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Inadequate maternal iodine intake affects thyroid function and may impair fetal brain development. This study investigated the association between maternal iodine intake during pregnancy and neurodevelopmental delay in offspring at 1 and 3 years of age using a nationwide birth cohort: the Japan Environment and Children's Study. We assessed dietary iodine intake during pregnancy using a food frequency questionnaire and child neurodevelopment using the Japanese translation of the Ages and Stages Questionnaire, Third Edition. The risk of delay (score below the cut-off value) for fine motor domain at 1 year of age was increased in the lowest quintile iodine intake group compared with the fourth quintile iodine intake group. The risk of delay for problem-solving at 1 year of age was increased in the lowest and second quintile iodine intake group and decreased in the highest quintile iodine intake group. The risk of delay for communication, fine motor, problem-solving, and personal–social domains at 3 years of age was increased in the lowest and second quintile iodine intake group compared with the fourth quintile iodine intake group, while the risk of delay for fine motor and problem-solving domains was decreased in the highest quintile iodine intake group. Low iodine intake levels in pregnancy may affect child neurodevelopment. [ABSTRACT FROM AUTHOR]

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models.Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age).Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: We sought to identify associations between aldehyde dehydrogenase 2 ( ALDH2), alcohol consumption, and hypertension in Japanese men. Methods: The study participants were 1,225 male Japanese workers. We collected lifestyle information, body measurements, blood biochemical parameters, blood pressure measurements, and ALDH2 genotyping data during medical examinations conducted between March 2004 and January 2005 at a work facility and an affiliated company. Lifestyle data on alcohol intake and smoking were collected using self-administered questionnaires at the same time as when the aforementioned measurements were obtained. Results: The genotype frequencies of ALDH2 genetic polymorphisms were 62.6, 32.7, and 4.7 % for *1/*1, *1/*2, and *2/*2, respectively. Systolic blood pressure and diastolic blood pressure in the *1/*2 or *2/*2 group were significantly lower than those in the *1/*1 group ( P < 0.001). Multiple regression analysis (stepwise method) for blood pressure according to ALDH2 genetic polymorphism revealed that the amount of daily alcohol intake affected systolic blood pressure in participants who harbored the ALDH2 genetic polymorphism *1/*2 or *2/*2. Conclusions: The interaction between alcohol intake and ALDH2 genetic polymorphisms might affect systolic blood pressure in adult male workers. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to determine the correlation between mental health and multiple chemical sensitivity (MCS). Method: The present study was conducted at two companies in 2011; both in Kyushu, Japan. The 'subjective symptoms' subscale of the 'Self-diagnosis Checklist for Assessment of Workers' Accumulated Fatigue' was used as a mental health subscale. To determine if multiple chemical exposure has an impact on mental health, we composed an original path model using structural equation analysis. Result: Our final path model can be regarded as good: CMIN/DF = 1.832, CFI = 0.996, and RMSEA = 0.038, AIC = 71.158. As expected, chemical sensitivity and other chemical sensitivity scores predicted the health effects of multiple chemical exposure ( β = 0.19, 0.64). Mental health was predicted by symptom severity and life impact ( β = 0.56 and 0.12), which were both affected by multiple chemical exposure ( β = 0.38 and 0.89, respectively). Conclusion: As far as we are aware, this is the first study using path analysis to explore whether MCS can indicate mental health in worker populations worldwide, and we found a significant causal relationship between them. This could indicate that more focus should be placed on the impact of MCS on mental health in future investigations. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women. Methods: The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables. Results: Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 μg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 μIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 μg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status. Conclusions: Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones. [ABSTRACT FROM AUTHOR]

Background/Purpose: We hypothesized that polymorphic differences among individuals might cause variations in the effect that environmental endocrine disruptors (EEDs) have on male genital malformations (MGMs). In this study, individual variation in the genetic response to low-dose bisphenol A (BPA) was investigated in human foreskin fibroblast cells (hFFCs) derived from child cryptorchidism (CO) and hypospadias (HS) patients. Methodology/Principal Findings: hFFCs were collected from control children without MGMs (n = 5) and child CO and HS patients (n = 8 and 21, respectively). BPA exposure (10 nM) was found to inhibit matrix metalloproteinase-11 (MMP11) expression in the HS group (0.74-fold, P = 0.0034) but not in the control group (0.93-fold, P = 0.84) and CO group (0.94-fold, P = 0.70). Significantly lower levels of MMP11 expression were observed in the HS group compared with the control group (0.80-fold, P = 0.0088) and CO group (0.79-fold, P = 0.039) in response to 10 nM BPA. The effect of single-nucleotide polymorphism rs5000770 (G.A), located within the aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) locus, on individual sensitivity to low-dose BPA was investigated in the HS group. A significant difference in neurotensin receptor 1 (NTSR1) expression in response to 10 nM BPA was observed between AA and AG/GG groups (n = 6 and 15, respectively. P = 0.031). However, no significant difference in ARNT2 expression was observed (P = 0.18). Conclusions/Significance: This study advances our understanding of the specificity of low-dose BPA effects on human reproductive health. Our results suggest that genetic variability among individuals affects susceptibility to the effects of EEDs exposure as a potential cause of HS. [ABSTRACT FROM AUTHOR]

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 D 3 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/m 2 , with 74.5% of the women having a BMI of 18.5-24.9 kg/m 2 . 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Multiple chemical sensitivity (MCS) is an acquired chronic disorder characterized by nonspecific symptoms in multiple organ systems associated with exposure to low-level chemicals. Diagnosis of MCS can be difficult because of the inability to assess the causal relationship between exposure and symptoms. No standardized objective measures for the identification of MCS and no precise definition of this disorder have been established. Recent technological advances in mass spectrometry have significantly improved our capacity to obtain more data from each biological sample. Metabolomics comprises the methods and techniques that are used to determine the small-level molecules in biofluids and tissues. The metabolomic profile-the metabolome-has multiple applications in many biological sciences, including the development of new diagnostic tools for medicine. We performed metabolomics to detect the difference between 9 patients with MCS and 9 controls. We identified 183 substances whose levels were beyond the normal detection limit. The most prominent differences included significant increases in the levels of both hexanoic acid and pelargonic acid, and also a significant decrease in the level of acetylcarnitine in patients with MCS. In conclusion, using metabolomics analysis, we uncovered a hitherto unrecognized alteration in the levels of metabolites in MCS. These changes may have important biological implications and may have a significant potential for use as biomarkers.

Objectives: The objectives of this study were to assess the possibility of utilization of genetic testing and to determine the effect of participant characteristics on genetic testing awareness in Japanese workers., Methods: The subjects of this study consisted of 998 workers from two companies located in Kyusyu, Japan, from June to July, 2014. We examined the participant characteristics and genetic testing awareness using paper questionnaires. Ultimately, the data from 737 subjects (73.8%) was included in our analysis., Results: Regarding participant characteristics, the percentage of respondents who replied "I have heard of genetic testing" (including knowledge about genetic testing) and "I would like to have genetic testing" were 82.5% and 58.2%, respectively. A significant age difference in genetic testing awareness was also observed in our study. Logistic regression analysis revealed both significant adjust odds ratios (ORs) of 3.02 (95% CI 1.67-5.46) and 3.82 (95% CI 1.71-8.53) in the 40-49-year-old group and the over 50 year old group, respectively, compared with the 20-29-year-old group. In addition, females and the participants who graduated from graduate schools showed greater interest in genetic testing., Conclusions: This survey showed that about 80% of Japanese workers know about genetic testing and about 60% would like to have a test. The results of our survey also suggest that the awareness of genetic testing is influenced by participant characteristics, namely age, sex, and education.

Objectives: The lead content of excavated bone samples from archaeological sites in Hokkaido was measured to obtain insight into the source of human lead contamination known in the historic Japanese Edo era., Methods: Fifty-seven rib samples excavated from 11 sites of five different eras in Hokkaido were analyzed for lead (Pb), calcium (Ca), and iron (Fe) contents by ICP mass spectrometry and ICP emission spectrometry., Results: The Pb/Ca ratio (mg Pb/kg Ca) was low (approximately 2.0) and constant from the Jomon (approximately 5000 BP) to the Satsumon (approximately 750 BP) eras; however, its median increased to 11 in the Modern era. This elevation of Pb/Ca ratio in the bone samples from sites of the Modern era was not considered to be due to a greater bone contamination with soil particles because of similar Fe concentrations in the bone samples from this era to those in other eras. This historic trend of Pb/Ca ratio was similar to that observed in other parts of Japan. The elevated Pb/Ca ratio in the bone samples excavated from sites in the Modern era in other parts of Japan, that is, Edo era, has been ascribed to the usage of face powder containing Pb; however, people inhabiting Hokkaido in those days, the Ainu, were not considered to have the custom of using face powder., Conclusions: Contamination source(s) other than face powder was postulated in the Modern era of both Hokkaido and other parts of Japan.

Objectives: To quantitatively assess the intra- and inter-individual variation of urinary iodine concentration in Japanese to determine whether urinary analysis is applicable to assessing habitual iodine intake in subjects on an individual basis., Methods: Five urine samples (first void) were taken from each of the 14 healthy female subjects at 2-3 week intervals over 4-5 months. Information on diet and medication use on the previous day of urine sampling was obtained by a questionnaire during each urine sampling. The concentration of iodine in urine samples was measured by inductively coupled plasma mass spectrometry (ICP-MS). Intra- and inter-individual variation was assessed by intra class correlation coefficient (ICC)., Results: The median concentration of iodine in 70 urine samples was 91 µg/g-cre (range: 15-4400 µg/g-cre). The mean iodine concentration in urine samples from subjects who took iodine-rich foods/medications on the day before sampling was statistically significantly higher than that from subjects who did not take such foods/medications (p < 0.01, t-test). The ICC of urinary iodine concentration of the 14 subjects was 0.55, indicating good reproducibility; however, this was 0.28 when one subject who routinely used an iodine-containing gargle was excluded from analysis., Conclusions: Urine sampled on a single occasion is not a suitable medium for the assessment of long-term intake levels of iodine in subjects on an individual basis.