Urinary BPA Levels During Pregnancy and Preterm Birth Risk
Urinary BPA Levels During Pregnancy and Preterm Birth Risk
Background: Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB.
Objectives: In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB.
Methods: A nested case–control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston, Massachusetts, during 2006–2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as "spontaneous," which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or "placental," which was preceded by preeclampsia or intrauterine growth restriction.
Results: Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant's sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males.
Conclusions: These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.
Preterm birth (PTB), defined as delivery before 37 weeks completed gestation, is a leading cause of infant mortality and significant precursor to future morbidity. Overall rates of PTB in the United States are significantly higher than several decades ago, with persistent racial and economic disparity [Institute of Medicine (IOM) 2006]. The etiology of preterm birth is recognized to have a multitude of overlapping factors, many of which are understudied, leading to the inability of clinicians and health care providers to provide good prevention and/or treatment options. One critical area that is understudied with regard to potential contribution to the etiology of PTB is environmental contaminant exposure. Many environmental exposures are modifiable through behavioral change and thus represent an attractive target for prevention.
Bisphenol A (BPA) is a high production–volume chemical most commonly used in the manufacturing of epoxy resins and polycarbonate polymers. Downstream applications include, but are not limited to, a variety of consumer products such as food can linings, water bottles, dental sealants, thermal receipts, medical equipment, flooring, reusable food and drink containers, and water supply pipes. As these products age or are exposed to high heat or acidic/basic conditions, monomers can be released to the environment (Arnold 1996; Brede et al. 2003; Nerín et al. 2003). Because of their widespread use and leaching from consumer products, it is not surprising that detectable urinary BPA concentrations have been found in various populations, including pregnant women (Calafat et al. 2008; He et al. 2009; Meeker et al. 2013; Vandenberg et al. 2012; Ye et al. 2008). BPA has also been detected in the serum of pregnant women, follicular fluid, placental tissue and cord blood; but of particular concern, due to the sensitive developmental period for fetuses, is evidence of higher amniotic fluid BPA concentrations in early compared with late pregnancy (Edlow et al. 2012; Ikezuki et al. 2002; Lee et al. 2008; Philippat et al. 2013; Yamada et al. 2002). Of particular note, it has been shown that even during pregnancy urinary BPA levels can widely vary, with several studies indicating weak intraclass correlation coefficients (ICCs), suggesting the importance of taking multiple measurements to gain a greater understanding of the variance in exposure during this critical developmental period (Braun et al. 2011a, 2012; Meeker et al. 2013).
Toxicological evidence suggests that BPA exposure may affect pregnancy through a variety of hormone-mediated mechanisms. Initially considered to be a weak environmental estrogen, BPA more recently in experimental models has been shown to stimulate biological responses at very low concentrations and has been demonstrated to be as potent as estradiol (E2) in some of its effects (Alonso-Magdalena et al. 2005, 2008; Hugo et al. 2008; Zsarnovszky et al. 2005). Additionally, there is evidence that BPA can also alter thyroid signaling, bind to the glucocorticoid receptor, act as an anti-androgen, and trigger activation of a variety of signal transduction pathways affecting cell proliferation, apoptosis, and survival (Kaneko et al. 2008; Steinmetz et al. 1997; Wetherill et al. 2007; Zoeller 2007). For example, it has been demonstrated that BPA can affect the proliferative process of trophoblastic cells through estrogen-related receptor-γ (ERRγ1) (Morice et al. 2011) and has a dose-dependent effect upon apoptosis of primary human cytotrophoblast cells via tumor necrosis factor-α (Benachour and Aris 2009). These results imply a direct impact on placental function, which if perturbed can alter the normal course of pregnancy.
Current epidemiological evidence for the association of BPA exposure with adverse birth outcomes, specifically PTB, are extremely limited (Cantonwine et al. 2010; Padmanabhan et al. 2008; Weinberger et al. 2014; Wolff et al. 2008). In a small nested case–control study (n = 60) of PTB in Mexico City, researchers found that the adjusted odds ratio of delivering at < 37 weeks in relation to a 1-log increase in specific gravity–adjusted third-trimester BPA concentration was 2.5 [95% confidence interval (CI): 1.1, 6.0] (Cantonwine et al. 2010). Several other studies assessing gestational age as a continuous variable have found inconsistent results (Padmanabhan et al. 2008; Weinberger et al. 2014; Wolff et al. 2008). All of the above studies failed to account for the high variability in BPA exposure across pregnancy, using a single spot urine sample for exposure assessment, and the heterogeneous etiologies of preterm birth (IOM 2006; McElrath et al. 2008).
In the present study we examined the relationship between longitudinally measured urinary BPA concentrations during gestation and preterm birth. We further assessed the associations between gestational BPA exposure and more specific classifications of PTB.
Abstract and Introduction
Abstract
Background: Preterm birth (PTB), a leading cause of infant mortality and morbidity, has a complex etiology with a multitude of interacting causes and risk factors. The role of environmental contaminants, particularly bisphenol A (BPA), is understudied with regard to PTB.
Objectives: In the present study we examined the relationship between longitudinally measured BPA exposure during gestation and PTB.
Methods: A nested case–control study was performed from women enrolled in a prospective birth cohort study at Brigham and Women's Hospital in Boston, Massachusetts, during 2006–2008. Urine samples were analyzed for BPA concentrations at a minimum of three time points during pregnancy on 130 cases of PTB and 352 randomly assigned controls. Clinical classifications of PTB were defined as "spontaneous," which was preceded by spontaneous preterm labor or preterm premature rupture of membranes, or "placental," which was preceded by preeclampsia or intrauterine growth restriction.
Results: Geometric mean concentrations of BPA did not differ significantly between cases and controls. In adjusted models, urinary BPA averaged across pregnancy was not significantly associated with PTB. When examining clinical classifications of PTB, urinary BPA late in pregnancy was significantly associated with increased odds of delivering a spontaneous PTB. After stratification on infant's sex, averaged BPA exposure during pregnancy was associated with significantly increased odds of being delivered preterm among females, but not males.
Conclusions: These results provide little evidence of a relationship between BPA and prematurity, though further research may be warranted given the generalizability of participant recruitment from a tertiary teaching hospital, limited sample size, and significant associations among females and within the clinical subcategories of PTB.
Introduction
Preterm birth (PTB), defined as delivery before 37 weeks completed gestation, is a leading cause of infant mortality and significant precursor to future morbidity. Overall rates of PTB in the United States are significantly higher than several decades ago, with persistent racial and economic disparity [Institute of Medicine (IOM) 2006]. The etiology of preterm birth is recognized to have a multitude of overlapping factors, many of which are understudied, leading to the inability of clinicians and health care providers to provide good prevention and/or treatment options. One critical area that is understudied with regard to potential contribution to the etiology of PTB is environmental contaminant exposure. Many environmental exposures are modifiable through behavioral change and thus represent an attractive target for prevention.
Bisphenol A (BPA) is a high production–volume chemical most commonly used in the manufacturing of epoxy resins and polycarbonate polymers. Downstream applications include, but are not limited to, a variety of consumer products such as food can linings, water bottles, dental sealants, thermal receipts, medical equipment, flooring, reusable food and drink containers, and water supply pipes. As these products age or are exposed to high heat or acidic/basic conditions, monomers can be released to the environment (Arnold 1996; Brede et al. 2003; Nerín et al. 2003). Because of their widespread use and leaching from consumer products, it is not surprising that detectable urinary BPA concentrations have been found in various populations, including pregnant women (Calafat et al. 2008; He et al. 2009; Meeker et al. 2013; Vandenberg et al. 2012; Ye et al. 2008). BPA has also been detected in the serum of pregnant women, follicular fluid, placental tissue and cord blood; but of particular concern, due to the sensitive developmental period for fetuses, is evidence of higher amniotic fluid BPA concentrations in early compared with late pregnancy (Edlow et al. 2012; Ikezuki et al. 2002; Lee et al. 2008; Philippat et al. 2013; Yamada et al. 2002). Of particular note, it has been shown that even during pregnancy urinary BPA levels can widely vary, with several studies indicating weak intraclass correlation coefficients (ICCs), suggesting the importance of taking multiple measurements to gain a greater understanding of the variance in exposure during this critical developmental period (Braun et al. 2011a, 2012; Meeker et al. 2013).
Toxicological evidence suggests that BPA exposure may affect pregnancy through a variety of hormone-mediated mechanisms. Initially considered to be a weak environmental estrogen, BPA more recently in experimental models has been shown to stimulate biological responses at very low concentrations and has been demonstrated to be as potent as estradiol (E2) in some of its effects (Alonso-Magdalena et al. 2005, 2008; Hugo et al. 2008; Zsarnovszky et al. 2005). Additionally, there is evidence that BPA can also alter thyroid signaling, bind to the glucocorticoid receptor, act as an anti-androgen, and trigger activation of a variety of signal transduction pathways affecting cell proliferation, apoptosis, and survival (Kaneko et al. 2008; Steinmetz et al. 1997; Wetherill et al. 2007; Zoeller 2007). For example, it has been demonstrated that BPA can affect the proliferative process of trophoblastic cells through estrogen-related receptor-γ (ERRγ1) (Morice et al. 2011) and has a dose-dependent effect upon apoptosis of primary human cytotrophoblast cells via tumor necrosis factor-α (Benachour and Aris 2009). These results imply a direct impact on placental function, which if perturbed can alter the normal course of pregnancy.
Current epidemiological evidence for the association of BPA exposure with adverse birth outcomes, specifically PTB, are extremely limited (Cantonwine et al. 2010; Padmanabhan et al. 2008; Weinberger et al. 2014; Wolff et al. 2008). In a small nested case–control study (n = 60) of PTB in Mexico City, researchers found that the adjusted odds ratio of delivering at < 37 weeks in relation to a 1-log increase in specific gravity–adjusted third-trimester BPA concentration was 2.5 [95% confidence interval (CI): 1.1, 6.0] (Cantonwine et al. 2010). Several other studies assessing gestational age as a continuous variable have found inconsistent results (Padmanabhan et al. 2008; Weinberger et al. 2014; Wolff et al. 2008). All of the above studies failed to account for the high variability in BPA exposure across pregnancy, using a single spot urine sample for exposure assessment, and the heterogeneous etiologies of preterm birth (IOM 2006; McElrath et al. 2008).
In the present study we examined the relationship between longitudinally measured urinary BPA concentrations during gestation and preterm birth. We further assessed the associations between gestational BPA exposure and more specific classifications of PTB.
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