Naoyuki Kurokawa

Neurobehavioral effects of prenatal exposure to methylmercury and PCBs, and seafood intake: Neonatal behavioral assessment scale results of Tohoku study of child development

As factors affecting neonatal neurodevelopment, methylmercury, polychlorinated biphenyls (PCBs), and maternal seafood intake reflecting n-3 polyunsaturated fatty acids (PUFAs) are believed to have adverse or beneficial effects, but there are a few reports addressing such factors simultaneously. We carried out a birth cohort study to clarify the effects of these three factors on the Neonatal Behavioral Assessment Scale (NBAS), administered 3 days after birth. In a total of 498 mother-neonate pairs, the total mercury level (median, 1.96microg/g) in maternal hair at parturition and the summation operatorPCB level (45.5ng/g-lipid) in cord blood were analyzed, and maternal seafood intake was estimated using a semi-quantitative food frequency questionnaire. A negative relationship between the hair mercury level and the motor cluster of NBAS was observed, even after adjusting for PCBs, maternal seafood intake, and possible confounders such as maternal age, birth weight, and parity. The summation operatorPCB level was negatively correlated with the motor cluster, but this association was attenuated after adjusting for mercury and the confounders. There was seen to be a positive association between maternal seafood intake and the motor cluster when considering the effects of mercury and PCBs. In conclusion, our data suggest that prenatal exposure to methylmercury adversely affects neonatal neurobehavioral function; in contrast, maternal seafood intake appears to be beneficial. The neurobehavioral effect of prenatal exposure to PCBs remains unclear in our study. Further research is necessary to elucidate interactive effects of methylmercury, PCBs, and n-3 PUFAs, originating from fish, on child neurodevelopment.

Intervention study on cardiac autonomic nervous effects of methylmercury from seafood.

To scrutinize whether the provisional tolerable weekly intake (PTWI, 3.4 microg/kg body weight/week) of methylmercury in Japan is safe for adults, we conducted an intervention study using heart rate variability (HRV) that has been considered to reflect cardiac events. Fifty-four healthy volunteers were recruited and divided into experimental and control groups. The experimental group was exposed to methylmercury at the PTWI level through consumption of bigeye tuna and swordfish for 14 weeks, and HRV parameters were compared between the two groups. In the experimental group, mean hair mercury levels, determined before and after the dietary methylmercury exposure and after 15-week wash-out period following the cessation of exposure, were 2.30, 8.76 and 4.90 microg/g, respectively. The sympathovagal balance index of HRV was significantly elevated after the exposure, and decreased to the baseline level at the end of this study. Still, such changes in HRV parameters were not found in the control group with a mean hair mercury level of around 2.1 microg/g. In conclusion, the PTWI does not appear to be safe for adult health, because methylmercury exposure from fish consumption induced a temporary sympathodominant state. Rather, long-term exposure to methylmercury may pose a potential risk for cardiac events involving sympathovagal imbalance among fish-consuming populations.

Assessment of exposure to methylmercury in pregnant Japanese women by FFQ.

OBJECTIVE To examine whether an FFQ can be used for assessing exposure to methylmercury (MeHg) by estimating MeHg intake from seafood consumption using the FFQ and confirming the accuracy of the estimated value. DESIGN Seafood consumption of pregnant women was assessed using the FFQ. Total mercury (T-Hg) concentrations of maternal red blood cells (RBC) and hair were measured as exposure indices of MeHg. SETTING A prospective birth cohort study, the Tohoku Study of Child Development (TSCD), which has been ongoing since 2001. SUBJECTS The subjects were 609 pregnant Japanese women who were enrolled in the TSCD. RESULTS MeHg intake was estimated from seafood consumption determined using the FFQ and the MeHg concentrations in each type of seafood. The accuracy of the estimated value was confirmed by comparison with T-Hg in RBC and hair. Estimated MeHg intake was 42.3 microg/week, and 43.0 % of that was from large predatory fish. Compared with the Japanese tolerable weekly intake, in total 12.5 % of the subjects exceeded it. T-Hg concentrations in RBC and hair were significantly correlated with estimated MeHg intake: r = 0.325 (P < 0.0001) for RBC and r = 0.305 (P < 0.0001) for hair. CONCLUSIONS Estimated MeHg intake based on the FFQ was significantly associated with T-Hg concentrations in RBC and hair. Although the estimated value involves uncertainties, the FFQ appears to be a useful tool for assessment of exposure to MeHg.

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 β 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.

Prenatal exposures to environmental chemicals and birth order as risk factors for child behavior problems

OBJECTIVES To assess whether polychlorinated biphenyls (PCBs), methylmercury, lead, or parental child-rearing attitudes was most crucial for maladaptive behavior problems, we examined Japanese 30-month-old children followed up from pregnancy. METHODS The Child Behavior Checklist (CBCL) was used to assess the behavior problems in 306 children. The associations of cord-blood total PCBs (ΣPCB), total mercury (THg), and lead with each CBCL subscale were examined by multivariate analyses. RESULTS The median values in cord blood of the 306 children were 48.3 (5 and 95 percentiles, 18.6-116.3) ng/g-lipid for ΣPCB, 10.2 (4.1-24.5)ng/g for THg, and 1.0 (0.5-1.7)μg/dl for lead. The internalizing score of the CBCL was significantly correlated with ΣPCB (r=0.113) in the children, though no significant correlation was seen between any CBCL score and either THg or lead. The significant correlation disappeared when conducting multiple regression analysis with possible confounders; at that time, the birth order, home environment, and maternal intelligence quotient were significantly related to the internalizing score. Three CBCL scores and ΣPCB levels were significantly higher in the first-born children than in the second-born or following children, and the partial correlation coefficient with the adjustment for all confounders except birth order was significant between the internalizing score and ΣPCB in the latter children (r=0.175). CONCLUSIONS Internalizing behavior appears to be affected by prenatal exposure to PCBs at low levels. Under lower-level exposures, however, behavior problems may be more strongly associated with parental child-rearing attitudes involved in birth order, than with such hazardous chemicals.

No effect of the Trp64Arg variant of the β3-adrenergic receptor gene on weight loss by diet and exercise intervention among Japanese adults

Controversy remains as to whether the presence of the tryptophan-to-arginine (Trp64Arg) variant of the beta(3)-adrenergic receptor gene impedes the magnitude of body weight loss by diet and exercise intervention. The objectives of the present study were to compare the changes in body weight between carriers and noncarriers of the Trp64Arg variant before and after 6 months of diet and exercise interventions for weight loss. A total of 37 middle-aged Japanese individuals (12 carriers and 25 noncarriers of the Trp64Arg variant) participated in the study. There were no significant differences in body weight between the 2 groups at the baseline. There were significant reductions in body weight both in carriers and noncarriers, but no significant differences between the 2 groups with respect to changes in these variables. The weight changes were -2.52 kg (95% confidence interval [CI], -3.56 to -1.48) among carriers and -1.89 kg (95% CI, -2.65 to -1.13) among noncarriers, and the change in the variant carrier group minus the change in the variant noncarrier group was -0.47 (95% CI, -1.97 to 1.02). These results suggest that the presence of the Trp64Arg variant of the beta(3)-adrenergic receptor gene may not play a major role as a hindrance to weight reduction.

Recent trends of body mass index distribution among school children in Sendai, Japan: Decrease of the prevalence of overweight and obesity, 2003—2009

SUMMARY It was reported that the number of obese children increased during the final decades of the 20th century. However, it is unclear whether the prevalence of obesity has changed in recent years. The aim of this study was to examine trends in the body mass index (BMI) and prevalence of obesity in 6th grade primary school children (6thPS) and 3rd year junior high school students (3rdJHS) in Sendai, Japan between 2003 and 2009. BMI (kg/m(2)) was calculated and the prevalences of overweight and obesity were defined based on internationally agreed cutoff points. The mean BMI significantly decreased during the study period in all groups. In addition, the results of regression analysis revealed that significant decreases in BMI occurred in all percentiles in all groups as well. The mean prevalence rates of overweight and obese children as defined by international reference values during the observation period were 19.5% and 4.1% for boys in 6thPS, 13.6% and 2.2% for girls in 6thPS, 13.6% and 3.0% for boys in 3rdJHS and 12.2% and 1.9% for girls in 3rdJHS, respectively. There was a significant decreasing trend in the proportion of overweight and obese children from 2003 to 2009. The downward shifts of BMI might be due to effect modification in the lifestyle of children. Since we had no further data for characterization of Sendai school children and the period of this observation was only 7 years, the reasons for the change in the prevalence of obesity in this population remain speculative.:

Breastfeeding leads to lower blood pressure in 7-year-old Japanese children: Tohoku Study of Child Development

This study investigated the association between breastfeeding and both self-measured home blood pressure (HBP) and conventional blood pressure (CBP) in 7-year-old Japanese children. We obtained data pertaining to breastfeeding and blood pressure for 377 mother–offspring pairs from the Tohoku Study of Child Development, which is a prospective birth cohort study. Information on breastfeeding and other factors were obtained from parental questionnaires during the follow-up period. Based on the duration of breastfeeding as a major source of nutrition, mother–offspring pairs were divided into short-term (mean, 5.1 months) and long-term (mean, 11.3 months) breastfeeding groups. At the age of 7 years (84.4±1.8 months), each child’s blood pressure was measured. The HBP in the long-term breastfeeding (LBF) group (92.9 mm Hg systolic/55.1 mm Hg diastolic) was significantly lower (P=0.006/0.04) than in the short-term breastfeeding group (94.7/56.4 mm Hg); however, there were no significant differences in the CBP measurements between the short- and LBF groups. Using multiple regression analysis, the duration of breastfeeding (greater than 8 months) was more strongly associated with HBP (P=0.008/0.05) than with CBP (P=0.4/0.9). Furthermore, the adjusted R-squared values for HBP (0.25/0.12) tended to be higher than those for CBP (0.07/0.03). These findings were independent of the birth weight. In conclusion, breastfeeding has a protective effect against elevated blood pressure even in young children, and subtle, but important, differences were precisely detected by self-measurements performed at home.

Comparison of the effects of glimepiride and glibenclamide on adipose tissue tumour necrosis factor-alpha mRNA expression and cellularity.

Aim:  The aim of this study was to compare the effects of glimepiride and glibenclamide on tumour necrosis factor (TNF)‐α expression and adipocyte cellularity in spontaneously diabetic, obese rats.

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

BackgroundThe 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.MethodsThe 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.ResultsThe 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.ConclusionBirth 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.