Search

We assessed the associations between perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) levels in third trimester maternal serum, the maternal genotypes of genes encoding nuclear receptors, and birth outcomes. We studied a prospective birth cohort of healthy pregnant Japanese women (n = 372) recruited in Sapporo between July 2002 and October 2005. We analyzed PFOS and PFOA levels using liquid chromatography-tandem mass spectrometry and analyzed 13 single nucleotide polymorphisms (SNPs) of proliferator-activated receptor alpha, gamma, gamma coactivator 1A, delta, constitutive androstane receptor, liver X receptor alpha, and beta (LXRB) using real-time polymerase reaction (PCR). We employed multiple linear regression models to establish the influences of log10-transformed PFOS and PFOA levels and maternal genotypes on birth size. In female infants, we identified interactions between PFOS levels, the maternal genotype of LXRB (rs1405655), and birth weight. The estimated mean changes in birth weight in response to PFOS levels, the maternal genotype LXRB (rs1405655)-TC/CC (compared to TT), and their interactions were -502.9 g (95 % confidence interval [CI] = -247.3, -758.5 g), -526.3 g (95 % CI = -200.7, -852.0 g), and 662.1 g (95 % CI = 221.0, 1,103.2 g; pint = 0.003), respectively. Interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) also significantly affected birth chest circumference and the Ponderal index (pint = 0.037 and 0.005, respectively). Thus, interactions between PFOS levels and the maternal genotype of LXRB (rs1405655) affects birth sizes in female infants. We found that certain SNPs modify the effects of PFOS levels on birth size.

Organochlorine pesticides (OCPs) are environmental contaminants with potentially adverse effects on neurodevelopment. Previous findings on the association between prenatal exposure to OCPs and the maternal or infant thyroid hormone system are inconsistent. Moreover, the influence of exposure to multiple OCPs and other chemical compounds is not clearly understood. Our study therefore aimed to examine the association between OCP exposure and both maternal and infant thyroid hormone systems. We also explored multiple exposure effects of OCPs and the influence of each compound using weighted quantile sum (WQS) methods. The study population included 514 participants in the Hokkaido study, recruited from 2002 to 2005 at one hospital in Sapporo, Japan. To quantify 29 OCPs, maternal blood samples were analyzed using gas chromatography/mass spectrometry. Blood samples for measuring thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers during the early gestational stage (mean 11.4 weeks), and from infants between 7 and 43 days of age. The data of 333 mother child pairs with OCP and thyroid hormone measurements were included in the final analyses. Multivariate regression models showed a negative association between maternal FT4 and levels of o,p -dichlorodiphenyldichloroethylene (DDE), o,p'-dichlorodiphenyltrichlomethane (DDT), and dieldrin. The WQS analysis showed that o,p '-DDT (48.6%), cis-heptachlorepoxide (22.8%), dieldrin (15.4%) were the primary contributors to the significant multiple exposure effect of OCPs on maternal FT4. For infants, we found a positive association between FT4 and cis-nonachlor and mirex. The most contributory compounds in the multiple exposure effect were trans-nonachlor (27.1%) and cis-nonachlor (13.8%), while several compounds contributed to the WQS via small weights (0.4-9.1%). These results indicate that OCPs, even at very low levels, may influence maternal and child thyroid hormone levels, which could mo

Background: Prenatal exposure to polychlorinated dibenzo-p-dioxins (PCDDs) or polychlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dioxin-like compounds [DLCs]) through environmental chemicals may affect the neurodevelopment of children. In our previous study, an inverse association was observed between prenatal DLCs and neurodevelopment of infants aged 6 months in both sexes. However, studies are yet to determine how long these adverse effects last. Objective: To examine whether the effects of DLCs on cognitive development remains at 42 months. Methods: In this prospective cohort study conducted in Sapporo, Japan, pregnant mothers' blood was analyzed for the congener level of DLCs. The Kaufman Assessment of Battery for Children (K-ABC) was used to test their children's cognitive development at 42 months. A total of 141 mother-child pairs were included in the final analysis. The multiple linear regression analysis was used to examine the association between the K-ABC scores and DLC levels in the maternal blood. Results: Seven isomers (1,2,3,6,7,8-HxCDD, 2,3,4,7,8-PeCDF, 33'44'55'-HxCB(#169), 2344'5-PenCB(#114), 233'44'5-HexCB(#156), 233'44'5'-HexCB(#157), 23'44'55'-HexCB(#167), total PCDF, and TEQ-PCDD, PCDF, PCDD/DFs levels were positively associated with the achievement score (AS) of K-ABC. However, total non-ortho PCBs were negatively associated with the Mental Processing Composite Score (MPCS) of K-ABC in males. In females, increased TEQ-dl PCB and TEQ-PCDD/F/dl-PCB were also associated with increasing AS score. Conclusions: This study suggests that the negative effects of prenatal DLC exposure on children's cognitive development at 6 months were not observed in children aged 42 months. Regarding the sex-specific effects, AS and DLCs were positively correlated in females, whereas those of MPCS and DLCs were significantly negative in males.

Background: Prevalence rates of all anomalies classified as birth defects, including those identified before the 22nd gestational week, are limited in published reports, including those from the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR). In our birth cohort study, we collected the data for all birth defects after 12 weeks of gestation. Methods: Subjects in this study comprised 19,244 pregnant women who visited one of 37 associated hospitals in the Hokkaido Prefecture from 2003 through 2012, and completed follow-up. All birth defects after 12 weeks of gestation, including 55 marker anomalies associated with environmental chemical exposures, were recorded. We examined parental risk factors for birth defects and the association between birth defects and risk of growth retardation. Results: Prevalence of all birth defects was 18.9/1,000 births. The proportion of patients with birth defects delivered between 12 and 21 weeks of gestation was approximately one-tenth of all patients with birth defects. Among those with congenital malformation of the nerve system, 39% were delivered before 22 weeks of gestation. All patients with anencephaly and encephalocele were delivered before 22 weeks of gestation. We observed different patterns of parental risk factors between birth defect cases included in ISBDSR and cases not included. Cases included in ISBDSR were associated with an increased risk of preterm birth. Cases not included in ISBDSR were associated with an increased risk of being small for gestational age at term. Conclusions: Data from our study complemented the data from ICBDSR. We recommend that birth defects not included in ICBDSR also be analyzed to elucidate the etiology of birth defects.

Organochlorine pesticides (OCPs) are environmental contaminants that persist in the environment and bioaccumulate through the food chain in humans and animals. Although previous studies have shown an association between prenatal OCP exposure and subsequent neurodevelopment, the levels of OCPs included in these studies were inconsistent. A hospital-based prospective birth cohort study was conducted to examine the associations between prenatal exposure to relatively low levels of OCPs and neurodevelopment in infants at 6 (n = 164) and 18 (n = 115) months of age. Blood samples were analyzed using gas chromatography/mass spectrometry techniques to quantify 29 OCPs. The Bayley Scales of Infant Development 2nd edition (BSID-II) was used to assess the Mental and Psychomotor Developmental Index. After controlling for confounders, we found an inverse association between prenatal exposure to cis-heptachlor epoxide and the Mental Developmental Index at 18 months of age. Furthermore, infants born to mothers with prenatal concentrations of cis-heptachlor epoxide in the highest quartile had Mental Developmental Index scores -9.8 (95% confidence interval: -16.4, -3.1) lower than that recorded for infants born to mothers with concentrations of cis-heptachlor epoxide in the first quartile (p for trend < 0.01). These results support the hypothesis that prenatal exposure to OCPs, especially cis-heptachlor epoxide, may have an adverse effect on the neurodevelopment of infants at specific ages, even at low levels.

The International Clearinghouse for Birth Defects, Surveillance and Research reports a rise in the prevalence rate of spina bifida in Japan. We determined first-trimester folate status of Hokkaido women and identified potential predictors. Participants were 15 266 pregnant women of the Hokkaido Study on Environment and Children’s Health Cohort. Data were extracted from self-reported questionnaires and biochemical assay results. Demographic determinants of low folate status were younger maternal age (adjusted OR (AOR) 1·48; 95 % CI 1·32, 1·66), lower educational level (AOR 1·27; 95 % CI 1·17, 1·39) and lower annual income (AOR 1·11; 95 % CI 1·01, 1·22). Plasma cotinine concentrations of 1·19-65·21 nmol/l increased the risk of low folate status (AOR 1·20; 95 % CI 1·10, 1·31) and concentrations >65·21 nmol/l further increased the risk (AOR 1·91; 95 % CI 1·70, 2·14). The most favourable predictor was use of folic acid (FA) supplements (AOR 0·19; 95 % CI 0·17, 0·22). Certain socio-demographic factors influence folate status among pregnant Japanese women. Modifiable negative and positive predictors were active and passive tobacco smoking and use of FA supplements. Avoiding both active and passive tobacco smoking and using FA supplements could improve the folate status of Japanese women.

Sexually dimorphic brain development and behavior are known to be influenced by sex hormones exposure in prenatal periods. On the other hand, second-to forth digit ratio (2D/4D) has been used as an indirect method to investigate the putative effects of prenatal exposure to androgen. In the present study, we herein investigated the relationship between gender-role play behavior and the second-to-fourth digit ratio (2D/4D), which has been used as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children. Among 4981 children who became 8 years old by November 2014 and were contactable for this survey by The Hokkaido Study of Environment and Children's Health, 1631 (32.7%), who had data for 2D/4D and Pre-school Activities Inventory (PSAI) as well as data for the survey at baseline, were available for analysis. Parents sent reports of PSAI on the sex-typical characteristics, preferred toys, and play activities of children, and black and white photocopies of the left and right hand palms via mail. PSAI consisted of 12 masculine items and 12 feminine items, and a composite score was created by subtracting the feminine score from the masculine score, with higher scores representing masculine-typical behavior. While composite scores in PSAI were significantly higher in boys than in girls, 2D/4D was significantly lower in boys than in girls. Although the presence or absence of brothers or sisters affected the composite, masculine, and feminine scored of PSAI, a multivariate regression model revealed that 2D/4D negatively correlated with the composite scores of PSAI in boys, whereas no correlation was found in girls. Although 2D/4D negatively correlated with the masculine score in boys and girls, no correlation was observed between 2D/4D and the feminine score. In conclusion, although social factors, such as the existence of brother or sisters, affect dimorphic brain development and behavior in childhood, the present stud

Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are detected in humans worldwide. Laboratory animal studies have shown that PFAAs are associated with immunotoxic effects. However, epidemiological studies investigating the role of PFAAs, in particular PFAAs with longer chains than perfluorooctanoic acid, are scarce. We investigated associations between prenatal exposure to PFAAs, including long-chain compounds, and infant allergic diseases at 12 and 24 months in a large study population. The participants included mothers and their infants who enrolled in the Hokkaido Study on Environment and Children's Health 2003-2009. Eleven PFAAs were measured in maternal plasma taken at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. Characteristics of participants and information on infant allergic diseases were obtained from self-administered questionnaires and medical records. At 24 months, the adjusted odds ratio (OR) (first vs. fourth quartiles) for eczema in association with higher maternal perfluorotridecanoic acid (PFTrDA) levels was 0.62 (95% confidence interval (CI) 0.45, 0.86). After stratification by gender, the adjusted ORs in female infants from mothers with higher maternal perfluoroundecanoic acid (PFUnDA) and PFTrDA levels were also statistically significant (PFUnDA: OR = 0.50; 95% CI, 030, 0.81; PFTrDA: OR = 0.39; 95% CI, 0.23, 0.64). Our findings suggest that lower prenatal exposure to PFTrDA may decrease the risk of developing eczema in early childhood, only in female infants. 2014 Elsevier Ltd. All rights reserved.

Prenatal di(2-ethylhexyl) phthalate (DEHP) exposure can produce reproductive toxicity in animal models. Only limited data exist from human studies on maternal DEHP exposure and its effects on infants. We aimed to examine the associations between DEHP exposure in utero and reproductive hormone levels in cord blood. Between 2002 and 2005, 514 pregnant women agreed to participate in the Hokkaido Study Sapporo Cohort. Maternal blood samples were taken from 23–35 weeks of gestation and the concentration of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), was measured. Concentrations of infant reproductive hormones including estradiol (E2), total testosterone (T), and progesterone (P4), inhibin B, insulin-like factor 3 (INSL3), steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone were measured from cord blood. Two hundred and two samples with both MEHP and hormones' data were included in statistical analysis. The participants completed a self-administered questionnaire regarding information on maternal characteristics. Gestational age, birth weight and infant sex were obtained from birth records. In an adjusted linear regression analysis fit to all study participants, maternal MEHP levels were found to be associated with reduced levels of T/E2, P4, and inhibin B. For the stratified analyses for sex, inverse associations between maternal MEHP levels T/E2, P4, inhibin B, and INSL3 were statistically significant for males only. In addition, the MEHP quartile model showed a significant p-value trend for P4, inhibin B, and INSL3 decrease in males. Since inhibin B and INSL3 are major secretory products of Sertoli and Leydig cell, respectively, the results of this study suggest that DEHP exposure in utero may have adverse effects on both Sertoli and Leydig cell development in males, which agrees with the results obtained from animal studies. Comprehensive studies investigating phthalates' exposure in humans, as well as their

Objective: The aim of this study was to examine the effects of a depression prevention program based on stress inoculation training (SIT) for workers of two private companies, by means of a randomized controlled trial. Method: Ninety three workers of two private companies were assigned to intervention and control groups, and two sessions were conducted in the intervention group of each company at an interval of four weeks. The sessions included lectures on responses to stress and coping skills, problem-solving training, cognitive restructuring training, relaxation, group discussions and self-monitoring. After completing the sessions, two follow-up letters were sent to the participants at two-month intervals. Data from 38 intervention subjects and 39 control subjects were analyzed. Results: There were no major differences between the variables of intervention subjects and control subjects. After two sessions, there was a marginally significant increase of seeking social support in the intervention group (P = 0.052) and a significant decrease of avoidance in both groups (P < 0.05). Concerning the depression score changes, the “Improvement” group of the intervention subjects showed an adjusted OR of 6.83 that was higher compared to the control group, indicating a marginally significant difference (P = 0.083). Conclusion: The results suggest the possibility that the SIT-based program of this study was effective for improving coping and preventing depression. Further research is necessary to develop a depression prevention program adjusted to gender, individual, occupational and other differences of subjects.

Objective: This study aimed to determine the effect of a home visit program using a Functioning Improvement Tool (FIT) compared with a home visit using conversation alone. Methods: Twenty-eight participants (mean age, 78.6±7.5 years) were randomly assigned to an intervention (n = 13) or control (n = 15) group for 3 months. The intervention group received a 60-minute FIT home visit program; the control group received a 30-minute home visit using common conversational techniques. Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Geriatric Depression Scale (GDS) scores were evaluated. Results: The FAB score was significantly improved in the intervention group compared with the control group (2.5 vs -0.5, P = 0.02). Conclusions: Our FIT home visit program may help prevent dementia. Further studies with larger samples and longer follow-up periods are needed to assess the long-term effectiveness of an FIT home visit program on dementia prevention (UMIN-CTR number, UMIN000004767.)

General Trust (GT), defined as a default expectation of other people’s trustworthiness, is assumed to be a predictor for promotion of health and welfare in individuals as well as for strengthening of social capital in the community. An improvement of health and quality of life of the elderly is recently a crucial agenda. Thus, the purpose of the study was to explore which factors regarding health and life associated with GT among frail elderly people living at homes in Japanese rural area. The study selected the subjects who were designated within three mildest degrees in seven stages of long-term care levels and who met at an item and more in the national basic check-list. 209 participants were interviewed by trained health personnel using a structured questionnaire. GT was measured by a dichotomous outcome of inquiring “do you trust people in general?”. In the univariable analysis, educational status (p = 0.004), activity competence index including instrumental activity of daily living (IADL) (p = 0.020), Mini-Mental State Examination (MMSE) (p = 0.029) and Self-rating Depression Scale (SDS) (p = 0.010) were significantly related to GT. By logistic regression analysis using a stepwise method with a likelihood ratio, educational status alone was significantly associate with GT (p = 0.010, odds ratio = 1.195 [95% confidence interval; 1.043 - 1.371]). Health related factors had nothing to do with GT. Our finding suggested that the higher educated elderly might have had more opportunities to encounter the others and more indispensability to deliberately discern their trustworthiness than the lower, and consequently had higher GT through social intelligence being strengthened.