age 4 years were significantly associated with emotional problems and peer problems, and with hyperactivity/inattention attention-deficit hyperactivity disorder (ADHD) at ages 6-7 years. CONCLUSION: These findings demonstrate the ability to detect not only peer problems characteristic of ASD but also hyperactivity/inattention characteristic of ADHD longitudinally, which it might be related to the comorbidity of ASD and ADHD. This preliminary study highlights the potential for neurodevelopmental screening; however, further research is needed to validate the accuracy of these methods.

Adverse pregnancy outcomes (APOs) affect approximately 20% pregnant women, and their incidence is increasing. The aim of this study was to investigate the effect of cardiovascular health (CVH) during pregnancy on APOs. We analyzed data from 14,930 pregnant women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. CVH status during pregnancy was assessed using the eight components of Life's Essential 8. APOs were defined as composite outcomes encompassing preeclampsia, gestational diabetes mellitus, preterm birth, and small for gestational age. The numbers of participants with high, moderate, and low CVH status were 2891 (19.4%), 11,498 (77.0%), and 541 (3.6%), respectively. Poisson regression analyses with robust error variance, which adjusted for maternal age at conception, alcohol consumption, conception via in vitro fertilization, parity, psychological distress, social isolation, and household income, showed a positive association between moderate and low CVH levels and APOs (risk ratio and 95% confidence interval 1.15 [1.03-1.28] and 2.14 [1.78-2.58], respectively). Among pregnant women with low CVH, those who reported social isolation had a higher prevalence of APOs than did those without social isolation (36.4% vs. 27.4%). This difference was attenuated for pregnant women with high CVH status (13.6% vs. 13.1%). In conclusion, CVH status may be useful for assessing the risk of APOs. Socially isolated pregnant women are more vulnerable to the effects of low CVH status.

BACKGROUND: Adiposity rebound (AR) is the point when the BMI begins to rise again during early childhood. Early AR (before age 5) is associated with higher risk of lifelong obesity and metabolic disorders and may be influenced by breastfeeding. Although human milk oligosaccharides (HMOs) in breast milk are crucial for child growth, their association with AR status has not been studied. OBJECTIVES: This study aimed to explore the association between breast milk HMOs and AR status in children. METHODS: In this case-control study, we included 184 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation (TMM BirThree) Cohort Study (93 AR cases, 91 controls). Breast milk was collected 1 mo postpartum, and the concentration of 15 HMO molecules and α-diversity index (Inverse Simpson index) were quantified. Wilcoxon rank-sum test and partial least squares-discriminant analysis identified candidate HMOs, and multivariable logistic regression analysis evaluated associations between candidate HMOs and AR status. Analyses were stratified by maternal secretor status (secretor or nonsecretor). RESULTS: In secretor mothers, multivariable logistic regression showed that the inverse Simpson index [odds ratio (OR): 0.54; 95% CI: 0.36, 0.82), the sum of sialic acid-bound HMOs (OR: 0.61; 95% CI: 0.41, 0.91), and 3'-sialyllactose (OR: 0.67; 95% CI: 0.46, 0.98) were inversely associated with early AR in the fully adjusted model. A trend of interaction between sialyl-lacto-N-tetraose-a (LSTa) and maternal secretor status regarding AR was observed in the fully adjusted model (P-interaction = 0.051). CONCLUSIONS: α-Diversity, sialic acid-bound HMOs, and 3'-sialyllactose may involved in inhibiting AR in children of secretor mothers, and a trend of interactive effect between LSTa and maternal secretor status regarding AR is indicated. These findings offer novel perspectives on the associations between breastfeeding and a childhood adiposity as well as potential metabolic disorders later in life. This trial is registered at https://www.umin.ac.jp/ as UMIN000047160.

Gestational diabetes mellitus (GDM) is common in Japanese women, posing serious risks to mothers and offspring. This study investigated the influence of maternal genotypes on the risk of GDM and examined how these genotypes modify the effects of psychological and dietary factors during pregnancy. We analyzed data from 20,399 women in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort. Utilizing two customized SNP arrays for the Japanese population (Affymetrix Axiom Japonica Array v2 and NEO), we performed a meta-analysis to combine the datasets. Gene-environment interactions were assessed by modeling interaction terms between genome-wide significant single nucleotide polymorphisms (SNPs) and psychological and dietary factors. Our analysis identified two SNP variants, rs7643571 (p = 9.14 × 10-9) and rs140353742 (p = 1.24 × 10-8), located in an intron of the MDFIC2 gene, as being associated with an increased risk of GDM. Additionally, although there were suggestive patterns for interactions between these SNPs and both dietary factors (e.g., carbohydrate and fruit intake) and psychological distress, none of the interaction terms remained significant after Bonferroni correction (p < 0.05/8). While nominal significance was observed in some models (e.g., psychological distress, p = 0.04), the data did not provide robust evidence of effect modification on GDM risk once adjusted for multiple comparisons. These findings reveal novel genetic associations with GDM in Japanese women and highlight the importance of gene-environment interactions in its etiology. Given that previous genome-wide association studies (GWAS) on GDM have primarily focused on Western populations, our study provides new insights by examining an Asian population using a population-specific array.

Genomic information from pregnant women and the paternal parent of their fetuses may provide effective biomarkers for preeclampsia (PE). This study investigated the association of parental polygenic risk scores (PRSs) for blood pressure (BP) and PE with PE onset and evaluated predictive performances of PRSs using clinical predictive variables. In the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, 19,836 participants were genotyped using either Affymetrix Axiom Japonica Array v2 (further divided into two cohorts-the PRS training cohort and the internal-validation cohort-at a ratio of 1:2) or Japonica Array NEO (external-validation cohort). PRSs were calculated for systolic BP (SBP), diastolic BP (DBP), and PE and hyperparameters for PRS calculation were optimized in the training cohort. PE onset was associated with maternal SBP-, DBP-, and PE-PRSs and paternal SBP- and DBP-PRSs only in the external-validation cohort. Meta-analysis revealed overall associations with maternal PRSs but highlighted significant heterogeneity between cohorts. Maternal DBP-PRS calculated using "LDpred2" presented the most improvement in prediction models and provided additional predictive information on clinical predictive variables. Paternal DBP-PRS improved prediction models in the internal-validation cohort. In conclusion, Parental PRS, along with clinical predictive variables, is potentially useful for predicting PE.

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.

OBJECTIVES: Adiposity rebound (AR) corresponds to the start of the second rise in the body mass index curve during infant growth. Early AR (before age 5) confers increased risk of adiposity and metabolic disorders but is less likely to occur in breastfed infants. Although lipids in breast milk are important in child growth, information is limited regarding which lipids are involved in AR. The object of this study was to explore the association between breast milk lipids and AR status in children. METHODS: We designed a case-control study of 184 mother-child pairs (AR cases: n = 93; controls: n = 91) included from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Breast milk was collected 1 month postpartum and comprehensive lipid analysis was performed. Partial least square-discriminant analysis was used to explore candidate lipids, and multivariable logistic regression analysis was used to evaluate associations with the AR status of children. RESULTS: We detected 667 lipid molecules in 12 lipid classes in breast milk. Partial least square-discriminant analysis revealed the association of fatty acid-hydroxy fatty acid (FAHFA) and cholesterol ester (ChE) with AR status. Multivariable logistic regression analysis showed that in pairs with exclusive breastfeeding at 1 month postpartum, FAHFA (odds ratio 1.57 [95% confidence interval, 1.06-2.32]) was positively associated with early AR, and ChE (odds ratio 0.55 [95% confidence interval, 0.36-0.86]) was negatively associated. CONCLUSIONS: Breast milk lipids (FAHFA, ChE) associated with the AR status of children, indicating the potential to regulate a child's adiposity and possible metabolic disorders in adulthood.

BACKGROUND: The association of maternal hyperglycemia with childhood developmental delay has been examined; however, only 2 studies used maternal blood glucose level as a continuous variable as an exposure. A present study aimed to investigate the influence of maternal fasting plasma glucose (mFPG) level in early gestation on developmental delay in children. METHODS: This cohort study included 1541 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. mFPG level before 24 gestational weeks was obtained as a continuous and categorical variable. Developmental delay in 2-year-old children was assessed by mothers using the Ages and Stages Questionnaire (third edition). Associations between mFPG level and developmental delay in children were evaluated using multiple logistic regression analyses. RESULTS: The prevalence of mFPG level ≥95 mg/dL was 5.2%. At 2 years old, 15.1% of the children had developmental delays. mFPG level as a continuous variable was not associated with an increased risk of developmental delay across the 5 domains in children [adjusted odds ratio (aOR), 95% confidence interval (CI): 1.004, 0.990-1.018]. mFPG level ≤70 mg/dL was associated with developmental delay across 5 domains (aOR, 95% CI: 0.464, 0.229-0.943) in children than that with a mFPG level 71 to 94 mg/dL. No association was found between mFPG level ≤70 mg/dL and ≥95 mg/dL and developmental delay in any domains among children. CONCLUSION: mFPG level in early gestation was not associated with an increased risk of any developmental delays in 2-year-old children.

This study explores the behavioral and psychological impacts of a health information-sharing system that integrates wearable devices with a metaverse-based virtual environment, aiming to promote exercise and medication adherence among older adults. The proposed system allowed participants to visualize their own and others’ health behaviors—such as step counts, meal frequency, and medication adherence—via avatars acting as digital twins. These avatars reflected not only current health metrics but also projected future body composition based on collected data, thereby enhancing health awareness and risk perception. Ten participants, mainly older adults living in Gunma Prefecture, took part in a two-week intervention following a baseline monitoring phase. Health data collected through smartwatches were automatically transmitted to a tablet interface and visualized in a simplified metaverse environment. Importantly, the system was designed with minimal operational complexity—requiring only that users wear the device—thereby ensuring high usability even among first-time users of digital health technologies. Participants could passively observe anonymized avatars and data from others, fostering a sense of mutual recognition and engagement without the need for direct interaction. Statistical analysis revealed a significant increase in daily step counts after the intervention (paired t-test, p = 0.0001), while no meaningful change was observed in meal frequency (p = 0.343). Post-intervention interviews and survey results highlighted strong user satisfaction and acceptance. Participants consistently praised the intuitive interface, the motivating effect of avatar-based feedback, and the ease of use. Notably, average satisfaction scores ranged from 4.5 to 5.0 across items related to interface design, perceived usefulness, and behavioral impact—indicating that even a non-immersive, lightweight system can yield meaningful behavioral outcomes. These findings demonstrate that immersive VR is not a prerequisite for effective health promotion. Rather, simplified digital spaces leveraging mutual awareness, self-projection, and intuitive design can motivate behavioral change and enhance health literacy among older adults. This approach shows strong potential for real-world application, particularly when integrated with local healthcare services and conversational agents. The system also presents a scalable framework for future digital therapeutics targeting broader populations and specific chronic disease management.

INTRODUCTION: Traditional Japanese (Kampo) medicine containing Prunus persica kernel (KPK) is prescribed for treating menstrual- and pregnancy-related symptoms. However, no safety information is available regarding its use in pregnant women. In this study, we examined the associations of KPK prescriptions during the first trimester of pregnancy with preterm births and major congenital malformations (MCMs) in newborns. METHODS: From a large-scale Japanese health insurance claims database, we included pregnant women enrolled with the same healthcare insurer from 3 months before pregnancy to the date of delivery, who gave birth between 2010 and 2019, and whose data were linked to their infants. We then selected pregnant women who were prescribed KPK during the first trimester as the exposure group, and those who were prescribed tokishakuyakusan (TSS), commonly used for pregnancy-related symptoms, during the same period as controls. The association between KPK prescriptions and preterm birth or MCM among infants was examined using a multivariate logistic regression analysis. RESULTS: Of the 75,398 infants, TSS and KPK was prescribed to 2,548 (3.38%) and 283 (0.38%) women during the first trimester, respectively. In the TSS group, 311 of 2,491 infants (12.5%) experienced preterm births, whereas 40 of 283 infants (14.1%) in the KPK group experienced preterm births. The risk of preterm birth in the KPK group was not significantly different from that in the TSS group (adjusted risk ratio, 1.122; 95% confidence interval, 0.827-1.521). In the TSS group, 157 of 2,491 infants (6.3%) had MCMs, whereas 15 of 283 infants (5.3%) in the KPK group had MCMs. There was no significant difference in the incidence of MCM in the first year after birth between infants in the KPK and TSS groups (adjusted odds ratio, 0.820; 95% confidence interval, 0.475-1.415). CONCLUSION: There was no significant difference in the risk of preterm birth or MCMs between pregnant women prescribed KPK and those prescribed TSS during the first trimester.

BACKGROUND: Studies investigating whether respiratory syncytial virus (RSV) infection, non-RSV respiratory infections, respiratory-related disorders, and non-respiratory-related disorders are associated with subsequent wheezing are limited in Japan. We aimed to elucidate the relationship between hospitalization for RSV infection, non-RSV respiratory infections, respiratory-related disorders, as well as non-respiratory-related disorders and subsequence wheezing in Japanese children. METHODS: This study included 7340 children and was conducted under the TMM BirThree Cohort Study (Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study). Data was collected from birth records and questionnaires. We categorized hospitalization history into five categories: "no hospitalization," hospitalizations for "RSV infection," "non-RSV respiratory infections," "respiratory-related disorders," and "non-respiratory-related disorders." The association of the five categories with later wheezing at 3 years of age was evaluated using multivariable logistic regression analysis. RESULTS: After adjusting for covariates, an association was shown between hospitalization under 2 years of age and later wheezing (odds ratio [OR] = 2.78; 95% confidence interval [CI] = 1.97-3.88 for "RSV infection"; OR = 2.61; 95% CI = 1.44-4.57 for "non-RSV respiratory infections"; and OR = 3.33; 95% CI = 2.43-4.54 for "respiratory-related disorders"). CONCLUSION: Hospitalization of children under 2 years of age for RSV infection as well as non-RSV respiratory infections and respiratory-related disorders were associated with subsequent wheezing.

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.

AIM: The aim of this study was to evaluate depression at 6 and 12 months postpartum, using the Edinburgh Postpartum Depression Scale (EPDS) total score and its subitem regarding self-harm ideation (SHI) at 1 month postpartum. METHODS: A sample of 12,358 postpartum women answered the EPDS and questionaries at 1, 6, and 12 months postpartum longitudinally. RESULTS: For participants with postpartum depression (PPD; EPDS total score ≥9) and SHI (SHI sub-score ≥1) at 1 month postpartum, the risk of depression at 6 and 12 months postpartum (odds ratio [95% confidence interval] at 6 and 12 months postpartum: 20.03 [16.8-23.8] and 14.55 [12.3-17.2], respectively) was higher than for those with PPD but without SHI at 1 month postpartum (OR: 8.57 [7.36-10.0], and 6.24 [5.38-7.24], respectively). Additionally, SHI even without depressive symptoms at 1 month postpartum is also a risk for depression at 6 and 12 months postpartum. To support our longitudinal evaluation of depression at 6 and 12 months postpartum, these related factors were examined: traumatic events or relocations after the Great East Japan Earthquake, employment status, household income, personality traits, sleep status, psychological distress, and social networks. The result showed employment status, low household income and poor social networks were significantly associated with depression at 12 months postpartum but not at 6 months postpartum. CONCLUSION: This study showed a high risk of depression at 6 and 12 months postpartum for those who had depressive symptoms with SHI at 1 month postpartum. Our findings may contribute to the precise evaluation of depression at 6 and 12 months postpartum while considering sleep status, psychological distress and social network during pregnancy.

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.

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.

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.

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.

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.

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.

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.

IMPORTANCE: Whether some domains of child development are specifically associated with screen time and whether the association continues with age remain unknown. OBJECTIVE: To examine the association between screen time exposure among children aged 1 year and 5 domains of developmental delay (communication, gross motor, fine motor, problem-solving, and personal and social skills) at age 2 and 4 years. DESIGN, PARTICIPANTS, AND SETTING: This cohort study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Pregnant women at 50 obstetric clinics and hospitals in the Miyagi and Iwate prefectures in Japan were recruited into the study between July 2013 and March 2017. The information was collected prospectively, and 7097 mother-child pairs were included in the analysis. Data analysis was performed on March 20, 2023. EXPOSURE: Four categories of screen time exposure were identified for children aged 1 year (<1, 1 to <2, 2 to <4, or ≥4 h/d). MAIN OUTCOMES AND MEASURES: Developmental delays in the 5 domains for children aged 2 and 4 years were assessed using the Japanese version of the Ages & Stages Questionnaires, Third Edition. Each domain ranged from 0 to 60 points. Developmental delay was defined if the total score for each domain was less than 2 SDs from its mean score. RESULTS: Of the 7097 children in this study, 3674 were boys (51.8%) and 3423 were girls (48.2%). With regard to screen time exposure per day, 3440 children (48.5%) had less than 1 hour, 2095 (29.5%) had 1 to less than 2 hours, 1272 (17.9%) had 2 to less than 4 hours, and 290 (4.1%) had 4 or more hours. Children's screen time was associated with a higher risk of developmental delay at age 2 years in the communication (odds ratio [OR], 1.61 [95% CI, 1.23-2.10] for 1 to <2 h/d; 2.04 [1.52-2.74] for 2 to <4 h/d; 4.78 [3.24-7.06] for ≥4 vs <1 h/d), fine motor (1.74 [1.09-2.79] for ≥4 vs <1 h/d), problem-solving (1.40 [1.02-1.92] for 2 to <4 h/d; 2.67 [1.72-4.14] for ≥4 vs <1 h/d), and personal and social skills (2.10 [1.39-3.18] for ≥4 vs <1 h/d) domains. Regarding risk of developmental delay at age 4 years, associations were identified in the communication (OR, 1.64 [95% CI, 1.20-2.25] for 2 to <4 h/d; 2.68 [1.68-4.27] for ≥4 vs <1 h/d) and problem-solving (1.91 [1.17-3.14] for ≥4 vs <1 h/d) domains. CONCLUSIONS AND RELEVANCE: In this study, greater screen time for children aged 1 year was associated with developmental delays in communication and problem-solving at ages 2 and 4 years. These findings suggest that domains of developmental delay should be considered separately in future discussions on screen time and child development.

To examine whether body type at birth, body weight, and obesity in early childhood are associated with overweight/obesity during school age and puberty. Data from maternal and child health handbooks, baby health checkup information, and school physical examination information of participants at birth and three-generation cohort studies were linked. Association between body type and body weight at different time intervals (at birth and at 1.5, 3.5, 6, 11, and 14 years of age) were comprehensively analyzed using a multivariate regression model adjusted for gender, maternal age at childbirth, maternal parity, and maternal body mass index, and drinking and smoking statuses at pregnancy confirmation. Children who are overweight in young childhood had a greater risk of being overweight. Particularly, overweight at one year of age during checkup was associated with overweight at 3.5 years (adjusted odds ratio (aOR), 13.42; 95% confidence interval (CI), 4.46-45.42), 6 years (aOR, 6.94; 95% CI, 1.64-33.46), and 11 years (aOR, 5.22; 95% CI, 1.25-24.79) of age. Therefore, being overweight in young childhood could increase the risk of being overweight and obese during school age and puberty. Early intervention in young childhood may be warranted to prevent obesity during school age and puberty.