Prenatal Bisphenol A Exposure and Early Childhood Behavior

Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 12/2009; 117(12):1945-52. DOI: 10.1289/ehp.0900979
Source: PubMed

ABSTRACT Prenatal exposure to bisphenol A (BPA) increases offspring aggression and diminishes differences in sexually dimorphic behaviors in rodents.
We examined the association between prenatal BPA exposure and behavior in 2-year-old children.
We used data from 249 mothers and their children in Cincinnati, Ohio (USA). Maternal urine was collected around 16 and 26 weeks of gestation and at birth. BPA concentrations were quantified using high-performance liquid chromatography-isotope-dilution tandem mass spectrometry. Child behavior was assessed at 2 years of age using the second edition of the Behavioral Assessment System for Children (BASC-2). The association between prenatal BPA concentrations and BASC-2 scores was analyzed using linear regression.
Median BPA concentrations were 1.8 (16 weeks), 1.7 (26 weeks), and 1.3 (birth) ng/mL. Mean (+/- SD) BASC-2 externalizing and internalizing scores were 47.6 +/- 7.8 and 44.8 +/- 7.0, respectively. After adjustment for confounders, log(10)-transformed mean prenatal BPA concentrations were associated with externalizing scores, but only among females [beta = 6.0; 95% confidence interval (CI), 0.1-12.0]. Compared with 26-week and birth concentrations, BPA concentrations collected around 16 weeks were more strongly associated with externalizing scores among all children (beta = 2.9; 95% CI, 0.2-5.7), and this association was stronger in females than in males. Among all children, measurements collected at <or= 16 weeks showed a stronger association (beta = 5.1; 95% CI, 1.5-8.6) with externalizing scores than did measurements taken at 17-21 weeks (beta = 0.6; 95% CI, -2.9 to 4.1).
These results suggest that prenatal BPA exposure may be associated with externalizing behaviors in 2-year-old children, especially among female children.

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Available from: Kimberly Yolton, Sep 27, 2015
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    • "Concerns regarding the safety of early exposure to bisphenol A (BPA) have resulted in a number of studies; reports of sex differences are contradictory. Maternal BPA concentrations as early as 16 weeks of gestation were significantly associated with parentally reported externalizing behaviors in 2-year-old girls, but not boys (Braun et al., 2009). In a subsequent follow-up, girls with greater exposure to BPA concentrations were rated as exhibiting higher levels of depression and anxiety as well as externalizing behaviors (Braun et al., 2011). "
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    ABSTRACT: Despite long-standing interest in the role of sex on human development, the functional consequences of fetal sex on early development are not well understood. Here we explore the gestational origins of sex as a moderator of development. In accordance with the focus of this special issue, we examine evidence for a sex differential in vulnerability to prenatal and perinatal risks. Exposures evaluated include those present in the external environment (e.g., lead, pesticides), those introduced by maternal behaviors (e.g., alcohol, opioid use), and those resulting from an adverse intrauterine environment (e.g., preterm birth). We also provide current knowledge on the degree to which sex differences in fetal neurobehavioral development (i.e., cardiac and motor patterns) are present prior to birth. Also considered are contemporaneous and persistent sex of fetus effects on the pregnant woman. Converging evidence confirms that infant and early childhood developmental outcomes of male fetuses exposed to prenatal and perinatal adversities are more highly impaired than those of female fetuses. In certain circumstances, male fetuses are both more frequently exposed to early adversities and more affected by them when exposed than are female fetuses. The mechanisms through which biological sex imparts vulnerability or protection on the developing nervous system are largely unknown. We consider models that implicate variation in maturation, placental functioning, and the neuroendocrine milieu as potential contributors. Many studies use sex as a control variable, some analyze and report main effects for sex, but those that report interaction terms for sex are scare. As a result, the true scope of sex differences in vulnerability is unknown. Copyright © 2015. Published by Elsevier Ltd.
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    • "These alterations paralleled changes in ERRγ (Kundakovic et al., 2013) that may be a basis for altered social behavior. Even in nonsocial behaviors, for example , learning, emotion, and exploration, males and females displayed differential outcomes due to developmental BPA exposures (human: Perera et al., 2012; Braun et al., 2011, 2009; fish: Saili et al., 2012; mice: Jašarevi´c et al., 2013; Kundakovic et al., 2013; Palanza et al., 2008 rats: Jones et al., 2011). These behavioral disruptions are strongly correlated with a range of molecular, physiological, and organlevel mechanisms involved in sex-dependent behaviors, for example, brain ER gene expression (rat: Cao et al., 2013), fetal ovarian and gonadal development (fish: Chung et al., 2011; mice: Kundakovic et al., 2013; Tainaka et al., 2012; Xi et al., 2011a, 2011b; rat: Cao et al., 2013; sheep: Veifa-Lopez et al., 2013), pituitary and gonadotrophin development (mice: Brannick et al., 2012), brain and gonadal enzyme activity (rat: Nanjappa et al., 2012), altered hypothalamic–pituitary–gonadal (HPG) axis activity (mice: Xi et al., 2011a; rats: Ramos et al., 2003), and circulating testosterone levels (mice: Tanaka et al., 2006). "
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    ABSTRACT: Developmental bisphenol A (BPA) exposure is associated with adverse behavioral effects, although underlying modes of action remain unclear. Because BPA is a suspected xenoestrogen, the objective was to identify sex-based changes in adult zebrafish social behavior developmentally exposed to BPA (0.0, 0.1, or 1 μM) or one of two control compounds (0.1 μM 17β-estradiol [E2], and 0.1 μM GSK4716, a synthetic estrogen-related receptor γ ligand). A test chamber was divided lengthwise so each arena held one fish unable to detect the presence of the other fish. A mirror was inserted at one end of each arena; baseline activity levels were determined without mirror. Arenas were divided into three computer-generated zones to represent different distances from mirror image. Circadian rhythm patterns were evaluated at 1-3 (= AM) and 5-8 (= PM) h postprandial. Adult zebrafish were placed into arenas and monitored by digital camera for 5 min. Total distance traveled, percent of time spent at mirror image, and number of attacks on mirror image were quantified. E2, GSK4716, and all BPA treatments dampened male activity and altered male circadian activity patterns; there was no marked effect on female activity. BPA induced nonmonotonic effects (response curve changes direction within range of concentrations examined) on male percent of time at mirror only in AM. All treatments produced increased percent of time at the mirror during PM. Male attacks on the mirror were reduced by BPA exposure only during AM. There were sex-specific effects of developmental BPA on social interactions, and time of day of observation affected results.
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    • "Indeed, associations were found between phthalate and altered play preferences, autism, and attention-deficit hyperactivity disorder in boys (Kim et al., 2009; Swan et al., 2010). Effects on young females have been reported with phthalates reducing alertness (Engel et al., 2009) and bisphenol- A increasing aggressive behavior (Braun et al., 2009). PCBs, organochlorine pesticides, and dioxin are also suspected obesogens affecting the modulating hormone adiponectin and increasing the risk of diabetes (Everett et al., 2007). "
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