Seveso Women’s Health Study

  • The Seveso Women’s Health Study (SWHS) is a historical cohort study investigating the effects of dioxin exposure on reproductive health of women exposed during a 1976 industrial accident in Seveso, Italy.

What the Seveso Women’s Health Study (SWHS) investigates:

  • The impacts of dioxin exposure on reproductive health of women who were different ages at time of exposure.
  • Study conducted in two phases of data collection.

SWHS Findings – click here

What is Dioxin?

  • 2,3,7,8-tetrachloro-para-dibenzodioxin (TCDD or dioxin) is the most toxic member of a group of halogenated hydrocarbons that are widespread environmental contaminants.
  • Dioxin is produced by various chemical and industrial processes.
  • Dioxin is a known human carcinogen, a potent endocrine disruptor, and may be most harmful to those exposed during infancy and childhood.
  • It is an extremely stable, lipophilic, and water insoluble, allowing it to persist in the environment and bioaccumulate up the food chain.

The Source of Exposure: A Reactor Explosion in 1976

On July 10, 1976, a reactor explosion in a chemical plant in Seveso, Italy deposited over 30 kg of dioxin and other chemicals over an 18 km2 area, resulting in the highest residential human exposure to dioxin that has ever been recorded. High animal mortality was observed almost immediately and over 193 cases of chloracne (an acne-like skin condition specific to dioxin exposure) were reported.  The surrounding contaminated area was divided into three exposure zones: A, B and R (most heavily contaminated/exposed to least, respectively), based on surface soil dioxin measurements.

Shortly after the accident, as part of an ongoing health assessment, serum samples were collected from the residents of these three zones. Much of the serum was used for clinical chemistry tests, and the remaining portion was stored for future studies.

Our Study: The Seveso Women’s Health Study

This study has the benefit of being a large cohort with a wide range of exposures and a biologic measure of serum dioxin levels from blood samples collected soon after the explosion.  It is the only comprehensive study to date to investigate the reproductive health of women exposed to dioxin.

  • The SWHS cohort was established in 1996, about 20 years after the explosion and used the 1976 serum samples to study the effects of dioxin on reproductive health in 981 Seveso women.
  • An additional follow-up took place from 2008-2009, about 32 years after the explosion.

Exposure Studied:

  • 2,3,7,8-tetrachlorodibenzo-p­-dioxin (dioxin)

Health Outcomes Studied:

  • 20-year follow-up:

    • Age at menarche
    • Menstrual cycle characteristics
    • Ovarian function and hormone levels
    • Infertility and time to pregnancy
    • Birth outcomes
    • Lactation
    • Uterine fibroids
    • Endometriosis
    • Age at menopause
    • Breast cancer
    • Benign breast disease
  • 30-year follow-up:
    • Thyroid function of women
    • Neonatal thyroid function
    • Breast cancer and all cancer
    • Bone mineral density
    • Diabetes, obesity, and metabolic syndrome


  • ICMESA chemical plant near Seveso, Italy
    • 25 km north of Milan
    • The population in the surrounding 18 km2 area was exposed to the chemical cloud.
    • Almost 38,000 residents were exposed to dioxin as a result of the accident, about 750 of whom resided in Zone A, the most heavily contaminated area.

Study Participants:

  • Enrollment began in March 1996 and lasted through July 1998.
  • To be eligible, women must have been 0 to 40 years old at the time of the explosion, resided in Zones A or B, and have adequate stored serum to measure dioxin levels soon after the explosion.  A total of 981 women were enrolled in the study.
  • In the 30 year follow-up conducted from 2008-2009, 833 of the original 981 women agreed to participate.
  • The 981 women enrolled in the study were all Caucasian of European descent.  The average age of the women was 20.1 years at the time of the explosion and 40.2 years at the time of the interview.  Around 30% of the women were premenarche at the explosion.  At the time of the interview, over 80% had less than a high school education, 20% were current smokers, and 30% were overweight or obese.  Additionally, 27% were nulliparous at the time of the interview, and 28% had gone through menopause.

Data Collection (1998-1998):

  • The data collection for the 20-year follow up was conducted between 1996 and 1998.  Information was gathered from participants during a structured personal interview at Desio Hospital in Milan, Italy given by a trained nurse who was blinded to the participants’ serum dioxin levels and zone of residence.  The interview collected data on sociodemographic characteristics, work, and reproductive and medical history.  Additionally, data was collected through medical record abstraction and an additional blood draw for all women, and a pelvic exam, transvaginal ultrasound, and completion of a three-month daily menstruation diary for premenopausal women only.  The examinations and ultrasounds were performed at Mangigalli Hospital in Milan by physician investigators of the SWHS.  The stored serum samples collected from Seveso residents soon after the explosion were analyzed for dioxin levels using high-resolution mass spectrometry methods at the U.S. Centers for Disease Control and Prevention.
  • Of the 1,221 women invited to enroll, 981 (80%) completed the interview and blood draw. Of the 770 women still menstruating, 665 (86%) underwent the examination/ultrasound and 612 (79%) completed the daily diary.

Data Collection (2008-2009):

  • The data collection for the 30-year follow up was conducted from 2008 through 2009.  Women from the original SWHS cohort who were able to be reached and who agreed to participate underwent an additional interview that collected updated information on sociodemographics and reproductive and medical histories.  Participants also underwent another blood draw, a brief medical examination, and a bone density examination.  Additional data were abstracted from medical records and the Neonatal Thyroid Hormone Screen Registry in Milan.
  • Of the 981 original participants, 833 (85%) were able to be reached and agreed to participate in the follow-up study.  Eight-hundred and six (97%) completed the blood draw.  Among those women who were eligible for the bone density examination (less than 20 years old in 1976), 350 (82%) completed the procedure.  Data on neonatal thyroid levels were received for 319 pregnancies to 213 women.

Research Teams:

  • Marcy Warner, PhD
  • Brenda Eskenazi, PhD
  • Amelia Wesselink, MPH
  • Stephen Rauch, MPH, University of Cincinnati, School of Public Health
  • Paolo Mocarelli, MD, Hospital of Desio, University of Milano-Bicocca, School of Medicine
  • Paolo Brambilla, MD, Hospital of Desio, University of Milano-Bicocca, School of Medicine
  • Larry Needham, PhD, Centers for Disease Control and Prevention
  • Donald Patterson, PhD, Centers for Disease Control and Prevention
  • Steven Samuels, PhD, State University of New York
  • Paolo Vercellini, MD, Mangiagalli Hospital, University of Milano
  • Thomas Fuerst, PhD, Synarc Inc.
  • Alessandro Rubinacci, MD, Bone Metabolic Unit, San Raffaele Scientific Institute
  • Marcella Sirtori  MD, Bone Metabolic Unit, San Raffaele Scientific Institute
  • Stefano Signorini, MD, Hospital of Desio
  • David Olive, MD, University of Wisconsin School of Medicine and Public Health


Funded By: Duration: Study Contact:
  • The National Institute for Environmental  Health Sciences (NIEHS),
  • National Institutes of Health (NIH),
  • Endometriosis Association,
  • U.S. Environmental Protection Agency (EPA), and
  • Regione Lombardia and Fondazione Lombardia Ambiente, Milan, Italy.
1996-2012, ongoing Marcy Warner, PhD
Project Director, The Seveso Women’s Health Study
[email protected]

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