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.

Effects of perinatal dioxin exposure on neonatal electroencephalography (EEG) activity of the quiet sleep stage in the most contaminated area from Agent Orange in Vietnam.

OBJECTIVE: To investigate the effects of perinatal dioxin exposure indicated by dioxins in breast milk on neonatal electroencephalography (EEG) power in the quiet sleep stage, and associations with neurodevelopmental outcomes at 2 years of age. STUDY DESIGN: Fifty-one mother-newborn pairs were enrolled for neonatal EEG analysis in the quiet sleep stage from a birth cohort recruited at a prefecture hospital in Bien Hoa city, Vietnam. Relative EEG power in intra-burst-intervals and high-voltage-bursts in the trace alternant pattern were computed from EEG data during the quiet sleep stage. Forty-three mother-child pairs participated in a 2-year follow-up survey to examine neurodevelopment using the Bayley-III scale and gaze behavior exhibited by fixation duration on the face of a child talking in videos. The general linear model and regression linear model were used for data analysis after adjusting for confounding factors. RESULTS: Perinatal dioxin exposure, particularly 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, influenced relative EEG power values mainly in the intra-burst-interval part of the trace alternant pattern in the quiet sleep stage. In intra-burst-intervals, decreased frontal delta power and increased frontal and parietal alpha power values in the left hemisphere and temporal beta power values in the right hemisphere were associated with increased TCDD exposure, with significant dose-response relationships. Almost none of the relative power values in these brain regions were associated with Bayley III scores, but relative delta power values were significantly associated with face fixation duration in left frontal and parietal regions at 2 years of age. CONCLUSION: Perinatal dioxin exposure influences neuronal activity in the quiet sleep stage, leading to poor communication ability indicated by gaze behavior in early childhood.

Effects of perinatal dioxin exposure on learning abilities of 8-year-old children in Vietnam.

BACKGROUND: We have followed a birth cohort from 2008 to 2009 near a dioxin-contaminated area of Da Nang, Vietnam, and investigated the effects of perinatal dioxin exposure on neurodevelopment from infancy to pre-school age. The present study aimed to investigate the effects of perinatal dioxin exposure on the learning abilities of the elementary-school children from the Da Nang birth cohort. METHODS: From 241 mother-infant pairs recruited at baseline (134 boys and 107 girls), 185 (76.8%) participated in a follow-up when the children were 8 years of age (108 boys and 77 girls). The children's perinatal dioxin exposure was estimated using the dioxin levels in their mothers' breast milk. The Colorado Learning Difficulties Questionnaire (CLDQ) was used to evaluate the children's learning difficulties. Math- and language-achievement scores were obtained using paper-based tests. Reading fluency was examined by having the children read passages in Vietnamese. RESULTS: In boys exposed to high levels of 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TetraCDD), CLDQ reading scores were significantly higher (worse), and language achievement scores were significantly lower. Boys exposed to high levels of 2,3,7,8-TetraCDD as well as high levels of the toxic equivalent (TEQ) of polychlorodibenzodioxins and polychlorodibenzofurans (PCDDs/Fs) had higher numbers of reading errors. Reading errors were higher and math achievement scores were lower with increasing concentrations of 1,2,3,4,7,8-HexaCDD and 1,2,3,4,6,7,8-HeptaCDD. In girls, no significant differences of any learning ability markers were found between high and low exposure groups to TEQ-PCDDs/Fs and these 3 congeners. CONCLUSIONS: Perinatal dioxin exposure may have adverse effects on the learning abilities of school children, especially boys.

Perinatal dioxin exposure and neurodevelopment of 2-year-old Vietnamese children in the most contaminated area from Agent Orange in Vietnam.

Bien Hoa airbase is the most contaminated area of dioxin contamination from Agent Orange in Vietnam, but little is known about the neurodevelopmental effects of perinatal dioxin exposure on children living nearby. We recruited 210 mother-newborn resident pairs in 2012 and 78 pairs in 2015 and followed them for 2 years to assess the children's neurodevelopment. As a control group, we used 120 mother-child pairs recruited in 2014 in the Ha Dong district of Ha Noi City, an unexposed area. Perinatal dioxin exposure levels were indicated by levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and toxic equivalency values of polychlorodibenzodioxins, polychlorodibenzofurans, and nonortho-polychlorinated biphenyls (TEQ-PCDD/Fs/noPCBs) in maternal breast milk. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were used to assess neurodevelopment, and scores in each domain were compared between children with different exposure levels using general linear regression models and stratification by sex. Decreased expressive and composite language scores in boys and gross motor scores in girls were found in children exposed to TCDD ≥ 5.5 (pg/g lipid) compared with children with TCDD < 1.8. However, in matched pair analysis between children with TCDD ≥ 5.5 and <1.8 (pg/g lipid), lower expressive and composite language scores in boys exposed to TCDD ≥ 5.5 were significant, but lower gross motor scores in girls did not reach statistical significance. In addition, significant association was found between levels of PCDD congeners other than TCDD and gross motor scores in boys. These findings suggest that perinatal exposure of TCDD and other PCDD congeners affects development of language and gross motor skills, respectively, in boys at 2 years of age exposed to dioxins originating from Agent Orange in Vietnam.