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Epidemiology and Population Health

In utero dioxin exposure and cardiometabolic risk in the Seveso Second Generation Study

International Journal of Obesity (2019) | Download Citation



In 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.


In 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.


Children (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.


These 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.

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We gratefully acknowledge our collaborators at CDC including Donald G. Patterson, Jr., Wayman Turner, and the late Larry L. Needham for their significant contributions to exposure assessment and sample analysis in the Seveso Women’s Health and Second Generation Studies, the field staff at Hospital of Desio including Nicole Gelpi and Claudia Siracusa for coordinating data collection, and the participants and their families. This study was supported by Grant Numbers F06 TW02075-01 from the National Institutes of Health, R01 ES07171 and 2P30-ESO01896-17 from the National Institute of Environmental Health Sciences, R82471 from the U.S. Environmental Protection Agency, and #2896 from Regione Lombardia and Fondazione Lombardia Ambiente, Milan, Italy. Ms. JA was supported by F31ES026488 from the National Institutes of Health.

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  1. Center for Environmental Research and Children’s Health (CERCH), School of Public Health, University of California at Berkeley, Berkeley, CA, USA

    • Marcella Warner
    • , Stephen Rauch
    • , Jennifer Ames
    •  & Brenda Eskenazi
  2. Department of Laboratory Medicine, School of Medicine, Hospital of Desio, University of Milano-Bicocca, Desio-Milano, Italy

    • Paolo Mocarelli
    • , Paolo Brambilla
    •  & Stefano Signorini


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Correspondence to Marcella Warner.

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