Dataset Information

Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study.

ABSTRACT:

Background

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association.

Objectives

On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of the health of the women. In 2008, we followed up the cohort. Here, we evaluated the association between TCDD exposure and bone structure and geometry in adulthood, and considered whether timing of TCDD exposure before achievement of peak bone mass (assumed to occur 2 years after onset of menarche) modified the association.

Methods

Individual TCDD concentration was measured in archived serum collected soon after the explosion. In 2008, 350 women who were <20 years old in 1976 underwent a dual-energy X-ray absorptiometry (DXA) bone scan. Bone mineral density was measured at the lumbar spine and hip, and hip geometry was extracted from hip DXA scans using the hip structural analysis method.

Results

Among premenopausal women, TCDD serum levels were associated with some indexes indicating better bone structure in women exposed before peak bone mass (n=219), with stronger associations in those exposed before 5 years of age (n=46). In contrast, among postmenopausal women, TCDD levels were associated with evidence of better bone structure in women exposed after peak bone mass (n=48) than in other women (n=18).

Conclusions

Our current results do not support the hypothesis that postnatal TCDD exposure adversely affects adult bone health. Continued follow-up of women who were youngest at exposure is warranted. Future studies should also focus on those exposed in utero.

SUBMITTER: Eskenazi B

PROVIDER: S-EPMC3888571 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study.

Eskenazi Brenda B Warner Marcella M Sirtori Marcella M Fuerst Thomas T Rauch Stephen A SA Brambilla Paolo P Mocarelli Paolo P Rubinacci Alessandro A

Environmental health perspectives 20131115 1

<h4>Background</h4>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association.<h4>Objectives</h4>On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective coh ...[more]

PMID: 24240199

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Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is neurotoxic in animals but few studies have investigated its effects on the human brain. Related dioxin-like compounds have been linked to poorer cognitive and motor function in older adults, with effects more pronounced in women, perhaps due to the loss of neuro-protective estrogen in menopause. On 10 July 1976, a chemical explosion in Seveso, Italy, resulted in one of the highest known residential exposures to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of the health of the women who were newborn to 40 years old in 1976. Here, we investigate whether TCDD exposure is associated with physical functioning and working memory more than 20 years later. Individual TCDD concentration (ppt) was measured in archived serum collected soon after the explosion. In 1996 and 2008, we measured physical functioning (n=154) and working memory (n=459), respectively. We examined associations between serum TCDD and motor and cognitive outcomes with multivariate linear regression and semi-parametric estimators. A 10-fold increase in serum TCDD was not associated with walking speed (adjusted ?=0.0006ft/s, 95% Confidence Interval (CI): -0.13, 0.13), upper body mobility (adjusted ?=-0.06, 95% CI: -0.36, 0.23), or manual dexterity (adjusted ?=0.34, 95% CI: -0.65, 1.33). We observed an inverted U-shaped association in grip strength, with poorer strength in the lowest and highest TCDD exposure levels. There was no association between TCDD and the Wechsler digit and spatial span tests. Neither menopause status at assessment nor developmental timing of exposure modified associations between TCDD and working memory. Our findings, in one of the only studies of TCDD's effects on neuropsychological and physical functioning in women, do not indicate an adverse effect on these domains, with the exception of a U-shaped relationship with grip strength. Given the limited assessment and relative youth of the women at this follow-up, future work examining additional neuropsychological outcomes is warranted.

Project description:BackgroundPrenatal 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure has been shown to alter sexual differentiation of the brain in animal models, impacting pubertal development, behavior, cortical dominance, and cognition. The effects of early life exposure to dioxin-like compounds on human neurodevelopment, however, are less clear and warrant further investigation.MethodsThe Seveso Women's Health Study (SWHS), initiated in 1996, is a well-characterized cohort of 981 Italian women who lived in proximity to an industrial accident in July 1976 that resulted in one of the highest residential TCDD exposures on record. In 2014-2016, we enrolled offspring born after the accident into the Seveso Second Generation Health Study. Children aged 7-17 years old (n = 161) completed a neuropsychological assessment spanning executive function and reverse learning (Wisconsin Card Sort), non-verbal intelligence (Raven's Progressive Matrices), attention and hyperactivity (Connor's Continuous Performance (CPT), and memory (Rey's Auditory Verbal Learning). We used multivariate regression with robust standard error estimates accounting for clustering of siblings to model the associations between these outcomes and prenatal exposure defined as TCDD measured in maternal serum collected soon after the explosion and estimated to pregnancy.ResultsThe children (82 male, 79 female) averaged 13.1 (±2.9) years of age. Adjusting for covariates, a 10-fold increase in maternal serum TCDD was not adversely associated with reverse learning/set-shifting, memory, attention/impulsivity, or non-verbal intelligence. In sex-stratified models, prenatal TCDD was associated with more non-perseverative errors in boys but not in girls (pint = 0.04). TCDD was also associated with attention deficits on the CPT but only among children with the shortest breastfeeding histories.ConclusionsWhile overall, there were no significant associations, the observed differential neurotoxic sensitivities to TCDD by sex and lactation history may warrant confirmation in future studies.

Project description:BackgroundExposure to endocrine disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during susceptible developmental windows may alter risk of metabolic disease later in life. Animal studies of in utero and lactational TCDD exposure report associations with alterations in insulin sensitivity and energy homeostasis, but epidemiologic evidence is limited. We examined the relationship of prenatal TCDD exposure with markers of glucose homeostasis in the Seveso Second Generation study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 explosion in Seveso, Italy.MethodsWe included 426 children who were 18?years or older with complete follow-up data including a fasting blood draw. Insulin and glucose were measured and the updated homoeostatic model assessment was used to estimate insulin resistance (HOMA2-IR) and beta-cell function (HOMA2-B). Prenatal TCDD exposure was defined in two ways, as initial maternal serum TCDD concentration and TCDD estimated at pregnancy.ResultsThe children (222 female, 204 male) averaged 28.6 (±6.0) years. We found a 10-fold increase in TCDD estimated at pregnancy was inversely associated with insulin (adj-??=?-1.24 ?IU/mL, 95% confidence interval (CI): -2.38, -0.09) and HOMA2-B (adj-??=?-10.2% decrease, 95% CI: -17.8, -1.9) among daughters, but not sons (insulin: adj-??=?0.57 ?IU/mL, 95% CI: -0.84, 1.98, P for interaction?=?0.04; and HOMA2-B: adj-??=?0.8% increase, 95% CI -10.7, 13.9, P for interaction?=?0.11). Similar effect modification was observed for TCDD estimated at pregnancy and HOMA2-IR (P for interaction?=?0.13). The models for initial maternal serum TCDD showed similar effect modification by child sex. The observed associations in daughters showed evidence of mediation by body mass index, which we have previously found to be associated with prenatal TCDD exposure in female offspring.ConclusionThese results suggest prenatal exposure to TCDD is associated with lower insulin resistance and beta compensation in female offspring, and show evidence of mediation by body mass index.

Project description:BackgroundIn animal studies, perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters thyroid homoeostasis and thyroid hormone concentrations; epidemiologic evidence is limited.ObjectivesWe aimed to determine the association of prenatal exposure to TCDD with thyroid hormone concentrations in the Seveso Second Generation Study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 chemical factory explosion in Seveso, Italy.MethodsWe included 570 children (288 female, 282 male) with complete follow-up data, including a fasting blood draw. Serum levels of total and free thyroxine (T4), free triiodothyronine (T3), and thyroid stimulating hormone (TSH) were measured using immunoassays. We defined prenatal TCDD exposure as: 1) maternal initial TCDD concentration measured in serum collected soon after the explosion and 2) maternal TCDD estimated at pregnancy.ResultsCompared to the lowest quartile (Q1), maternal initial serum TCDD was associated with lower free T3 (Q2: adj-β = -0.13, 95%CI -0.26, 0.00; Q3: adj-β = -0.22, 95%CI -0.35, -0.09; Q4: adj-β = -0.14, 95%CI -0.28, 0.00; p-trend = 0.02). In participants with high thyroid antibody status, inverse associations between maternal initial serum TCDD and free T3 were significantly stronger than in participants with normal antibody status (p-interaction = 0.02). We also observed a positive association between maternal initial serum TCDD and TSH concentrations in participants with high thyroid antibody status (Q2: adj-β = 11.4%, 95%CI -25.2, 66.1; Q3: adj-β = 49.0%, 95%CI 3.0, 115.5; Q4: adj-β = 105.5, 95%CI 36.6, 209.2; p-trend < 0.01) but not in those participants with normal antibody status (p-interaction < 0.01). Similar results were found for TCDD estimated at pregnancy.DiscussionOur results suggest prenatal exposure to TCDD, a potent endocrine-disrupting compound, may alter thyroid function later in life. Populations with additional thyroid stress may be particularly susceptible to in utero exposure of thyroid disrupting chemicals.

Project description:Background/objectivesIn utero exposure to endocrine-disrupting compounds such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) may alter risk of obesity and related metabolic disease later in life. We examined the relationship of prenatal exposure to TCDD with obesity and metabolic syndrome (MetS) in children born to a unique cohort of TCDD-exposed women resulting from a 1976 explosion in Seveso, Italy.Subjects/methodsIn 2014, nearly 40 years after the explosion, we enrolled 611 post-explosion offspring, 2 to 39 years of age, in the Seveso Second Generation Study. In utero TCDD exposure was defined primarily as TCDD concentration measured in maternal serum collected soon after the explosion and alternately as TCDD estimated at pregnancy. We measured height, weight, waist circumference, body fat, blood pressure, and fasting blood levels of lipids and glucose, which were combined to assess body mass index (BMI) and MetS.ResultsChildren (314 female, 297 male) averaged 23.6 (±6.0) years of age. Among the 431 children ≥18 years, a 10-fold increase in initial maternal TCDD concentration was inversely associated with BMI in daughters (adj-β = -0.99 kg/m2; 95% CI -1.86, -0.12), but not sons (adj-β = 0.41 kg/m2; 95% CI -0.35, 1.18) (p-int = 0.02). A similar relationship was found in the younger children (2-17 years); a 10-fold increase in initial maternal TCDD was inversely associated with BMI z-score (adj-β = -0.59 kg/m2; 95% CI -1.12, -0.06) among daughters, but not sons (adj-β = 0.04 kg/m2; 95% CI -0.34, 0.41) (p-int = 0.03). In contrast, in sons only, initial maternal TCDD was associated with increased risk for MetS (adj-RR = 2.09, 95% CI 1.09, 4.02). Results for TCDD estimated at pregnancy were comparable.ConclusionsThese results suggest prenatal TCDD exposure alters cardiometabolic endpoints in a sex-specific manner. In daughters, in utero TCDD is inversely associated with adiposity measures. In sons, in utero TCDD is associated with increased risk for MetS.

Dataset Information

Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study.

Background

Objectives

Methods

Results

Conclusions

Publications

Serum dioxin concentrations and bone density and structure in the Seveso Women's Health Study.

Similar Datasets

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