Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin

Abstract

Background: Neonatal hypothyroidism has been associated in animal models with maternal exposure to several environmental contaminants; however, evidence for such an association in humans is inconsistent. We evaluated whether maternal exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a persistent and widespread toxic environmental contaminant, is associated with modified neonatal thyroid function in a large, highly exposed population in Seveso, Italy.

Methods and findings: Between 1994 and 2005, in individuals exposed to TCDD after the 1976 Seveso accident we conducted: (i) a residence-based population study on 1,014 children born to the 1,772 women of reproductive age in the most contaminated zones (A, very high contamination; B, high contamination), and 1,772 age-matched women from the surrounding noncontaminated area (reference); (ii) a biomarker study on 51 mother-child pairs for whom recent maternal plasma dioxin measurements were available. Neonatal blood thyroid-stimulating hormone (b-TSH) was measured on all children. We performed crude and multivariate analyses adjusting for gender, birth weight, birth order, maternal age, hospital, and type of delivery. Mean neonatal b-TSH was 0.98 microU/ml (95% confidence interval [CI] 0.90-1.08) in the reference area (n = 533), 1.35 microU/ml (95% CI 1.22-1.49) in zone B (n = 425), and 1.66 microU/ml (95% CI 1.19-2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 microU/ml was 2.8% in the reference area, 4.9% in zone B, and 16.1% in zone A (p < 0.001). Neonatal b-TSH was correlated with current maternal plasma TCDD (n = 51, beta = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, beta = 0.45, p = 0.005).

Conclusions: Our data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.

Figure 1. Distribution of Neonatal b-TSH by Dioxin Contamination Zone

Neonatal b-TSH distribution for children born between 1994 and 2005 to women from zone A (n = 54), the zone most contaminated by TCDD after the Seveso accident; zone B (n = 425); and the surrounding noncontaminated reference area (n = 533). The graph shows kernel density estimates by zones. *According to the WHO [1], the percentage at the population level of newborns with a b-TSH value greater than 5 μU/ml should be less than 3% in iodine-replete areas.

Figure 2. Plasma Dioxin Levels and Neonatal b-TSH

Neonatal b-TSH and maternal plasma levels of dioxin-related compounds estimated at the date of delivery for (A) TCDD; (B) PCDDs, PCDFs, coplanar PCB TEQs; (C) non-coplanar PCB TEQs; and (D) total TEQs (i.e., the sum of TEQs from all measured congeners, including PCDDs, PCDFs, coplanar PCBs, and non-coplanar PCBs). Number of mother–child pairs (n), standardized regression coefficients (β), and p-values (p) from models using generalized estimating equations are reported.