森 千里

Compared with the relatively well-investigated effects of childhood exposure to lead on neurocognitive deficits, those of prenatal exposure remain relatively inconclusive. We aimed to investigate the association between prenatal blood lead levels and neurodevelopmental delay during the first three years of life. From a prospective cohort of the Japan Environment and Children’s Study, we analyzed a total of 80,759 children. The exposure factors were prenatal lead concentrations measured from maternal whole blood in the second/third trimesters and umbilical cord blood at birth. Neurodevelopment was assessed at 6, 12, 18, 24, 30, and 36 months old using a screening tool, the Ages and Stages Questionnaires, third edition (ASQ). The outcome measures were any suspected neurodevelopmental delay (sNDD) identified via the ASQ during the first (sNDD-1Y), second (sNDD-2Y), and third (sNDD-3Y) years of life. sNDD-1Y, 2Y, and 3Y were identified in 18.0%, 16.2%, and 17.2% of children, respectively. The geometric means of blood lead concentration in this study were much lower (0.62 μg/dL in maternal blood and 0.50 μg/dL in cord blood) than previously investigated levels. Multivariable regression models revealed that there were no associations between maternal blood lead and sNDD-1Y and 2Y and between cord blood lead and sNDD-1Y, 2Y, and 3Y. Although a higher maternal blood lead was associated with a reduced risk of sNDD-3Y (adjusted relative risk: 0.84, 95% confidence interval 0.75–0.94, per 1 increase in common logarithm of lead concentration), there were no dose–response relationships in the analysis using quintiles of lead concentrations. Using a large-scale data set, the present study demonstrated no convincing evidence for an inverse association between levels of prenatal blood lead and neurodevelopment in early childhood. Longitudinal measurements of prenatal and postnatal lead levels are needed to understand the relationship between lead exposure and neurocognitive development.

<title>Abstract</title><sec> <title>Background</title> The extremes of maternal pre-pregnancy body mass index (BMI) are known to be risk factors associated with obstetric and adverse perinatal outcomes. Among Japanese women aged 20 years or older, the prevalence of underweight (BMI &lt; 18.5 kg/m²) was 11.5% in 2019. Maternal thinness is a health problem caused by the desire to become slim. This study aimed to investigate the association between the severity of maternal low pre-pregnancy BMI and adverse perinatal outcomes, including preterm birth (PTB), low birth weight (LBW), and small-for-gestational age (SGA). </sec><sec> <title>Methods</title> We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant individuals between 2011 and 2014. Pre-pregnancy BMI was categorized as severe-moderate underweight (BMI <underline>&lt;</underline> 16.9 kg/m²), mild underweight (BMI, 17.0–18.4 kg/m²), low-normal weight (BMI, 18.5–19.9 kg/m²), high-normal weight (BMI, 20.0–22.9 kg/m²), overweight (BMI, 23.0–24.9 kg/m²), and obese (BMI ≥ 25.0 kg/m²). The high-normal weight group was used as the reference for statistical analyses. Adjusted logistic regression was performed to evaluate the association between pre-pregnancy BMI and PTB, LBW, and SGA. </sec><sec> <title>Results</title> Of 92,260 singleton pregnant individuals, the prevalence was 2.7% for severe-moderate underweight, 12.9% for mild underweight, and 24.5% for low-normal weight. The prevalence of adverse outcomes was 4.6% for PTB, 8.1% for LBW, and 7.6% for SGA. The adjusted odds ratios (aORs) for PTB were 1.72 (95% confidence interval [CI], 1.46–2.03) for severe-moderate underweight and 1.26 (95% CI, 1.14–1.39) for mild underweight. The aORs of LBW were 2.55 (95% CI, 2.27–2.86) for severe-moderate underweight, 1.64 (95% CI, 1.53–1.76) for mild underweight, and 1.23 (95% CI, 1.16–1.31) for low-normal weight. The aORs of SGA were 2.53 (95% CI, 2.25–2.84) for severe-moderate underweight, 1.66 (95% CI, 1.55–1.79) for mild underweight, and 1.29 (95% CI, 1.21–1.38) for low-normal weight. </sec><sec> <title>Conclusions</title> A dose-response relationship was found between the severity of low pre-pregnancy BMI and PTB, LBW, and SGA. Even low-normal BMI (18.5–19.9 kg/m²) increased the risk of LBW and SGA. This study provides useful information for pre-conception counseling in lean individuals. </sec>

Abstract The Parenting Stress Index-Short Form (PSI-SF) has been widely employed to assess parenting stress in a number of research and clinical trials. To date, no parenting stress studies in Japan have examined the factor structure, validity, and reliability of the PSI-SF. Therefore, this study aimed to evaluate the psychometric properties of this 19-item version as administered in a national cohort study, the Japan Environment and Children’s Study, to two sample groups of mothers, those with a 1.5-year-old child and those with a 2.5-year-old child (n = 79,282 and 75,831, respectively). We performed exploratory factor analysis to re-examine the appropriate factor structure, confirmatory factor analysis to evaluate goodness of fit, and calculated Cronbach’s α and Pearson’s r coefficients to evaluate internal consistency and reproducibility over time, respectively. The results highlighted that a three-factor structure fit the instrument better than a two-factor structure, yielding better scores for the model fit indices and the α and r coefficients. In addition, the third factor identified in this study was strongly associated with having a relationship with and help from the husband. The findings suggest the importance of using a parenting stress scale with various factors to evaluate mothers’ parenting stress.

Rationale & Objective: Several maternal chronic diseases have been reported as risk factors for congenital anomalies of the kidney and urinary tract (CAKUT) in offspring. However, these investigations used case-control designs, and cases with isolated genitourinary CAKUT were not distinguished from cases in which CAKUT were present with extrarenal congenital anomalies (complicated CAKUT). We examined the association of maternal diseases with isolated and complicated CAKUT in offspring using data from a prospective cohort study. Study Design: A nationwide prospective birth cohort study. Setting & Participants: 100,239 children enrolled in the Japan Environment and Children's Study between January 2011 and March 2014 at 15 research centers. Physicians’ diagnoses in mothers and children were collected from medical record transcripts and questionnaires. Exposures: Medical histories of maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease. Outcomes: CAKUT diagnosed during the first 3 years of life, classified as isolated or complicated. Analytical Approach: Multivariable Poisson regression with generalized estimating equations accounting for clustering by clinical center. Results: Among the 100,239 children, 560 (0.6%) had CAKUT, comprising 454 (81%) isolated and 106 (19%) complicated forms. The risk of isolated CAKUT was increased in children of mothers who experienced kidney disease (adjusted risk ratio [RR], 1.80 [95% CI, 1.12-2.91]) or cancer (RR, 2.11 [95% CI, 1.15-3.86]). Furthermore, the risk of complicated CAKUT was increased in children of mothers with diabetes mellitus (RR, 3.04 [95% CI, 1.64-5.61]). Limitations: Lack of standardization or prespecification of clinical definitions, diagnostic criteria, measurements, and testing. Genetic testing was not performed. Conclusions: Isolated CAKUTs and complicated CAKUTs were associated with different maternal diseases. The results may inform clinical management of pregnancy and highlight potential differences in the genesis of isolated and complicated forms of CAKUT.

BACKGROUND: The association between maternal antibiotic exposure during pregnancy and childhood obesity is still unclear. OBJECTIVES: The study aimed to evaluate the association between prenatal exposure to antibiotics and obesity at age 3 years using data from a large Japanese birth cohort. METHODS: The Japan Environment and Children's Study is a nationwide birth cohort study. In this study, singleton vaginal full-term births were included. Obesity was defined as body mass index ≥95th percentile according to child growth standards. Prenatal antibiotic exposure was defined as antimicrobial agent use during pregnancy and was collected from maternal interviews and medical record transcripts. Logistic regression analysis was performed to evaluate the association of prenatal antibiotic exposure with child obesity at 3 years. RESULTS: In the crude and adjusted models with all children, maternal antibiotic exposure during pregnancy showed a marginal relationship with child obesity at 3 years. In the analyses according to exposure period and sex, exposure to antibiotics during the second/third trimester was significantly associated with obesity at the age of 3 years in female infants, but not in male infants, although the exposure during the first trimester was not in both sexes. CONCLUSION: Maternal antibiotic exposure during mid/late pregnancy may result in child obesity.

AIMS: Acute lung injury (ALI) is an acute inflammatory disorder. However, the precise mechanisms underlying the pathology of ALI remain elusive. An increasing evidence suggests the role of the gut-microbiota axis in the pathology of lung injury. This study aimed to investigate whether antibiotic-induced microbiome depletion could affect ALI in mice after lipopolysaccharide (LPS) administration. MAIN METHODS: The effects of antibiotic cocktail (ABX) on ALI in the mice after intratracheally administration of LPS (5 mg/kg) were examined. Furthermore, 16s rRNA analysis and measurement of short-chain fatty acids in feces samples and metabolomics analysis of blood samples were performed. KEY FINDINGS: LPS significantly increased the interleukin-6 (IL-6) levels in the bronchoalveolar lavage fluid (BALF) of water-treated mice. Interestingly, an ABX significantly attenuated the LPS-induced increase in IL-6 in BALF and lung injury scores. Furthermore, ABX and/or LPS treatment markedly altered the α- and β-diversity of the gut microbiota. There were significant differences in the α- and β-diversity of the water + LPS group and ABX + LPS group. LEfSe analysis identified Enterococusfaecalis, Clostriumtertium, and Bacteroidescaecimyris as potential microbial markers for ABX + LPS group. Untargeted metabolomics analysis identified several plasma metabolites responsible for discriminating water + LPS group from ABX + LPS group. There were correlations between the relative abundance of the microbiome and plasma metabolites. Integrative network analysis showed correlations between IL-6 levels in BALF and several gut microbes (or plasma metabolites). SIGNIFICANCE: These data suggest that ABX-induced microbiome depletion could protect against LPS-induced ALI via the gut-microbiota-lung axis.

Introduction: The ratio of placental weight to birthweight (PW/BW ratio) is well known as a simple indicator of the prenatal intrauterine environment and placental functioning. We assessed the impact of PW/BW ratio on the risk of neurodevelopmental delay in 3-year-olds. Methods: We used data of 71 205 mother–child pairs enrolled in the Japan Environment and Children's Study. Low PW/BW ratio was defined as a PW/BW ratio below the 10th percentile of the study population, high PW/BW ratio was defined as above the 90th percentile, and normal PW/BW ratio was defined as between the low and high PW/BW ratio. Neurodevelopment was assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Associations between PW/BW ratio and risk of developmental delay were examined using multivariable models. Results: Compared with boys in the normal PW/BW group, boys in the high PW/BW group had higher risk for developmental delays in all domains except fine motor skills (communication: adjusted risk ratio [aRR], 1.17; 95% confidence interval [CI], 1.04–1.33; gross motor skills: aRR, 1.28; 95% CI, 1.13–1.46; problem solving: aRR, 1.20; 95% CI, 1.09–1.31; personal–social: aRR, 1.26; 95% CI, 1.10–1.43), and boys in the low PW/BW group also had higher risk for developmental delays in some domains. For girls, there was almost no association between PW/BW ratio and developmental delay. Discussion: An unbalanced PW/BW ratio, especially high PW/BW ratio, might indicate intrauterine suboptimality, which affects child neurodevelopment in a sex-specific manner.

Increasing epidemiological evidence shows that the use of cannabis during adolescence could increase the risk for psychosis in adulthood. However, the precise mechanisms underlying long-lasting cannabis-induced risk for psychosis remain unclear. Accumulating evidence suggests the role of gut microbiota in the pathogenesis of psychiatric disorders. Here, we examined whether gut microbiota plays a role in the risk for psychosis of adult after exposure of cannabinoid (CB) receptor agonist WIN55,212-2 during adolescence. Repeated administration of WIN55,212-2 (2 mg/kg/day) during adolescence (P35-P45) significantly increased the expression of Iba1 (ionized calcium-binding adapter molecule 1) in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) of adult mice after administration of lipopolysaccharide (LPS: 0.5 mg/kg). In contrast, there were no changes in blood levels of pro-inflammatory cytokines between the two groups. Although alpha-diversity and beta-diversity of gut microbiota were no differences between the two groups, there were several microbes altered between the two groups. Interestingly, there were significant correlations between the relative abundance of microbiota and Iba1 expression in the mPFC and NAc. Furthermore, there were also significant correlations between the relative abundance of microbiota and several metabolites in the blood. These findings suggest that gut microbiota may play a role in the microglial activation in the mPFC and NAc of adult mice after repeated WIN55,212-2 exposure during adolescence. Therefore, it is likely that gut-microbiota-microglia crosstalk might play a role in increased risk for psychosis in adults with cannabis use during adolescence.

Neonicotinoid pesticides (NPs) are neurotoxic substances. They are highly effective as insecticides owing to their water solubility, permeability, and long-lasting activity. These molecules are structurally similar to nicotine and act as nicotinic acetylcholine receptor agonists. The administration of NPs to experimental animals reportedly causes neuromuscular and reproductive disorders. Moreover, recently reported problems caused by NPs include damage to land-dwelling creatures (such as mammals and birds), hydrobiology, and ecosystems. This review summarizes the recent reports on NP concentrations detected in river systems in several Japanese regions. These values were lower than the environmental standard values; however, seasonal variations were observed. Furthermore, reports on NP-induced testicular and ovarian toxicity were examined, revealing that the mechanism of injury is mainly driven by oxidative stress. The use of NPs is declining worldwide, except in Japan; therefore, continuous monitoring remains necessary.

Urinary cotinine concentration (UCC) reflects smoking status. However, in pregnant women, its association with adverse birth outcomes related to fetal growth is not widely known. Thus, we aimed to explore this relationship by focusing on dose-response relationships. We investigated 86,638 pregnant women enrolled between 2011 and 2014 in a prospective cohort study in Japan and observed three birth outcomes (preterm birth, low birth weight, and small-for-gestational age). We measured UCC in the second or third trimester, and categorized the participants using cut-off values (negative cotinine concentration, passive cotinine concentration, and active cotinine concentration corresponding to non-smokers, passive smokers, and active smokers, respectively). Logistic regression analyses were conducted to evaluate the risks, and dose-response relationships were visualized using restricted cubic spline curves. Analyses based on self-reported smoking status were also performed. We found that in low active and highly active cotinine concentrations, the adjusted odds ratios (aORs) of birth outcomes were significantly increased (preterm birth, 1.24 [95% CI 1.06-1.46], 1.39 [95% CI 1.19-1.62]; low birth weight, 1.40 [95% CI 1.24-1.58], 2.27 [95% CI 2.05-2.53]; small-for-gestational age, 1.35 [95% CI 1.19-1.52], 2.39 [95% CI 2.16-2.65]). Restricted cubic spline curves demonstrated risk elevations in the active cotinine concentration range. Our research revealed dose-response relationships between UCC during pregnancy and the risks of preterm birth, low birth weight, and small-for-gestational age. Measurement of UCC to ascertain smoking status during pregnancy may be a useful approach for predicting the risks of these birth outcomes.

Imiquimod (IMQ) is widely used as animal model of psoriasis, a chronic inflammatory skin disorder. Although topical application of IMQ to back skin causes splenomegaly in mice, how the spleen affects the psoriasis-like phenotype of IMQ-treated mice remains unclear. In this study, we analyzed the cellular composition of spleen and measured metabolites in blood of IMQ-treated mice. We also investigated whether splenectomy influences the degree of skin inflammation and pathology in IMQ-treated mice. Flow cytometry showed that the numbers of CD11b+Ly6c+ neutrophils, Ter119+ proerythroblasts, B220+ B cells, F4/80+ macrophages, and CD11c+ dendritic cells in the spleen were significantly higher in IMQ-treated mice compared to control mice. An untargeted metabolomics analysis of blood identified 14 metabolites, including taurine and 2,6-dihydroxybenzoic acid, whose levels distinguished the two groups. The composition of cells in the spleen and blood metabolites positively correlated with the weight of the spleen. However, splenectomy did not affect IMQ-induced psoriasis-like phenotypes compared with sham-operated mice, although splenectomy increased the expression of interleukin-17A mRNA in the skin of IMQ-treated mice. These data suggest that the spleen does not play a direct role in the development of psoriasis-like phenotype on skin of IMQ-treated mice, though IMQ causes splenomegaly.

Abstract Background Using cohort data from the Japan Environment and Children’s Study (JECS), we previously reported that the risk of sleep deprivation in 1-year-old children was reduced with a higher maternal intake of fermented foods, particularly miso. The present study, which evaluates children from the same cohort at 3 years of age, is a continuation of that work. Methods After applying exclusion criteria to 104,062 records in the JECS dataset, we evaluated 64,200 mother-child pairs in which the child was 3 years old. We examined the association of the dietary intake of fermented foods during pregnancy with child sleep duration &lt; 10 h at the age of 3 years. Results Multivariable logistic regression analysis with the lowest quartile used as a reference revealed adjusted odds ratios (95% confidence intervals) for the second through fourth quartiles of 0.98 (0.90–1.06), 0.93 (0.85–1.01), and 0.85 (0.78–0.94) for cheese intake. Conclusions The consumption of fermented foods during pregnancy is associated with reduced risk of sleep deprivation in 3-year-old children, albeit in a limited way.

Excessive screen media use has been reported to cause shorter sleep; however, the types of media environments that affect early childhood sleep are less known. This study examined the association of multiple media use, screen time for each device, and the purpose of smartphone and tablet use with delayed bedtime among 4-8-year-olds. Participants were recruited from the Japan Environment and Children's Study, a nationwide birth cohort study. Mothers of 1837 children reported screen media use and bedtime in a questionnaire. The association between delayed bedtimes (after 22:00 h) and media device use (smartphones, tablets, portable and console games, and TV/DVDs) was examined by logistic regression analysis. Children who used three or more devices besides TV/DVDs were more likely to have delayed bedtimes. Delayed bedtimes were associated with smartphone use, even with a 0.1-1 h/day screen time, and with prolonged screen time for tablets, portable games, and console games, but not for TV/DVDs. Gaming on smartphones and tablets was also associated with delayed bedtime. To ensure adequate sleep for young children, families must develop feasible measures to discourage children's use of multiple devices and prolonged device use, especially for games, and a social environment that supports such measures.

Depression is a high risk for osteoporosis, suggesting an association between depression and low bone mineral density (BMD). We reported that the novel antidepressant (R)-ketamine could ameliorate the reduced BMD in the ovariectomized (OVX) mice which is an animal model of postmenopausal osteoporosis. Given the role of gut microbiota in depression and bone homeostasis, we examined whether gut microbiota plays a role in the beneficial effects of (R)-ketamine in the reduced BMD of OVX mice. OVX or sham was operated for female mice. Subsequently, saline (10 ml/kg/day, twice weekly) or (R)-ketamine (10 mg/kg/day, twice weekly) was administered intraperitoneally into OVX or sham mice for the six weeks. The reduction of cortical BMD and total BMD in the OVX mice was significantly ameliorated after subsequent repeated intermittent administration of (R)-ketamine. Furthermore, there were significant changes in the α- and β-diversity between OVX + saline group and OVX + (R)-ketamine group. There were correlations between several OTUs and cortical (or total) BMD. There were also positive correlations between the genera Turicibacter and cortical (or total) BMD. Moreover, there were correlations between several metabolites in blood and cortical (or total) BMD. These data suggest that (R)-ketamine may ameliorate the reduced cortical BMD and total BMD in OVX mice through anti-inflammatory actions via gut microbiota. Therefore, it is likely that (R)-ketamine would be a therapeutic drug for depressed patients with low BMD or patients with osteoporosis.

Cadaver surgical training (CST), which ensures medical safety by improving the skills of surgeons, is popular overseas. However, training involves ethical issues given the use of cadavers. In 2012, the Japan Surgical Society and the Japanese Association of Anatomists compiled and opened the "Guidelines for Cadaver Dissection in Education and Research of Clinical Medicine (Guideline 2012)" to the public. This has allowed Japan to conduct CST or research under the regulations of Postmortem Examination and Corpse Preservation Act and the Body Donation Act. However, its dissemination has been sluggish. The Clinical Anatomy Lab (CAL), established in 2010 at Chiba University, is a facility for conducting CST and research. In the 11 years since its inception, 250 programs have been implemented. Orthopedics had the most implemented in the clinical field, with 120 (48%), followed by emergency and critical care medicine with 27 (10.8%), and neurological surgery with 27 (10. 8%). Based on the purpose of the training, the most common objective for the programs (approximately 83%) was education. Further, the highest number of programs was recorded in 2018 (34) and participants in 2017 (631). The implementation of CST requires more than just guiding surgeons to a dissection practice room. There are several methods of preserving cadavers to make them suitable for CST. For various surgical simulations, an operating table is more suitable than a dissection table. The current paper provides information on how to implement CST in universities that have so far only worked on anatomy education for medical students.

BACKGROUND: Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches. METHODS: Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children's Study (JECS). Measurements of infant birth size-including body weight, body length, and head and chest circumference-were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR). RESULTS: Of the 103,060 JECS pregnancies, 93,739 mother-infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese-but not mercury-were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect. CONCLUSION: Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention.

Existing evidence on the correlation between maternal vitamin D concentrations and birth outcomes is conflicting. Investigation of these associations requires accurate assessment of vitamin D status, especially in individuals with low 25-hydroxyvitamin D (25(OH)D) concentrations. This study examined the correlations between birth outcomes and the maternal vitamin D metabolite ratio (VMR) 1 (defined as the ratio of 24,25(OH)2D3 to 25(OH)D) and VMR2 (defined as the ratio of 3-epi-25(OH)D3 to 25(OH)D) using data from the Japan Environment and Children's Study at Chiba Regional Center. A total of 297 mother-neonate pairs were analyzed. Using liquid chromatography-tandem mass spectrometry, we measured 25(OH)D2, 25(OH)D3, 24,25(OH)2D3, and 3-epi-25(OH)D3 concentrations in maternal serum samples. These data were analyzed in relation to birth anthropometric data using multivariable linear regression. Of the study participants, 85.2% showed insufficient vitamin D concentrations. VMR1 was strongly correlated with 25(OH)D concentrations, whereas VMR2 showed a weak correlation. Only VMR2 was associated with all anthropometric data. VMR2 in pregnant women with low vitamin D blood concentrations is a useful marker for neonatal anthropometric data and is independent of 25(OH)D. Accurate measurement of vitamin D metabolites could help better understand the effects of vitamin D on birth outcomes.

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.

A decline in the proportion of male births (secondary sex ratio, SSR) has been seen in several countries including Japan in recent years. Although previous studies have reported that the SSR is affected by exposure to chemical substances such as dioxins and polychlorinated biphenyls, as well as heavy metals such as methylmercury, the effects of lead exposure on the SSR have been little studied. The aim of this study was to determine the association between maternal lead exposure and SSR. In a large-scale nationwide birth cohort study, maternal blood lead level (BLL) was determined using whole blood from the second or third trimester of pregnancy. The association between SSR and maternal BLL was estimated using multivariable logistic models. Binomial distribution was applied to examine the differences in SSR by dividing the participants into five groups based on BLL. The primary outcome was SSR, and the child sex was obtained from the medical record transcripts. Of 104,062 fetal records, 85,171 were examined for analysis. The median maternal BLL was 5.85 ng/g (5th-95th percentile 3.45-10.6 ng/g). The overall proportion of males among participating infants was 0.512. In logistic regression models adjusted for covariates, the analysis revealed an increased odds ratio for SSR with higher blood lead concentrations [Group 2: adjusted OR 1.082, 95% confidence interval 1.037 to 1.129, Group 3: 1.122, 1.074 to 1.171, Group 4: 1.214, 1.163 to 1.268, Group 5: 1.279, 1.224 to 1.336]. Compared to the general birth probability in Japan, the group with low BLL had a lower SSR and the group with high BLL had a higher SSR. Higher maternal lead exposures during pregnancy were associated with increased SSR. Further investigations including assessment of paternal lead exposure are necessary to understand the association between lead exposure and SSR.

Introduction: Studies on the relationship between maternal self-reported smoking status and placental weight report inconsistent results. This study examined the relationships between maternal urinary cotinine concentration and placental weight and the ratio of placental weight to birth weight (PW/BW ratio). The study also examined the relationship between maternal smoking status, as determined by cotinine concentration, with placental weight and with PW/BW ratio, stratified by sex of offspring. Methods: Our analysis used information of 91,049 mother–child pairs enrolled in the Japan Environment and Children's Study. Maternal urinary cotinine concentration was quantified (during the second or third trimester) with high-performance liquid chromatography-tandem mass spectrometry. Using restricted cubic splines, placental weight and PW/BW ratio were plotted against natural log-transformed cotinine concentration. Taking cotinine levels of <0.17 ng/mL, 0.17 to <21.5 ng/mL (natural log-transformed values, −1.77 to 3.07), and ≥21.5 ng/mL as indicative of non-smokers, passive smokers, and active smokers, respectively, the relationships between maternal smoking status and placental weight and PW/BW ratio were examined, adjusting for confounders. Results: Placental weight and PW/BW ratio increased with increasing cotinine concentration. After cotinine reached a certain concentration, the placental weight decreased in male offspring whereas it plateaued in female offspring. Compared with not smoking, active smoking during pregnancy significantly increased placental weight and PW/BW ratio. Conclusion: Placental weight responded as an inverted U-shape whereas the PW/BW ratio followed a J-shape with increasing maternal urinary cotinine concentration measured during pregnancy, suggesting exposure to tobacco smoke induces a disproportionate reduction in fetal growth. The effect of tobacco smoke on placental growth varied by sex of offspring.

Abstract This study aimed to evaluate the association of neonatal transfer with the risk of neurodevelopmental outcomes at 3 years of age. Data were obtained from the Japan Environment and Children’s Study. A general population of 103,060 pregnancies with 104,062 fetuses was enrolled in the study in 15 Regional Centers between January 2011 and March 2014. Live-born singletons at various gestational ages, including term infants, without congenital anomalies who were followed up until 3 years were included. Neurodevelopmental impairment was assessed using the Ages and Stages Questionnaire, third edition (ASQ-3) at 3 years of age. Logistic regression was used to estimate the adjusted risk and 95% confidence interval (CI) for newborns with neonatal transfer. Socioeconomic and perinatal factors were included as potential confounders in the analysis. Among 83,855 live-born singletons without congenital anomalies, 65,710 children were studied. Among them, 2780 (4.2%) were transferred in the neonatal period. After adjustment for potential confounders, the incidence of neurodevelopmental impairment (scores below the cut-off value of all 5 domains in the ASQ-3) was higher in children with neonatal transfer compared with those without neonatal transfer (communication: 6.5% vs 3.5%, OR 1.42, 95% CI 1.19–1.70; gross motor: 7.6% vs 4.0%, OR 1.26, 95% CI 1.07–1.49; fine motor: 11.3% vs 7.1%, OR 1.19, 95% CI 1.03–1.36; problem solving: 10.8% vs 6.8%, OR 1.29, 95% CI 1.12–1.48; and personal-social: 6.2% vs 2.9%, OR 1.52, 95% CI 1.26–1.83).    Conclusion: Neonatal transfer was associated with a higher risk of neurodevelopmental impairment at 3 years of age.<table><tbody><tr><td colspan="2">What is Known:• Neonatal transfer after birth in preterm infants is associated with adverse short-term outcomes.• Long-term outcomes of outborn infants with neonatal transfer in the general population remain unclear.</td> </tr><tr><td colspan="2">What is New:• This study suggests that neonatal transfer at birth is associated with an increased risk of neurodevelopmental impairment.• Efforts for referring high-risk pregnant women to higher level centers may reduce the incidence of neonatal transfer, leading to improved neurological outcomes in the general population.</td> </tr></tbody></table>

BACKGROUND: Manganese (Mn) is an essential trace metal and a neurotoxicant. Adverse effects of Mn exposure on the neurodevelopment of children have been reported. However, there is limited information on the effects of maternal exposure during pregnancy. OBJECTIVES: We aimed to investigate the association between maternal and cord blood Mn levels and neurodevelopment in children aged between 6 months and 3 years using data from a Japanese nationwide birth cohort study. METHODS: We used the data of 63,767 mother-child pairs with maternal blood Mn measurements recorded during the second and third trimester and of 3,787 mother-child pairs with cord blood Mn measurements. Neurodevelopment was assessed using the Japanese version of the Ages and Stages Questionnaires, third edition (J-ASQ-3), which was completed by parents or guardians at 6 months, 1 year, 1.5 years, 2 years, 2.5 years, and 3 years of age. RESULTS: The median maternal and cord blood Mn levels were 15.2 and 44.5 ng/g, respectively. After adjusting for covariates, both maternal and cord blood Mn levels were negatively associated with J-ASQ-3 scores. Maternal blood Mn levels were negatively associated with gross motor function scores at all ages except for that at 1.5 years (adjusted β: -0.55 to -1.23 for a two-fold increase in maternal Mn levels). The risk of developmental delay (score below the cut-off) in gross motor function increased at the same time points (adjusted odds ratio: 1.08 to 1.13). In the subgroup, cord blood Mn levels were negatively associated with gross motor function scores at 1, 2, and 2.5 years (adjusted β: -1.84 to -3.27). DISCUSSION: Maternal blood Mn levels during pregnancy and cord blood Mn levels were negatively associated with neurodevelopment in children up to 3 years of age. Excessive maternal and fetal exposure to Mn may have adverse effects on neuromotor function in children.

Polychlorinated biphenyls (PCBs) have been prohibited for two decades in Japan and Taiwan. The aim of this study was to compare the PCB congeners in maternal and cord serum between two countries. Our study subjects were 248 and 100 mother-child pairs in Japan and Taiwan. The measured levels of 23 serum PCB congeners between two countries were analyzed using gas chromatography-electron capture negative ionization quadrupole mass spectrometry (GC-NICI-qMS). The statistical comparisons were conducted by Student's t-test and principal component analysis with further stratification by maternal age and parity. The maternal total PCBs levels in Japan (426 ± 244 pg/g wet wt) were significantly higher than those in Taiwan (254 ± 155 pg/g wet wt), and the similar results were found in cord total PCBs levels (97 ± 76 and 58 ± 87 pg/g wet wt). It showed different distributions of PCB congeners between two countries. Whether in maternal or cord serum, the CB138, CB153 and CB180 were the highest detectable congeners whether in Japan or Taiwan. And, the CB66, CB99, CB206 and CB209 were only detected in maternal serum of Taiwan. The women of advanced maternal age had higher levels of PCB congeners, especially in Taiwan, and the primiparous women had higher levels of PCB congeners in two countries. In summary, the PCB congeners in Japan's mother-child pairs were with higher levels and different distributions when compared to those in Taiwan, and the maternal age and parity were important factors associated with the PCB levels.

Abstract Otitis media (OM) is common among young children and is related to hearing loss. We investigated the association between maternal insecticide use, from conception to the first and second/third trimesters, and OM events in children in the first year of age. Data from Japan Environment and Children's Study were used in this prospective cohort study. Characteristics of patients with and without history of OM during the first year of age were compared. The association between history of OM in the first year and insecticide use was evaluated using logistic regression analysis. The study enrolled 98,255 infants. There was no significant difference in the frequency of insecticide use between groups. Insecticide use of more than once a week from conception to the first trimester significantly increased the occurrence of OM in children in the first year (odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.01–1.67). The association between OM in the first year and insecticide use from conception to the first trimester was only significant in the group without daycare attendance (OR 1.76, 95% CI 1.30–2.38). Maternal insecticide use more than once a week from conception to the first trimester significantly increased OM risk in offspring without daycare attendance.

Maternal exposure to polychlorinated biphenyls (PCBs) during pregnancy is associated with a low birth weight; however, the congener-specific effects of PCB congeners are not well defined. In this study, we used maternal serum samples from the Chiba Study of Mother and Child Health (C-MACH) cohort, collected at 32 weeks of gestational age, to analyze the effects of PCB congener exposure on birth weight by examining the relationship between newborn birth weight and individual PCB congener levels in maternal serum (n = 291). The median total PCB level in the serum of mothers of male and female newborns at approximately 32 weeks of gestation was 39 and 37 ng g−1 lipid wt, respectively. The effect of the total PCB levels and the effects of PCB congener mixtures were analyzed using a linear regression model and a generalized weighted quantile sum regression model (gWQS). The birth weight of newborns was significantly associated with maternal exposure to PCB mixtures in the gWQS model. The results suggest that exposure to PCB mixtures results in low newborn birth weight. However, specific impacts of individual PCB congeners could not be related to newborn birth weight.

Background: Daily toothbrushing prevents early childhood caries, but reinforcement depends on facilitative parenting behaviours. Mother-to-infant bonding, the maternal affection towards the infant, is an environmental factor that strongly influences parenting. Aim: This study examined the association between maternal bonding and children's daily toothbrushing frequency. Design: The sample consisted of 83 954 mother-infant pairs at two years postpartum, derived from the initial sample of JECS (cohort study), which included 104 062 foetuses. Maternal bonding disorders were assessed using the Mother-to-Infant Bonding Scale (MIBS). After multiple imputation for missing data, a multinomial logistic regression analysis was conducted with adjustments for several maternal (eg, age at delivery) and child-related (eg, self-performed toothbrushing) variables. Results: The odds ratio (95% confidence interval) for the association of maternal bonding disorders with the low (once per day) and the very low child toothbrushing frequency (<1 per day) was 1.12 (1.07-1.17) and 1.23 (0.91-1.66), respectively, after covariate adjustments. Furthermore, the univariate general linear model showed that the mean MIBS scores significantly decreased as the daily child toothbrushing frequency increased. Conclusions: The prevalence of maternal bonding disorders at one year postpartum was prospectively associated with a lower frequency of child toothbrushing at two years of age.

Abstract Purpose This study aimed to investigate neurodevelopment in children conceived via in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with several types of embryo transfers. Methods We analyzed data for 77 928 children and their mothers included in a Japanese birth cohort study. Among the included children, 4071 were conceived via IVF, while 1542 were conceived via ICSI. Neurodevelopmental delay at the age of 3 years was assessed using the Japanese version of the Ages and Stages Questionnaires, 3rd edition. Results In the crude model, the odds ratios for developmental delay in 1–4 domains were higher among children conceived via IVF, ICSI, and non‐ART (ovulatory induction or intrauterine insemination) than in spontaneously conceived children. After adjusting for parental background factors and the child's sex, there were no differences in the risk of developmental delay when comparing singletons conceived by IVF, ICSI, or non‐ART and those conceived spontaneously. Higher odds ratios for developmental delay in one domain were observed in singleton girls conceived via IVF when compared with those who were spontaneously conceived. Conclusion Most cases of developmental delay may be associated with multiple pregnancies and factors related to infertility, such as parental age, irrespective of the use of ART.

Lead poisoning is often considered a traditional disease; however, the specific mechanism of toxicity remains unclear. The study of Pb-induced alterations in cellular metabolic pathways is important to understand the biological response and disorders associated with environmental exposure to lead. Metabolomics studies have recently been paid considerable attention to understand in detail the biological response to lead exposure and the associated toxicity mechanisms. In the present study, wild rodents collected from an area contaminated with lead (N = 18) and a control area (N = 10) were investigated. This was the first ever experimental metabolomic study of wildlife exposed to lead in the field. While the levels of plasma phenylalanine and isoleucine were significantly higher in a lead-contaminated area versus the control area, hydroxybutyric acid was marginally significantly higher in the contaminated area, suggesting the possibility of enhancement of lipid metabolism. In the interregional least-absolute shrinkage and selection operator (lasso) regression model analysis, phenylalanine and isoleucine were identified as possible biomarkers, which is in agreement with the random forest model. In addition, in the random forest model, glutaric acid, glutamine, and hydroxybutyric acid were selected. In agreement with previous studies, enrichment analysis showed alterations in the urea cycle and ATP-binding cassette transporter pathways. Although regional rodent species bias was observed in this study, and the relatively small sample size should be taken into account, the present results are to some extent consistent with those of previous studies on humans and laboratory animals.

Background: The adequate maternal sleep duration required for favorable obstetric outcomes is unknown. We evaluated the association between maternal sleep duration and low birth weight infants, small for gestational age infants, and macrosomia. Methods: Participants enrolled in the Japan Environment and Children’s Study, a nationwide birth cohort study, with singleton pregnancies after 22 weeks, who gave birth between 2011 and 2014 were enrolled and categorized into five groups according to maternal sleep duration during pregnancy: &lt 6.0 h, 6.0–7.9 h, 8.0–8.9 h, 9.0–9.9 h, and 10.0–12.0 h. We evaluated the association between maternal sleep duration and the incidence of low birth weight infants (&lt 2500 g), very low birth weight infants (&lt 1500 g), small for gestational age infants, and macrosomia (&gt 4000 g), with women with maternal sleep duration of 6.0–7.9 h as the reference, using a multiple logistic regression model. Results: In total, 82,171 participants were analyzed. The adjusted odds ratios (95% confidence intervals) for low birth weight infants in women with maternal sleep duration of 9.0–9.9 h and 10.0–12.0 h and for small for gestational age infants in women with maternal sleep duration of 9.0–9.9 h were 0.90 (0.83–0.99), 0.86 (0.76–0.99), and 0.91 (0.82–0.99), respectively, before adjusting for excessive gestational weight gain. No significant association was observed between maternal sleep duration and these outcomes after adjusting for excessive gestational weight gain. Among women with appropriate gestational weight gain, the adjusted odds ratios (95% confidence intervals) for low birth weight infants and for small for gestational age infants with sleep duration of 9.0–9.9 h were 0.88 (0.80–0.97) and 0.87 (0.78–0.97), respectively. Conclusions: Maternal sleep duration of 9.0–9.9 h was significantly associated with the decreased incidence of low birth weight infants and small for gestational age infants in pregnant women with appropriate gestational weight gain, compared with that of 6.0–7.9 h. Care providers should provide proper counseling regarding the association between maternal sleep duration and neonatal birth weight and suggest comprehensive maternal lifestyle modifications to prevent low birth weight and small for gestational age infants.

A high maternal body mass index (BMI) is associated with increased risks of asphyxia-related neonatal morbidity. We evaluated the association between maternal pre-pregnancy BMI and foetal acidosis while accounting for the mode of delivery. Participants from the Japan Environment and Children’s Study with singleton pregnancies after 22 weeks of gestation who gave birth during 2011–2014 were included. The participants (n = 71,799) were categorised into five groups according to the pre-pregnancy BMI: G1 (BMI &lt 18.5 kg/m2), G2 (18.5 to &lt 20.0 kg/m2), G3 (20.0 to &lt 23.0 kg/m2), G4 (23.0 to &lt 25.0 kg/m2), and G5 (≥ 25.0 kg/m2). Foetal acidosis was defined as umbilical artery pH (UmA-pH) &lt 7.20 or &lt 7.10. Multiple logistic regression analyses were used to evaluate the effect of pre-pregnancy BMI on foetal acidosis risk, accounting for the mode of delivery. In Japanese women, pre-pregnancy BMI ≥ 25.0 kg/m2 significantly increased the likelihood of foetal acidosis in newborns delivered vaginally. We found no association between pre-pregnancy BMI and foetal acidosis in newborns delivered via caesarean section. Counselling for body weight control before pregnancy and adequate management and selection of the mode of delivery in pregnant women with a high BMI who are in labour may be essential to avoid foetal acidosis.

Background: The association between a slower physical growth and poorer neurodevelopment has been established in infants born preterm or small for gestational age. However, this association is inconsistent in term-born infants, and detailed investigations in infancy, when intervention is most beneficial for improving outcomes, are lacking. We therefore examined this association separately by sex during the first year of life in term-born infants. Methods: Using data collected until children reached 12 months old in an ongoing prospective cohort of the Japan Environment and Children’s Study, we analyzed 44,264 boys and 42,541 girls with singleton term-birth. The exposure variables were conditional variables that disentangle linear growth from weight gain relative to linear growth, calculated from the length and weight at birth and 4, 7 and 10 months old. Neurodevelopmental delay was identified using the Japanese-translated version of Ages & Stages Questionnaires, third edition. Results: A reduced risk of neurodevelopmental delay at 6 months old was observed in children with a higher birth weight (adjusted relative risks [aRRs]: 0.91 and 0.93, 95 % confidence intervals [95 % CIs]: 0.87–0.96 and 0.88–0.98 in boys and girls, respectively) and increased linear growth between 0 and 4 months old (aRRs: 0.85 and 0.87, 95 % CIs: 0.82–0.88 and 0.83–0.91 in boys and girls, respectively). A reduced risk at 12 months was found in children with an increased linear growth between 0 and 4 months (aRRs: 0.92 and 0.90, 95 % CIs: 0.87–0.98 and 0.84–0.96 in boys and girls, respectively), boys with an increased relative weight gain between 0 and 4 months (aRR: 0.90, 95 % CI: 0.84–0.97), and girls with a higher birth weight (aRR: 0.89, 95 % CI: 0.83–0.96). Conclusions: These results suggest that a slow physical growth by four months old may be a predictor of neurodevelopmental delay during infancy.

Background: Pregnant women in Japan express various reasons for limiting gestational weight gain (GWG). We aimed to identify and characterise groups where the women share common reasons to limit GWG and to examine how these groups are associated with inappropriate GWG and abnormal foetal size. Methods: We prospectively studied information from the Japan Environment and Children’s Study (JECS) on 92,539 women who gave birth to live singletons from 2011 through 2014. Pregnant women were recruited during early pregnancy. Their reasons for limiting GWG and other information were collected through self-reported questionnaires and medical records. We applied latent class analysis to group the women based on their reported reasons. We used multinomial logistic regression to compare the risks of inappropriate (inadequate and excessive) GWG and abnormal foetal size (determined by new-born weight for gestational age) between the identified groups. Results: We identified three groups: Group 1 (76.7%), concerned about delivery and new-born health (health-conscious women); Group 2 (14.5%), concerned about body shape, delivery, and new-born health (body-shape- and health-conscious women); and Group 3 (8.8%), women without strong reasons to limit GWG (women lacking body-shape and health consciousness). Compared with Group 1 members, Group 2 members tended to be younger, have lower pre-pregnancy weight, be unmarried, be nulliparous, have practiced weight loss before pregnancy, and not have chronic medical conditions. Group 3 members tended to be less educated, unmarried, multiparous, smokers, and have a higher prevalence of pre-pregnancy underweight and previous caesarean delivery. Relative to Group 1, Group 2 had a lower unadjusted risk for inadequate GWG (relative risk ratio [RRR] = 0.86, 95% CI: 0.81–0.90) and large-for-gestational-age birth (RRR = 0.91, 95% CI 0.86–0.97), whereas Group 3 had a higher unadjusted risk for excessive GWG (RRR = 1.36, 95% CI: 1.29–1.43) and small-for-gestational-age (SGA) births (RRR = 1.15, 95% CI: 1.05–1.25). Conclusions: In this Japanese nationwide birth cohort study, pregnant women who were less conscious about body shape and health had complex risks for excessive GWG and SGA birth. Health care providers should consider a woman’s perception of GWG when addressing factors affecting GWG and foetal growth.

Background: The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD. Methods: We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD. Results: A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050). Conclusions: The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.

<title>Abstract</title>We examined the association between maternal air purifier use during pregnancy and neurodevelopmental delay in toddlers by analysing data from 82,457 mother-toddler pairs. Air purifier use was measured using a simple yes/no question. Developmental delays at 1.5, 2.0, 2.5, and 3.0 years were assessed using the Ages and Stages Questionnaire, Third Edition. Generalized additive mixed model analysis with 21 covariates revealed that air purifier use was associated with lower prevalence of developmental delay in all five areas—communication, gross motor, fine motor, problem solving, and personal-social—at all four time points (adjusted risk ratios ranged from 0.827 to 0.927, and only one 95% confidence interval crossed the reference). These findings suggest a negative association between air purifier use during pregnancy and neurodevelopmental delay in toddlers. Trial registration: UMIN000030786 (15/01/2018).

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The study aim was to obtain epidemiological data on vitamin D levels for the pediatric population in Japan. We assessed the prevalence of vitamin D deficiency and insufficiency in 2-year-old Japanese children using data from a large ongoing birth cohort study.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Data for analysis was obtained from the Japan Environment and Children’s Study (JECS) and a Sub-Cohort Study (SCS) of JECS. We evaluated the children’s serum 25(OH) D levels by 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, and the rates of vitamin D deficiency or insufficiency. We also presented a weighted prevalence rate for vitamin D deficiency or insufficiency among all children in JECS.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>After excluding children with missing 25(OH)D2 or 25(OH)D3 data, we analyzed 4655 remaining children, of whom 24.7% (95% CI, 23.5–26.0%) had vitamin D deficiency (&lt; 20 ng/mL), and 51.3% (95% CI, 49.8–52.7%) were at risk of vitamin D insufficiency (20–30 ng/mL). The estimated prevalence of vitamin D deficiency and insufficiency among all children in JECS were 25.4% (95% CI, 24.1–26.7%) and 50.9% (95% CI, 49.4–52.4%). Vitamin D deficiency was found in 22.9% of boys and 26.5% of girls. Median serum 25(OH) D concentrations were lower among participants measured during winter and spring than among those measured in summer and autumn. The highest rate of vitamin D deficiency was observed in Hokkaido, the northernmost prefecture of Japan.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>We analyzed data on serum 25(OH) D levels from a birth cohort study and found that vitamin D deficiency and insufficiency are very common among 2-year-old Japanese children. Sex, season, and latitude affect serum 25(OH) D concentrations.</jats:p> </jats:sec>

This prospective cohort study aimed to examine the associations between mold growth, type of stoves, and fragrance materials and early childhood wheezing and asthma, using data from the Japan Environment and Children's Study. Mold growth at home, usage of kerosene/gas stove, wood stove/fireplace, and air freshener/deodorizer were surveyed using a questionnaire at 1.5-year-old, and childhood wheezing and doctor-diagnosed asthma during the previous year were obtained using a 3-year-old questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between exposure to childhood wheezing and asthma. A total of 60 529 children were included in the analysis. In multivariate analyses, mold growth and wood stove/fireplace had significantly higher odds ratios (ORs) for wheezing (mold growth: 1.13; 95% CI, 1.06-1.22; wood stove/fireplace: 1.23; 95% CI, 1.03-1.46). All four exposures had no significant ORs for childhood doctor-diagnosed asthma; however, in the supplemental analysis of northern regions, wood stove/fireplace had a significantly higher OR for asthma. Mold growth and wood stove/fireplace had significant associations with childhood wheezing in the northern regions. Mold elimination in the dwellings and use of clean heating (no air pollution emissions) should be taken into consideration to prevent and improve childhood wheezing and asthma.

Background: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. Methods: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. Results: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1–10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270–1.624 ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341–2.078 asthma: 1–10 cigarettes/day: aOR 1.389, 95% CI 1.087–1.774 ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045–2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083–1.256 asthma: aOR 1.258, 95% CI 1.075–1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739–2.317 asthma: aOR 1.995, 95% CI 1.528–2.605). Conclusions: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.