Sex steroid hormones and allergic diseases in children: a pilot birth cohort study in the Japan Environment and Children's Study cohort.

BACKGROUND: Numerous studies suggest that sex steroids might play a role in sex disparity observed in allergic diseases in adults. However, whether sex hormones influence allergic diseases in children remains unclear. The aim of the present study was to examine the association of sex steroid hormones with allergic disease in Japanese children. METHODS: The present cross-sectional study included 145 6-year-old children participating in a pilot birth cohort study in the Japan Environment and Children's Study. Data on allergic diseases were obtained from questionnaires, and serum levels of sex steroid hormones and allergen-specific IgE were measured. Logistic regression was performed to evaluate the association of sex hormones with allergic diseases. RESULTS: After adjusted sex, amount of body fat at 6 years, parental history of allergic disease, and exposure to tobacco smoke, serum dehydroepiandrosterone sulfate level was significantly associated with reduced odds of any allergic disease (adjusted odds ratio, 0.58; 95% confidence interval, 0.36-0.93; P = 0.024) and serum follicle-stimulating hormone level was significantly associated with increased odds of any allergic disease (adjusted odds ratio, 2.04; 95% confidence interval, 1.01-4.11, P = 0.046). Dehydroepiandrosterone sulfate level showed a significant association with number of allergic diseases. CONCLUSIONS: The current study findings suggest that sex hormones may play an important role in the development of allergic diseases in prepubertal children.

Study Design and Participants' Profile in the Sub-Cohort Study in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles. METHODS: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. RESULTS: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. CONCLUSION: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Indoor air quality of 5,000 households and its determinants. Part A: Particulate matter (PM2.5 and PM10-2.5) concentrations in the Japan Environment and Children's Study.

Exposure to particulate matter (PM) is one of the important risk factors for morbidity and mortality. Although PM concentrations have been assessed using air quality monitoring stations or modelling, few studies have measured indoor PM in large-scale birth cohorts. The Japan Environment and Children's Study (JECS) measured indoor and outdoor air quality in approximately 5000 households when the participating children were aged 1.5 and 3 years. PM was collected using portable pumps for 7 days (total of 24 h), inside and outside each home. Prediction models for indoor PM concentrations were built using data collected at age 1.5 years and post-validated against data collected at age 3 years. Median indoor/outdoor PM2.5 and PM10-2.5 concentrations at age 1.5 years [3 years] were 12.9/12.7 [12.5/11.3] µg/m3 and 5.0/6.3 [5.1/6.1] µg/m3, respectively. Random forest regression analysis found that the major predictors of indoor PM2.5 were indoor PM10-2.5, outdoor PM2.5, indoor smoking, observable smoke and indoor/outdoor temperature. Indoor PM2.5, outdoor PM10-2.5, indoor humidity and opening room windows were important predictors of indoor PM10-2.5 concentrations. Indoor benzene, acetaldehyde, ozone and nitrogen dioxide concentrations were also found to predict indoor PM2.5 and PM10-2.5 concentrations, possibly due to the formation of secondary organic aerosols. These findings demonstrate the importance of reducing outdoor PM concentrations, avoiding indoor smoking, using air cleaner in applicable and diminishing sources of VOCs that could form secondary organic aerosols, and the resulting models can be used to predict indoor PM concentrations for the rest of the JECS cohort.

Indoor air quality of 5,000 households and its determinants. Part B: Volatile organic compounds and inorganic gaseous pollutants in the Japan Environment and Children's study.

Volatile organic compounds (VOCs) are major indoor air pollutants. Quantification of indoor concentrations of VOCs and identification of factors associated with these concentrations can help manage indoor air quality. This study measured the concentrations of VOCs and inorganic gaseous pollutants in around 5000 households in Japan and utilised a random forest model to estimate these concentrations and identify important determinants. The homes of 5017 randomly selected participants in the Japan Environment and Children's Study (JECS) were visited twice, when the children were aged 1.5 and 3 years. Twelve VOCs and inorganic gaseous pollutants were measured during 7 days by passive samplers. Various factors in these households, including household appliances, building characteristics, cooking styles, use of consumer products, renovation, pets, personal behaviours and ventilation were recorded. A random forest model with recursive feature elimination was utilised to identify factors predictive of VOCs and inorganic gaseous pollutants. Toluene, formaldehyde and acetaldehyde were the dominant indoor VOCs. The 95th percentiles of indoor p-dichlorobenzene concentrations at 1.5 and 3 years were 67 µg/m3 and 71 µg/m3, respectively. Random forest models with coefficients of determination ranging from 0.34 to 0.76 outperformed the traditional linear regression models. Factors associated with indoor VOC and inorganic gaseous pollutant concentrations included their outdoor concentrations, indoor and outdoor temperature and relative humidity, month of the year, hours windows were open, kerosene heater use and times of operation and building age. The results provided basic descriptions of indoor VOCs and inorganic gaseous pollutants in Japan and identified several determinants of these concentrations. These determinants should be considered to maintain indoor air quality. These results can be used in epidemiological assessments of the effects of VOCs and inorganic gaseous pollutants on health in children.

Associations between urinary heavy metal concentrations and blood pressure in residents of Asian countries.

BACKGROUND: Previous studies have suggested that exposures to heavy metals (arsenic, cadmium, lead, and selenium) may be associated with differences in blood pressure. However, the findings of these studies have been inconsistent. This study was performed to examine the associations between urinary heavy metal concentrations and blood pressure among residents of four Asian countries (Bangladesh, Indonesia, Nepal, and Vietnam). METHODS: This cross-sectional study examined 1899 adults in four Asian countries. Urinary concentrations of heavy metals were measured by inductively coupled plasma mass spectrometry. A questionnaire survey was administered regarding individual characteristics. Anthropometric measurements (height and weight) were performed. Systolic and diastolic blood pressures were measured after a short rest. Multiple linear regression models were applied to investigate associations between urinary heavy metal concentrations and blood pressure after adjustments for age, sex, and body mass index. RESULTS: The geometric means of the urinary concentrations of arsenic, cadmium, lead, and selenium were 84.6, 0.885, 2.09, and 16.5 µg/g creatinine, respectively. The urinary arsenic concentrations were slightly higher than those typically reported in non-polluted populations, while urinary cadmium, lead, and selenium concentrations were equivalent or slightly lower. The urinary lead concentrations were positively associated with both systolic and diastolic blood pressure, but urinary selenium concentrations were negatively associated with them. CONCLUSIONS: Variations in the urinary concentrations of lead and selenium were associated with blood pressure at low levels of exposure/intake.

Maternal intake of one-carbon metabolism-related B vitamins and anorectal malformations in the Japan Environment and Children's Study.

The occurrence of anorectal malformations (ARM) is thought to be reduced with sufficient folate intake. However, there is no apparent evidence. We focused on enzyme cofactors for one-carbon metabolism, including folate (vitamin B9), vitamin B6 and vitamin B12, and explored the association between maternal combined intake of these B vitamins and the risk of ARM. Using baseline data from a Japanese nationwide birth cohort study between 2011 and 2014, we analysed data of 89 235 women (mean age at delivery = 31·2 years) who delivered singleton live births without chromosomal anomalies. Information on dietary intake was obtained via a FFQ focused on early pregnancy and used to estimate B vitamin intake. We also collected information on the frequency of folic acid supplement use. ARM occurrence was ascertained from medical records. We identified forty-three cases of ARM diagnosed up to the first month after birth (4·8 per 10 000 live births). In terms of individual intake of the respective B vitamins, high vitamin B6 intake was non-significantly associated with reduced odds of ARM. Compared with women in the low combined B vitamin intake group, the OR of having an infant with ARM was 0·4 (95 % CI 0·2, 1·0) in the high intake group (folate ≥400 µg/d, and upper half of vitamin B6 and/or vitamin B12). In conclusion, our cohort analysis suggested an inverse association between the combined intake of one-carbon metabolism-related B vitamins in early pregnancy and ARM occurrence.

Maternal dietary intake of vitamin A during pregnancy was inversely associated with congenital diaphragmatic hernia: the Japan Environment and Children's Study.

The pathogenesis of congenital diaphragmatic hernia (CDH) is largely unknown; however, vitamin A seems to play a role in diaphragmatic development. Previous case-control studies reported that maternal dietary vitamin A intake was inversely associated with the risk of CDH. To our knowledge, however, there is no prospective evidence regarding this association. Our aim was to examine whether maternal intake of vitamin A was associated with CDH occurrence. Baseline data, from the Japan nationwide birth cohort study (2011-2014) of 89 658 mothers (mean age at delivery = 31·2 years) who delivered singleton live births, were analysed. We assessed dietary habits using an FFQ focused on the first trimester and estimated the daily intake of total vitamin A (retinol activity equivalents), retinol, provitamin A carotenoids and vegetables. The occurrence of CDH was ascertained from medical records. A total of forty cases of CDH were documented. The adjusted OR of CDH occurrence for the high total vitamin A intake category (median = 468 µg/d) was 0·6 (95 % CI 0·3, 1·2) with reference to the low intake category (230 µg/d). When we restricted to mothers with a prepregnancy BMI of 18·5-24·9 kg/m2, vitamin A intake was inversely associated with the risk of their children being born with CDH (OR 0·5, 95 % CI 0·2, 1·0). Even given the limited number of cases in the study, our findings provide additional evidence to link vitamin A with CDH.

Physical growth and diets of school children: Trends from 2001 to 2015 in rural West Java, Indonesia.

OBJECTIVES: This study aimed to assess changes in physical growth and diets of school children in rural West Java, Indonesia, between 2001 and 2015, a period of rapid socioeconomic change. METHODS: In 2001 and 2015, anthropometric measurements (height, weight, mid-upper arm circumference, skin-fold thickness), food consumption surveys, and questionnaires on socioeconomic status were completed by fourth-grade school children in a rural village in West Java. RESULTS: Height increments of 5.9 cm for boys and 4.7 cm for girls during this 14-year period were calculated as 4.21 cm per decade for boys and 3.36 cm per decade for girls, which is equivalent to height increments observed during rapid economic development periods in other countries. Weights also increased by 3.8 kg for boys and 2.0 kg for girls during this period. Variations in weight status significantly increased in 2015; while 98% of the children were within the 'normal' range in 2001, the prevalence of overweight increased from 2.4% in 2001 to 13.7% in 2015 and that of thinness was 4.3% in 2015. Energy, protein, and fat intakes significantly increased in 2015. In 2015, a significant correlation between nutritional intake and weight status was observed, especially among boys. CONCLUSIONS: Socioeconomic changes between 2001 and 2015 caused increased heights and weights and greater variation in weight status, especially among boys.

Developmental stage-dependent influence of environmental factors on growth of rural Sundanese children in West Java, Indonesia.

This study investigated the growth trajectories and the relative relevance levels of nutrition, disease, and hormonal status at various developmental stages among children in adverse environments to provide population-based empirical evidence for the life history theory. Three years of longitudinal anthropometric data in 1-year intervals were obtained from 418 boys and girls aged 0 to 12 years at recruitment. Following the final measurement, the main survey, which included blood and feces sampling, 3-h interval food consumption recall surveys for energy and nutrient intakes and anthropometry, was performed. Blood and feces were used for detecting, respectively, anemia and hormonal (IGF-I and IGFBP-3) levels as well as intestinal helminthiasis (Ascaris, Trichuris, and hookworm). The major findings of this study are summarized as follows: 1) the growth velocity of the subject children lagged behind international standards during childhood and juvenility but caught up during early adolescence; 2) diseases, both intestinal helminths and anemia, had significant effects on growth in childhood but not at older ages; and 3) hormonal status significantly affected growth in the children, with its highest significance in early adolescence. A larger growth than international standards in early adolescence likely follows programmed hormonal mechanisms after the onset of puberty. The onset of puberty might be associated with adequate amounts of nutrient intake and be mediated by hormonal function, because the IGF-IZ score was significantly correlated with energy and protein intakes at the transitional period from juvenility to adolescence, when puberty occurs.

Longitudinal analyses of maternal and cord blood manganese levels and neurodevelopment in children up to 3 years of age: The Japan Environment and Children's Study (JECS).

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 ß: -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 ß: -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.

Contribution of Agriculture to Health Promotion.

Agriculture has been an important source of the human diet throughout human history, but its relationship with human societies has transformed over the long course of more than 10,000 y. Urbanization and agricultural commercialization are significant among such changes and wield considerable impact on human diets, nutrition, and health. This paper presents four studies examining the influence of agriculture on diet and general health: 1) the impact of urban allotment gardening on human health and wellbeing in Japan, 2) the preference of people in Japan for collaborations between citizens' farms and food-support organizations 3) the linkages between dietary diversity and agriculture in Indonesia, and 4) food sources and child nutrition in the deforested frontiers of Cambodia.

Baseline Complete Blood Count and Chemistry Panel Profile from the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study of environmental factors affecting children's health and development. We summarize the complete blood count and chemistry panel statistical data from pregnant women enrolled in JECS. METHODS: Statistical data of up to 58,056 mother's sample in their first (gestational age ≤ 13 weeks) and second trimester (22-27 weeks) were calculated. RESULTS: Mean (SD) values in the first trimester were: white blood cell count, 7866 (1906)/µL; red blood cell count, 417 (33) 104/µL; hemoglobin, 12.4 (1.0) g/dL; hematocrit, 37.1 (2.6)%; mean corpuscular volume, 89.2 (4.7) fL; mean corpuscular hemoglobin, 29.8 (1.9) pg; mean corpuscular hemoglobin concentration, 33.3 (0.9)%; platelet count, 24.8 (5.2) 104/µL; HbA1c, 5.26 (0.26)%; total cholesterol, 181 (28) mg/dL; low density lipoprotein cholesterol, 95 (23) mg/dL; high density lipoprotein cholesterol, 73 (13) mg/dL; free cholesterol, 41 (7) mg/dL; triglycerides, 109 (47) mg/dL; total protein, 6.9 (0.4) g/dL; and albumin, 4.1 (0.2) g/dL. Mean values (SD) in the second trimester were: total cholesterol, 246 (38) mg/dL; free cholesterol, 61 (9) mg/dL; triglycerides, 183 (70) mg/dL; total protein, 6.5 (0.4) g/dL; and albumin, 3.6 (0.2) g/dL. CONCLUSIONS: These data will be useful for future JECS studies.

Maternal Metals Exposure and Infant Weight Trajectory: The Japan Environment and Children's Study (JECS).

BACKGROUND: To our knowledge, the association of maternal exposure to metallic elements with weight trajectory pattern from the neonatal period has not been investigated. OBJECTIVES: The goals of this study were to identify infant growth trajectories in weight in the first 3 y of life and to determine the associations of maternal blood levels of lead, cadmium, mercury, selenium, and manganese with growth trajectory. METHODS: This longitudinal study, part of the Japan Environment and Children Study, enrolled 103,099 pregnant women at 15 Regional Centres across Japan between 2011 and 2014. Lead, cadmium, mercury, selenium, and manganese levels were measured in blood samples collected in the second (14-27 wk gestational age) or third trimester (≥28wk). Growth trajectory of 99,014 children was followed until age 3 y. Raw weight values were transformed to age- and sex-specific weight standard deviation (SD) scores, and latent-class group-based trajectory models were estimated to determine weight trajectories. Associations between maternal metallic element levels and weight trajectory were examined using multinomial logistic regression models after confounder adjustment. RESULTS: We identified 5 trajectory patterns based on weight SD score: 4.74% of infants were classified in Group I, very small to small; 31.26% in Group II, moderately small; 21.91% in Group III, moderately small to moderately large; 28.06% in Group IV, moderately large to normal; and 14.03% in Group V, moderately large to large. On multinomial logistic regression, higher maternal lead and selenium levels tended to be associated with increased odds ratios (ORs) of poor weight SD score trajectories (Groups I and II), in comparison with Group III. Higher levels of mercury were associated with decreased ORs, whereas higher levels of manganese were associated with increased ORs of "moderately large" trajectories (Groups IV and V). DISCUSSION: Maternal lead, mercury, selenium, and manganese blood levels affect infant growth trajectory pattern in the first 3 y of life. https://doi.org/10.1289/EHP10321.

Exposure to heavy metals modifies optimal gestational weight gain: A large nationally representative cohort of the Japan Environment and Children's Study.

Clinical guidelines including those set by the US Institute of Medicine, have based optimal gestational weight gain (GWG) on maternal pre-pregnancy body mass index (BMI), but have not considered the role of environmental toxicants such as heavy metals that can disrupt these processes. This study designed to determine optimal GWG ranges in women grouped according to BMI, and to assess whether blood concentrations of heavy metals alter the relationships between GWG and outcomes. A total of 103,060 participants in the Japan Environment and Children's Study recruited between 2011 and 2014 were followed until their children reached 3 years of age. Outcomes included 1 min Apgar score <7, caesarean delivery, childhood obesity, gestational diabetes, pregnancy-induced hypertension, low birth weight, large for gestational age, macrosomia, operative vaginal delivery, postpartum weight retention, preterm birth and small for gestational age. The optimal GWG ranges were determined using multivariate logistic regression models. Stratified analyses were performed to determine optimal GWG ranges according to quartiles of heavy metals. Optimal GWGs for underweight, normal weight and overweight women were found to be 10.0 to <14.0 kg, 6.0 to <12.0 kg and 4.0 to <8.0 kg, respectively. However, the benefits of optimal GWG were attenuated in women exposed to high concentrations of mercury (Hg), lead (Pb) and cadmium (Cd). Despite being within optimal GWG, underweight women with Hg > 5.21 ng/g and overweight women with Hg 3.67-5.21 ng/g, Pb > 7.31 ng/g and Cd > 0.66 ng/g had null effects. Heavy metals can modify the associations between GWG and outcomes, particularly for underweight and overweight women. Because of the complex interactions of environmental toxicants with pre-pregnancy BMI, GWG and adverse outcomes, GWG guidelines should be interpreted cautiously. Environmental toxicants may influence the determination of a clinical guideline.

Urinary Metabolites of Organophosphate Pesticides among Pregnant Women Participating in the Japan Environment and Children's Study (JECS).

Organophosphate pesticides (OPPs) exhibit neurodevelopmental toxicity. To evaluate the effect of prenatal exposure to OPPs in the Japan Environment and Children's Study, a nationally representative birth cohort study, 4575 maternal urine samples were analysed for six OPP metabolites, i.e., dialkylphosphates (DAPs). This study aimed to investigate predictors of urinary DAPs using machine learning approaches and to assess the cumulative risk based on relative potency factors among Japanese pregnant women. The median creatinine-normalised urinary concentrations (interquartile ranges) of dimethylphosphate, dimethylthiophosphate and diethylphosphate, which had a detection rate of 50% or higher, were 3.53 (1.91-6.78), 4.09 (1.66-10.8) and 3.28 (1.88-5.98) µg/g-creatinine, respectively. Possible predictors of urinary DAP concentrations were the month of urine sampling, consumption of apple and maternal body mass index. When fenitrothion was used as an index chemical for cumulative risk assessment, 0.36% of participants exceeded the lower 95% confidence limit of the benchmark dose10.

Association of prenatal exposure to cadmium with neurodevelopment in children at 2 years of age: The Japan Environment and Children's Study.

BACKGROUND: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics. METHODS: We recruited 3545 mother-child pairs from the Japan Environment and Children's Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders. RESULTS: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52-0.95) and 0.04 (0.03-0.06) µg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (ß = -1.4, 95% confidence interval (CI): -2.7, -0.038), DQ in children of mothers who smoked during pregnancy (ß = -2.9, 95% CI: -5.7, -0.12), P-M (ß = -5.4, 95% CI: -10, -0.67), C-A (ß = -6.1, 95% CI: -11, -1.8), L-S (ß = -9.0, 95% CI: -13, -4.8) and DQ scores (ß = -6.4, 95% CI: -9.6, -3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (ß = -6.0., 95% CI: -11, -0.91) in children born to mothers with gestational diabetes. CONCLUSIONS: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings.

Comparison of Simultaneous Quantitative Analysis of Methylmercury and Inorganic Mercury in Cord Blood Using LC-ICP-MS and LC-CVAFS: The Pilot Study of the Japan Environment and Children's Study.

Prenatal exposure to methylmercury (MeHg) affects child development after birth. However, many epidemiological studies have evaluated total mercury levels without analyzing speciation. Biomonitoring of MeHg and inorganic mercury (IHg) is essential to reveal each exposure level. In this study, we compared a high-throughput analysis for mercury speciation in blood using liquid chromatography-inductively coupled plasma-mass spectrometry (LC-ICP-MS) and liquid chromatography-cold vapor atomic fluorescence spectrometry (LC-CVAFS). The validated LC-ICP-MS method was applied to 101 maternal blood and 366 cord blood samples in the pilot study of the Japan Environment and Children's Study (JECS). The accuracy of the LC-CVAFS method ranged 90-115% determined by reference material analysis. To evaluate the reliability of 366 cord blood samples, fifty cord blood samples were randomly selected and analyzed using LC-CVAFS. The median (5th-95th percentile) concentrations of MeHg and IHg were 5.4 (1.9-15) and 0.33 (0.12-0.86) ng/mL, respectively, in maternal blood, and 6.3 (2.5-15) and 0.21 (0.08-0.49) ng/mL, respectively, in cord blood. Inter-laboratory comparison showed a relatively good agreement between LC-ICP-MS and LC-CVAFS. The median cord blood:maternal blood ratios of MeHg and IHg were 1.3 and 0.5, respectively. By analyzing speciation, we could focus on the health effects of each chemical form.

Measles antibody seropositivity among children with allergic diseases: A cross-sectional study in the Japan Environment & Children's Pilot Study.

BACKGROUND: The relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population. METHODS: The cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates. RESULTS: This study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls. CONCLUSIONS: Children with allergies mount and maintain a comparable immune response to the measles vaccine.

Determination of Urinary Cotinine Cut-Off Concentrations for Pregnant Women in the Japan Environment and Children's Study (JECS).

Few studies have assessed the accuracy of self-reported questionnaires to determine smoking habits relative to urinary biomarkers. This study investigated urinary cotinine cut-off concentrations distinguishing active, passive and non-smokers among pregnant women who participated in the Japan Environment and Children's Study, a nationwide birth cohort study. Pregnant participants with measured urinary cotinine concentrations (UCCs) and who completed self-reported questionnaires on smoking status were included (n = 89,895). The cut-off values (COVs) for active and passive smokers were calculated by fitting mixed normal distribution functions to UCCs. The sensitivity and specificity of the questionnaires were subsequently evaluated. The median (interquartile range) UCC was 0.24 (0.083-0.96) µg/g-creatinine, with the detection rate of 89%. The COV for distinguishing active smokers from passive and non-smokers was 36.8 µg/g-creatinine. When this COV was considered to represent the true condition, the questionnaire had a sensitivity of 0.523, a specificity of 0.998, a positive predictive value (PPV) of 0.967 and a negative predictive value (NPV) of 0.957. The COV for distinguishing passive smokers from non-smokers was 0.31 µg/g-creatinine, with the questionnaire having a sensitivity of 0.222, a specificity of 0.977, a PPV of 0.868 and an NPV of 0.644. As many as 78% of passive smokers might be misclassified as non-smokers.

Does overweight before pregnancy reduce the occurrence of gastroschisis?: the Japan Environment and Children's Study.

OBJECTIVE: For several observational studies that have reported the factors related to gastroschisis, the target population in these studies was mainly residents of Europe or the US, and there is little data on the Asian population. In this study, we summarised characteristics of Japanese women who delivered infants with gastroschisis, particularly focusing on the pre-pregnancy body mass index (BMI), which was found to be inversely associated with gastroschisis in past studies, because the distribution of BMI is clearly different in Asia and the West. RESULTS: We used data from a nationwide birth cohort study which recruited pregnant women between 2011 and 2014. Among 92,796 women who delivered singleton live births, the frequency of underweight (pre-pregnancy BMI < 18.5 kg/m2) was 16.2%, reference weight (18.5-24.9 kg/m2) 73.1%, and overweight (≥ 25.0 kg/m2) 10.6%. We identified only 9 infants with gastroschisis, 2 of whose women were underweight (frequency of gastroschisis = 0.01%), 5 were in the reference group (0.01%), and 2 were overweight (0.02%). Of these 9 women, none were aged < 20 years, 2 were aged 20-29 years (frequency = 0.01%), and 7 were aged 30-39 years (0.01%). No reduction in the occurrence of gastroschisis was apparent among Japanese women who were overweight before pregnancy.