Neonatal Thyroid Function in Seveso 25 Years after Maternal Exposure to Dioxin

Abstract

BackgroundNeonatal 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 FindingsBetween 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 μU/ml (95% confidence interval [CI] 0.90–1.08) in the reference area (n = 533), 1.35 μU/ml (95% CI 1.22–1.49) in zone B (n = 425), and 1.66 μU/ml (95% CI 1.19–2.31) in zone A (n = 56) (p < 0.001). The proportion of children with b-TSH > 5 μU/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, β = 0.47, p < 0.001) and plasma toxic equivalents of coplanar dioxin-like compounds (n = 51, β = 0.45, p = 0.005).ConclusionsOur data indicate that environmental contaminants such as dioxins have a long-lasting capability to modify neonatal thyroid function after the initial exposure.

Ancestral TCDD exposure promotes epigenetic transgenerational inheritance of imprinted gene Igf2: Methylation status and DNMTs

“…Exposure to high levels of dioxin has also been associated with adverse pregnancy outcomes (Tsukimori et al, 2008), including higher risk of birth defects and lower birth weight. Studies have shown that dioxins can not only affect hormone homeostasis (Gupta et al, 2006) and reproductive parameters (Mocarelli et al, 2008) in directly exposed individuals, but also have implications in hormone dysfunction (Baccarelli et al, 2008) and behavioral sexual dimorphism (Winneke et al, 2013) in the offspring.…”

Thyroid and growth hormone concentrations in 8-year-old children exposed <i>in utero</i> to dioxins and polychlorinated biphenyls

“…Other studies to date have involved newborns, infants, or young children (Alvarez-Pedrerol et al, 2008;Baccarelli et al, 2008;Otake et al, 2007;Wang et al, 2005). Multivariate logistic regression analyses, adjusting for BA/CA, BMI, SBP, and DBP, revealed that the level of in utero exposure to PCDD/F + PCBs was significantly associated with TBG concentrations.…”

“…There is also evidence suggesting that thyroid hormone concentrations are altered in newborns and in children exposed in utero to PCDD/F and PCBs (Alvarez-Pedrerol et al, 2008;Baccarelli et al, 2008;Otake et al, 2007;Su et al, 2010;Wang et al, 2005). This is important, given that thyroid hormones, by affecting metabolism, play a critical role in regulating growth and development in children (Tarim, 2011).…”

“…This is important, given that thyroid hormones, by affecting metabolism, play a critical role in regulating growth and development in children (Tarim, 2011). The importance of thyroid hormones for growth and development is most clearly demonstrat-ed in children with hypothyroidism (Bettendorf, 2002), who are short in stature, have delayed bone development, and other growth abnormalities (Baccarelli et al, 2008;Bucher et al, 1985;Yen, 2001). The evidence for altered thyroid hormone concentrations in response to in utero exposure to organic pollutants is not conclusive, as outlined in a recent weight of evidence analysis considering both prenatal and postnatal exposure (Goodman et al, 2010).…”

Scientific statement on the health‐based guidance values for dioxins and dioxin‐like PCBs

“…From each of these studies a POD (shown in Table 2) was estimated from the NOAEL/LOAEL identified for the critical effect observed in the key studies. The Baccarelli et al (2008) and Mocarelli et al (2008) studies were selected to be co-principal studies for the RfD as they were determined to describe the most sensitive endpoints. The endpoints of increased thyroid-stimulating hormone (TSH) in neonates and decreased sperm count and motility were designated as co-critical effects and an adjusted LOAEL of 20 pg/kg b.w.…”