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

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 mu U/ml (95% confidence interval [ CI] 0.90 - 1.08) in the reference area (n 533), 1.35 lU/ ml ( 95% CI 1.22 - 1.49) in zone B (n = 425), and 1.66 mu U/ ml (95% CI 1.19 - 2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b- TSH. 5 mu U/ 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, b = 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.