The association between prenatal per-and polyfluoroalkyl substance levels and Kawasaki disease among children of up to 4 years of age: A prospective birth cohort of the Japan Environment and Children's study.

Kawasaki disease (KD) is common among pediatric patients and is associated with an increased risk of later cardiovascular complications, though the precise pathophysiology of KD remains unknown. Per- and polyfluoroalkyl substances (PFAS) have gathered notoriety as the causal pathogens of numerous diseases as well as for their immunosuppressive effects. The present epidemiological study aims to assess whether PFAS may affect KD risk. We evaluated research participants included in the ongoing prospective nationwide birth cohort of the Japan Environment and Children's Study (JECS). Among the over 100,000 pregnant women enrolled in the JECS study, 28 types of PFAS were measured in pregnancy in a subset of participants (N = 25,040). The JECS followed their children born between 2011 and 2014 (n total infants = 25,256; n Kawasaki disease infants = 271), up to age four. Among the 28 types of PFAS, those which were detected in >60 % of participants at levels above the method reporting limit (MRL) were eligible for analyses. Multivariable logistic regressions were implemented on the seven eligible PFAS, adjusting for multiple comparison effects. Finally, we conducted Weighted Quantile Sum (WQS) and Bayesian kernel machine regression (BKMR) to assess the effects of the PFAS mixture on KD. Therefore, we ran the BKMR model using kernel mechanical regression equations to examine PFAS exposure and the outcomes of KD. Upon analysis, the adjusted multivariable regression results did not reach statistical significance for the seven eligible substances on KD, while odds ratios were all under 1.0. WQS regression was used to estimate the mixture effect of the seven eligible PFAS, revealing a negative correlation with KD incidence; similarly, BKMR implied an inverse association between the PFAS mixture effect and KD incidence. In conclusion, PFAS exposure was not associated with increased KD incidence.

Vitamin D deficiency associated with neurodevelopmental problems in 2-year-old Japanese boys.

AIM: While associations between vitamin D deficiency and neurodevelopmental disorders have been found, large studies on child vitamin D, neurodevelopment, and sex differences among the general population are lacking. This study aimed to investigate the association between child serum 25-hydroxyvitamin D (25(OH)D)) levels and neurodevelopmental problems (NDPs). METHODS: Serum 25(OH)D and NDPs were measured at age two among the subcohort study of the Japan Environment and Children's Study. NDPs were assessed with the Kyoto Scale of Psychological Development 2001 (Kyoto scale). Adjusted odds ratios (aORs) for the Kyoto-scale developmental quotient scores <70 were calculated, for postural-motor, cognitive-adaptive, and language-social domains and overall scores, adjusted for test month, latitude, small for gestational age, maternal age, and daycare attendance. RESULTS: Among 2363 boys and 2290 girls, boys had higher 25(OH)D levels, but scored lower in the Kyoto scale. For boys in the vitamin D deficiency (<20 ng/mL) group, aORs of scoring the Kyoto-scale DQs <70 were 2.33 (p = 0.006) for overall DQs, 1.91 (p = 0.037) for cognitive-adaptive, and 1.69 (p = 0.024) for language-social domains. For girls, results were inconclusive. CONCLUSION: Only boys showed a clear and cross-modal association between vitamin D deficiency and NDPs.

Association between eating habits during adolescence and gestational diabetes: data from the Japan environment and children's study.

Purpose: It is difficult to change pre-pregnancy eating habits, yet establishing healthy eating habits before pregnancy is important for preventing gestational diabetes mellitus (GDM). This study aimed to examine whether the weight-loss behavior of avoiding between-meal and midnight snacking in teenagers is associated with a reduction in the risk of subsequent GDM. Methods: We used a dataset (jecs-an-20,180,131) from a nationwide, prospective birth cohort study, the Japan Environment and Children's Study (JECS). We included 89,227 (85.7% of the total) mother-infant pairs with live births. Participants in their second or third trimester were asked to report their weight-loss behavior during their teenage years. The prevalence of GDM was investigated. Differences in maternal characteristics were examined using chi-square tests. Crude and adjusted logistic regression models were constructed to assess the associations of various maternal characteristics with the weight-loss behavior of avoiding between-meal and midnight snacking during teenage years. Results: A total of 2,066 (2.3%) participants had GDM. Weight-loss behavior in teenagers was associated with a decreased risk of GDM. Among participants with normal weight or overweight prior to pregnancy, the adjusted odds ratios were 0.79 (95% confidence interval, 0.70-0.89) and 0.82 (95% confidence interval, 0.69-0.98), respectively. Conclusions: The results suggest that teenage weight-loss behaviors, such as avoiding between-meal and midnight snacking, are associated with a decreased risk of developing GDM. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01294-2.

Association between maternal urinary neonicotinoid concentrations and child development in the Japan Environment and Children's Study.

BACKGROUND: Recent studies have reported the effect of neonicotinoid (NEO) exposures on development in human. However, information about the risk of childhood development delays due to NEO exposures is limited. OBJECTIVES: The study aimed to examine the association between NEO exposure and child development up to 4 years of age using data of the Japan Environment and Children's Study. METHODS: The study employed urinary NEO and metabolite concentrations in the first and second or third trimesters; the Japanese translation of the Ages and Stages Questionnaire (third edition; J-ASQ-3) scores on developmental delay in five domains, namely communication, gross motor skills, fine motor skills, problem solving, and personal-social characteristics from 6 months to 4 years of age; and self-reported questionnaire data. The associations between urinary NEO concentrations and J-ASQ-3 results were analysed using the treed distributed lag mixture model. A total of 8538 participants were included in statistical analyses. RESULTS: The determination rates of urinary acetamiprid-N-desmethyl (dm-ACE), clothianidin (CLO), dinotefuran (DIN) and thiamethoxam (THX) were greater than 50%. Median urinary dm-ACE, CLO, DIN and THX concentrations were 0.34, 0.14, 0.22 and 0.05 ng/ml, respectively, in samples collected during gestational weeks < 23, and 0.28, 0.12, 0.18 and 0.04 ng/ml, respectively, in those collected during gestational weeks ≥ 23. The binomial scores divided by the cut-off values of the J-ASQ were used in the treed distributed lag mixture model. The highest percentage for a domain with a value less than the cut-off value was 'problem solving' at 6 months of age among all the J-ASQ-3 scores (10.5%). There was no statistically significant association between maternal urinary dm-ACE, CLO, DIN and THX concentrations during pregnancy and the J-ASQ-3 results up to 4 years of age. Objective assessment of child development in different populations may be warranted to confirm our findings.

Association Between Maternal Factors in Early Pregnancy and Congenital Heart Defects in Offspring: The Japan Environment and Children's Study.

Background Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. Conclusions Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.

Health-related quality of life of mothers and developmental characteristics of very low birth weight children at 2.5 years of age: results from the Japan Environment and Children's Study (JECS).

BACKGROUND: The level of child development may be associated with the risk of poor maternal health-related quality of life (HRQoL). The objective of this study was to describe the developmental characteristics of very low birth weight (VLBW) children at 2.5 years of age and to examine associations between maternal HRQoL and the degree of child development based on the Japanese version of Ages and Stages Questionnaire (J-ASQ-3). METHODS: A cross-sectional study was performed using the data from a nationwide prospective birth cohort study in Japan. Among a total of 104,062 fetal records, the VLBW infants (birth weight ≤ 1500 g) were analyzed using linear regression models, adjusted for potential covariates. Subgroup analysis was also conducted to assess the association between social connection or cooperation of the partner and maternal HRQoL by the level of child development. RESULTS: The final study subjects included 357 VLBW children and mothers. The suspected developmental delays (SDDs) in at least two domains was significantly associated with lower maternal mental HRQoL regression coefficient -2.314 (95%CI: -4.065 to -0.564). There was no association between the status of child development and maternal physical HRQoL. After adjusting for child and maternal covariates, the maternal HRQoL was not significantly associated with child development. Amongst women who indicated having some social support, having a child with a SDD in two or more domains was negatively associated with mental HRQoL compared with women whose child was less developmental delay, regression coefficient -2.337 (95%CI: -3.961 to -0.714). Amongst women who indicated having partner's cooperation to child-rearing, having a child with a SDD in two or more domains was negatively associated with mental HRQoL compared with women whose child was less developmental delay, regression coefficient -3.785 (95%CI: -6.647 to -0.924). CONCLUSIONS: Our findings indicate that the lower maternal mental HRQoL was independently associated with the SDDs evaluated by the J-ASQ-3, whereas there was no association after adjusting for covariates. Further research is warranted to elucidate the impact of social connection and partner's cooperation on maternal HRQoL and child development. This study urges that particular attention should be paid to mothers of VLBW children with SDDs and also to provide early intervention and continued support.

Association between maternal cholesterol level during pregnancy and placental weight and birthweight ratio: data from the Japan Environment and Children's Study.

BACKGROUND: Placental weight to birthweight ratio (PW/BW ratio), or its inverse, is used as an indicator of placental efficiency. Past studies have shown an association between an abnormal PW/BW ratio and adverse intrauterine environment, however, no previous studies have examined the effect of abnormal lipid levels during pregnancy on PW/BW ratio. We aimed to evaluate the association between maternal cholesterol levels during pregnancy and placental weight to birthweight ratio (PW/BW ratio). METHODS: This study was a secondary analysis using the data from the Japan Environment and Children's Study (JECS). 81 781 singletons and their mothers were included in the analysis. Maternal serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels during pregnancy were obtained from participants. Associations between maternal lipid levels and placental weight and PW/BW ratio were assessed by regression analysis using restricted cubic splines. RESULTS: Dose-response relationships were observed between maternal lipid level during pregnancy and placental weight and PW/BW ratio. High TC and LDL-C levels were associated with heavy placental weight and high PW/BW ratio, i.e., inappropriately heavy placenta for birthweight. Low HDL-C level was also associated with inappropriately heavy placenta. Low TC and LDL-C levels were associated with low placental weight and low PW/BW ratio, i.e., inappropriately light placenta for birthweight. High HDL-C was not associated with PW/BW ratio. These findings were independent of pre-pregnancy body mass index and gestational weight gain. CONCLUSIONS: Abnormal lipid levels such as elevated TC and LDL-C, and low HDL-C level, during pregnancy were associated with inappropriately heavy placental weight.

Multiple pregnancy as a potential risk factor for postpartum depression: The Japan Environment and Children's Study.

BACKGROUND: Postpartum depression (PPD) results in adverse consequences for both mother and infant. However, the association between multiple pregnancy and PPD is unknown because of the difference in the estimated prevalence rate of PPD based on country, ethnicity, and study type. Thus, this study aimed to determine whether Japanese women with multiple pregnancy were at a high risk of developing PPD at 1 and 6 months postpartum. METHODS: In this nationwide prospective cohort study (the Japan Environment and Children's Study), conducted between January 2011 and March 2014, 77,419 pregnant women were enrolled. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS) 1 and 6 months postpartum. A score of ≥13 points implied "positive" for PPD. Multiple logistic regression analyses estimated the association between multiple pregnancy and PPD risk. RESULTS: Overall, 77,419 pregnancies (singleton, n = 76,738; twins, n = 676; triplets, n = 5) were included; 3.6 % and 2.9 % of pregnant women had PPD at 1 and 6 months postpartum, respectively. Compared with singleton pregnancy, multiple pregnancy was not associated with PPD at 1 month, but at 6 months postpartum (adjusted odd ratios: 0.968 [95 % confidence interval {CI}, 0.633-1.481] and 1.554 [95 % CI, 1.046-2.308], respectively). LIMITATIONS: 1) Some potential PPD risk factors could not be evaluated, 2) PPD was not diagnosed by psychiatrists, and 3) depressive symptoms at 6 months postpartum were considered PPD; however, definitions may vary. CONCLUSIONS: Japanese women with multiple pregnancy may be regarded as a target group for follow-up and postpartum depression screening for at least 6 months during the initial postpartum period.

Secondhand smoke exposure is associated with the risk of hypertensive disorders of pregnancy: the Japan Environment and Children's Study.

Hypertensive disorders of pregnancy (HDP) are associated with poor maternal and neonatal prognoses. Although several studies have indicated an effect of secondhand smoke (SHS) exposure on HDP, such evidence is lacking in Japan. Therefore, we analyzed data from the Japan Environment and Children's Study, a large-scale epidemiological investigation, to elucidate a possible link between SHS exposure and HDP risk. Data were obtained from the all-birth fixed datasets and included information on 104,062 fetuses and their parents. SHS exposure was assessed in terms of the frequency (rarely, 1-3, or 4-7 days/week) and the daily duration of exposure (<1, 1-2, or ≥2 h(s)/day). Modified Poisson regression model analyses were performed with adjustment for known risk factors for HDP. Additionally, the population attributable fractions (PAFs) of SHS exposure and maternal smoking to HDP prevalence were estimated. The relative risks of developing HDP among individuals with SHS exposures of 4-7 days/week and ≥2 h/day were 1.18 and 1.27 (95% confidence interval: 1.02-1.36 and 0.96-1.67), respectively, compared to the reference groups (rare exposure and <1 h/day). The PAFs for the risk of HDP due to SHS exposure and perinatal smoking were 3.8% and 1.8%, respectively. Japanese women with greater exposure to SHS have a higher risk of HDP after adjustment for possible confounding factors; thus, relevant measures are required to reduce SHS exposure to alleviate HDP risk. The association between second-hand smoking exposure and hypertensive disorders of pregnancy risk was analyzed using the JECS data. The relative risks in 4-7 days/week and ≥2 h/day of SHS exposures were 1.18 and 1.27, respectively. The PAFs due to SHS exposure and maternal smoking were 3.80% and 1.81%, respectively.

Congenital Anomalies in Infants in Fukushima from 2011 to 2014: The Japan Environment and Children's Study.

Introduction: This study aimed to assess congenital anomalies among infants from 2011 to 2014 in Fukushima and compare the assessment with that from other geographical regions in Japan. Methods: We used the dataset of the Japan Environment and Children's Study (JECS), which is a nationwide prospective birth cohort study. For the JECS, participants were recruited through 15 regional centers (RC), including Fukushima. Pregnant women were recruited between January 2011 and March 2014. The Fukushima RC recruited all municipalities in the Fukushima Prefecture, from where we compared congenital anomalies in infants from the Fukushima RC to those in the infants from 14 other RCs. Crude and multivariate logistic regression analyses were also performed, with the multivariate logistic regression analysis being adjusted for maternal age, maternal body mass index (kg/m2), infertility treatment, multiple pregnancies, maternal smoking, maternal alcohol consumption, pregnancy complications, maternal infection, and infant sex. Results: In the Fukushima RC, 12,958 infants were analyzed, and 324 infants were diagnosed with major anomalies (2.50%). In the remaining 14 RCs, 88,771 infants were analyzed and 2,671 infants were diagnosed with major anomalies (3.01%). Crude logistic regression analysis demonstrated that the odds ratio for the Fukushima RC was 0.827 (95% confidence interval, 0.736-0.929) using the other 14 RCs as a reference. Multivariate logistic regression analysis also demonstrated that the adjusted odds ratio was 0.852 (95% confidence interval, 0.757-0.958). Conclusions: Fukushima Prefecture was found not to be an area at high risk for the occurrence of congenital anomalies in infants compared nationwide in Japan from 2011 to 2014.

Association between maternal prenatal psychological distress and autism spectrum disorder among 3-year-old children: The Japan Environment and Children's Study.

Maternal prenatal psychological distress, which includes depression and anxiety, affects the onset of autism spectrum disorder (ASD). However, there is no consistent knowledge regarding at which term during pregnancy psychological distress affects the risk of ASD among children. We used a dataset obtained from the Japan Environment and Children's Study, which is a nationwide prospective birth cohort study, to evaluate the association between the six-item Kessler Psychological Distress Scale (K6) and ASD among 3-year-old children. A total of 78,745 children were analyzed, and 355 of them were diagnosed with ASD (0.45%). The maternal K6 was administered twice during pregnancy: at a median of 15.1 weeks (M-T1) and at that of 27.4 weeks (M-T2) of gestation. Multivariate logistic regression analyses demonstrated that the group with a maternal K6 score of ≥5 at both M-T1 and M-T2 was significantly associated with ASD among the children (adjusted odds ratio, 1.440; 95% confidence interval, 1.104-1.877) compared to the group with a score of ≤4 at both M-T1 and M-T2. There was no significant difference between the group with a score of ≥5 only at M-T1 or M-T2 and that with a score of ≤4 at both M-T1 and M-T2. In conclusion, from the first to the second half of pregnancy, continuous maternal psychological distress was associated with ASD among 3-year-old children. Contrarily, in the group without persistent maternal psychological distress during pregnancy, there was no significant association.

Population attributable fraction of risk factors for low birth weight in the Japan Environment and Children's Study.

BACKGROUND: Low birth weight (LBW), which is considered a birth weight of <2500  g, poses significant health problems for children. However, population attributable fraction (PAF) of risk factors for LBW have not been well studied. OBJECTIVE: We aimed to re-evaluate associations between risk factors for LBW reported in previous studies that used the Japan Environment and Children's Study (JECS) data, and to estimate the magnitude of risk using PAF. METHODS: Data including 91,559 mother-child dyads were obtained from JECS. Risk factors identified by previous studies that used JECS data were used to calculate odds ratios for LBW using a Bayesian logistic regression model. Based on calculated odds ratios, the PAF was calculated. RESULTS: Parity, history of adenomyosis, hypertension disorder of pregnancy, maternal age at birth, prepregnancy body mass index, gestational weight gain (GWG), maternal smoking and lead (Pb) exposure were all significantly associated with LBW. The sum of the PAF of all factors was 79.4 %, with the largest PAF among single risk factors being GWG (16.5 %); the environmental portion of the PAF (Pb exposure, 14.6 % + maternal smoking, 12.1 %) surpassed the PAF of GWG. CONCLUSION: Our findings suggest that the number of births classified as LBW can be reduced by approximately 27% if Pb exposure is reduced to the lowest quartile and maternal smoking is eliminated. Further investigations are needed to identify unknown risk factors for LBW.

Association of epidural analgesia during labor with neurodevelopment of children during the first three years: the Japan Environment and Children's Study.

BACKGROUND: Epidural analgesia relives pain during labor. However, the long-term effects on neurodevelopment in children remain unclear. We explored associations between exposure to epidural analgesia during labor and childhood neurodevelopment during the first 3 years of life, in the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: Pregnant women were recruited between January 2011 and March 2014, and 100,304 live births of singleton children born at full-term by vaginal delivery, and without congenital diseases were analyzed. Data on mothers and children were collected using a self-administered questionnaires and medical record transcripts. The children's neurodevelopment was repeatedly assessed for five domains (communication, gross motor, fine motor, problem solving, and personal-social), using the Ages and Stages Questionnaires, Third Edition, at six time points from age 6 to 36 months. After adjusting for potential confounders, the associations between exposure to epidural analgesia during labor and children's neurodevelopment at each time point were assessed. RESULTS: Of the 42,172 children with valid data at all six time points, 938 (2.4%) were born to mothers who received epidural analgesia during labor. Maternal exposure to epidural analgesia was associated with neurodevelopmental delays during the first 3 years after birth. Delay risks in gross and fine motor domains were the greatest at 18 months (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.40 [1.06, 1.84] and 1.54 [1.17, 2.03], respectively), subsequently decreasing. Delay risks in communication and problem-solving domains were significantly high at 6 and 24 months, and remained significant at 36 months (aOR [95% CI]: 1.40 [1.04, 1.90] and 1.28 [1.01, 1.61], respectively). Exposure to epidural analgesia was also associated with the incidence of problem solving and personal-social delays from 18 to 24 months old. Neurodevelopmental delay risks, except for communication, were dominant in children born to mothers aged ≥30 years at delivery. CONCLUSIONS: This study showed that maternal exposure to epidural analgesia during labor was associated with neurodevelopmental delays in children during the first 3 years after birth.

Impact of prenatal exposure to mercury and selenium on neurodevelopmental delay in children in the Japan environment and Children's study using the ASQ-3 questionnaire: A prospective birth cohort.

Neurodevelopmental delay is associated with neurodevelopmental disorders. Prenatal metal exposure can potentially cause neurodevelopmental delays in children. This study examines whether prenatal exposure to mercury (Hg) and selenium (Se) is associated with the risk of neurodevelopmental delays in children up to 4 years of age. Children enrolled in a prospective birth cohort of the Japan Environment and Children's Study were examined. Hg and Se levels in maternal (nchild = 48,731) and cord (nchild = 3,083) blood were analyzed by inductively coupled plasma-mass spectrometry. Neurodevelopmental delays were assessed in children between the ages of 0.5 to 4 years using the Ages and Stages Questionnaires, Third Edition. The association between exposure and outcomes was examined using the generalized estimation equation models. In maternal blood, compared to participants with Se levels in the first quartile (83.0 to < 156 ng/g), the odds ratio (95 % confidence intervals) for problem-solving ability in children of mothers in the third (168 to < 181 ng/g) and fourth quartiles (181 to 976 ng/g) were 1.08 (1.01 to 1.14) and 1.10 (1.04 to 1.17), respectively. Furthermore, communication, gross and fine motor skills, and problem-solving delays were also observed. However, prenatal Hg levels in maternal and cord blood and Se levels in the latter were not associated with neurodevelopmental delays in children. Thus, the findings of this study suggest an association between Se levels in maternal blood and slightly increased risks of neurodevelopmental delays in children up to the age of 4 years.

The Association Between Maternal Shaking Behavior and Inappropriate Infant Parenting: The Japan Environment and Children's Study.

Background: Although many studies have identified risk factors for maternal shaking behavior, it is unknown whether mothers who have shaken their infants repeat shaking behavior or show other inappropriate parenting behaviors. Using data from the Japan Environment and Children's Study (JECS) birth cohort study, we investigated the associations between continuous shaking behavior and the associations between shaking behavior and other inappropriate parenting behaviors. Methods: JECS data starting from 2011 were used. Logistic regression was used to perform a cross-sectional analysis. The explanatory variable was shaking behavior and the dependent variables were leaving the infant home alone and hitting the infant (both at 1 month postpartum), and non-vaccination and infant burns (both at 6 months postpartum). A longitudinal analysis using logistic regression was also performed; here the explanatory variable was shaking behavior at 1 month postpartum and the dependent variables were shaking behavior, non-vaccination of the infant, and infant burns (all at 6 months postpartum). Results: In this study, 16.8% and 1.2% of mothers reported shaking behavior at 1 month and 6 months postpartum, respectively. Mothers who shook their infants at 1 month postpartum were approximately five times more likely to shake them at 6 months postpartum compared with mothers who had not shown previous shaking behavior (OR = 4.92, 95% CI [4.22, 5.73], p < 0.001). In Cross-sectional study, there were associations between shaking behavior and inappropriate parenting behavior such as hitting the infant and infant burns. Conclusion: The findings suggest that mothers who report early shaking behavior tend to subsequently repeat this behavior, and that shaking behavior may be associated with other inappropriate parenting behaviors.

Early life exposure to indoor air pollutants and the risk of neurodevelopmental delays: The Japan Environment and Children's Study.

Air pollution has been associated with childhood neurodevelopment. However, the role of indoor air pollution, especially volatile organic compounds (VOCs), on childhood neurodevelopment has been poorly explored to date. We investigated the association between indoor air pollutants and childhood neurodevelopment in 5,017 randomly selected children from the Japan Environment and Children's Study. When the participants reached 1.5 and 3 years of age, they were followed up with home visits and neurodevelopmental tests using the Ages and Stages Questionnaire (ASQ). At both ages, we collected indoor air samples for 1 week and measured 13 indoor air pollutants: particulate matter with an aerodynamic diameter of ≤2.5 µm, ozone, nitrogen dioxide, sulfur dioxide, and nine VOCs. The associations between air pollutants and ASQ scores were estimated using linear mixed effects models and weighted quantile sum regressions (WQS) at each age separately. Stratified analysis by sex was conducted. Exposure to m,p-xylene at the age of 3 was associated with lower communication, fine motor, and overall ASQ scores (coefficients: -0.18 [99% confidence intervals (CI): -0.35, -0.02], -0.23 [99 %CI: -0.43, -0.03], and - 0.72 [99 %CI: -1.41, -0.04] per 1 µg/m3 increase, respectively). Exposure to o-xylene at the age of 3 was associated with lower communication, gross motor, fine motor, and overall ASQ scores (coefficients: -0.48 [99 %CI: -0.90, -0.07], -0.45 [99 %CI: -0.78, -0.13], -0.65 [99 %CI: -1.14, -0.16], and -2.15 [99 %CI: -3.83, -0.47] per 1 µg/m3 increase, respectively). The WQS index was associated with lower gross motor ASQ scores at the age of 3 (coefficient: -0.27 [95 %CI: -0.51, -0.03] for one-unit WQS index increases), which was attributed to benzene (33.96%), toluene (26.02%), o-xylene (13.62%), and ethylbenzene (9.83%). Stratified analysis showed similar results. Although further investigations are required, our results suggest an association of neurodevelopmental delays with indoor low-level exposure to m,p-xylene and o-xylene in early life.

Early neurodevelopmental problems and risk for avoidant/restrictive food intake disorder (ARFID) in 4-7-year-old children: A Japanese birth cohort study.

Background: An overrepresentation of neurodevelopmental problems (NDPs) has been observed in individuals with avoidant/restrictive food intake disorder (ARFID). Previous studies on the association between ARFID and NDPs have been limited by cross-sectional data from clinical samples of small size. This study aimed to extend previous research by using prospectively collected data in a non-clinical child cohort. We examined the occurrence of early NDPs in 4-7-year-old children with suspected ARFID and how predictive early NDPs are of ARFID. Methods: Data were collected via parent-report a sub-sample of the Japan Environment and Children's Study (JECS) including 3728 children born 2011-2014 in Kochi prefecture. NDPs were assessed biannually between 0.5 and 3 years of age with the Ages and Stages Questionnaire-3, at age 2.5 years with the ESSENCE-Q, and at age 1 and 3 years via parent-reported clinical diagnoses. ARFID was identified cross-sectionally (at age 4-7 years) using a newly developed screening tool. Logistic regressions were used to test association of (1) a composite early NDP risk score, (2) specific early NDPs, and (3) neurodevelopmental trajectories over time with ARFID. Results: Children in the highest risk percentiles of the NDP risk score had roughly three times higher odds of having suspected ARFID; the absolute risk of later ARFID for children above the 90th percentile was 3.1%. Early NDPs (excluding early feeding problems) were more predictive of later ARFID than were early feeding problems. Specific NDPs predictive of ARFID were problems with general development, communication/language, attention/concentration, social interaction, and sleep. Neurodevelopmental trajectories of children with and without suspected ARFID started to divert after age 1 year. Conclusions: The results mirror the previously observed overrepresentation of NDPs in ARFID populations. In this non-clinical child cohort, early feeding problems were common and rarely developed into ARFID; however, our findings imply that they should be monitored closely in children with high NDP risk to prevent ARFID.

Development of a parent-reported screening tool for avoidant/restrictive food intake disorder (ARFID): Initial validation and prevalence in 4-7-year-old Japanese children.

The prevalence of avoidant/restrictive food intake disorder (ARFID) in the general child population is still largely unknown and validated screening instruments are lacking. The aims of this study were (1) to investigate the prevalence of children screening positive for ARFID in a Japanese birth cohort using a newly developed parent-reported screening tool, (2) to estimate the prevalence of children with ARFID experiencing physical versus psychosocial consequences of their eating pattern, and (3) to provide preliminary evidence for the validity of the new screening tool. Data were collected from 3728 4-7-year-old children born between 2011 and 2014 in Kochi prefecture, Japan (response rate was 56.5%); a sub-sample of the Japan Environment and Children's Study (JECS). Parents completed a questionnaire including the ARFID screener and several other measures to assess convergent validity. The point prevalence of children screening positive for ARFID was 1.3%; half of them met criteria for ARFID based on psychosocial impairment alone, while the other half met diagnostic criteria relating to physical impairment (and additional psychosocial impairment in many cases). Sensory sensitivity to food characteristics (63%) and/or lack of interest in eating (51%) were the most prevalent drivers of food avoidance. Children screening positive for ARFID were lighter in weight and shorter in height, they showed more problem behaviors related to mealtimes and nutritional intake, and they were more often selective eaters and more responsive to satiety, which together provides preliminary support for the validity of the new screening tool. This is the largest screening study to date of ARFID in children up to 7 years. Future studies should examine the diagnostic validity of the new ARFID screener using clinically ascertained cases. Further research on ARFID prevalence in the general population is needed.

Breastfeeding and risk of febrile seizures in the first 3 years of life: The Japan Environment and Children's Study.

OBJECTIVE: Our study was conducted to examine the association between breastfeeding and febrile seizures (FS) in the first 3 years of life. METHODS: We analyzed the dataset of the Japan Environment and Children's Study (JECS), which is a birth cohort study undertaken to elucidate the influence of environmental factors on children's health during the fetal period and early childhood. Information on feeding duration and feeding pattern, as well as information on febrile seizures, were obtained from questionnaires sent to mothers/caregivers. We categorized a child as having experienced FS if the child was reported as having been diagnosed with FS in the first 3 years. Modified Poisson regression with a robust error variance was used to estimate the effect of duration of breastfeeding and the risk of FS. RESULTS: Of the 84,321 children included in the analysis, 6264 (7.4%) were reported to have experienced FS at least once in the first 3 years of life. Multivariate analyses showed that the risk of FS during the first 3 years of life tended to decrease as the duration of breastfeeding increased. Male sex and frequent fever episodes were also associated with an increased risk of FS. CONCLUSIONS: Continued breastfeeding until 2 years of age, the most susceptible age for FS, had a small but protective effect on FS.