Nozomi Tatsuta

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.

Methylmercury in the breast milk of Japanese mothers and lactational exposure of their infants.

The human fetus is known to be exposed to methylmercury (MeHg), but little is known about the risk of infant exposure via breast milk. To evaluate the lactational exposure to MeHg via breast milk in Japanese infants, the levels of total mercury (THg) and MeHg were determined in breast milk and maternal blood using samples from a birth cohort study at the Tohoku Study of Child Development. Maternal blood and breast milk were collected one day postpartum and one month after delivery, respectively. The median THg (and MeHg) concentrations in maternal RBCs, plasma and breast milk were 17.8 ng g(-1) (17.8 ng g(-1)), 1.51 ng g(-1) (1.33 ng g(-1)) and 0.81 ng g(-1) (0.45 ng g(-1)), respectively (n=27). The median percentage of MeHg in THg was 54% in breast milk. Breast milk contained substantial amounts of MeHg, which was strongly associated with the internal accumulation of MeHg and the lipid content of the milk (r=0.684). The range of lipid contents in milk varied widely from 0.50 to 6.60 g/100 g of milk, with a median of 3.60 g/100 g. The median (range) weekly average intake of MeHg via breast milk was estimated to be 0.63 μg kg(-1) (0.08-1.68 μg kg(-1)) BW/week. Because the MeHg and lipid contents in milk substantially fluctuate, an investigation of the variations of MeHg and lipid content in breast milk may be required for a more precise risk assessment.

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.

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.

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.

Factors associated with aberrant imprint methylation and oligozoospermia

Disturbingly, the number of patients with oligozoospermia (low sperm count) has been gradually increasing in industrialized countries. Epigenetic alterations are believed to be involved in this condition. Recent studies have clarified that intrinsic and extrinsic factors can induce epigenetic transgenerational phenotypes through apparent reprogramming of the male germ line. Here we examined DNA methylation levels of 22 human imprinted loci in a total of 221 purified sperm samples from infertile couples and found methylation alterations in 24.8% of the patients. Structural equation model suggested that the cause of imprint methylation errors in sperm might have been environmental factors. More specifically, aberrant methylation and a particular lifestyle (current smoking, excess consumption of carbonated drinks) were associated with severe oligozoospermia, while aging probably affected this pathology indirectly through the accumulation of PCB in the patients. Next we examined the pregnancy outcomes for patients when the sperm had abnormal imprint methylation. The live-birth rate decreased and the miscarriage rate increased with the methylation errors. Our research will be useful for the prevention of methylation errors in sperm from infertile men, and sperm with normal imprint methylation might increase the safety of assisted reproduction technology (ART) by reducing methylation-induced diseases of children conceived via ART.

Prevalence and determinants of inadequate use of folic acid supplementation in Japanese pregnant women: the Japan Environment and Children’s Study (JECS)

Abstract Objective: The aim of the study was to clarify the prevalence and determinants of inadequate use of folic acid supplementation in pregnant Japanese women. Methods: This study was part of the Japan Environment and Children’s Study, a nationwide and government-funded birth cohort study. We collected information on the use of folic acid supplementation before and during pregnancy and characteristics of participants using self-administered questionnaire. Results: Among 9849 women who completed the data collection for this study, the prevalence of inadequate users was 92.6% of the total population and varied from 84.5% to 96.2% among regions. On the basis of multivariate logistic regression analysis, younger age, not married, lower family income, multipara, natural conception and no history of spontaneous abortion were found to be determinants for inadequate users of folic acid supplementation. Conclusion: Most Japanese pregnant women show inadequate folic acid supplementation use. Japanese women of child-bearing age need to be specifically informed about the need for periconceptional intake of folic acid to prevent neural tube defects.

Drug Use before and during Pregnancy in Japan: The Japan Environment and Children’s Study

Purpose: To elucidate drug use before and during pregnancy in Japan. Methods: The Japan Environment and Children’s Study (JECS) is an ongoing nationwide birth cohort study. We analyzed data from JECS involving cases where drugs were used for 12 months before pregnancy was diagnosed, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy. Results: We analyzed data from 97,464 pregnant women. The percentages of pregnant women who had taken one or more drugs and supplements before diagnosis of pregnancy, between the time of diagnosis of pregnancy until week 12 of pregnancy, and after week 12 of pregnancy, were 78.4%, 57.1%, and 68.8% respectively. Excluding iron supplements, folic acid, and other vitamins and minerals, the percentages of women taking supplements were 75.3%, 36.0%, and 51.7% at each respective time point. The following drugs and supplements were frequently used for 12 months before pregnancy diagnosis: Commercially available antipyretics, analgesics, and/or medicine for treating common cold (34.7%), antipyretics, analgesics, and/or medicine for treating common colds, which were prescribed in hospitals (29.8%), antimicrobial drugs (14.0%), and anti-allergy drugs (12.5%). The following drugs and supplements were frequently used from the time of pregnancy diagnosis until week 12 of pregnancy, and after week 12 of pregnancy: folic acid (28.9% and 26.2%), antipyretics, analgesics and/or medicines for treating common cold, that were prescribed in hospitals (7.8% and 13.3%), Chinese herbal medicines (6.0% and 9.4%, and uterine relaxants (5.1% and 15.2%). Conclusions: The analysis of a nationwide cohort study showed that a high percentage of Japanese pregnant women were taking medicinal drugs. Further research is required to elucidate the relationship between drug use during pregnancy and birth defects in Japan.

Total mercury levels in hair of children aged 7 years before and after the Great East Japan Earthquake

The Great East Japan Earthquake on March 11, 2011 caused severe damage to the Sanriku coastal area, where we have been conducting a birth cohort study. The disaster occurred in the middle of 7-year-old examination. The mother-child pairs who participated in our study were compulsorily divided into two groups: the examination was finished for 157 children before the disaster, and for 335 after the disaster. We examined whether the disaster affected total mercury (THg) levels of the cohort, as well as a relationship between the THg levels at birth and at present. Although there was no significant difference between the predisaster and postdisaster groups for THg levels in cord blood (16.3 and 16.1ngg-1, respectively) or maternal hair at parturition (2.57 and 2.55μgg-1, respectively), the THg in hair of the 7-year-old children was significantly lower in the postdisaster group (1.79μgg-1) than in the predisaster group (2.51μgg-1). The difference remained significant after adjusting for the prenatal exposure level of THg. In the 492 mother-child pairs, the cord-blood THg was significantly correlated with the THg in maternal hair at parturition (r=0.846) and in hair of the 7-year-old children (r=0.147). In conclusion, the 29% decrease in hair THg after the disaster appears to have been due to the fact that children in the affected area could not consume fish/seafood as usual, probably because of destructive damage to the fishery. Nevertheless, the THg levels at 7years of age reflected the prenatal exposure levels to some extent.