久田 文

Fipronil, a widely used phenylpyrazole insecticide, is known to disrupt circulating thyroid hormone (TH) levels in rodents. Concentrations of fipronil and its metabolites (fipronil sulfone and fipronil sulfide) in serum samples collected in 2009-2011 were measured for 131 Japanese pregnant women by a sensitive and accurate liquid chromatography-tandem mass spectrometric method developed in our laboratory to relate TH levels. Fipronil sulfone was detected in all the subjects with the median being 21 ng/L (min-max: 6.8-89), but fipronil and fipronil sulfide were detected in none of the subjects (detection limit: 5.0 and 1.2 ng/L, respectively), indicating a rapid and exclusive oxidative conversion to fipronil sulfone upon exposure. The median concentration of fipronil sulfone was lower than those previously reported for general populations in other countries by one order of magnitude. There were no attributes or dietary habits of the subjects that significantly vary the serum fipronil sulfone concentrations. Multiple regression analyses found no significant association between serum concentrations of fipronil sulfone and free thyroxine- or thyroid-stimulating hormone levels, indicating the absence of adverse effects on circulating TH levels probably due to the lower exposure levels of the present subjects. The present result would be valuable for establishing a dose-effect relationship of fipronils in humans on population levels.

Background/Objectives: Isoflavone (ISO) may have immunosuppressive and promoting effects. In this study, we aimed to examine the association between maternal dietary ISO intake during pregnancy and childhood allergic rhinoconjunctivitis at the age of 3 years using the Japanese Birth Cohort data. Methods: Overall, 78,549 mother-child pairs were studied. Maternal dietary ISO intake (the sum of genistein and daidzein) during pregnancy was evaluated using a food frequency questionnaire. Information on physician-diagnosed allergic rhinoconjunctivitis was collected from the caregiver-reported questionnaire. After classifying ISO intake into quartiles (Q1: reference), multivariable logistic regression analysis was employed to explore the association with allergic rhinoconjunctivitis. Results: No association was observed between maternal ISO intake and allergic rhinoconjunctivitis in any child. However, in the sex-stratified analysis, maternal ISO intake linked to allergic rhinoconjunctivitis in female children positively (Q2, adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.06-1.40; Q3, aOR: 1.17, 95% CI: 1.01-1.35; Q4, aOR: 1.24, 95% CI: 1.07-1.44). Conclusions: Maternal dietary ISO intake during pregnancy was sex-specifically linked to childhood allergic rhinoconjunctivitis in children. These findings provide insights into the need for estimating the optimal ISO consumption during pregnancy for allergy avoidance in children.

BACKGROUND: Coronavirus disease 2019 (COVID-19) in children is often asymptomatic, posing challenges in detecting infections. Additionally, factors contributing to infection remain poorly understood. This study aimed to investigate trends in anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid antibody seroprevalence, the relationship between seroprevalence and parental perception of child infection, and factors related to COVID-19 in children. METHODS: In December 2020, 355 children aged 6-12 years in one elementary school were enrolled in the study. The anti-SARS-CoV-2 nucleocapsid antibody seroprevalence was assessed, and questionnaires were administered annually for three years. Parents' perceptions of infection and factors contributing to infection were examined. RESULTS: The seroprevalence was 0.6%, 2.2%, and 60.9% in the first, second, and third years, respectively. The third-year seroprevalence among children reported as 'infected,' 'not tested but had symptoms,' and 'not infected' by parents was 97.3%, 83.3%, and 35.7%, respectively. Increased odds of seropositivity at the third-year measurement were observed in lower grades (adjusted odds ratio [aOR]=2.79 compared with higher grades) and in children more likely to play with others (aOR=3.97 for 'somewhat' and 2.84 for 'often,' compared with 'rarely'). No significant associations with seropositivity were found for sex, siblings, body mass index, serum 25-OH vitamin D3 concentration, or sleep duration. CONCLUSION: The Omicron variant outbreak from the end of 2021 led to a sharp increase in seroprevalence among children, with many unaware of their infection. Frequent play with others may facilitate transmission in children. These data provide useful information for developing countermeasures against COVID-19 and other future pandemics.

PURPOSE: Epidemiological studies have reported that environmental factors from fetal period to early childhood can influence the risk of non-communicable diseases in adulthood. This concept has been termed the developmental origins of health and disease (DOHaD). The Chiba study of Mother and Child Health (C-MACH) is a DOHaD concept-based birth cohort study which started in 2014. This study aims to investigate the effects of genetic and environmental factors, particularly fetal and postnatal living environment, on children's health. We also aim to identify candidate biomarkers for their health status. Moreover, the second phase study of C-MACH which was initiated in 2021 aimed at expanding the sample size, especially for gut microbiota and epigenomic analysis; it also aimed at clarifying the impact of the coronavirus disease 2019 (COVID-19) pandemic on children's health. PARTICIPANTS: This study consists of four hospital-based cohorts. Women who were <13 weeks pregnant and their partners were enrolled in the study. All data and biological samples will be stored in the Chiba University Centre for Preventive Medical Sciences. FINDINGS TO DATE: A total of 561 women and their partners provided their consent to participate in this study. Of these women, 505 completed the questionnaire during the early gestational period. The mean age of the 505 women at enrolment was 33.0 (SD, 4.5) years. The mean prepregnancy body mass index (BMI) was 21.7 (SD, 3.6) kg/m2, with 74.5% of the women having a BMI of 18.5-24.9 kg/m2. About 5.2% of the women smoked cigarettes during the early stages of pregnancy. FUTURE PLANS: The primary study outcomes are allergies, obesity, endocrine and metabolic disorders and developmental difficulties in children. Variables related to genome, metabolome, epigenome, gut microbiota and exposome will be evaluated as health-related factors. The relationships between these outcomes and the health-related factors will be analysed.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.