Human maternal and umbilical cord blood concentrations of polybrominated diphenyl ethers

Abstract

Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants in commercial products, have become ubiquitous environmental contaminants. Although adult human exposure to PBDEs is well documented, developmental exposure is less well characterized. The objectives of this study were to measure maternal and fetal exposure to nine PBDE congeners and to investigate potential associations with birth weight. PBDE congeners were quantified in maternal serum at 24–28 weeks of pregnancy, delivery, and umbilical cord serum (UCS) by gas chromatography–mass spectrometry (GC/MS/MS). Complete blood sample sets were obtained from 97 pregnant women (mean age 33.1 ± 0.5 years). PBDE-28, -47 and -99 were quantified in all samples tested and PBDE-47 was the most abundant congener measured in both maternal (mid-pregnancy and delivery samples geometric mean = 26.9 and 26.9, respectively) and UCS (GM = 56.0 ng g⁻¹ lipid). The UCS concentration for all congeners with the exception of PBDE-153 was higher vs. maternal delivery samples (p < 0.001). Only the UCS concentration of PBDE-17 and -99 were significantly associated (β = −49.860, p = 0.032, and β = −3.645, p = 0.05) with birth weight. However, after adjustment for potential confounders only the association between PBDE-99 and birth weight remained significant (β = −3.951 and p = 0.016). We conclude that: the fetus is exposed to PBDEs from at least the second trimester of pregnancy onward; PBDE congeners are higher in UCS compared to maternal serum samples collected at delivery; and that developmental PBDE exposure is potentially associated with lower birth weight.

Introduction

Polybrominated diphenyl ethers (PBDEs) are endocrine toxic chemicals that are extensively used as flame retardants in the manufacture of household furnishings, appliances, textiles, paints, and electronics including televisions, cell phones, and computers (Jones-Otazo et al., 2005, Stapleton et al., 2008, Wang et al., 2008). Commercial PBDE mixtures are thought to represent a human health concern because of similarities with polychlorinated biphenyls (PCBs) in terms of their lipophilicity, bioaccumulation, long-range transport, and persistence in the environment (de Wit, 2002, Sjodin et al., 2003). Furthermore, accumulating evidence from in vitro studies and animal experiments suggests that PBDEs are estrogenic chemicals (Meerts et al., 2001) that adversely affect neurodevelopment (Kuriyama et al., 2005, Costa and Giordano, 2007), thyroid and reproductive physiology (Stoker et al., 2004, Kuriyama et al., 2005, Talsness et al., 2005, Talsness et al., 2008). Quantitative structure–activity relationship modeling suggests the potential for PBDEs to act as endocrine toxicants (Harju et al., 2007) and thus underscores the concern that exposure to these chemicals may pose a threat to human health.

The most important sources of nonoccupational human exposure include food and house dust whereas the main sources for infant and toddlers are breastfeeding and ingestion or inhalation of house dust, respectively (Zuurbier et al., 2006, Schecter et al., 2006, Gevao et al., 2006, Wu et al., 2007, Sudaryanto et al., 2008, Sjodin et al., 2008, Anderson et al., 2008, Thomsen et al., 2008, Spliethoff et al., 2008). Adult human serum, adipose and liver PBDE exposure has been relatively well documented (Kunisue et al., 2007, Covaci et al., 2008, Pulkrabova et al., 2009) with concentrations in North Americans that are 10–100 fold higher than those reported in European and Asian studies (Inoue et al., 2006, Hooper et al., 2007, Harrad and Porter, 2007, Toms et al., 2008). Worldwide PBDE-47 is the dominant compound in blood samples, followed by PBDE-153 (Furst, 2006, Harrad and Porter, 2007). In contrast to adults, human developmental exposure is less well characterized. In several studies from Europe, the United States of America (USA), and Asia, the majority of which involve relatively small samples sizes (4–48 study participants), PBDE congeners have been quantified in the serum of pregnant women, umbilical cord blood, placenta, and breast milk (Mazdai et al., 2003, Guvenius et al., 2003, Covaci and Voorspoels, 2005, Gomara et al., 2007, Chao et al., 2007, Kawashiro et al., 2008, Frederiksen et al., 2010, Herbstman et al., 2010). Of note, the concentrations of PBDEs in maternal and umbilical cord blood in the USA (Mazdai et al., 2003, Herbstman et al., 2007) are higher than comparable samples from Europe (Guvenius et al., 2003, Covaci and Voorspoels, 2005, Fangstrom et al., 2005, Gomara et al., 2007, Meijer et al., 2008) and Asia (Bi et al., 2006, Kawashiro et al., 2008, Kim et al., 2009). Unfortunately, exposure data for a comparable population of Canadian women is not available and thus it is unclear if higher exposure documented in the USA is unique to this population or is representative of North American exposures in pregnant women and their fetuses. Comparison of the PBDE concentrations in maternal serum and umbilical cord blood appears to be strongly correlated in some studies (Mazdai et al., 2003, Bi et al., 2006) whereas statistically significant differences between maternal and umbilical cord serum PBDE concentrations has been reported (Gomara et al., 2007). While overall these data demonstrate placental transfer of PBDE congeners, exposure during earlier stages of pregnancy has not been determined and it is unclear if there are real differences between maternal and fetal exposure.

The similarity between PBDEs and PCBs together with evidence for wide-spread human exposure especially during development, a period considered to be of increased sensitivity to the toxic effects of endocrine active chemicals (Pryor et al., 2000), highlights concern that fetal development and newborn health could be adversely affected by these exposures. Potential adverse health effects in humans are unclear owing to the scarcity of epidemiological studies and the ambiguity of the published results. The potential relationship between PBDE exposure and thyroid function has been investigated in several studies with divergent results. Serum PBDE-100 concentration was associated with an increased odds of low umbilical cord total thyroxine (TT4) concentration and PBDE-153 was associated with an increased odds of low TT4 and free thyroxine (FT4), yet no PBDE congener was associated with an increased odds of high circulating thyroid stimulating hormone (TSH) concentration (Herbstman et al., 2008). In contrast, no association was found between seven PBDE congener concentrations in umbilical cord blood and thyroid hormone concentrations in Korean infants (Kim et al., 2009). Equally ambiguous are potential effects of PBDE exposure on birth weight. A positive association was found for milk PBDE concentration and lower birth weight, length, head and chest circumference after results were adjusted for maternal age, pre-pregnant body mass index (BMI), and parity (Chao et al., 2007). Conflicting results were reported in another albeit small (n = 12) study (Mazdai et al., 2003), which found no correlation between maternal serum PBDE concentrations and birth weight. Although, presentation of exposure results has been fairly consistent across studies making comparisons of published results fairly straightforward, the studies conducted to date have been underpowered. Hence, the relationship between perinatal exposure to PBDEs and potential adverse human health effects remain uncertain. Therefore, the aim of the present study was to measure the concentration of PBDE congeners in maternal serum at mid-pregnancy (24–28 weeks of pregnancy) and delivery, and in umbilical cord blood collected at delivery from the offspring of healthy pregnant women from Hamilton, Ontario, Canada, and to examine the relationship between exposure and birth weight.