Associations between Prenatal Exposure to Polychlorinated Biphenyls and Neonatal Thyroid-Stimulating Hormone Levels in a Mexican-American Population, Salinas Valley, California Jonathan Chevrier,1 Brenda Eskenazi,1 Asa Bradman,1 Laura Fenster,2 and Dana B. Barr3 1Center for Children's Environmental Health Research, School of Public Health, University of California, Berkeley, California, USA; 2California Department of Health Services, Division of Environmental and Occupational Disease Control, Richmond, California, USA; 3National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA Abstract Background: Studies have reported that prenatal exposure to polychlorinated biphenyls (PCBs) may alter neurodevelopment in both humans and animals. Furthermore, prenatal exposure to some PCB congeners and commercial mixtures has been shown to decrease free and total thyroxine (T4) blood levels in animals. Because thyroid hormones (TH) are essential for normal neurologic development, it has been suggested that the deleterious neurodevelopmental effect of PCBs may occur through TH disruption. PCBs may in turn affect TH levels by inducing the microsomal enzyme uridinediphosphate glucuronosyltransferase (UDP-GT) , which is involved in TH elimination. Objectives: Our goals were to group PCB congeners based on their potential to induce microsomal enzymes in animals, and to examine the relationship between neonatal TSH levels and prenatal exposure to PCB congeners grouped according to their structure and potential mechanisms of action. Methods: We measured the concentration of 34 PCB congeners in serum samples collected from 285 pregnant women and the thyroid-stimulating hormone (TSH) levels in their children's blood collected shortly after birth. Results: We found no association between the sum of PCB congeners, the toxic equivalents, or structure-based groupings (mono- or di-ortho substituted congeners) , and TSH blood concentration. However, we found a positive association between the sum of congeners suspected to be UDP-GT inducers (more specifically cytochrome P450 2B inducers) in animals and neonatal TSH levels. In individual congener analyses, PCBs 99, 138, 153, 180, 183, 187, 194, and 199 were positively associated with neonatal TSH levels after adjustment for covariates. PCBs 194 and 199 remained significant after adjustment for multiple hypothesis testing. Conclusions: Our results support grouping PCB congeners based on their potential mechanism of action of enzyme induction when investigating associations with TH. Findings also suggest that PCBs affect TH homeostasis even at the low background level of exposure found in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) population. Key words: cytochrome P450, enzyme inducers, in utero, microsomal enzymes, neonatal, polychlorinated biphenyls, prenatal, thyroid hormone, TSH, UDP-glucuronosyltransferase. Environ Health Perspect 115:1490–1496 (2007) . doi:10.1289/ehp.9843 available via http://dx.doi.org/ [Online 29 June 2007] Address correspondence to B. Eskenazi, Center for Children's Environmental Health Research, School of Public Health, UC Berkeley, 2150 Shattuck Ave., Suite 600, Berkeley, CA 94704-7380 USA. Telephone: (510) 642-3496. Fax: (510) 642-9083. E-mail: eskenazi@berkeley.edu We gratefully acknowledge P. Buffler (genetic disease branch data) ; S. Dudoit, R.E. Aguilar Schall, and A. Marks (statistical consultation) ; and M. Warner (manuscript review) . This publication was supported by grants RO1 OH007400 from the National Institute for Occupational Safety and Health, RD 83171001 from the U.S. Environmental Protection Agency, and PO1 ES009605 from the National Institute of Environmental Health Sciences. Additional funding was provided by the Fonds de la Recherche en Santé du Québec and the Canadian Institutes for Health Research. Its contents are solely the responsibility of the authors and do not necessarily represent funders' or CDC's official views. The authors declare they have no competing financial interests. Received 19 October 2006 ; accepted 28 June 2007. The full version of this article is available for free in HTML or PDF formats. |