Impacts of dioxin exposure on brain connectivity estimated by DTI analysis of MRI images in men residing in contaminated areas of Vietnam.

Introduction: Effects of dioxin exposure on gray matter volume have been reported in previous studies, but a few studies reported effects of dioxin exposure on white matter structure. Therefore, this study was undertaken to investigate the impact of dioxin exposure on white matter microstructure in men living in the most severely dioxin-contaminated areas in Vietnam. Methods: In 2019 brain MRI scans from 28 men living near Bien Hoa airbase were obtained at Dong Nai General Hospital, Vietnam, on a 3 T scanner using a conventional diffusion tensor imaging sequence. Two exposure markers were indicated by perinatal exposure estimated by assessment of maternal residency in a dioxin-contaminated area during pregnancy and by measurement of blood dioxin levels. A general linear model was used to compare fractional anisotropy (FA) values in 11 white matter tracts in both hemispheres between groups with and without perinatal dioxin exposure and groups with high and low blood dioxin levels after adjusting for covariates. Results: The adjusted mean FA value in the left cingulum hippocampal part (CGH) was significantly lower in the perinatal dioxin exposure group compared with the group without perinatal dioxin exposure. The high blood TCDD group showed significantly reduced FA values in the left and right CGH and right uncinate fasciculus (UNC). Moreover, the high blood TEQ-PCDDs group showed significantly lower FA values in the left and right CGH and the left UNC. There were no significant differences in FA values between the groups with high and low TEQ-PCDFs levels or between the groups with high and low TEQ-PCDD/Fs levels. Discussion: It was concluded that dioxin exposure during the perinatal period and adulthood may alter the microstructure of white matter tracts in individuals with neurodevelopmental disorders.

Altered Sex Ratio at Birth with Maternal Exposure to Dioxins in Vietnamese Infants.

Excess female births (lower sex ratio at birth) associated with paternal exposure to 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) have been reported in Italy. However, no significant effects of maternal TCDD exposure on the sex ratio were reported. We investigated the effects of maternal TCDD exposure and the toxic equivalent quantity of polychlorinated dibenzo-p-dioxins/dibenzofurans (TEQ-PCDD/Fs) on the sex ratio at birth in 576 Vietnamese infants from three birth cohorts. TCDD and TEQ-PCDD/Fs in breast milk were stratified (low, mild, moderate, and high) as maternal exposure markers. Logistic regression analysis was used to investigate associations between female birth and dioxin exposure groups after adjusting for confounders. In sprayed and unsprayed areas, adjusted odds ratios (ORs) of female birth (reference: low-TCDD group) were 2.11 in the moderate-TCDD group and 2.77 in the high-TCDD group, which were significantly associated with increased TCDD exposure. In sprayed areas, a significantly increased OR in the high-TCDD group was observed. No significant associations, however, were found between having a girl and TEQ-PCDD/F levels. These results suggest that maternal TCDD exposure may alter the sex ratio at birth among Vietnamese residents of areas with high dioxin contamination.

The Effects of Neighborhood Trust and Support on Parenting Stress of Mothers With Young Children in Japan.

INTRODUCTION: While childrearing can enhance mothers' psychological well-being, parenting can also increase mental stress for mothers with young children, which is considered a risk factor for child maltreatment. A lack of social capital reportedly influences mothers' parenting, but few studies have investigated the effects of social capital on the perception of mental stress and well-being associated with childrearing among mothers with young children. Therefore, we investigated the effects of lower perceived neighborhood trust and support on higher mental stress and/or lower well-being associated with childrearing among Japanese mothers with children aged 2 to 3 years. METHODS: A total of 570 mothers with children (aged 2-3 years) in nursery school were invited to join the survey. The childrearing perspective scale for mothers (CPS-M97) was used to evaluate mothers' perceptions of mental stress and well-being associated with childrearing. Odds ratios (ORs) reflecting lower satisfaction/fulfillment scores (ie, well-being) and/or higher burdened/anxious scores (ie, mental stress) associated with perceived social capital levels were analyzed, after adjusting for confounding factors. RESULTS: The OR for lower satisfaction/fulfillment scores was significantly higher (OR = 1.77) for mothers with lower neighborhood trust. Significantly increased ORs for higher burdened/anxious scores were found in mothers with lower neighborhood trust (OR = 1.50) and support (OR = 1.49). The ORs for poor mental status, with lower satisfaction/fulfillment scores and higher burdened/anxious scores, were significantly increased in mothers with lower neighborhood trust (OR = 1.96) and lower neighborhood support (OR = 2.10). CONCLUSIONS: Higher social capital was associated with higher psychological well-being and/or lower mental stress in Japanese childrearing mothers. These results suggest that enhancing social capital is necessary to facilitate successful parenting that contributes to the prevention of child maltreatment.

Impacts of perinatal dioxin exposure on gaze behavior in 2-year-old children in the largest dioxin-contaminated area in Vietnam.

Fifty-five children aged 2 years from a birth cohort in the largest dioxin-contaminated area in Bien Hoa city, Vietnam participated in this survey to examine gaze behavior. Exposure levels were indicated by 2,3,7,8-tetrachlorodibenzo-p-dibenzodioxin (TCDD) and toxic equivalent of polychlorinated dibenzo-p-dioxin and polychlorinated dibenzofuran (TEQ-PCDD/Fs) levels in maternal breast milk. The percentage of the total fixation duration on the face (% Face), mouth (% Mouth), and eye areas (% Eyes) when viewing silent and conversation scenes was used as gaze behavior indices. When they reached 3-year-old, autistic behavior was assessed using the Autism Spectrum Rating Scale (ASRS). A general linear model adjusted for confounding factors was used to compare gaze indices and ASRS scores between high and low dioxin exposure groups. Effects of perinatal dioxin exposure on gaze behavior were found only when viewing conversation scenes indicated by lower % Face for boys in high TCDD exposure group and lower % Eyes for girls in high TEQ-PCDD/Fs group. Increased autistic traits showed by higher ASRS scores at 3-year-old were found in both gender in the high TCDD exposure group. These findings indicate that perinatal TCDD and TEQ-PCDD/Fs exposure may reduce gaze behavior in 2-year-old children, predicting increased autistic traits at 3-year-old.

Impact of dioxin exposure on brain morphometry and social anxiety in men living in the most dioxin-contaminated area in Vietnam.

BACKGROUND: Previously, we reported that the global brain volume was significantly higher in men with estimated perinatal dioxin exposure in Vietnam. In this study, we aimed to clarify which brain lobes, consisting of several gyri, contributed to the increased global brain volume. We then analyzed associations between changes in brain volume and social anxiety symptoms to investigate the role of structural changes of the brain on social anxiety following perinatal dioxin exposure. METHODS: Thirty-three men living near the dioxin-contaminated Bien Hoa airbase, underwent MRI examination. The regional gray matter volumes were extracted using the SPM12 in a MATLAB environment, and compared between subgroups with and without perinatal dioxin exposure estimated from their maternal residency in Bien Hoa during pregnancy. The social anxiety questionnaire for adults (SAQ-A30) was used to assess social anxiety. RESULTS: In both hemispheres, higher gray matter volume in the frontal and temporal lobes, particularly in the superior frontal gyrus, superior temporal gyrus, and temporal pole were found in men with perinatal dioxin exposure. Superior temporal gyrus volume was significantly higher in men with perinatal exposure also after adjusting for reduction of its volume associated with increasing 1,2,3,7,8-PentaCDD levels in blood. Increased volume of these gyri, which showed higher volume in men with perinatal exposure, was associated with increased SAQ-A30 scores. CONCLUSION: Perinatal dioxin exposure may increase the brain volume of gyri involved in social behavior, which was associated with increased social anxiety symptoms, suggesting functional effects accompanied the morphological effects of dioxin exposure.

Effect of renal tubular damage on non-cancer mortality in the general Japanese population living in cadmium non-polluted areas.

This study aimed to clarify the cause-effect relationship between renal tubular damage and non-cancer mortality in the general Japanese population. We conducted a 19-year cohort study including 1110 men and 1,03 women who lived in three cadmium-non-polluted areas in 1993 or 1994. Mortality risk ratios based on urinary ß2-microglobulin (ß2MG) and N-acetyl-ß-glucosaminidase (NAG) concentrations were estimated for specific non-cancer diseases using the Fine and Gray competing risks regression model. In men, continuous urinary NAG (+1 µg/g cre) concentrations were significantly correlated with increased mortality caused by diseases of the respiratory system (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15). Urinary ß2MG (+100 µg/g cre) concentrations were significantly correlated with increased mortalities caused by kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.03), renal diseases (HR: 1.01, 95% CI: 1.00-1.03), renal failure (HR: 1.02, 95% CI: 1.00-1.03), and external causes of mortality (HR: 1.01, 95% CI: 1.00-1.02). In women, urinary NAG (+1 µg/g cre) concentrations were significantly associated with increased mortality caused by ischemic heart diseases (HR: 1.02, 95% CI: 1.00-1.04) and kidney and urinary tract diseases (HR: 1.01, 95% CI: 1.00-1.04). Urinary ß2MG (+100 µg/g cre) concentrations were significantly correlated with increased mortality caused by cardiovascular diseases (HR: 1.01, 95%CI: 1.00-1.02), ischemic heart diseases (HR: 1.01, 95%CI: 1.00-1.02), and kidney and urinary tract diseases (HR: 1.02, 95% CI: 1.01-1.03). The present study indicates that renal tubular damage was significantly related to several non-cancer disease causes of mortality in Japan's general population living in cadmium-non-polluted areas.

Dioxin and Dioxin-like Compounds and Human Health.

In epidemiological studies, associations of dioxin and dioxin-like (dl)-compound exposure with metabolic diseases, including diabetes and metabolic syndrome, in adults and with neurodevelopmental problems and earlier/later puberty in children have been suggested in the general population and in environmentally exposed populations [...].

[Associations between Maternal Postpartum Depression and Psychosocial Factors Including Marital Relationship and Social Support].

OBJECTIVES: We aimed to investigate the psychosocial factors for postpartum depression as indicated by a high score of the Edinburgh Postnatal Depression Scale (EPDS), including marital relationship and social support. Relevant factors for antenatal depression were also analyzed. METHODS: Thirty-five wife-and-husband pairs who visited University Hospital A for the wife's antenatal health check-up participated in a questionnaire survey using the Japanese version of the EPDS. Social support from the wife's husband, kins, and others including friends at the third trimester of pregnancy and 1 month after birth was assessed. The Marital Love Scale (MLS) was also used, and two marital relationship questions were asked regarding the husband's and wife's considerate actions toward each other during pregnancy. Binary logistic regression analysis was conducted to determine adjusted associations between higher EPDS scores (≥5 for postpartum depression and ≥7 for antenatal depression) and indicators for social support and marital relationships. RESULTS: The most relevant factor for higher postpartum EPDS scores was a higher antenatal EPDS score, followed by the couple's poor communication skills (the wife did not feel any appreciation from her husband) during pregnancy and no support from the wife's husband during the postpartum period. The wife's poor marital communication skills and the husband's low MLS scores during pregnancy were associated (borderline significance) with the wife's higher antenatal EPDS scores. CONCLUSIONS: A good marital relationship before birth and support by the husband after birth may be important for preventing postpartum depression.

Foods and Nutrients at Risk for Insufficient Intake by Community-Dwelling Healthy Older Women Eating Alone and Together in Japan-A Preliminary Finding.

Eating alone and poor dental status have been reported to influence dietary intake in older adults. First, we compared nutrient and food intake and dental markers between women eating alone and together, who participated in a home health management program conducted by Kanazawa Medical University. The results showed the significantly higher intake of fresh fruit and some micro-nutrients and a lower decayed, missing, and filled teeth (DMFT) index (better dental status) in women eating alone after adjusting for age, suggesting that dental status may mediate the association between commensality and dietary intake. Then, we investigated nutrients and foods at risk for insufficient intake and associated with increasing dental markers. The risks for the insufficient intake of protein and n-3 and n-6 polyunsaturated fatty acids (PUFAs) were significantly increased with an increasing DMFT index. The risk for n-3 PUFA intake also increased with increasing numbers of missing teeth in women. Foods at risk for insufficient consumption included beans for women with an increasing DMFT index and green and yellow vegetables, fresh fruits, and meat and fish for women with increasing numbers of missing teeth. These findings suggest that good health management, including the treatment of decayed teeth, is important for the prevention of malnutrition in community-dwelling healthy older women.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans in blood samples from historically herbicide-sprayed areas and rural and industrialized unsprayed areas in Vietnam.

We investigated dioxin concentrations in the blood of residents living in areas with different sources of dioxin pollution in Vietnam. A total of 823 individual blood samples were collected in 2014-2015 from residents of 16 provinces in Vietnam who were born between 1972 and 1976, and who lived in rural unsprayed areas (the control area), industrialized unsprayed areas (the industrialized area), and areas in which herbicides were sprayed during the Vietnam War (the sprayed area). After blood collection, pooled samples were obtained by combining 10-25 individual samples by age and sex for each area. A total of 6, 10, and 26 pooled blood samples were obtained for the control area, industrialized area, and sprayed area, respectively. The concentrations of 17 polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans were quantified in each pooled blood sample. The concentrations of TCDD, 1,2,3,7,8,9-HxCDD, 1,2,3,7,8-PeCDF, and OCDF were significantly higher in the sprayed area than in the unsprayed area, which comprised the control and industrialized areas. The toxic equivalents of PCDDs, TCDD, 1,2,3,7,8-PeCDF, and 1,2,3,6,7,8-HxCDF were significantly higher in the sprayed area than in the control area. No significant difference in dioxin concentration was found between the sprayed and industrialized areas after adjusting for sex. The 1,2,3,6,7,8-HxCDF concentration was significantly higher in the industrialized area than in the control area. The findings indicate that there are different dioxin congener blood profiles in residents of industrialized areas and areas in which herbicides were historically sprayed during the Vietnam War.

Neurodevelopmental Effects of Perinatal TCDD Exposure Differ from Those of Other PCDD/Fs in Vietnamese Children Living near the Former US Air Base in Da Nang, Vietnam.

This study reports that children exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD), the major toxin in Agent Orange, from the breast milk of mothers residing near the former Da Nang US air base in Vietnam may have specific alterations in higher brain functions, resulting in social and communication deficits, including autism spectrum disorder (ASD). After the age of 8 years, girls with high TCDD showed increased attention deficit hyperactivity disorder (ADHD)-like behaviors and altered mirror neuron activity, which is often observed in children with ASD. However, no significant relationship between autistic traits and toxic equivalency values of polychlorinated dibenzodioxins and polychlorinated dibenzofurans (TEQ-PCDD/Fs) was found in these children. Notably, boys with high levels of TEQ-PCDD/Fs showed poor language and motor development in the first 3 years of life, although boys with high TCDD levels did not. However, at 8 years of age, boys with high TCDD showed reading learning difficulties, a neurodevelopmental disorder. These findings suggest that perinatal TCDD exposure impacts social-emotional cognitive functions, leading to sex-specific neurodevelopmental disorders-learning difficulty in boys and ADHD in girls. Future studies with a greater number of children exposed to high levels of TCDD are necessary to estimate the threshold values for neurodevelopmental effects.

Dioxin Congener Patterns in Breast Milk Samples from Areas Sprayed with Herbicide during the Vietnam War 40 Years after the War Ended.

Large amounts of herbicides containing polychlorinated dibenzo-p-dioxins and dibenzo-furans (PCDD/Fs) were sprayed in South Vietnam during the Vietnam War. Levels of PCDD/Fs in the environment of South Vietnam remained high even 40 years later. A total of 861 breast milk samples (597 from three areas sprayed with herbicides, Quang Tri, Da Nang, and Bien Hoa, and 264 from three unsprayed areas in North Vietnam) were collected between 2007 and 2015 and the PCDD/F concentrations in the samples were determined. Levels of TEQ-PCDD/Fs and 17 PCDD/F congeners were higher in the sprayed area samples than the unsprayed area samples. We found particular PCDD/F congener patterns for different areas. High tetrachlorodibenzo-p-dioxin (TCDD) concentrations were found in Bien Hoa, high TCDD and 1,2,3,6,7,8-hexadibenzo-p-dioxin concentrations were found in Da Nang, and high 1,2,3,4,6,7,8-heptadibenzo-p-dioxin concentrations were found in Quan Tri. High 1,2,3,4,7,8-hexadibenzofuran and 1,2,3,4,6,7,8-heptadibenzofuran concentrations were also found in Da Nang and Quang Tri. However, breast feeding may have caused associations between the TCDD and polychlorinated dibenzofuran congener concentrations. Advanced statistical analysis will need to be performed in future to assess the characteristic PCDD/F congener profiles in breast milk samples from areas of Vietnam previously sprayed with herbicides.

Perinatal Dioxin Exposure and Attention Deficit Hyperactivity Disorder (ADHD) Symptoms in Children Living in a Dioxin Contamination Hotspot in Vietnam.

We examined children in Da Nang, a dioxin contamination hotspot in Vietnam, twice at 5 and 8 years of age, and investigated sex- and age-dependent differences in the effects of dioxin exposure on attention deficit hyperactivity disorder (ADHD) symptoms. We also studied autistic traits in children with ADHD symptoms. A total of 163 children participated in follow-up surveys at 5 and 8 years of age and were included in the present analysis. ADHD symptoms were assessed using an ADHD rating scale with inattention and hyperactivity-and-impulsivity (hyperactivity) subscales. Autistic behaviors were evaluated using the Autism Spectrum Rating Scale (ASRS). Perinatal dioxin exposure was indicated by dioxin levels in maternal breast milk. In boys, hyperactivity scores were significantly higher in the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) group only at 5 years of age. In girls, hyperactivity scores at 8 years of age were significantly higher in the high TCDD group, which was significantly associated with those at 5 years of age. In girls, ASRS unusual behavior scores were significantly higher with higher TCDD exposure and hyperactivity scores at 8 years of age. These results suggest that high perinatal TCDD exposure may increase ADHD likelihood and autistic traits, particularly in girls of 7-8 years of age.

Effect of Perinatal Dioxin Exposure Originating from Agent Orange on Gaze Behavior in 3-Year-Old Children Living in the Most Dioxin-Contaminated Areas in Vietnam.

We investigated the effect of perinatal dioxin exposure indicated by dioxins in breast milk on children's gaze behavior. We studied 142 children aged 3 years from the 2012 Bien Hoa birth cohort in a hotspot of dioxin contamination in Vietnam. Children's faces were viewed using the eye-tracking method. Associations between gaze behavior of faces and neurodevelopmental indices and head circumference were analyzed to determine whether poor gaze behavior indicates increased autistic traits in these children. The gaze fixation duration on facial areas when viewing 10 still images of children was calculated as the gaze behavior index. Autistic behavior was assessed using the Autism Spectrum Rating Scale, and language development was evaluated by the Bayley Scales of Infant and Toddler Development, Ver. 3. The face fixation duration (%) significantly decreased as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations increased in a dose−effect manner in girls, which suggested atypical gaze behavior for watching human faces. Furthermore, these girls with atypical gaze behavior showed lower social communication scores and smaller head sizes, suggesting increased autistic traits in girls. In conclusion, our findings show sex-specific effects (girls > boys) of perinatal TCDD exposure on gaze behavior in young children.

Adverse effects of dioxins on cognitive ability and motor performance of 5-year-old children residing in a hotspot of dioxin contamination originating from Agent Orange in Vietnam: A prospective cohort study.

Bien Hoa airbase is the most dioxin-polluted hotspot in Vietnam. In 2012, a birth cohort living around Bien Hoa airbase was recruited for assessment of physical and neurological development. In the present study, neurodevelopment scores at 5 years of age were assessed by the Kaufman Assessment Battery for Children, Second Edition and the Movement Assessment Battery for Children, Second Edition for 185 children in Bien Hoa and 104 children in Ha Dong (unexposed control group) to clarify the effects of dioxin. 2,3,7,8-tetrachlorodibenzo-p-dioxin concentrations in breast milk of women in Bien Hoa were approximately three times higher than those of women in Ha Dong (2.33 vs. 0.69 pg/g fat, p < 0.001). In general, neurodevelopment scores were lower in Bien Hoa children than in Ha Dong children. In boys, scores differed for number recall (12.6 vs. 14.0, p = 0.036), triangles (10.7 vs. 12.4, p = 0.005), manual dexterity (8.3 vs. 9.7, p = 0.037), balance (7.4 vs. 10.3, p < 0.001), and total movement scores (8.0 vs. 10.1, p = 0.003). After adjusting for covariates, linear regression analysis indicated that the scores of the triangles, balance, and total movement tests were inversely associated with levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin and of toxic equivalency of polychlorinated dibenzodioxins and polychlorinated dibenzofurans. In girls, scores differed for the triangles test (11.0 vs. 12.6, p = 0.005), hand movement test (9.6 vs. 11.3, p = 0.003), and balance test (9.1 vs. 10.7, p = 0.050); toxic equivalency of polychlorinated dibenzofurans was inversely associated with hand movement and balance scores. Overall, perinatal dioxin exposure appears to have a long-term impact on neurodevelopment.

Renal tubular dysfunction and cancer mortality in the Japanese general population living in cadmium-non-contaminated areas.

The relationship between cadmium exposure, exposure-related renal tubular dysfunction, and mortality have been reported, mainly in the residents of Cd-contaminated areas in Japan. The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and cancer mortality in the general population in non-contaminated areas. A 19-year cohort study was conducted in 1110 men and 1703 women in 1993 or 1994, who lived in three cadmium-non-contaminated areas. Mortality risk ratios of urinary ß2-microglobulin (ß2MG) and N-acetyl-ß-glucosaminidase (NAG) for all malignant neoplasms and specific cancers were estimated using the Fine and Gray competing risks regression model. Significant hazard ratios (HRs) for liver and pancreas cancer were observed for NAG (liver: HR corresponding to an increase of 1 IU/g cr, 1.10, 95%CI, 1.02-1.19, pancreas: HR, 1.10, 95%CI, 1.02-1.19) in men. In women, a negative HR was observed for NAG (lung cancer: HR 0.80, 95% CI, 0.67-0.96) and for ß2MG (all malignant neoplasms: HR, 0.97, 95% CI, 0.93-1.00). The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium-non-contaminated areas in Japan.

Alterations in Regional Brain Regional Volume Associated with Dioxin Exposure in Men Living in the Most Dioxin-Contaminated Area in Vietnam: Magnetic Resonance Imaging (MRI) Analysis Using Voxel-Based Morphometry (VBM).

To clarify the influence of dioxin exposure on brain morphometry, the present study investigated associations between dioxin exposure at high levels and brain structural irregularities in 32 Vietnamese men. Two exposure markers were used: blood dioxin levels, as a marker of exposure in adulthood, and perinatal dioxin exposure, estimated by maternal residency in a dioxin-contaminated area during pregnancy. All subjects underwent brain magnetic resonance imaging (MRI) scans. We analyzed correlations between regional gray matter volumes and blood dioxin levels, and compared regional volumes between men with and without perinatal dioxin exposure using the voxel-based morphometry (VBM) tool from Statistical Parametric Mapping 12 (SPM12). Blood 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was associated with low volume of the medial temporal pole and fusiform gyrus. Toxic equivalency (TEQ)-PCDDs were correlated with low medial temporal pole volume. However, 1,2,3,4,7,8-HxCDD was associated with high middle frontal gyrus and cerebellum volume. In men with perinatal dioxin exposure, the left inferior frontal gyrus pars orbitalis volume was significantly lower than in those without perinatal exposure. These results suggest that dioxin exposure during the perinatal period and in adulthood may alter regional brain volume, which might lead to cognitive deficits and unusual social emotional behavior in Vietnamese men living in dioxin-contaminated areas.

The Relationship between the Urinary Cadmium Concentration and Cause-Specific Mortality in Subjects without Severe Renal Damage: A 35-Year Follow-Up Study in a Cadmium-Polluted Area of Japan.

We evaluated the association between urinary cadmium concentration (uCd, µg/g Cr) and risk of cause-specific mortality according to urinary ß2-microglobulin (MG) concentration. Participants were 1383 male and 1700 female inhabitants of the Cd-polluted Kakehashi River basin. The uCd and ß2-MG were evaluated in a survey in 1981-1982, where those participants were followed-up over 35 years later. Among the participants with a urinary ß2-MG < 1000, the hazard ratios (HRs) (95% confidence interval) for mortality were significantly higher in those with a uCd of ≥10.0 compared with <5.0 for cardiovascular disease [HR 1.92 (1.08-3.40) for men, 1.71 (1.07-2.71) for women], pneumonia or influenza [2.10 (1.10-4.00) for men, 2.22 (1.17-4.19) for women], and digestive diseases [for men; 3.81 (1.49-9.74)]. The uCd was significantly associated with mortality from heart failure in women and digestive diseases in men, after adjustment for other causes of death using the Fine and Gray competing risk regression model. For participants with a urinary ß2-MG of ≥1000, no significant association was observed between uCd and any major cause of death. In the absence of kidney damage, Cd may increase the risk of death from cardiovascular disease, pneumonia, and digestive diseases.

Effects of perinatal dioxin exposure on mirror neuron activity in 9-year-old children living in a hot spot of dioxin contamination in Vietnam.

BACKGROUND: For 8 years, we have followed up a birth cohort comprising 241 mother-and-infant pairs living around the Da Nang airbase, a hot spot of dioxin contamination in Vietnam, and have reported the impacts of perinatal dioxin exposure on the neurodevelopment of children at various ages. In the present study, 9 years after birth, we investigated the effects of perinatal dioxin exposure on mu and theta rhythms by analyzing EEG power during the execution and observation of hand movements, which indicate mirror neuron system activity. METHODS: One hundred fifty-five 9-year-old children (86 boys and 69 girls) from the Da Nang birth cohort participated in the EEG examination with free viewing of hand movements. The dioxin levels in their mothers' breast milk, measured 1 month after birth, were used as perinatal dioxin exposure markers. A log transform of the ratio of EEG power during execution or observation of the hand movements relative to the power during observation of a bouncing ball for theta and mu rhythms was used to evaluate mirror neuron activity. RESULTS: In both brain hemispheres, the log power ratio in the theta band was significantly higher (i.e., less reduction of power) during observation of hand movements in girls exposed to high levels of TCDD. In boys, however, dioxin congeners other than TCDD, including HxCDDs and several PCDF congeners, contributed to increased log power ratios in the theta band. Particularly for PCDF congeners, the log power ratios in the lowest group among 4 exposure groups were lowest and significantly increased (i.e., decreasing reduction of power) with increasing dose. CONCLUSION: Perinatal TCDD exposure may influence the mirror neuron system of the brain, which plays an important role for social-emotional behavior in children, particularly in girls living in a hot spot of dioxin contamination in Vietnam.

Nutritional Intervention with Dried Bonito Broth for the Amelioration of Aggressive Behaviors in Children with Prenatal Exposure to Dioxins in Vietnam: A Pilot Study.

Dioxins have been suggested to induce inflammation in the intestine and brain and to induce neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), partly due to deficits in parvalbumin-positive neurons in the brain that are sensitive to inflammatory stress. Previously, we reported ADHD traits with increased aggressiveness in children with prenatal exposure to dioxins in Vietnam, whereas dried bonito broth (DBB) has been reported to suppress inflammation and inhibit aggressive behavior in animal and human studies. In the present study, we investigated the association between dioxin exposure and the prevalence of children with highly aggressive behaviors (Study 1), as well as the effects of DBB on the prevalence of children with highly aggressive behaviors (Study 2). METHODS: In Study 1, we investigated the effects of dioxin exposure on the prevalence of children with high aggression scores, which were assessed using the Children's Scale of Hostility and Aggression: Reactive/Proactive (C-SHARP) in dioxin-contaminated areas. The data were analyzed using a logistic regression model after adjusting for confounding factors. In Study 2, we performed nutritional intervention by administering DBB for 60 days to ameliorate the aggressiveness of children with high scores on the C-SHARP aggression scale. The effects of DBB were assessed by comparing the prevalence of children with high C-SHARP scores between the pre- and post-intervention examinations. RESULTS: In Study 1, only the prevalence of children with high covert aggression was significantly increased with an increase in dioxin exposure. In Study 2, in the full ingestion (>80% of goal ingestion volume) group, the prevalence of children with high covert aggression associated with dioxin exposure was significantly lower in the post-ingestion examination compared with in the pre-ingestion examination. However, in other ingestion (<20% and 20-79%) groups and a reference (no intervention) group, no difference in the prevalence of children with high covert aggression was found between the examinations before and after the same experimental period. CONCLUSIONS: The findings suggest that DBB ingestion may ameliorate children's aggressive behavior, which is associated with perinatal dioxin exposure.