Urinary amino acid alterations in 3-year-old children with neurodevelopmental effects due to perinatal dioxin exposure in Vietnam: a nested case-control study for neurobiomarker discovery.

In our previous study of 3-year-old children in a dioxin contamination hot spot in Vietnam, the high total dioxin toxic equivalent (TEQ-PCDDs/Fs)-exposed group during the perinatal period displayed lower Bayley III neurodevelopmental scores, whereas the high 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-exposed group displayed increased autistic traits. In autistic children, urinary amino acid profiles have revealed metabolic alterations in the amino acids that serve as neurotransmitters in the developing brain. Therefore, our present study aimed to investigate the use of alterations in urinary amino acid excretion as biomarkers of dioxin exposure-induced neurodevelopmental deficits in highly exposed 3-year-old children in Vietnam. A nested case-control study of urinary analyses was performed for 26 children who were selected from 111 3-year-old children whose perinatal dioxin exposure levels and neurodevelopmental status were examined in follow-up surveys conducted in a dioxin contaminated hot spot. We compared urinary amino acid levels between the following 4 groups: (1) a high TEQ-PCDDs/Fs and high TCDD-exposed group; (2) a high TEQ-PCDDs/Fs but low TCDD-exposed group; (3) a low TEQ-PCDDs/Fs exposed and poorly developed group; and (4) a low TEQ-PCDDs/Fs exposed and well-developed group. Urinary levels of histidine and tryptophan were significantly decreased in the high TEQ-PCDDs/Fs and high TCDD group, as well as in the high TEQ-PCDDs/Fs but low TCDD group, compared with the low TEQ-PCDDs/Fs and well-developed group. However, the ratio of histidine to glycine was significantly lower only in the high TEQ-PCDDs/Fs and high TCDD group. Furthermore, urinary histidine levels and the ratio of histidine to glycine were significantly correlated with neurodevelopmental scores, particularly for language and fine motor skills. These results indicate that urinary histidine is specifically associated with dioxin exposure-induced neurodevelopmental deficits, suggesting that urinary histidine may be a useful marker of dioxin-induced neurodevelopmental deficits and that histaminergic neurotransmission may be an important pathological contributor to dioxin-mediated neurotoxicity.

Maternal risk factors associated with increased dioxin concentrations in breast milk in a hot spot of dioxin contamination in Vietnam.

This study looked to identify determinants of exposure to dioxin in breast milk from breast-feeding women in a hot spot of dioxin exposure in Vietnam. Breast milk was collected from 140 mothers 1 month after delivery. The risk factors investigated included length of residency, drinking of well water and the frequency of animal food consumption. Cluster analysis was performed to identify dietary patterns of fish and meat portions, fish variety and egg variety. Residency, age and parity were clearly associated with increased dioxin levels. Drinking well water and the consumption of marine crab and shrimps were related to higher levels of furans in breast milk. The consumption of quail eggs also appeared to be associated with increased levels of some dioxin isomers in this area. Some mothers who ate no or less meat than fish and mothers who consumed more freshwater fish than marine fish had lower levels of dioxins in their breast milk. However, the type of water and the eating habits of mothers contributed only partly to the increased dioxin levels in their breast milk; the length of residency was the most important risk factor associated with increased dioxin body burdens of mothers.

Dioxin exposure in breast milk and infant neurodevelopment in Vietnam.

OBJECTIVES: Dioxin levels in the breast milk of mothers residing near hot spots of dioxin contamination areas in South Vietnam remain much higher than in unsprayed areas, suggesting that fetuses and breast-fed infants may be exposed to high levels of dioxins. The present study investigated the association of infant neurodevelopment in early infancy and dioxin exposure during the perinatal period. METHODS: The study involved 216 mother-infant pairs living near the Da Nang airbase, a dioxin contaminated area in Vietnam. Mothers and infants were followed from birth until infants were 4 months old. Dioxin levels in breast milk were measured to estimate the perinatal dioxin exposure, including the infant daily dioxin intake (DDI) via breastfeeding. Infant neurodevelopmental parameters, including cognitive, language and motor domains were assessed at approximately 4 months using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). RESULTS: The level of 2,3,7,8-tetrachlorodibenzo-p-dioxin and polychlorinated dibenzo-p-dioxins/furans-toxic equivalents in breast milk and the infant DDI showed significant inverse correlations with neurodevelopmental scores. When the subjects were divided into four groups according to dioxin levels in breast milk, the moderate and high DDI groups had significantly lower cognitive, composite motor and fine motor scores, and the high polychlorinated dibenzo-p-dioxins/furans-toxic equivalents group had significantly lower fine motor score than the low exposure group. For all domains, neurodevelopmental scores were decreased with increase in the level of 2,3,7,8-tetrachlorodibenzo-p-dioxin. CONCLUSION: The present study demonstrates a considerable impact of perinatal dioxin exposure on neurodevelopment in 4-month-old infants living in contaminated areas in Vietnam.

Impact of perinatal dioxin exposure on infant growth: a cross-sectional and longitudinal studies in dioxin-contaminated areas in Vietnam.

Dioxin exposure levels remain elevated in residents living around former US Air Force bases in Vietnam, indicating potential adverse impacts on infant growth. In this study, 210 mother-infant pairs in dioxin-contaminated areas in Vietnam were recruited at the infants' birth and followed up for 4 months. Perinatal dioxin exposure levels were estimated by measurement of polychlorinated dibenzo-p-dioxins/furans toxic equivalent (PCDDs/Fs-TEQ) in breast milk. The infants' size was measured at birth and 1 and 4 months after birth, and neurodevelopment was evaluated using the Bayley Scales III at 4 months of age. Among 4 dioxin groups (<25, 25-50, 50-75, ≥75 percentile of PCDDs/Fs-TEQ), cross-sectional comparisons of body size and neurodevelopment scales and comparisons of longitudinally assessed body size were performed respectively. At birth, head circumference of girls in the ≥75 percentile group was significantly larger than those in the <25 and 50-75 percentile groups. At 4 months of age, the weight and body mass index (BMI) of boys in the ≥75 percentile group were significantly lower than those in the other groups. Increase in weight was significantly lower in the ≥75 percentile group in both sexes from birth to 1 month but only in boys at 1-4 months of age. Estimated marginal mean values in a mixed model of weight and BMI during the first 4 months of life were significantly lower in the ≥75 percentile group in boys. In girls, marginal mean values for head circumference were increased with increase in dioxin levels. Only in boys, cognitive, language, and fine motor scores in the ≥75 percentile group were significantly lower than those in the other groups. These results suggested a considerable impact of perinatal dioxin exposure on infant growth, particularly in boys exposed to dioxins at high level of PCDDs/Fs-TEQ.

Dioxin concentrations in breast milk of Vietnamese nursing mothers: a survey four decades after the herbicide spraying.

In an operation by United States Armed Forces during 1961 to 1971, large quantities of herbicides were sprayed in South Vietnam. These herbicides contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD), the most toxic congener of dioxins. Several decades after the herbicide spraying ceased, dioxin concentrations in the environment and human remained elevated in the sprayed areas. Breast milk samples from 520 nursing mothers residing in areas including the hot spots as well as the sprayed and unsprayed areas were collected to quantify the levels of dioxins. The total toxic equivalents of 2,3,7,8-substitued PCDDs/PCDFs in breast milk of mothers living in the hot spots, and the sprayed and unsprayed areas were 14.10 pg/g lipid, 10.89 pg/g lipid, and 4.09 pg/g lipid for primiparae and 11.48 pg/g lipid, 7.56 pg/g lipid, and 2.84 pg/g lipid for multiparae, respectively, with significant differences in the values among the three areas. In the hot spots, dioxin levels were highly correlated with the residency of mothers after adjustment for their age and parity.