Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

Background Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy. Objectives Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women. Methods We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation. Results Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (∑PBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), −20.6 to 0.0] and 18.7% (95% CI, −29.2 to −4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ∑PBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ∑PBDEs. Conclusions Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development.

[1]  R. B. Wilcox,et al.  Accuracy of free thyroxine measurements across natural ranges of thyroxine binding to serum proteins. , 2000, Thyroid : official journal of the American Thyroid Association.

[2]  B. Velkeniers,et al.  Female infertility and the thyroid. , 2004, Best practice & research. Clinical endocrinology & metabolism.

[3]  A. Bos,et al.  Prenatal Exposure to Organohalogens, Including Brominated Flame Retardants, Influences Motor, Cognitive, and Behavioral Performance at School Age , 2009, Environmental health perspectives.

[4]  J. Dashe,et al.  Subclinical Hyperthyroidism and Pregnancy Outcomes , 2006, Obstetrics and gynecology.

[5]  L. Wartofsky,et al.  Graves' disease. , 2007, The Journal of clinical endocrinology and metabolism.

[6]  Dennis R. Helsel,et al.  Less than obvious - statistical treatment of data below the detection limit , 1990 .

[7]  L. Hagmar,et al.  Plasma Levels of Persistent Organohalogens and Hormone Levels in Adult Male Humans , 2001, Archives of environmental health.

[8]  John D Meeker,et al.  Polybrominated diphenyl ether (PBDE) concentrations in house dust are related to hormone levels in men. , 2009, The Science of the total environment.

[9]  K M Crofton,et al.  Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[10]  M. Pickard,et al.  Influence of maternal hyperthyroidism in the rat on the expression of neuronal and astrocytic cytoskeletal proteins in fetal brain. , 2002, The Journal of endocrinology.

[11]  M. Wade,et al.  Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  L. Goldman,et al.  Birth Delivery Mode Modifies the Associations between Prenatal Polychlorinated Biphenyl (PCB) and Polybrominated Diphenyl Ether (PBDE) and Neonatal Thyroid Hormone Levels , 2008, Environmental health perspectives.

[13]  Asa Bradman,et al.  PBDE Concentrations in Women’s Serum and Fecundability , 2010, Environmental health perspectives.

[14]  D. Glinoer,et al.  The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. , 1997, Endocrine reviews.

[15]  R. B. Wilcox,et al.  Underestimates of serum free thyroxine (T4) concentrations by free T4 immunoassays. , 1994, The Journal of clinical endocrinology and metabolism.

[16]  N. Holland,et al.  Effects of exposure to polychlorinated biphenyls and organochlorine pesticides on thyroid function during pregnancy. , 2008, American journal of epidemiology.

[17]  R. Letcher,et al.  Metabolism of Polybrominated Diphenyl Ethers (PBDEs) by Human Hepatocytes in Vitro , 2008, Environmental health perspectives.

[18]  D. Pisarek-Miedzínska,et al.  [Hyperthyroidism in pregnancy]. , 1983, Ginekologia polska.

[19]  I. Chahoud,et al.  Developmental Exposure to Low-Dose PBDE-99: Effects on Male Fertility and Neurobehavior in Rat Offspring , 2004, Environmental health perspectives.

[20]  P. Darnerud,et al.  Polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs) and chlorinated paraffins (CPs) in rats-testing interactions and mechanisms for thyroid hormone effects. , 2002, Toxicology.

[21]  P. Berbel,et al.  A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration. , 2004, Endocrinology.

[22]  J. Nelson,et al.  Direct determination of free thyroxin in undiluted serum by equilibrium dialysis/radioimmunoassay. , 1988, Clinical chemistry.

[23]  B. Haugen Drugs that suppress TSH or cause central hypothyroidism. , 2009, Best practice & research. Clinical endocrinology & metabolism.

[24]  S. Waisbren,et al.  "Maternal Thyroid Deficiency During Pregnancy and Subsequent Neuropsychological Development of the Child" (1999), by James E. Haddow et al. , 2014 .

[25]  S. Mandel,et al.  Are detection and treatment of thyroid insufficiency in pregnancy feasible? , 2005, Thyroid : official journal of the American Thyroid Association.

[26]  Guoying Sheng,et al.  Polybrominated diphenyl ethers in South China maternal and fetal blood and breast milk. , 2006, Environmental pollution.

[27]  H. Anderson,et al.  Hormone Disruption by PBDEs in Adult Male Sport Fish Consumers , 2008, Environmental health perspectives.

[28]  J. Lazarus Thyroid disease in pregnancy and childhood. , 2005, Minerva endocrinologica.

[29]  J. Selby The Thyroid: A Fundamental and Clinical Text , 1992 .

[30]  Jean-François Focant,et al.  Semiautomated high-throughput extraction and cleanup method for the measurement of polybrominated diphenyl ethers, polybrominated biphenyls, and polychlorinated biphenyls in human serum. , 2004, Analytical chemistry.

[31]  Paula R. Latovick Protection for Trade Secrets Under the Toxic Substances Control Act of 1976 , 1980 .

[32]  Anders Fredriksson,et al.  Neonatal exposure to polybrominated diphenyl ether (PBDE 153) disrupts spontaneous behaviour, impairs learning and memory, and decreases hippocampal cholinergic receptors in adult mice. , 2003, Toxicology and applied pharmacology.

[33]  P. Laurberg,et al.  Biologic variation is important for interpretation of thyroid function tests. , 2003, Thyroid : official journal of the American Thyroid Association.

[34]  Jing Yuan,et al.  Elevated serum polybrominated diphenyl ethers and thyroid-stimulating hormone associated with lymphocytic micronuclei in Chinese workers from an E-waste dismantling site. , 2008, Environmental science & technology.

[35]  Jean-François Focant,et al.  Retrospective time-trend study of polybrominated diphenyl ether and polybrominated and polychlorinated biphenyl levels in human serum from the United States. , 2004, Environmental health perspectives.

[36]  K. Norén,et al.  Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20-30 years. , 2000, Chemosphere.

[37]  Kevin M Crofton,et al.  Developmental exposure to brominated diphenyl ethers results in thyroid hormone disruption. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[38]  N. Fisk,et al.  Permeability of Human Placenta and Fetal Membranes to Thyrotropin-Stimulating Hormone in Vitro , 1998, Pediatric Research.

[39]  D. Lenoir,et al.  Terminal elimination half-lives of the brominated flame retardants TBBPA, HBCD, and lower brominated PBDEs in humans , 2004 .

[40]  J. Mestman Hyperthyroidism in pregnancy. , 1997, Best practice & research. Clinical endocrinology & metabolism.

[41]  D. Helsel More than obvious: better methods for interpreting nondetect data. , 2005, Environmental science & technology.

[42]  S. Harrad,et al.  Concentrations of polybrominated diphenyl ethers in blood serum from New Zealand. , 2007, Chemosphere.

[43]  D. Barr,et al.  Associations between Prenatal Exposure to Polychlorinated Biphenyls and Neonatal Thyroid-Stimulating Hormone Levels in a Mexican-American Population, Salinas Valley, California , 2007, Environmental Health Perspectives.

[44]  L. Needham,et al.  Serum concentrations of polybrominated diphenyl ethers (PBDEs) and polybrominated biphenyl (PBB) in the United States population: 2003-2004. , 2008, Environmental science & technology.

[45]  I. Bryngelsson,et al.  Polybrominated diphenyl ethers—plasma levels and thyroid status of workers at an electronic recycling facility , 2005, International archives of occupational and environmental health.

[46]  J. Vena,et al.  Environmental exposure to PBDEs and thyroid function among New York anglers. , 2008, Environmental toxicology and pharmacology.

[47]  A. Tremblay,et al.  Body weight loss increases plasma and adipose tissue concentrations of potentially toxic pollutants in obese individuals , 2000, International Journal of Obesity.

[48]  I. Meerts,et al.  Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[49]  P. Darnerud,et al.  Reduced thyroxine levels in mice perinatally exposed to polybrominated diphenyl ethers. , 2005, Environmental toxicology and pharmacology.

[50]  Maria Teresa Landi,et al.  Handling of dioxin measurement data in the presence of non-detectable values: overview of available methods and their application in the Seveso chloracne study. , 2005, Chemosphere.

[51]  D. Phillips,et al.  Chlorinated hydrocarbon levels in human serum: Effects of fasting and feeding , 1989, Archives of environmental contamination and toxicology.

[52]  P. Darnerud,et al.  Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice , 2001, Archives of Toxicology.

[53]  Arnold Schecter,et al.  Polybrominated Diphenyl Ether Flame Retardants in the U.S. Population: Current Levels, Temporal Trends, and Comparison With Dioxins, Dibenzofurans, and Polychlorinated Biphenyls , 2005, Journal of occupational and environmental medicine.

[54]  Deliang Tang,et al.  Prenatal Exposure to PBDEs and Neurodevelopment , 2010, Environmental health perspectives.

[55]  L. Hagmar,et al.  Flame retardant exposure: polybrominated diphenyl ethers in blood from Swedish workers. , 1999, Environmental health perspectives.

[56]  L. Braverman,et al.  Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain. , 1992, Endocrinology.

[57]  D. Wing,et al.  Low birth weight and preeclampsia in pregnancies complicated by hyperthyroidism , 1995 .

[58]  P. Ayotte,et al.  Thyroid Function and Plasma Concentrations of Polyhalogenated Compounds in Inuit Adults , 2009, Environmental health perspectives.

[59]  K. Crofton,et al.  Comparative responsiveness of hypothyroxinemia and hepatic enzyme induction in Long-Evans rats versus C57BL/6J mice exposed to TCDD-like and phenobarbital-like polychlorinated biphenyl congeners. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[60]  J. Cerhan,et al.  Epidemiologic evaluation of measurement data in the presence of detection limits. , 2005, Environmental health perspectives.

[61]  Stephen J Bosch,et al.  Toxicological profile for polybrominated biphenyls and polybrominated diphenyl ethers , 2004 .

[62]  J. Franklyn,et al.  Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. , 2004, JAMA.

[63]  G. Muckle,et al.  Temporal and spatial changes of brominated diphenyl ethers (BDEs) and other pops in human milk from Nunavik (Arctic) and Southern Quebec , 2003 .

[64]  Hiroshi Watanabe,et al.  Effect of Thyroid Hormone on the Activity of CYP3A Enzyme in Humans , 2010, Journal of clinical pharmacology.

[65]  Nathan G Dodder,et al.  Polybrominated diphenyl ethers in maternal and fetal blood samples. , 2003, Environmental health perspectives.