Aoi Noda

Background: Women who experienced the Great East Japan Earthquake (GEJE) and subsequently became pregnant may have children who are more likely to exhibit emotional and behavioral problems. However, few longitudinal studies have investigated the developmental outcomes among children born to mothers who experienced natural disasters before pregnancy and continued to experience stress symptoms thereafter.Purpose: This study aimed to examine the association between maternal traumatic stress related to the GEJE and behavioral problems in their children.Methods: A total of 21,656 mother-child pairs were included in the analysis; 52.0% of the offspring were male. Maternal traumatic stress symptoms related to the GEJE were assessed using items evaluating recollection, emotional distress, somatic reactions, and avoidance behaviors (Cronbach α=0.681). Child behavioral outcomes at 2 and 3 years of age were assessed using the Child Behavior Checklist for Ages 1½–5 (CBCL/1½–5). Missing data were addressed by multiple imputation, and a multivariable logistic regression was performed with adjustment for maternal psychological distress, social isolation, sleep problems, parity, breastfeeding, disaster-related exposure, parental history of mental illness, and socioeconomic characteristics. Covariate selection was guided by a directed acyclic graph.Results: Compared with mothers who reported no traumatic stress symptoms, those reporting one or 2 symptoms had a higher odds of their children exhibiting internalizing (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.06–1.69), externalizing (OR, 1.29; 95% CI, 1.07–1.55) and total problems (OR, 1.38; 95% CI, 1.11–1.72) at age 2 and internalizing (OR, 1.38; 95% CI, 1.13–1.69), externalizing (OR, 1.21; 95% CI, 1.01–1.45) and total problems (OR, 1.37; 95% CI, 1.10–1.71) at age 3. Mothers reporting 3 or 4 symptoms showed stronger associations, a pattern consistent with a dose-response relationship supported by a formal test for trends for most outcomes. These findings were consistent with those of sensitivity analyses using continuous CBCL scores.Conclusion: These findings suggest that maternal mental health support beyond pregnancy may be important for women of reproductive age in disaster-affected areas and could help inform preventive strategies addressing the intergenerational effects of trauma following largescale disasters such as the GEJE.

This study aimed to evaluate the prevalence of antipsychotic prescriptions before, during, and after pregnancy in Japan, with a focus on new prescriptions and continuation after pregnancy confirmation. We conducted a claims‐based analysis using a Japanese claims database (analytic period: 2010–2022). Antipsychotic prescription prevalence and new prescriptions were assessed from 180 days before pregnancy through 180 days postpartum. To assess continuation after pregnancy confirmation, prescription status was evaluated across gestational weeks 0–4, 5–13, and from 14 weeks to delivery. Among 120 735 women, 1698 (140.6/10 000 deliveries) received at least one antipsychotic prescription, including 809 (67.0/10 000 deliveries) during pregnancy. Prescription prevalence decreased during the first and second trimesters but increased postpartum. New prescriptions were less frequent during pregnancy but increased after delivery. Among 611 women prescribed antipsychotics during 0–4 weeks' gestation, 482 (78.9%) continued and 129 (21.1%) discontinued prescription during weeks 5–13; of those who continued prescription during 5–13 weeks, 334 (54.7%) continued until delivery. Evaluation of major indications showed that continuation until delivery was highest in those with schizophrenia (63.6%), followed by bipolar disorder (51.0%). This study provides the first comprehensive description of perinatal antipsychotic prescription trends in Japan. Substantial prescription discontinuation occurred after pregnancy confirmation. Increases in postpartum prescriptions might reflect new prescriptions or resumption among women who had discontinued treatment during pregnancy. These findings offer foundational epidemiological insights into real‐world perinatal antipsychotic use.

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 7747 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 ages 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 ST 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 evaluate the association between benzodiazepine exposure during early pregnancy and the risk of miscarriage, with a focus on dose–response, half-life, and individual agents. Methods: This nested case–control study was conducted using a large Japanese administrative database. Cases were defined as pregnancies ending in miscarriage between 2005 and 2023. Controls were randomly selected through risk-set sampling with replacement and matched in a 3:1 ratio. Conditional logistic regression, adjusted for confounders, was used to assess the associations. Results: Overall, 44,118 cases were matched with 132,317 controls, with a mean age of 33.2 years. The prevalence of benzodiazepine exposure was 1.7% and 1.2% among cases and controls, respectively. Etizolam (0.3%) had the highest prevalence, followed by alprazolam (0.3%) and brotizolam (0.2%) in both groups. Adjusted odds ratio (OR) for benzodiazepine exposure during early pregnancy was 1.241 (95% confidence interval: 1.136–1.357). Adjusted ORs for high-dose (1.212 [1.050–1.400]) and medium-dose (1.189 [1.037–1.363]) exposure were numerically higher than that for low-dose exposure (1.111 [0.934–1.322]). Adjusted OR for long-acting benzodiazepines (1.308 [1.124–1.522]) was numerically higher than those for intermediate- (1.132 [0.999–1.284]) and short-acting (1.157 [1.030–1.300]) agents. Adjusted ORs for etizolam, alprazolam, and brotizolam were 0.929 (0.782–1.103), 0.853 (0.707–1.030), and 1.454 (1.180–1.791), respectively. Conclusions: Benzodiazepine exposure during early pregnancy was modestly associated with an increased risk of miscarriage. Although associations tended to be stronger with higher dose levels and longer half-life categories, estimates across subgroups lacked precision and should be interpreted with caution.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that primarily develops during childhood. Residential greenness has been reported to be associated with AD onset. However, findings are inconsistent and may not apply to Japanese settings because vegetation and residential environments vary regionally. Therefore, this study aimed to examine early‐life exposure to residential greenness and subsequent AD development in Japanese children. Methods: We analyzed data from 14,932 children in the Tohoku Medical Megabank Project Birth and Three‐Generation Cohort Study. The exposure was residential greenness during the first 6 months of life, quantified using the normalized difference vegetation index (NDVI) within 250‐, 500‐, and 1000‐m buffers around each birth postal code and categorized into tertiles (low [reference], moderate, high). The outcome was AD incidence between 6 months and 5 years of age, assessed via maternal reporting. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were estimated using modified Poisson regression. Analyses were stratified by urbanization levels, child's sex, and parental history of allergic diseases. Results: A significant protective association was observed among children in the high NDVI tertile within the 250‐m buffer (adjusted RR: 0.80, 95% CI: 0.67–0.95), whereas the moderate tertile was not significant (adjusted RR: 0.94, 95% CI: 0.83–1.06). A similar pattern was observed at 500 m. Stratification showed similar associations across urbanization levels, which were stronger in boys and observed only among children without parental allergic history. Conclusion: Early‐life exposure to residential greenness was associated with a decreased risk of AD in Japanese children.

Aim: Traditional Japanese (Kampo) medicines containing ephedra (KE) are prescribed for cold during pregnancy; however, detailed safety information on their use in pregnant women is lacking. This study aimed to clarify the association between prescription of KE during the first trimester of pregnancy and major congenital malformations (MCMs) in newborns. Methods: Data from a large Japanese administrative claims database were analyzed: we included records of pregnant women who continued to be covered in the same health insurance society from 3 months before pregnancy until delivery, who gave birth between 2010 and 2019; the selected records included data relating to the infants until first year from birth. Pregnant women who were prescribed acetaminophen, commonly used to treat colds, in the first trimester of pregnancy and their infants were treated as the controls in our analysis. Results: Of 75,398 infants, 4607 (6.1%) were diagnosed with MCMs within the first year of birth. Among the 7820 infants whose mothers were prescribed acetaminophen, 497 (6.4%) had MCMs. Of the 4772 infants were born to women prescribed KE, among whom 327 (6.9%) had MCMs. adjusting for covariates with propensity score overlap weights identified no significant difference in MCM risk between the two types of prescriptions (overlap‐weighted odds ratio 1.077, 95% confidence interval 0.932−1.245). Conclusion: The results of this study indicated that the risk of MCMs did not differ between women prescribed KE and those prescribed acetaminophen in the first trimester of pregnancy.

This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with first‐trimester exposure to antipsychotics, using a large claims database in Japan. This retrospective cohort study was based on data from a large claims database in Japan. We used a large claims database from 2010 to 2019. Dates of pregnancy onset and delivery were estimated using the developed algorithms. Overall MCMs were defined according to the International Classification of Diseases, 10th revision codes. To address confounding by indication, the risk of MCM in relation to first‐trimester antipsychotic use was evaluated among pregnant women with psychiatric disorders diagnosed before the end of the first‐trimester. We compared the prevalence of MCMs among infants born to pregnant women with or without first‐trimester exposure to antipsychotics and estimated the weighted odds ratios (wORs) using propensity‐score overlap weights. The prevalence of psychiatric diagnoses before the end of the first‐trimester was 6291 women among the 91 390 who delivered between 2010 and 2019. Among the 6291 diagnosed with psychiatric disorders, 317 were exposed to any antipsychotics during the first‐trimester of pregnancy. The prevalence of overall MCMs among live births was 411 (6.9%) among women unexposed to any antipsychotics and 24 (7.6%) among those exposed. The first‐trimester exposure to any antipsychotics was not significantly associated with overall MCMs when wORs were calculated using propensity‐score overlap weights (wOR 1.144, 95% confidence intervals 0.727–1.799). Exposure to any antipsychotics during the first‐trimester of pregnancy was not associated with an increased risk of overall MCMs in infants.

Background: Kampo medicine is commonly prescribed alongside Western pharmaceuticals. Its use during pregnancy has become increasingly common; however, there are concerns regarding safety due to the inclusion of multiple herbal components. Objective: We aim to summarize the current evidence on the use and safety of Kampo medicines during pregnancy in Japan. Methods: A comprehensive literature review was conducted using nine key studies, including claims database analyses and large birth cohort investigations. These were divided into two main categories: (1) studies describing the prevalence and patterns of Kampo medicine use during pregnancy, and (2) studies investigating safety outcomes such as congenital malformation, birth weight, preterm birth, hospitalization, and live birth rates. Results: The proportion of pregnant women using Kampo medicines ranges from 4% to 10%, with common formulations including tokishakuyakusan, shoseiryuto, and kakkonto. Studies from both claims databases and cohort‐based self‐reports confirm widespread use. Regarding safety, multiple observational studies report no significant increase in congenital malformations, low birth weight, or preterm birth associated with Kampo medicine use. Some studies even suggest beneficial effects, such as reduced hospitalization for hyperemesis and increased live birth rates in women with recurrent pregnancy loss. However, caution is warranted for Kampo formulations containing potentially teratogenic substances such as ephedra and rhubarb. Conclusion: Kampo medicine is widely used among pregnant women in Japan and appears to have a generally favorable safety profile when prescribed appropriately. Nonetheless, more rigorous prospective studies are needed to confirm safety across various Kampo formulations and patient populations.