Browsing by Author "Liu, Jiaying"
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Item Open Access Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study(2017-05-19) Giesbrecht, Gerald F; Ejaredar, Maede; Liu, Jiaying; Thomas, Jenna; Letourneau, Nicole; Campbell, Tavis; Martin, Jonathan W; Dewey, DeborahAbstract Background Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3 month old infants. Methods Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010–2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize changes in infant cortisol as a function of prenatal BPA exposure. Results Higher maternal BPA was associated with increases in baseline cortisol among females (β = 0.13 log μg/dL; 95% CI: 0.01, 0.26), but decreases among males (β = −0.22 log μg/dL; 95% CI: -0.39, −0.05). In contrast, higher BPA was associated with increased reactivity in males (β = .30 log μg/dL; 95% CI: 0.04, 0.56) but decreased reactivity in females (β = −0.15 log μg/dL; 95% CI: -0.35, 0.05). Models adjusting for creatinine yielded similar results. Conclusions Prenatal BPA exposure is associated with sex-specific changes in infant HPA axis function. The biological plausibility of these findings is supported by their consistency with evidence in rodent models. Furthermore, these data support the hypotheses that sexually dimorphic changes in children’s behaviour following prenatal BPA exposure are mediated by sexually dimorphic changes in HPA axis function.Item Open Access Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study(Springer Nature, 2017-05-19) Giesbrecht, G. F.; Ejaredar, Maede; Liu, Jiaying; Thomas, Jenna C.; Letourneau, Nicole Lyn; Campbell, Tavis S.; Martin, Jonathan W.; Dewey, Deborah; APrON Study TeamBackground: Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually-dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3-month-old infants. Methods: Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010–2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize changes in infant cortisol as a function of prenatal BPA exposure. Results: Higher maternal BPA was associated with increases in baseline cortisol among females (β = 0.13 log μg/dL; 95% CI: 0.01, 0.26), but decreases among males (β = −0.22 log μg/dL; 95% CI: -0.39, −0.05). In contrast, higher BPA was associated with increased reactivity in males (β = .30 log μg/dL; 95% CI: 0.04, 0.56) but decreased reactivity in females (β = −0.15 log μg/dL; 95% CI: -0.35, 0.05). Models adjusting for creatinine yielded similar results. Conclusions: Prenatal BPA exposure is associated with sex-specific changes in infant HPA axis function. The biological plausibility of these findings is supported by their consistency with evidence in rodent models. Furthermore, these data support the hypotheses that sexually dimorphic changes in children’s behaviour following prenatal BPA exposure are mediated by sexually-dimorphic changes in HPA axis function. Keywords: Bisphenol-A, Fetal exposure, Cortisol, Hypothalamic-pituitary-adrenal axis, Infant stress reactivityItem Open Access Prenatal maternal and childhood bisphenol a exposure and brain structure and behavior of young children(2019-10-15) Grohs, Melody N; Reynolds, Jess E; Liu, Jiaying; Martin, Jonathan W; Pollock, Tyler; Lebel, Catherine; Dewey, DeborahAbstract Background Bisphenol A (BPA) is commonly used in the manufacture of plastics and epoxy resins. In North America, over 90% of the population has detectable levels of urinary BPA. Human epidemiological studies have reported adverse behavioral outcomes with BPA exposure in children, however, corresponding effects on children’s brain structure have not yet been investigated. The current study examined the association between prenatal maternal and childhood BPA exposure and white matter microstructure in children aged 2 to 5 years, and investigated whether brain structure mediated the association between BPA exposure and child behavior. Methods Participants were 98 mother-child pairs who were recruited between January 2009 and December 2012. Total BPA concentrations in spot urine samples obtained from mothers in the second trimester of pregnancy and from children at 3–4 years of age were analyzed. Children participated in a diffusion magnetic resonance imaging (MRI) scan at age 2–5 years (3.7 ± 0.8 years). Associations between prenatal maternal and childhood BPA and children’s fractional anisotropy and mean diffusivity of 10 isolated white matter tracts were investigated, controlling for urinary creatinine, child sex, and age at the time of MRI. Post-hoc analyses examined if alterations in white matter mediated the relationship of BPA and children’s scores on the Child Behavior Checklist (CBCL). Results Prenatal maternal urinary BPA was significantly associated with child mean diffusivity in the splenium and right inferior longitudinal fasciculus. Splenium diffusivity mediated the relationship between maternal prenatal BPA levels and children’s internalizing behavior (indirect effect: β = 0.213, CI [0.0167, 0.564]). No significant associations were found between childhood BPA and white matter microstructure. Conclusions This study provides preliminary evidence for the neural correlates of BPA exposure in humans. Our findings suggest that prenatal maternal exposure to BPA may lead to alterations in white matter microstructure in preschool aged children, and that such alterations mediate the relationship between early life exposure to BPA and internalizing problems.Item Open Access Urinary bisphenol A is associated with dysregulation of HPA-axis function in pregnant women: Findings from the APrON cohort study.(Elsevier, 2016-11) Giesbrecht, Gerald; Liu, Jiaying; Ejaredar, Maede; Dewey, Deborah; Letourneau, Nicole; Campbell, Tavis; Martin, JonathanBackground: Bisphenol A (BPA) is associated with dysregulation of hypothalamic-pituitary-adrenal (HPA) axis activity in rodents, but evidence in humans is lacking.Objective: To determine whether BPA exposure during pregnancy is associated with dysregulation of the HPA-axis, we examined the association between urinary BPA concentrations and diurnal salivary cortisol in pregnant women. Secondary analyses investigated whether the association between BPA and cortisol was dependent on fetal sex. Methods: Diurnal salivary cortisol and urinary BPA were collected during pregnancy from 174 women in a longitudinal cohort study, the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Associations between BPA and daytime cortisol and the cortisol awakening response (CAR) were estimated using mixed models after adjusting for covariates. Results: Higher concentrations of total BPA uncorrected for urinary creatinine were associated with dysregulation of the daytime cortisol pattern, including reduced cortisol at waking, β=−.055, 95% CI (−.100, −.010) and a flatter daytime pattern, β=.014, 95% CI (.006, .022) and β=−.0007 95% CI (−.001, −.0002) for the linear and quadratic slopes, respectively. Effect sizes in creatinine corrected BPA models were slightly smaller. None of the interactions between fetal sex and BPA were significant (all 95% CI's include zero). Conclusions: These findings provide the first human evidence suggesting that BPA exposure is associated with dysregulation of HPA-axis function during pregnancy.