Dietary intake of methylmercury by 0-5 years children using the duplicate diet method in Japan.

BACKGROUND: The developing brains are sensitive to methylmercury (MeHg). However, the exposure to MeHg in baby foods and toddler meals remains unknown. This study aimed to determine MeHg intake from baby food or toddler meals, and to investigate the relationship with child hair total mercury (THg). METHODS: A total of 3 days of 24-hour dietary diet and hair samples were collected from 260 consenting children aged 0-5 years. We measured the concentrations of THg and MeHg in the diet and THg in the hair. RESULTS: The results of measuring THg were below both the method detection and method quantification limits or either of both in powdered milk (93.8%), 5-6 months (53.3%), and 7-8 months (39.5%). The median daily THg intake was 20.3 (95% confidence interval 0.72-232.5) ng/kgbw. MeHg was not detected in 213 samples with dietary THg concentrations below 1 ng/g. The MeHg concentration with THg concentrations of 1 ng/g or higher was 1.70 (0.87-6.21) ng/g, and MeHg percentage in THg was 90.0%. To estimate MeHg intake, we multiplied the THg concentration by 90.0%, resulting in an estimated MeHg intake of 18.3 (0.65-209.2) ng/kgbw/day. The THg in children's hair was 1.05 (0.31-3.96) ppm, and a weak positive correlation was observed between hair THg and dietary MeHg (r = 0.170). CONCLUSIONS: This study highlights the accurate estimation of MeHg intake in children using a duplicate method. Japanese children consume fish, the MeHg intakes exceeded the reference dose and/or provisional tolerable weekly intake in several children. Further discussion based on epidemiological data is required.

Association between whole blood metallic elements concentrations and gestational diabetes mellitus in Japanese women: The Japan environment and Children's study.

BACKGROUND: Exposure to several metallic elements has been suggested as a risk factor for gestational diabetes mellitus (GDM), but inconsistent findings have been reported. This study aimed to examine the association between the maternal whole blood concentration of metallic elements (Hg, Pb, Cd, Mn, and Se) and GDM using the dataset of the Japan Environment and Children's Study (JECS), a nationwide birth cohort study, which was designed to examine the adverse effects of pre/post-natal exposure to hazardous environment. METHODS: The data of 78,964 pregnant women who were participants of JECS were used. Blood samples were collected from the pregnant women at second/third trimester of gestation. We employed logistic regression analysis, quantile g-computation (QGC) and a distributed lag nonlinear model (DLNM) to examine the association between the blood concentration of metallic elements and the risk of GDM. RESULTS: The prevalence of GDM was 2.1%. In the logistic regression analyses, maternal blood Hg was associated with an increased risk of GDM. In QGC analysis, although metallic elements mixtures were not related to an increased risk of GDM, Hg (52.6%) may be the main contributor. According to the results of DLNM, for maternal exposure to Hg, 4.99 ng/g was identified as its susceptible minimum window for elevated risk of GDM. CONCLUSIONS: Our findings highlighted an association between Hg exposure and an increased risk of GDM. Studies of the underlying mechanisms and potential contributing factors, including fish intake, of this association are warranted.

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.

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.

Prenatal and postnatal lead exposures and intellectual development among 12-year-old Japanese children.

BACKGROUND: Low-level lead exposure during childhood is associated with deficit in child IQ. However, the association between prenatal lead exposure and child IQ remains inconsistent. The objective of our study was to examine the association between prenatal/postnatal lead exposure and child IQ at the age of 12. METHODS: We obtained data pertaining to cord-blood and child-blood lead levels and IQ for 286 children from a prospective birth cohort study (Tohoku Study of Child Development). IQ was assessed using the Wechsler Intelligence Scale for Children-Fourth Edition. Simultaneously, the Boston Naming Test (BNT) was used to assess the children's language ability. RESULTS: The median lead level in the cord blood was 0.8 µg/dL (5th-95th percentiles, 0.4-1.4 µg/dL), and that in the blood of 12-year-old children was 0.7 µg/dL (0.4-1.1 µg/dL). IQ and BNT scores were significantly lower in boys than in girls; therefore, multiple regression analysis was conducted separately for boys and girls. Among boys, IQ was associated with child-blood lead (B = -16.362, p = 0.033) but not cord-blood lead (B = -6.844, p = 0.309). When boys were divided into four groups according to the child-blood lead levels, there was a significant decreasing trend for IQ. The score with cues of the BNT was associated with both cord-blood (B = -5.893, p = 0.025) and child-blood (B = -7.108, p = 0.022) lead concentrations in boys. Among girls, there was no significant association of the outcomes with cord-blood or child-blood lead level. CONCLUSIONS: These findings suggest that postnatal lead exposure adversely affects the intellectual ability in boys. Furthermore, the language ability is sensitive to prenatal/postnatal lead exposure in boys.

Estimated postnatal p,p'-DDT and p,p'-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children.

BACKGROUND: Children are exposed to p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children's exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age. METHODS: We used data from a birth cohort (n = 290) of the Tohoku Study of Child Development. p,p'-DDT and p,p'-DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0-6 months, 6-12 months, 12-24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models. RESULTS: We found no significant association between levels of p,p'-DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimated p,p'-DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimated p,p'-DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0-6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6-12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12-24 months exposure period. CONCLUSION: In this study of Japanese children, estimated postnatal p,p'-DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that early-life exposure to p,p'-DDE may be associated with higher BMI during childhood.

Correction to: Estimated postnatal p,p'-DDT and p,p'-DDE levels and body mass index at 42 months of age in a longitudinal study of Japanese children.

An amendment to this paper has been published and can be accessed via the original article.

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.

Fish consumption in early pregnancy and congenital gastrointestinal tract atresia in the Japan Environment and Children's Study.

Current evidence suggests that the aetiology of congenital gastrointestinal (GI) tract atresia is multifactorial, and not based solely on genetic factors. However, there are no established modifiable risk factors for congenital GI tract atresia. We used data from a Japanese nationwide birth cohort study launched in 2011, and examined whether fish consumption in early pregnancy was associated with congenital GI tract atresia. We analysed data of 89 495 women (mean age at delivery=31·2 years) who delivered singleton live births without chromosomal anomalies. Based on the results of the FFQ, we estimated the daily intake of fish and n-3 PUFA consumption in early pregnancy. We defined a composite outcome (oesophageal atresia, duodenal atresia, jejunoileal atresia and/or anorectal malformation) as congenital GI tract atresia. In this population, median fish intake was 31·9 g/d, and seventy-four cases of congenital GI tract atresia were identified. Fish consumption in early pregnancy was inversely associated with the composite outcome (multivariable-adjusted OR for the high v. low consumption category=0·5, 95 % CI 0·3, 1·0). For all the specific types of atresia, decreased OR were observed in the high consumption category, although not statistically significant. Reduced atresia occurrence was observed even beyond the US Food and Drug Administration's recommended consumption of no more than 340 g/week. Also, n-3 PUFA-rich fish and n-3 PUFA consumptions tended to be inversely associated with atresia. Fish consumption in early pregnancy may be a preventive factor for congenital GI tract atresia.

Exposure profile of mercury, lead, cadmium, arsenic, antimony, copper, selenium and zinc in maternal blood, cord blood and placenta: the Tohoku Study of Child Development in Japan.

BACKGROUND: The effects of prenatal exposure to toxic elements on birth outcomes and child development have been an area of concern. This study aimed to assess the profile of prenatal exposure to toxic elements, arsenic (As), bismuth (Bi), cadmium (Cd), mercury (total mercury (THg), methylmercury (MHg), inorganic mercury (IHg)), lead (Pb), antimony (Sb) and tin (Sn), and essential trace elements, copper (Cu), selenium (Se) and zinc (Zn), using the maternal blood, cord blood and placenta in the Tohoku Study of Child Development of Japan (N = 594-650). METHODS: Inductively coupled plasma mass spectrometry was used to determine the concentrations of these elements (except mercury). Levels of THg and MeHg were measured using cold vapour atomic absorption spectrophotometry and a gas chromatograph-electron capture detector, respectively. RESULTS: Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the maternal blood were 4.06 (2.68-6.81), 1.18 (0.74-1.79), 10.8 (8.65-13.5), 0.2 (0.06-0.40) and 0.2 (0.1-0.38) ng mL-1 and 5.42 (3.89-7.59) ng g-1, respectively. Median concentrations (25th-75th) of As, Cd, Pb, Sb, Sn and THg in the cord blood were 3.68 (2.58-5.25), 0.53 (0.10-1.25), 9.89 (8.02-12.5), 0.39 (0.06-0.92) and 0.2 (0.2-0.38) ng mL-1 and 9.96 (7.05-13.8) ng g-1, respectively. CONCLUSIONS: THg and Sb levels in the cord blood were twofold higher than those in the maternal blood. Cord blood to maternal blood ratios for As, Cd and Sb widely varied between individuals. To understand the effects of prenatal exposure, further research regarding the variations of placental transfer of elements is necessary.

Dioxins levels in human blood after implementation of measures against dioxin exposure in Japan.

BACKGROUND: Over the past few decades, the Japanese Ministry of the Environment has been biomonitoring dioxins in the general Japanese population and, in response to public concerns, has taken measures to reduce dioxin exposure. The objectives of this study were to assess the current dioxin dietary intake and corresponding body burden in the Japanese and compare Japanese dioxin data from 2011 to 2016 and 2002-2010 surveys. We also examined the relationship between blood dioxins and health parameters/clinical biomarkers. METHODS: From 2011 to 2016, cross-sectional dioxin surveys were conducted on 490 Japanese (242 males and 248 females, aged 49.9 ± 7.6 years) from 15 Japanese prefectures. Blood (n = 490) and food samples (n = 90) were measured for 29 dioxin congeners including polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated biphenyls (Co-PCBs) using gas chromatography coupled with high-resolution mass spectrometry. Using the 2006 World Health Organization toxic equivalence factors, the toxic equivalents (TEQs) were calculated. Clinical biomarkers and anthropometric parameters were also measured and information on lifestyle behaviours collected. Data imputations were applied to account for blood dioxins below the detection limit. RESULTS: The median (95% confidence interval or CI) blood levels and dioxin dietary intake was respectively 9.4 (8.8-9.9) pg TEQ/g lipid and 0.3 (0.2-0.4) pg TEQ/kg body weight/day. The median blood dioxin level in the 2011-2016 survey was found to have decreased by 41.3% compared to the 2002-2010 surveys. Participants who were older were found to be more likely to have higher dioxin levels. Blood dioxins were also significantly associated with body mass index, triglycerides, docosahexaenoic acid, eicosapentaenoic acid, and dihomo-gamma-linoleic acid levels in blood. Furthermore, associations between blood dioxin and dietary dioxin intake were evident in the unadjusted models. However, after adjusting for confounders, blood dioxins were not found to be associated with dietary dioxin intake. CONCLUSIONS: Blood dioxin levels declined over the past decade. This study showed that the measures and actions undertaken in Japan have possibly contributed to these reductions in the body burden of dioxins in the Japanese population.

For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate.

In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a "super-aging" society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.

Baseline Profile of Participants in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS), known as Ecochil-Chosa in Japan, is a nationwide birth cohort study investigating the environmental factors that might affect children's health and development. We report the baseline profiles of the participating mothers, fathers, and their children. METHODS: Fifteen Regional Centres located throughout Japan were responsible for recruiting women in early pregnancy living in their respective recruitment areas. Self-administered questionnaires and medical records were used to obtain such information as demographic factors, lifestyle, socioeconomic status, environmental exposure, medical history, and delivery information. In the period up to delivery, we collected bio-specimens, including blood, urine, hair, and umbilical cord blood. Fathers were also recruited, when accessible, and asked to fill in a questionnaire and to provide blood samples. RESULTS: The total number of pregnancies resulting in delivery was 100,778, of which 51,402 (51.0%) involved program participation by male partners. Discounting pregnancies by the same woman, the study included 95,248 unique mothers and 49,189 unique fathers. The 100,778 pregnancies involved a total of 101,779 fetuses and resulted in 100,148 live births. The coverage of children in 2013 (the number of live births registered in JECS divided by the number of all live births within the study areas) was approximately 45%. Nevertheless, the data on the characteristics of the mothers and children we studied showed marked similarity to those obtained from Japan's 2013 Vital Statistics Survey. CONCLUSIONS: Between 2011 and 2014, we established one of the largest birth cohorts in the world.

Questionnaire results on exposure characteristics of pregnant women participating in the Japan Environment and Children Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nation-wide birth cohort study investigating environmental effects on children's health and development. In this study, the exposure characteristics of the JECS participating mothers were summarized using two questionnaires administered during pregnancy. METHODS: Women were recruited during the early period of their pregnancy. We intended to administer the questionnaire during the first trimester (MT1) and the second/third trimester (MT2). The total number of registered pregnancies was 103,099. RESULTS: The response rates of the MT1 and MT2 questionnaires were 96.8% and 95.1%, respectively. The mean gestational ages (SDs) at the time of the MT1 and MT2 questionnaire responses were 16.4 (8.0) and 27.9 (6.5) weeks, respectively. The frequency of participants who reported "lifting something weighing more than 20 kg" during pregnancy was 5.3% for MT1 and 3.9% for MT2. The Cohen kappa scores ranged from 0.07 to 0.54 (median 0.31) about the occupational chemical use between MT1 and MT2 questionnaires. Most of the participants (80%) lived in either wooden detached houses or steel-frame collective housing. More than half of the questionnaire respondents answered that they had "mold growing somewhere in the house". Insect repellents and insecticides were used widely in households: about 60% used "moth repellent for clothes in the closet," whereas 32% applied "spray insecticide indoors" or "mosquito coil or an electric mosquito repellent mat." CONCLUSIONS: We summarized the exposure characteristics of the JECS participants using two maternal questionnaires during pregnancy.

Psychomotor Ability in Children Prenatally Exposed to Methylmercury: The 18-Month Follow-Up of Tohoku Study of Child Development.

Fish contain nutrients essential to the developing fetal brain, but they are contaminated with methylmercury. The Tohoku Study of Child Development, now underway in the Sanriku coastal area of Miyagi prefecture, Japan, follows mother-child pairs to examine the risks and benefits of fish consumption during pregnancy, especially the effects of prenatal exposures to methylmercury, selenium, and docosahexaenoic acid (DHA) on child neurodevelopment. Children aged 18 months were administered the Bayley Scales of Infant Development second edition (BSID-II) and Kyoto Scale of Psychological Development (KSPD) in 2004-2008. Complete data of cord-blood total mercury (THg), cord-plasma selenium, maternal-plasma DHA, the above test scores, and confounders for 566 mother-child pairs were available. The median cord-blood THg level was 15.7 (range, 2.7-96.1) ng/g. Since the BSID-II and KSPD scores were significantly lower in the 285 boys than in the 281 girls, analyses were conducted separately. The Psychomotor Development Index (PDI) of BSID-II was significantly correlated with cord-blood THg only in the boys, and significance of the association remained unchanged after adjusting for possible confounders; i.e., a 10-fold increase in cord-blood THg was associated with a 8.3-point decrease in the score of the PDI. Other significant correlations of THg were not seen in the boys or girls. Selenium and DHA showed no significant correlations with the BSID-II or KSPD scores in either sex. In conclusion, intrauterine methylmercury exposure may affect psychomotor development, and boys appear to be more vulnerable to the exposure than girls.

Effects of intrauterine exposures to polychlorinated biphenyls, methylmercury, and lead on birth weight in Japanese male and female newborns.

BACKGROUND: The effects of prenatal exposures to polychlorinated biphenyls (PCBs), methylmercury, and lead on birth weight remain disputable. The aim of this study was to investigate whether these chemicals affect birth weight of Japanese newborns, with special emphasis on determining whether these effects differ between males and females. METHODS: The subjects from Tohoku Study of Child Development, which was designed to examine the developmental effects of prenatal exposures to such hazardous chemicals, were 489 mother-newborn pairs with complete data including smoking habit during pregnancy. RESULTS: The mean birth weight of all newborns was 3083 (range, 2412-4240) g. The median values of biomarkers in cord blood were 46.0 (5th and 95th percentiles, 18.6-113.8) ng/g-lipid for total PCBs, 10.1 (4.3-22.4) ng/g for total mercury (THg), and 1.0 (0.6-1.7) µg/dL for lead. The birth weight was significantly heavier in the 252 male newborns than in the 237 female ones. A negative association between total PCBs and birth weight was observed in both male and female newborns, even after adjusting for possible confounders. However, a negative association of THg with birth weight was found only in the male newborns. There was no significant relationship between lead and birth weight in both groups. CONCLUSION: Birth weight appears to be affected by prenatal PCB exposure in Japanese male and female newborns, and the effect of methylmercury exposure on male fetal growth may be stronger than that for females. This implication is that the effects on fetal growth should be assessed in males and females separately.

A methodological consideration for blood lead concentrations obtained from the earlobe in Japanese adults occupationally unexposed to lead.

BACKGROUND: Neuropsychological effects of considerably low levels of lead exposure are observed in children, and a reliable and possibly painless technique that can detect such levels is required for the assessment of such exposure. We examined whether the blood lead (BPb) concentrations obtained from the earlobe were as valid and useful as those from the median cubital vein. METHODS: Paired blood samples were collected from the earlobe and cubital vein of 112 Japanese participants occupationally unexposed to lead, and the BPb levels were determined using ICP-MS. RESULTS: The limit of detection of BPb for the ICP-MS method was 0.015 µg/dL, and there was no participant with a BPb level below this limit. The median values of BPb concentrations were 0.91 (range, 0.41-2.48) µg/dL for earlobe blood using a 175-µL capillary tube and 0.85 (0.35-2.39) µg/dL for venous blood using a 5-mL vacuum tube. There was a significant correlation between the earlobe BPb levels and cubital vein BPb levels (Spearman rank correlation r S = 0.941), though the earlobe BPb levels were significantly higher than the cubital vein BPb levels. Most of the participants regarded earlobe puncture as a painless method. CONCLUSIONS: These data suggest that earlobe BPb levels can be used to assess lead exposure in children. Blood collection using a capillary tube should be done carefully and promptly because slow withdrawal may lead to measurement bias.

Impacts of prenatal exposures to polychlorinated biphenyls, methylmercury, and lead on intellectual ability of 42-month-old children in Japan.

BACKGROUND: The age-specific impacts of perinatal exposures to polychlorinated biphenyls (PCB), methylmercury (MeHg), and lead on child neurodevelopment remain controversial. Since we have already reported the prenatal effects of these chemicals on neurodevelopment in 3-day-old and 30-month-old children of a birth cohort, the following effects were analyzed in the 42-month-old children in the same cohort. METHODS: The Kaufman Assessment Battery for Children (K-ABC), comprised of four scales, was used to assess their intelligence and achievement. The relationships between the chemicals and K-ABC scores were analyzed using multivariate analyses. RESULTS: The median values of chemicals in cord blood of 387 children were 46.5 (5th and 95th percentiles, 16.7-115.7)ng/g-lipid for total PCB, 10.1 (4.3-22.2)ng/g for total mercury (THg), and 1.0 (0.5-1.8) µg/dL for lead. Of the highly chlorinated PCB homologs, 9 CBs was negatively correlated with the sequential and mental processing score of the K-ABC (p<0.05). There were no significant correlations between any K-ABC score and either THg or lead. The negative effect of 9 CBs remained even after adjusting for THg, lead, and other confounders. The K-ABC scores were significantly lower in the boys than in the girls, and the standardized ß of 9 CBs for the sequential and mental processing scores in multiple regression analysis was statistically significant in boys. CONCLUSIONS: These findings suggest that intellectual ability in the developmental stage may be impaired by prenatal exposures to highly chlorinated PCB homologs, especially in Japanese boys.