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.

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.

Objectives This study aimed to examine the association between infertility treatment and neurodevelopment in children at 2 and 3.5 years of age. Design Prospective cohort study. Setting and participants The study population consisted of mother–child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Miyagi and Iwate Prefectures, Japan. Pregnant women were recruited in obstetric clinics or hospitals and their children were followed up by the questionnaire. Outcome measures The children’s neurodevelopmental outcomes were assessed at 2 and 3.5 years of age using the Ages and Stages Questionnaire, third edition (ASQ-3), which consists of questions on five developmental domains. We performed a multivariate logistic regression analysis of the association between infertility treatment (including ovulation induction (OI), artificial insemination with husband’s sperm (AIH) and assisted reproductive technology (ART)) and the clinical range of ASQ-3. Results Of 9655 mother–child pairs, 273 (2.8%) and 487 (5.0%) were conceived through OI/AIH and ART, respectively. The odds of having developmental delays at 2 years of age were higher in children conceived through OI/AIH (OR, 1.36; 95% CI 1.00 to 1.85) and ART (OR, 1.36; 95% CI 1.07 to 1.72) than in those conceived naturally. Additionally, OI/AIH and ART were significantly associated with communication (OR, 1.93; 95% CI 1.25 to 2.98) and gross motor (OR, 1.50; 95% CI 1.08 to 2.09) delays, respectively. There were no statistically significant differences in the odds of having developmental delays at 3.5 years of age in children conceived through OI/AIH (OR, 1.13; 95% CI 0.79 to 1.61) and ART (OR, 1.03; 95% CI 0.78 to 1.37). Conclusion In this study, we found a significant association between infertility treatment and children’s neurodevelopment at 2 years of age, whereas no statistically significant differences were found at 3.5 years of age.

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.