Neurodevelopmental associations of prenatal and postnatal methylmercury exposure among first-grade children in the Kinan region, Japan.

The most severe effects of methylmercury (MeHg) exposure during child development are thought to result from exposure during fetal life and childhood. However, comparing the neurodevelopmental effects of prenatal and postnatal MeHg exposure (PreMeHg and PostMeHg, respectively) remains unclear. We aimed to investigate the associations between neurodevelopmental indicators and PreMeHg or PostMeHg. The participants were 134 children in the first grade of elementary schools aged 7-8 years from the Kinan region, an area with high consumption of MeHg-rich whales and tunas in Japan. We measured MeHg levels in preserved umbilical cord tissues and total mercury (T-Hg) levels in children's hair to estimate PreMeHg and PostMeHg levels, respectively. Neuropsychological (intelligence quotient testing and Boston Naming Test) and neurophysiological (brainstem auditory evoked potential [BAEP], visual evoked potential [VEP], and color vision tests) studies were performed to evaluate the neurodevelopmental status. Multiple regression analyses were conducted according to sex. The geometric mean MeHg levels in preserved umbilical cord tissues and T-Hg levels in children's hair were 0.11 µg/g and 2.94 µg/g, respectively. Neither PreMeHg nor PostMeHg was related to neuropsychological indicators. Some associations between MeHg exposure and neurophysiological results were observed only in boys. N145 latency in VEPs was significantly prolonged with increasing PreMeHg (ß: 12.01, 95% confidence interval [CI]: 0.648, 23.38). The III-V interpeak intervals in BAEP were significantly prolonged with increasing PreMeHg or PostMeHg (ß [95% CI]: 0.142 [0.041, 0.243] and 0.159 [0.052, 0.265], respectively). After adjusting for PreMeHg, the association between PostMeHg and BAEP latencies disappeared. In conclusion, the latency in the auditory and visual pathways was significantly prolonged with increasing PreMeHg in boys. These findings suggest that male fetuses may be more susceptible to MeHg exposure.

Plasma and red blood cells distribution of total mercury, inorganic mercury, and selenium in maternal and cord blood from a group of Japanese women.

Fetuses are a high-risk group for methylmercury (MeHg) exposure. The main objective of this study was to compare the characteristic profiles of total mercury (THg), inorganic mercury (IHg), MeHg, and selenium in plasma and red blood cells (RBCs) between maternal and cord blood at parturition collected from a group of Japanese women. Furthermore, correlations of THg in RBCs, which is a biomarker of MeHg, and THg in plasma, which is an IHg exposure biomarker, were examined in maternal and cord blood. Fifty-five pairs of maternal and cord blood samples obtained at parturition were collected from pregnant women in Fukuoka, Japan. THg in RBCs and plasma were significant correlated between maternal and cord blood. THg in RBCs was 13.9 ng/mL for cord and 9.16 ng/mL for maternal blood, with a cord:maternal RBCs ratio for THg of 1.58, suggesting that MeHg is actively transferred from the mother to the fetus via the placenta. THg in plasma showed a positive correlation with THg in RBCs for maternal and cord blood. This result suggests that measuring THg in plasma can overestimate the exposure level to IHg in fish-eating populations. The percentages of IHg in cord plasma and RBCs were 31% and 1.7%, respectively, and those in maternal plasma and RBCs were 46% and 5.9%, respectively. These results suggest that cord blood is rich in MeHg and can easily transfer to the fetal brain. Selenium in cord plasma was 67 ng/mL and that in maternal plasma was 97 ng/mL, with a cord:maternal plasma ratio for Se of 0.69, suggesting that the protective effects of Se against MeHg toxicity in fetuses may be weaker than those expected in adult mothers.

Cesarean delivery rates for overall and multiple pregnancies in Japan: A descriptive study using nationwide health insurance claims data.

AIM: Due to the lack of national perinatal registries, population-wide descriptive statistics on cesarean deliveries in Japan are unknown. We aim to describe cesarean deliveries for overall and multiple pregnancies using the Japan National Database of health insurance claims. METHODS: We calculated the national and prefectural cesarean delivery rates for overall and multiple pregnancies in 2014. We described maternal morbidities (e.g., blood transfusion) and the place and type of the institutions providing prenatal and perinatal care. RESULTS: The national cesarean delivery rates were 18.6% overall and 82.7% for women with multiple pregnancies. Prefectural cesarean delivery rates for overall and multiple pregnancies varied from 12.5% to 24.2% and from 49.2% to 100%, respectively, showing a moderate positive correlation (r = 0.59, p < 0.001). Overall, 1.4% of cesarean patients received an allogeneic blood transfusion, compared to 3.2% for those with multiple pregnancies. In addition, 65.9% of overall cesarean deliveries occurred at hospitals with ≥20 beds, whereas 94.6% of cesarean patients with multiple pregnancies delivered at hospitals. Older patients were more likely to receive their cesarean section at a different institution than their first visit within the same prefecture, but trans-prefectural movement during pregnancy covered by health insurance was most frequent among those in their early thirties: 7.0% overall and 10.7% for multiple pregnancies. CONCLUSIONS: The overall cesarean delivery rate in Japan was optimal, but the rate was high for multiple pregnancies, with large regional differences. Data on patient movement across institutions and areas would help to improve the perinatal care system.

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.

Dose-dependent associations between prenatal caffeine consumption and small for gestational age, preterm birth, and reduced birthweight in the Japan Environment and Children's Study.

BACKGROUND: Few previous studies have investigated the association between prenatal caffeine intake and birth size (small for gestational age [SGA], preterm birth, and birthweight Z-score) in Japan. OBJECTIVES: We examined the dose-dependency of this association (prenatal caffeine consumption and birth size) as part of the Japan Environment and Children's Study. METHODS: A prospective birth cohort included 94 876 fetuses in Japan. Participants were enrolled between January 2011 and March 2014. Adjusted multiple linear regression and Cox regression models were used to examine the association between prenatal caffeine levels and infant birth size. RESULTS: The median estimated caffeine consumption during pregnancy was 125.5 mg/day, as determined by self-administered questionnaires. There were 7252 SGA infants (7.6%) and 4281 preterm birth infants (4.5%). Compared with infants of mothers whose caffeine consumption during pregnancy was in the lowest quartile (4.2 to <86.4 mg/day), infants of mothers whose caffeine consumption was in the highest quartile 4 (205.5-5080.0 mg/day) were at an increased risk of SGA (relative risk [RR] 1.18, 95% confidence interval [CI] 1.10, 1.27), and at an increased risk of preterm birth at the second trimester of gestation (RR 1.94, 95% CI 1.12, 3.37), with a 0.32-day reduction in gestational age (95% CI -0.52, -0.12) and with a 0.07 reduction in birthweight Z-score observed (95% CI -0.09, -0.05). CONCLUSIONS: Prenatal caffeine consumption was associated with birth size. However, as the association between prenatal caffeine consumption and birth size was likely confounded by unpredicted potential factors, our confidence in the true causality of the association is moderate.

Associations of environmental exposures to methylmercury and selenium with female infertility: A case-control study.

BACKGROUND: Methylmercury exposure is a common health risk resulting from daily fish intake. However, studies addressing the link between methylmercury and infertility are limited and also inconsistent. In addition, no previous epidemiological studies have accounted for the interaction between methylmercury and selenium. We aimed to investigate the association between environmental exposures to metals and female fertility. METHODS: This case-control study included 98 infertile women receiving fertility treatment (infertile group) and 43 female workers in their thirties (control group) who provided blood samples and returned a questionnaire on lifestyles and dietary characteristics. Blood levels of mercury, lead, cadmium, arsenic, manganese, zinc, and selenium were compared between the groups. Spearman correlation analyses between anti-Müllerian hormone and the metals were conducted. RESULTS: The mean selenium level in blood (±â€¯SD) and the selenium/mercury molar ratio were significantly lower in the infertile group (189 ±â€¯25 µg/L and 94.6 ±â€¯44.3, respectively) than in the control group (200 ±â€¯25 µg/L and 118.4 ±â€¯70.5). By contrast, blood mercury levels after adjusting for blood selenium and age were significantly higher in the infertile group than in the control group. Multiple logistic regression analyses with the adjustment for the other metals and potential confounders confirmed significant associations of infertility with elevated mercury and reduced selenium levels. No significant correlations were observed between anti-Müllerian hormone and metals. CONCLUSIONS: Methylmercury and selenium exposures appear to have adverse and protective effects on female fertility, respectively. This is the first report to suggest the antagonistic interaction between methylmercury and selenium in relation to human female fertility.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

BACKGROUND: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan. METHODS: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß2-microglobulin and blood and urinary cadmium levels were measured. RESULTS: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß2-microglobulin level higher than 10,000 µg/g cr. and a blood cadmium level higher than 6 µg/L or urinary cadmium level higher than 10 µg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy. CONCLUSIONS: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants. REGISTRATION NUMBER: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).

Two-year follow-up of a randomized controlled trial: knowledge and reproductive outcome after online fertility education.

STUDY QUESTION: What are the long-term effects of fertility education on knowledge and reproductive outcome? SUMMARY ANSWER: Participants in the intervention group retained some knowledge after 2 years and the partnered women had a new child more quickly than the comparison group. WHAT IS KNOWN ALREADY: Fertility education improves knowledge, at least in the short-term. Attitudes toward childbearing and its timing can change after exposure to educational materials. STUDY DESIGN, SIZE, DURATION: Participants were recruited via an online social research panel. In the original randomized controlled trial (RCT), knowledge of reproductive-aged participants was assessed before (T1) and immediately after (T2) receiving one of three information brochures: fertility (intervention group), healthy pre-pregnancy (focused on intake of folic acid during pregnancy, control group 1), or family policies in Japan (childcare provision, control group 2). The present follow-up study was conducted 2 years later in January 2017 (T3) with the same participants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of the T1 participants (n = 1455), 383 men and 360 women (51%) responded to the T3 survey. Fertility knowledge measured with the Japanese version of the Cardiff Fertility Knowledge Scale (CFKS-J) and fertility status (e.g. new births, new medical consultations, and the timing of new birth) was assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline (T1) characteristics of the T3 participants were well balanced between groups, but T3 participants were older, married, and more educated compared to those lost to follow-up. A repeated-measures analysis of variance showed significant knowledge gains among the intervention group from T1 to T3 (11.2% and 7.0% among men and women, respectively) but no significant change over time for the control groups. There were no differences between groups in the incidence of new births or new medical consultations. However, subgroup analysis showed that timing of new births was accelerated for partnered individuals in the intervention group. Specifically, the proportion of partnered participants at T1 who had a new birth in the first year subsequent to presentation of information was higher in the intervention group versus control group 1 (folic acid): 8.8% versus 1.4% (P = 0.09) among men and 10.6% versus 2.3% (P = 0.03) among women, respectively. The odds ratios (adjusted for age) were 7.8 (95% CI: 0.86-70.7) and 5.2 (95% CI: 1.09-25.0) among men and women, respectively. The timing of births and the proportion of new births during the 2-year follow-up period in the intervention group were similar to that of control group 2 (family policy). The incidence of new medical consultation was higher in the male intervention group (12.0%) than in male control group 2 (family policy, 1.5%, P = 0.04) but similar among women in all groups. LIMITATIONS REASONS FOR CAUTION: First, the high attrition rate may limit the generalizability of these findings for longer-term acquisition of fertility knowledge, especially when applied to younger people who were more likely to be lost to follow-up. Second, this is a 2-year follow-up study and the results may change in the longer-term. Finally, we relied on self-reported questionnaire data and there is a possibility that some women were unknowingly pregnant at T1 but this risk should be distributed equally in the three groups through randomization. WIDER IMPLICATIONS OF THE FINDINGS: Effects of one-time education were limited but retained beyond baseline levels. Importantly, education was found to potentially accelerate decision-making about achieving births in partnered subgroups compared to receiving healthy pre-pregnancy information. However, this finding should be confirmed in future stratified RCTs designed to evaluate effects in these subgroups. Follow-up 'booster' education sessions might help people retain knowledge and facilitate reproductive decisions for longer. In view of the high attrition rate, especially among young populations, novel educational strategies to retain young people in fertility education cohorts should be explored. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by National Center for Child Health and Development, the Daiwa Anglo-Japanese Foundation, Pfizer Health Research Foundation, and the Japan Society for the Promotion of Science. E.M. reports joint research funds from a public interest incorporated foundation '1 more Baby Ohendan.'

Brain methylmercury uptake in fetal, neonate, weanling, and adult rats.

Fetuses and neonates are known to be highly susceptible to methylmercury (MeHg) toxicity, but little is known about the relative uptake of MeHg from blood to the developing brain. We measured time-course changes in mercury (Hg) concentrations in the brain of fetal, neonate, weanling, and adult rats after an injection of 0.08 µg (0.4 nmol) Hg/g MeHg. In the prenatal experiment, MeHg was subcutaneously injected to pregnant dams on embryonic days 17, 18, 18.5, 19, 19.5, or 20, and Hg concentrations in tissues were measured in both mothers and fetuses on embryonic day 21 (1 day before parturition). Brain Hg levels in fetuses peaked 2 days after injection and were approximately 1.5 times higher than in mothers. In the postnatal experiment, the same MeHg dose was injected subcutaneously to male rats on postnatal days 1 (neonates), 35 (weanlings), or 56 (adults). Mercury concentrations in tissues were measured 1, 2, 3, 4, 5, or 6 days after the injection. Brain Hg levels peaked most rapidly in neonates, and were approximately 1.5 times higher than levels in weanlings or adults. Throughout the examined period, peak Hg levels in the brain and the Hg brain/blood ratio 24 h after injection were highest in fetuses, followed by the levels in neonates, and decreased with life stage. These findings suggest that relatively higher brain MeHg uptake is an important factor in the vulnerability of fetuses and neonates to MeHg exposure.

Cesarean section rates and local resources for perinatal care in Japan: A nationwide ecological study using the national database of health insurance claims.

AIM: High cesarean section (CS) rates in middle and high-income countries are partly attributable to provider factors, such as staffing patterns and fear of litigation. However, the relationship between CS rates and healthcare resources in the community is poorly understood. Official data on CS rates has been particularly limited in Japan. In this study, we examined nationwide CS statistics and evaluated the association with local resources for perinatal care. METHODS: We used accumulated data for CS registered in the Japan National Database of health insurance claims in 2013 and calculated crude and age-standardized CS rates at national and prefectural levels. We analyzed the ecological associations with supply of obstetricians and institution and scale of obstetric facilities using multiple regression models. RESULTS: There were 190 361 cesarean deliveries in 2013, giving an overall CS rate of 18.5% (elective CS rates 11.0%), which varied by prefecture from 14.0% to 25.6%. In multiple regression analyses, the areal number of obstetricians (standardized regression coefficient [ß] = -0.58), the proportion of births at small-scale institutions (ß = 0.36) and the number of beds at neonatal intensive care units per birth (ß = -0.20) were significantly associated with the age-standardized elective CS rate after adjusting for socioeconomic factors (R2 for the model = 0.40). CONCLUSIONS: Higher elective CS rates might be associated with limited or unconsolidated medical resources. Policymakers should be aware of regional differences and the possible effects of perinatal care resources on CS rates.

Stable and episodic/bolus patterns of methylmercury exposure on mercury accumulation and histopathologic alterations in the nervous system.

The main purpose of the present study was to compare the blood and brain mercury (Hg) accumulation and neurological alterations in adult male and pregnant female/fetal rats following stable and episodic/bolus patterns of methylmercury (MeHg) exposure. In addition, MeHg accumulation in the human body was estimated by a one-compartment model using three different patterns of MeHg exposure. In the adult male rat experiment, doses of 0.3 and 1.5mg MeHg/kg/day were orally administered to the stable groups for 5 weeks, while 7-fold higher doses of 2.1 and 10.5mg MeHg/kg/once a week were administered to the bolus groups. The blood Hg levels increased constantly in the stable groups, but increased with repeated waves in the bolus groups. At completion of the experiment, there were no significant differences in the brain Hg concentrations or neurological alterations between the stable and bolus groups, when the total doses of MeHg were the same. In the pregnant female rat experiment, a dose of 1mg MeHg/kg/day was administered orally to the stable group for 20 days (until 1day before expected parturition), while a 5-fold higher dose of 5mg MeHg/kg/once every 5 days was administered to the bolus group. In the brains of the maternal/fetal rats, there were no significant differences in the Hg concentrations and neurological alterations between the stable and bolus groups. The mean Hg concentrations in the fetal brains were approximately 2-fold higher than those in the maternal brains for both stable and bolus groups. Using the one-compartment model, the Hg accumulation curves in humans at doses of 7µg MeHg/day, 48µg MeHg/once a week, and 96µg MeHg/once every 2 weeks were estimated to be similar, while the bolus groups showed dose-dependent amplitudes of repeated waves. These results suggest that stable and episodic/bolus patterns of MeHg exposure do not cause differences in Hg accumulation in the blood and brain, or in neurological alterations, when the total doses are the same.

The Association between Work-Related Stress and Autonomic Imbalance among Call Center Employees in Japan.

There is little epidemiological evidence linking subjective stress to objective etiologic indicators. To clarify an association between work-related stress and autonomic nervous function, we examined call center employees (167 males and 371 females) undergoing electrocardiography (ECG) at the time of annual health checkups. The questionnaire was composed of the Brief Job Stress Questionnaire based on the demand-control-support model and the Social Readjustment Rating Scale including detailed contents of home stress. The Bazett's corrected QT (QTc) interval, QT index, and heart rate were obtained from the ECG data. The male employees showed significantly higher scores of job demand, job control, and supervisor support than the female ones. In the male employees, QT index indicating the extent of autonomic imbalance and heart rate were associated with high score of supervisor support and low score of coworker support (P < 0.05), but no significant relationships were seen between QTc interval and either job strain (i.e., job demand and job control) or home stress. By contrast, the female employees showed no significant links between any autonomic indicators and either work-related stress or home stress. These data suggest that work-related stress affected QT index in male employees suffering specific occupational stressors such as emotional abuse from unsatisfied customers. Specifically, supports from supervisors and coworkers were paradoxically associated with QT index, implying that supervisors may have failed to effectively support such male employees. Also, autonomic nervous function in male employees appears to be more vulnerable to work-related stress than that in female ones.

Precarious Employment Is Not Associated with Increased Depressive Symptoms: A Cross-Sectional Study in Care Service Workers of Japan.

Some epidemiological studies with a large number of subjects, like a national health study, reported that precarious employment was associated with increased depressive symptoms, but this hypothesis may not be applicable to precarious workers of all industry types. We examined the association between precarious employment and depressive symptoms in light of work-related stress in care work environments. The self-administered questionnaire, composed of the Job Content Questionnaire based on the demand-control-support model and the Center of Epidemiological Studies Depression Scale (CES-D), was distributed, and a total of 1,338 permanent and 531 precarious employees responded to it with complete forms. In the precarious employees, scores of CES-D, job demand and job control were lower and supervisor support score was higher compared with the permanent employees, though there was no significant difference in the proportion of CES-D score ≥16 between the two groups. Multivariate analysis with adjustment for possible confounders revealed that increased depressive symptoms were associated with low coworker support in the precarious employees and with high demand and low control at work, low support from supervisors and coworkers in the permanent employees. However, precarious employment was not significantly associated with depressive symptoms in the male or female employees. In conclusion, our results do not support the above hypothesis at least in care service workers. Such a hypothesis should be verified in employees of each industry separately. Instead, coworker support within each workplace appears to be important for the preventive strategy of depression in workers including precarious employees.

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.

Implications of mercury concentrations in umbilical cord tissue in relation to maternal hair segments as biomarkers for prenatal exposure to methylmercury.

In this study, we investigated how mercury (Hg) concentrations in umbilical cord tissue are correlated with those in biomarkers for prenatal exposure to methylmercury (MeHg). Total Hg (T-Hg) concentrations were measured in 54 mother-child paired samples of maternal blood, umbilical cord tissue, cord blood, and maternal hair segments (1-cm incremental segments from the scalp) collected at parturition. MeHg concentrations were also measured in the cord tissue. Median T-Hg and MeHg concentrations in cord tissue on a dry-weight basis (d.w.) were 62.2ng/g and 56.7ng/g, respectively. Proportions of MeHg to T-Hg were approximately 95%. Both T-Hg and MeHg in cord tissue (d.w.) showed better correlations with T-Hg in cord blood than did T-Hg in cord tissue on a wet-weight basis (w.w.). Median T-Hg concentrations in maternal blood, cord blood, and maternal hair (0-1cm from the scalp) were 3.79ng/g, 7.26ng/g, and 1.35 µg/g, respectively. Median T-Hg concentration in cord blood was 1.92 times higher than that in maternal blood. T-Hg in cord tissue (d.w.) showed a strong correlation with that in cord blood (r=0.912, p<0.01). Among the hair segments, T-Hg in cord tissue (d.w.) showed the strongest correlation (r=0.854, p<0.01) with that in maternal hair at 0-1cm from the scalp, reflecting growth for approximately 1 month before parturition. Based on the present results, T-Hg and MeHg concentrations in cord tissue may be useful biomarkers for prenatal MeHg exposure of the fetus, especially reflecting the maternal MeHg body burden during late gestation. The conversion factors for T-Hg and MeHg concentrations in cord tissue (d.w.) to T-Hg concentrations in maternal hair (0-1cm from the scalp) were calculated to be 22.37 and 24.09, respectively. This information will be useful for evaluating maternal MeHg exposure levels in retrospective studies using preserved umbilical cord tissue.

Impact of the Great East Japan Earthquake on Child's IQ.

OBJECTIVE: To assess the neurodevelopmental effects of the Great East Japan Earthquake in resident children. STUDY DESIGN: The disaster on March 11, 2011, caused severe damage to the Sanriku coastal area, where we had been conducting a birth cohort study since 2003. It occurred in the middle of our 7-year-old examination. Approximately 500 mother-child pairs were compulsorily divided into 2 groups: 123 children finished the examination in the predisaster period, and 289 did in the postdisaster period. The remainder died or moved from that area. At the time of 7-year-old examination, we administered the Wechsler Intelligence Scale for Children-Third Edition and electrocardiography to assess autonomic function. According to the Child Behavior Checklist for ages 2-3 years and the Kaufman Assessment Battery for Children that had been administered at 30 months and 42 months of age, respectively, there were no significant differences in them between the 2 groups. RESULTS: Verbal IQ, including information, arithmetic, and vocabulary subscores of the Wechsler Intelligence Scale for Children-Third Edition, at 7 years of age was significantly lower in the postdisaster group than in the predisaster group. However, there were no significant differences in performance IQ, full-scale IQ, or autonomic nervous indicators between the 2 groups. CONCLUSIONS: Since many schools were utilized as primary refuges after the disaster, the deficits in verbal IQ of 7-year-old children may have been due to the interrupted schooling. Further follow-up and more specific posttraumatic stress disorder testing will be required to determine the cause and long-term implications.

Significance of fingernail and toenail mercury concentrations as biomarkers for prenatal methylmercury exposure in relation to segmental hair mercury concentrations.

OBJECTIVE: To investigate the appropriateness of mercury (Hg) concentrations in fingernails and toenails at parturition for detecting prenatal exposure to methylmercury (MeHg). METHODS: Total Hg concentrations were measured in 54 paired samples of fingernails, toenails, maternal blood, and maternal hair (1cm incremental segments from the scalp toward the tip) collected at 4th weeks of (early) pregnancy, and the same specimens and cord blood collected at parturition. RESULTS: Strong correlations were observed between Hg concentrations in fingernails and toenails at early pregnancy (r=0.923, p<0.01) and at parturition (r=0.895, p<0.01). At early pregnancy, Hg concentrations in fingernails and toenails showed the strongest correlations with those in hair 3-4 cm from the scalp (r=0.818 and r=0.747, p<0.01, respectively) among the 1cm incremental hair segments. Mercury concentrations in fingernails and toenails at parturition represented strong correlations with those in cord blood (r=0.803, p<0.01 for fingernails and r=0.792, p<0.01 for toenails, respectively). At parturition, Hg concentrations in fingernails had the highest correlation with those in hair 0-1cm from the scalp (r=0.918, p<0.01), and Hg concentrations in toenails showed the highest correlation with those in hair at 2-3 cm from the scalp (r=0.872, p<0.01). In addition, Hg concentrations in both finger and toe nails at parturition had equally high (p<0.01) correlation coefficients with hair segments at 0-1, 1-2, and 2-3 cm from the scalp. CONCLUSIONS: Mercury in fingernails and toenails at early pregnancy reflected the maternal Hg body burden level approximately 5 months retroactively. At parturition, Hg levels in fingernails and toenails also showed strong correlations with those in cord blood. In addition, Hg levels in fingernails and toenails at parturition reflected more recent MeHg exposure, compared with those at early pregnancy. These results suggest that fingernails and toenails at parturition are useful biomarkers for prenatal MeHg exposure for mothers and fetuses, especially during the third-trimester of gestation.

Mercury speciation and selenium in toothed-whale muscles.

Mercury accumulates at high levels in marine mammal tissues. However, its speciation is poorly understood. The main goal of this investigation was to establish the relationships among mercury species and selenium (Se) concentrations in toothed-whale muscles at different mercury levels. The concentrations of total mercury (T-Hg), methylmercury (MeHg), inorganic mercury (I-Hg) and Se were determined in the muscles of four toothed-whale species: bottlenose dolphins (n=31), Risso's dolphins (n=30), striped dolphins (n=29), and short-finned pilot whales (n=30). In each species, the MeHg concentration increased with increasing T-Hg concentration, tending to reach a plateau. In contrast, the proportion of MeHg in T-Hg decreased from 90-100% to 20-40%. The levels of T-Hg and Se showed strong positive correlations. Se/I-Hg molar ratios rapidly decreased with the increase of I-Hg and reached almost 1 in all species. These results suggested that the demethylated MeHg immediately formed Se/I-Hg equimolar complex of mercury selenide (HgSe) in their muscles. In addition, an X-ray absorption fine structure analysis (XAFS) of a bottlenose dolphin muscle confirmed that the dominant chemical form of the Se/I-Hg equimolar complex was HgSe. HgSe was mainly localized in cells near the endomysium using electron probe microanalysis (EPMA). These results suggested that the demethylated MeHg finally deposits within muscle cells of bottlenose dolphin as an inert HgSe.