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.

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.

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.

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.

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.

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.