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Dioxin Exposure and Time to Pregnancy in Seveso

Eskenazi, B*; Warner, M*; Marks, A*; Samuels, S; Needham, L; Mocarelli, P§

doi: 10.1097/

*University of California, Berkeley, United States; †State University of New York, Albany, United States; ‡Centers for Disease Control and Prevention, United States; and §University of Milano-Bicocca, Italy.


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Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, has been associated with reduced fertility in multiple animal species at doses below toxic levels. To date, no epidemiologic studies have examined the association of TCDD exposure with infertility in women. On July 10, 1976, as a result of a chemical explosion, residents of Seveso, Italy, experienced the highest levels of TCDD in a human population. Twenty years later, we initiated the Seveso Women's Health Study (SWHS), a retrospective cohort study of the reproductive health of the women. We examined the association between TCDD exposure and fertility as measured by time to pregnancy (TTP).

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Materials and Methods:

The SWHS cohort comprises 981 women who were 0 to 40 years in 1976, resided in the most contaminated areas, and had adequate archived sera collected soon after the explosion. Individual serum TCDD exposure was measured by high-resolution mass spectrometry. We examined the relation of serum TCDD with TTP or the number of months to become pregnant, using a discrete-time analogue of the Cox proportional hazards model. TTP (months) was treated as a continuous variable and censored at 13 months if women had reported attempting to conceive for a period of 12 months or longer.

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Of 475 women who reported a post-explosion pregnancy, 340 had a planned or noncontracepted pregnancy resulting in a live birth. The median TTP was 3.0 months. Preliminary results suggest that women with higher serum TCDD levels took longer to become pregnant. Adjusting for parity, and parental smoking and age, a 10-fold increase in TCDD was associated with a 32% reduced odds of achieving pregnancy (adj-fOR = 0.76, 95% CI: 0.61, 0.94).

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These results suggest TCDD exposure may be associated with reduced fertility in the Seveso cohort. The results will be interpreted in light of study advantages and limitations.

© 2007 Lippincott Williams & Wilkins, Inc.