Research | Children’s Health Associations between Polybrominated Diphenyl Ether (PBDE) Flame Retardants, Phenolic Metabolites, and Thyroid Hormones during Pregnancy Heather M. Stapleton,1 Sarah Eagle,1 Rebecca Anthopolos,1 Amy Wolkin,2 and Marie Lynn Miranda1,3 1Nicholas School of the Environment, Duke University, Durham, North Carolina, USA; 2National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; 3Department of Pediatrics, Duke University, Durham, North Carolina, USA Background : Polybrominated diphenyl ethers (PBDEs) are chemical additives used as flame retardants in commercial products. PBDEs are bioaccumulative and persistent and have been linked to several adverse health outcomes. o Bjectivs : This study leverages an ongoing pregnancy cohort to measure PBDEs and PBDE metabolites in serum collected from an understudied population of pregnant women late in their third trimester. A secondary objective was to determine whether the PBDEs or their metabolites were associated with maternal thyroid hormones. Methods : One hundred forty pregnant women > 34 weeks into their pregnancy were recruited into this study between 2008 and 2010. Blood samples were collected during a routine prenatal clinic visit. Serum was analyzed for a suite of PBDEs, three phenolic metabolites (i.e., containing an –OH moiety), and five thyroid hormones. r sulte : PBDEs were detected in all samples and ranged from 3.6 to 694 ng/g lipid. Two hydrox­ c onclusi ylated BDE congeners (4´O­HB­DE 49 and 6O­HB­DE 47) were detected in > 67% of the samples. BDEs 47, 99, and 100 were significantly and positively associated with free and total thyroxine (T4) levels and with total triiodothyronine levels above the normal range. Associations between T4 and PBDEs remained after controlling for smoking status, maternal age, race, gestational age, and parity. : PBDEs and OHB­DEs are prevalent in this cohort , and levels are similar to those in the general population. Given their long halfl­ives, PBDEs may be affecting thyroid regulation throughout pregnancy. Further research is warranted to determine mechanisms through which PBDEs affect thyroid hormone levels in developing fetuses and newborn babies. k ey words : flame retardants, OHB­DEs, PBDEs, pregnancy, thyroid hormones. Environ Health Perspect 119:1454–1459 (2011). http://dx.doi.org/10.1289/ehp.1003235 [Online 29 June 2011] Polybrominated diphenyl ethers (PBDEs) are chemical additives applied to numerous types of furniture and electronic and electrical items to meet state and federal flammability standards. Historically, three PBDE com- mercial mixtures have been used in consumer products (Alaee et al. 2003; de Wit 2002). These three mixtures are referred to as pent- aBDE, octaBDE, and decaBDE. The use of pentaBDE and octaBDE has been phased out or banned in the United States and different areas of the world starting in 2002. DecaBDE continues to be used in consumer products, although manufacturers have recently agreed to phase out the use of decaBDE by 2012 (Hess 2009). Despite this phaseout, products containing PBDEs (e.g., furniture, TVs) are still in use in many homes, and exposure will likely continue for some time. Several studies have now demonstrated that PBDEs are ubiquitous contaminants commonly detected in human tissues (Hale et al. 2003; Sjodin et al. 2003, 2008). The dominant PBDE congeners detected in human tissues are from those found in the pentaBDE mixture, likely due to the greater historical use of pentaBDE in North American furniture relative to other regions. PBDEs have a chemical structure simi- lar to thyroid hormones, most notably thy- roxine (T4). In laboratory animal studies, PBDEs affect thyroid regulation by decreasing 1454 circulating levels of thyroid hormones, alter- ing expression of genes that encode thyroid- regulating proteins, and reducing activity of thyroid-regulating enzymes. Furthermore, in vitro studies have shown that PBDEs and their CYP P450–mediated metabolites, hydroxylated PBDEs, can compete for binding sites on thyroid hormone transporters in serum (Marchesini et al. 2008; Meerts et al. 2000). PBDE levels in maternal and cord blood tissues have been associated with cryptorchid- ism in male infants, lower birth weights in babies, and neurodevelopmental and behavior problems in children, including reductions in IQ (Chao et al. 2007; Herbstman et al. 2010; Main et al. 2007; Roze et al. 2009). In adults, PBDE levels have been associated with signifi- cant alterations in hormone levels and fecund- ability in women (Harley et al. 2010; Meeker et al. 2009). These studies raise concerns about expo- sure of women to PBDEs during pregnancy and the potential of PBDEs to affect growth and development of the fetus. Thyroid hor- mones are supplied to the developing fetus via placental transfer during the first half of preg- nancy. Late in the second trimester, the fetus begins to produce its own thyroid hormones; however, the fetus still relies on maternal inputs to stabilize the thyroid hormone sup- ply. Thyroid hormone delivery to the fetus is essential for fetal brain development. A recent study (Chevrier et al. 2010) examined PBDE levels and thyroid hormones in serum col- lected from pregnant women during their second trimester. They observed an inverse association between PBDEs and thyroid- stimulating hormone (TSH) but no rela- tionship with T4. The odds of subclinical hyperthyroidism (low TSH but normal T4) were significantly higher in individuals with the highest PBDE levels relative to individuals with the lowest PBDE levels. The goal of this study was to exam- ine PBDE levels in a pregnancy cohort in North Carolina and provide more data on the associations between PBDEs and thyroid hormones. Samples were from an ongoing pregnancy cohort study examining social and environmental risk factors for adverse preg- nancy outcomes. To complement the existing literature and to determine whether previ- ously noted associations between PBDEs and thyroid hormone levels observed during the second trimester existed during the third tri- mester, we examined these relationships in women > 34 weeks pregnant. This study also expands previous research by including meas- urements of hydroxylated PBDEs, which have been hypothesized, but not previously tested, to have more potent effects on thyroid hor- mone regulation than PBDEs. In addition, our study focuses primarily on a cohort of African-American women, a population gener- ally understudied in PBDE exposure research. Address correspondence to H. Stapleton, Nicholas School of the Environment, Duke University, LSRC, Box 90328, Durham, NC 27708 USA. Telephone: (919) 613-8717. Fax: (919) 684-8741. E-mail: heather.stapleton@duke.edu Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1003235). We thank all of our recruiters and participants in this study, and E. Cooper for the LC/MSMS analy- sis. A special thanks to P. Maxson for managing the recruitment effort and to C. Osgood for data manage- ment support. This work was supported by a grant from the U.S. Environmental Protection Agency (RD-83329301). H.M.S. was also partially supported by grant R01 ES016099 from the National Institute of Environmental Health Sciences and by funds from the Centers for Disease Control and Prevention (CDC). The findings and conclusions in this article are those of the authors and do not necessarily repre- sent the views of the CDC or the Agency for Toxic Substances and Disease Registry. The authors declare they have no actual or potential competing financial interests. Received 22 November 2010; accepted 29 June 2011. ovlume 119 | number 10 | October 2011 • Environmental Health Perspectives