Prenatal exposure to TCDD and atopic conditions in the Seveso second generation: a prospective cohort study.

Background2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant that can bioaccumulate in humans, cross the placenta, and cause immunological effects in children, including altering their risk of developing allergies. On July 10, 1976, a chemical explosion in Seveso, Italy, exposed nearby residents to a high amount of TCDD. In 1996, the Seveso Women's Health Study (SWHS) was established to study the effects of TCDD on women's health. Using data from the Seveso Second Generation Health Study, we aim to examine the effect of prenatal exposure to TCDD on the risk of atopic conditions in SWHS children born after the explosion.MethodsIndividual-level TCDD was measured in maternal serum collected soon after the accident. In 2014, we initiated the Seveso Second Generation Health Study to follow-up the children of the SWHS cohort who were born after the explosion or who were exposed in utero to TCDD. We enrolled 677 children, and cases of atopic conditions, including eczema, asthma, and hay fever, were identified by self-report during personal interviews with the mothers and children. Log-binomial and Poisson regressions were used to determine the association between prenatal TCDD and atopic conditions.ResultsA 10-fold increase in 1976 maternal serum TCDD (log10TCDD) was not significantly associated with asthma (adjusted relative risk (RR) = 0.93; 95% CI: 0.61, 1.40) or hay fever (adjusted RR = 0.99; 95% CI: 0.76, 1.27), but was significantly inversely associated with eczema (adjusted RR = 0.63; 95% CI: 0.40, 0.99). Maternal TCDD estimated at pregnancy was not significantly associated with eczema, asthma, or hay fever. There was no strong evidence of effect modification by child sex.ConclusionsOur results suggest that maternal serum TCDD near the time of explosion is associated with lower risk of eczema, which supports other evidence pointing to the dysregulated immune effects of TCDD

In utero DDT and DDE exposure and obesity status of 7-year-old Mexican-American children in the CHAMACOS cohort.

BackgroundIn utero exposure to endocrine disrupting compounds including dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE) has been hypothesized to increase risk of obesity later in life.ObjectivesThe Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study is a longitudinal birth cohort of low-income Latinas living in a California agricultural community. We examined the relation of in utero DDT and DDE exposure to child obesity at 7 years of age. We also examined the trend with age (2, 3.5, 5, and 7 years) in the exposure-obesity relation.MethodsWe included 270 children with o,p´-DDT, p,p´-DDT, and p,p´-DDE concentrations measured in maternal serum during pregnancy (nanograms per gram lipid) and complete 7-year follow-up data including weight (kilograms) and height (centimeters). Body mass index (BMI; kilograms per meter squared) was calculated and obesity was defined as ≥ 95th percentile on the sex-specific BMI-for-age Centers for Disease Control and Prevention 2000 growth charts.ResultsAt 7 years, 96 (35.6%) children were obese. A 10-fold increase in o,p´-DDT, p,p´-DDT, or p,p´-DDE, was nonsignificantly associated with increased odds (OR) of obesity [o,p´-DDT adjusted (adj-) OR = 1.17, 95% CI: 0.75, 1.82; p,p´-DDT adj-OR = 1.19, 95% CI: 0.81, 1.74; p,p´-DDE adj-OR = 1.22, 95% CI: 0.72, 2.06]. With increasing age at follow-up, we observed a significant trend toward a positive association between DDT and DDE exposure and odds of obesity.ConclusionWe did not find a significant positive relation between in utero DDT and DDE exposure and obesity status of 7-year-old children. However, given the observed trend with age, continued follow-up will be informative

Dioxin Exposure and Cancer Risk in the Seveso Women’s Health Study

Background: 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD), a widespread environmental contaminant, disrupts multiple endocrine pathways. The International Agency for Research on Cancer classified TCDD as a known human carcinogen, based on predominantly male occupational studies of increased mortality from all cancers combined

Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis

Serum Dioxin Concentrations and Age at Menopause

2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), a halogenated compound that binds the aryl hydrocarbon receptor, is a by-product of numerous industrial processes including waste incineration. Studies in rats and monkeys suggest that TCDD may affect ovarian function. We examined the relationship of TCDD and age at menopause in a population of women residing near Seveso, Italy, in 1976, at the time of a chemical plant explosion. We included 616 of the women who participated 20 years later in the Seveso Women’s Health Study. All women were premenopausal at the time of the explosion, had TCDD levels measured in serum collected soon after the explosion, and were ≥ 35 years of age at interview. Using proportional hazards modeling, we found a 6% nonsignificant increase in risk of early menopause with a 10-fold increase in serum TCDD. When TCDD levels were categorized, compared with women in the lowest quintile (< 20.4 ppt), women in quintile 2 (20.4–34.2 ppt) had a hazard ratio (HR) of 1.1 (p = 0.77), quintile 3 (34.3–54.1 ppt) had an HR of 1.4 (p = 0.14), quintile 4 (54.2–118 ppt) had an HR of 1.6 (p = 0.10), and quintile 5 (> 118 ppt) had an HR of 1.1 (p = 0.82) for risk of earlier menopause. The trend toward earlier menopause across the first four quintiles is statistically significant (p = 0.04). These results suggest a nonmonotonic dose-related association with increasing risk of earlier menopause up to about 100 ppt TCDD, but not above

Serum Dioxin Concentrations and Age at Menarche

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is associated with delays in pubertal development in animal studies. On 10 July 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD exposure experienced by a human population. Twenty years later, we initiated the Seveso Women’s Health Study (SWHS), a retrospective cohort study of female residents of the most contaminated areas, to determine whether the women were at higher risk for reproductive disease. We examined the association of TCDD serum levels, based on measurements in serum collected soon after the explosion, with reported age at menarche among the 282 SWHS women who were premenarcheal at the time of the explosion. We found no change in risk of onset of menarche with a 10-fold increase in TCDD (e.g., 10–100 ppt; hazard ratio = 0.95; 95% confidence interval, 0.83–1.09; p-value for trend = 0.46). When TCDD levels were categorized, there was also no evidence of a dose–response trend (p = 0.65). In summary, we found that individual serum TCDD measurements are not significantly related to age at menarche among women in the SWHS cohort. The women in this study experienced substantial TCDD exposure during the postnatal but prepubertal developmental period. Given that animal evidence suggests in utero exposure has the most significant effect on onset of puberty, continued follow-up of the offspring of the SWHS cohort is important

Serum Dioxin Concentrations and Quality of Ovarian Function in Women of Seveso

BACKGROUND: Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been associated with alterations in ovarian function and hormones in animals, it has not been studied in humans. On 10 July 1976, an explosion exposed residents of Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later, we initiated the Seveso Women’s Health Study to study reproductive health. OBJECTIVE: We related TCDD levels measured in sera collected near the time of explosion and ovarian function (ovarian cysts, ovarian follicles, ovulation rate, serum hormones) at follow-up. METHODS: We included 363 women who were 20–40 years of age and nonusers of oral contraceptives. We examined the relationship of 1976 serum TCDD levels with ultrasound-detected ovarian follicles among 96 women in the menstrual follicular phase and serum hormone levels (estradiol, progesterone) among 129 women in the menstrual luteal phase at follow-up. Ovulation was defined by serum progesterone levels > 3 ng/mL. RESULTS: The median serum TCDD level was 77.3 ppt, lipid-adjusted. Serum TCDD was not associated with number or size of ovarian follicles. Of women in the luteal phase, 87 (67%) ovulated. Serum log(10)TCDD was not associated with odds of ovulation [adjusted odds ratio = 0.99; 95% confidence interval (CI), 0.5 to 1.9]. Among those who had ovulated, serum log(10)TCDD was not associated with serum progesterone [adjusted beta (adj-β ) = −0.70; 95% CI, −2.4 to 1.0] or estradiol (adj-β = −1.81; 95% CI, −10.4 to 6.8). CONCLUSIONS: We found no clear evidence that 1976 TCDD exposure was associated with ovarian function 20 years later in women exposed to relatively high levels in Seveso, Italy