High maternal dioxin exposure affects children decades later

On July 10, 1976, an explosion at a chemical factory in Seveso, northern Italy, unleashed a mysterious toxic cloud over a large residential area. Laboratory tests of soil samples confirmed the chemical cloud had deposited 2,3,7,8-Tetrachlorodibenzo-p-dioxin, a toxic chemical. The contaminated area was divided into three zones ranging from severe to trace amounts. Within a month, all people from the severely affected zone A, as well as pregnant women and children from the less affected zone B were evacuated. Houses were destroyed. Contaminated soils were removed.

Seveso remains the only known place where a large number of women were exposed to high levels of dioxin, noted Andrea Baccarelli, adjunct assistant professor of environmental epigenetics in the HSPH Department of Environmental Health. This summer, Baccarelli and his colleagues published a paper in PLoS Medicine on what happened to the progeny of women exposed to dioxin after the accident. The researchers found that newborns born to these women were 6.6 times more likely to have reduced thyroid function compared to babies of non-exposed mothers. Animal studies had previously and consistently showed congenital hypothyroidism from prenatal exposure, but evidence in people was not as clear.

"The results show quite clearly that thyroid function in these children was affected by the accident 20 to 30 years earlier," said Baccarelli. The researchers are conducting further studies to learn if and to what extent the reduced neonatal thyroid function may have led to developmental or clinical problems in the children.

Baccarelli and his co-authors tracked down 1,772 women of childbearing age from the two most contaminated zones and the newborn screening results of their 1,014 children born between 1994 and 2005. About day three after birth, babies in Italy are screened for a number of disorders that could be serious or fatal if untreated. The tests include measurement of thyroid-stimulating hormone (TSH). Excessively high TSH levels indicate hypothyroidism, which can cause severe mental retardation if untreated, and occur in about every 1 in 1,000 newborns.

The researchers also tracked down an equal number of age-matched women from the surrounding non-contaminated area and data about their children for comparison.

In addition to their main findings, the researchers found subtler indications of thyroid dysfunction. Elevated TSH levels in 16 percent of newborns of women from zone A and five percent from zone B exceed the three percent intervention threshold set by the World Health Organization for hypothyroidism caused by another environmental exposure, iodine deficiency.

The higher the maternal blood dioxin levels, the higher the neonatal TSH levels, he and his colleages found in a companion analysis of blood serum of 51 mother-child pairs. Animal studies show fetuses are exposed to dioxin in utero through the placenta. Subsequent breastfeeding could have exposed the children to more dioxin, Baccarelli suggested.

"The study really shows that persistence of dioxin in the human population may potentially cause health problems in their children as well," said Baccarelli, who has returned to his faculty position at the University of Milan in Italy after two years as a visiting scientist at HSPH. He retains an adjunct position at the School.

He added, "Once someone is exposed, it takes about 10 years for the blood concentration to get down to 50 percent of the peak level. Some of the people had concentrations 5,000 times higher than background in measurements taken one year after the accident."

Baccarelli remains concerned about the still-unknown impact on children's health and development. Even in the absence of overt clinical symptoms, epidemiological studies in areas with mild to moderate iodine deficiency have found impaired development affecting intelligence, perception, and motor skills.

-Carol Cruzan Morton.  Image by iStockPhoto.com / Razberry