| 1. |
- Zheng, Jing, et al.
(författare)
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The effects of prenatal bisphenol A exposure on brain volume of children and young mice
- 2022
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 214, part 3
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Tidskriftsartikel (refereegranskat)abstract
- Bisphenol A (BPA) is a synthetic chemical used for the manufacturing of plastics, epoxy resin, and many personal care products. This ubiquitous endocrine disruptor is detectable in the urine of over 80% of North Americans. Although adverse neurodevelopmental outcomes have been observed in children with high gestational exposure to BPA, the effects of prenatal BPA on brain structure remain unclear. Here, using magnetic resonance imaging (MRI), we studied the associations of maternal BPA exposure with children's brain structure, as well as the impact of comparable BPA levels in a mouse model. Our human data showed that most maternal BPA exposure effects on brain volumes were small, with the largest effects observed in the opercular region of the inferior frontal gyrus (ρ = −0.2754), superior occipital gyrus (ρ = −0.2556), and postcentral gyrus (ρ = 0.2384). In mice, gestational exposure to an equivalent level of BPA (2.25 μg BPA/kg bw/day) induced structural alterations in brain regions including the superior olivary complex (SOC) and bed nucleus of stria terminalis (BNST) with larger effect sizes (1.07≤ Cohens d ≤ 1.53). Human (n = 87) and rodent (n = 8 each group) sample sizes, while small, are considered adequate to perform the primary endpoint analysis. Combined, these human and mouse data suggest that gestational exposure to low levels of BPA may have some impacts on the developing brain at the resolution of MRI.
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| 2. |
- Dewey, Deborah, et al.
(författare)
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Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort
- 2023
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Ingår i: Neurotoxicology. - 0161-813X .- 1872-9711. ; 98, s. 48-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is inconsistent evidence regarding the sex-specific associations between prenatal phthalate exposure and children's neurodevelopment. This could be due to differences in the phthalate exposures inves-tigated and the neurodevelopmental domains assessed.Objective: To evaluate the associations between prenatal phthalate exposure and sex-specific outcomes on measures of cognition, language, motor, executive function, and behaviour in children 2 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.Methods: We evaluated the associations between prenatal phthalate exposure and sex-specific neuro-developmental outcomes in children at 2 years of age using data from 448 mothers and their children (222 girls, 226 boys). Nine phthalate metabolites were measured in maternal urine collected in the second trimester of pregnancy. Children's cognitive, language, and motor outcomes were assessed using the Bayley Scales of Infant Development - Third Edition (Bayley-III). Parents completed questionnaires on children's executive function and behavior, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) and Child Behavior Checklist (CBCL), respectively. Sex-stratified robust multivariate regressions were performed.Results: Higher maternal concentrations of & sigma;DEHP and its metabolites were associated with lower scores on the Bayley-III Cognitive (& beta;'s from-11.8 to-0.07 95% CI's from-21.3 to-0.01), Language (& beta;'s from-11.7 to-0. 09, 95% CI's from-22.3 to-0.02) and Motor (& beta;'s from-10.9 to-0.07, 95% CI from-20.4 to-0.01) composites in boys. The patterns of association in girls were in the opposite direction on the Cognitive and Language composites; on the Motor composite they were in the same direction as boys, but of reduced strength. Higher concentrations of & sigma;DEHP and its metabolites were associated with higher scores (i.e., more difficulties) on all measures of executive function in girls: inhibitory self-control (B's from 0.05 to 0.11, 95% CI s from-0.01 to 0.15), flexibility (B's from 0.04 to 0.11, 95% CI s from 0.01 to 0.21) and emergent metacognition (B's from-0.01 to 0.06, 95% CIs from-0.01 to 0.20). Similar patterns of attenuated associations were seen in boys. Higher concentrations of & sigma;DEHP and its metabolites were associated with more Externalizing Problems in girls and boys (B's from 0.03 to 6.82, 95% CIs from-0.08 to 12.0). Two phthalates, MMP and MBP, had sex-specific adverse associations on measures of executive function and behaviour, respectively, while MEP was positively associated with boys' cognitive, language, and motor performance. Limited associations were observed between mixtures of maternal phthalates and sex-specific neurodevelopmental outcomes.Conclusions: Maternal prenatal concentrations of DEHP phthalates were associated with sex specific difference on measures of cognition and language at 2 years of age, specifically, poorer outcomes in boys. Higher exposure to DEHP was associated with poorer motor, executive function, and behavioural outcomes in girls and boys but the strength of these associations differed by sex. Limited associations were noted between phthalate mixtures and child neurodevelopment.
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| 3. |
- England-Mason, Gillian, et al.
(författare)
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Postnatal BPA is associated with increasing executive function difficulties in preschool children
- 2021
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 89, s. 686-693
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Tidskriftsartikel (refereegranskat)abstract
- Background Early bisphenol exposure may have consequences for executive function development, but less is known about potential sex effects. We hypothesized that early bisphenol A (BPA) and bisphenol S (BPS) exposures would be associated with sex-dependent changes in preschool executive function. Methods A subsample of the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort (n = 312) provided maternal second trimester (prenatal) and 3-month postpartum (postnatal) urine samples, from which BPA and BPS concentrations were quantified. When children were age 2 and 4, mothers completed the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Changes in standardized T scores on the BRIEF-P indexes of inhibitory self-control, flexibility, and emergent metacognition were investigated. Results Adjusted multivariate regression analyses showed that child sex modified the associations between maternal postnatal BPA and changes in executive function. Higher maternal postnatal BPA concentrations predicted increasing difficulties from age 2 to 4 in the domains of inhibitory self-control and emergent metacognition in female, but not male children. The other bisphenol concentrations were not associated with changes in executive function. Conclusion Due to the ubiquity of BPA exposure among breastfeeding women, these findings justify further investigation on the effects of postnatal bisphenol exposure on child cognitive development. Impact Higher concentrations of maternal BPA at 3-month postpartum were associated with increasing difficulties in inhibitory self-control and emergent metacognition from age 2 to 4 in girls, but not boys. Prenatal BPA and prenatal/postnatal BPS were not significant predictors of changes in executive function in boys and girls. The current study extends previous research to show that maternal postnatal BPA could also impact child executive function. Due to the ubiquity of BPA exposure among breastfeeding women, the current findings suggest that additional precautions may be needed to protect infants' neurodevelopment from indirect exposure to BPA.
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| 4. |
- England-Mason, Gillian, et al.
(författare)
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Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants : An epigenome-wide association study
- 2022
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood.Objective: Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs).Methods: Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders.Results: One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs.Discussion: Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.
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| 5. |
- England-Mason, Gillian, et al.
(författare)
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Similar names, different results : Consistency of the associations between prenatal exposure to phthalates and parent-ratings of behavior problems in preschool children
- 2020
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 142
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental health research has reported mixed findings on the associations between prenatal exposure to phthalates and parent-ratings of child behavioral problems.Objective: We examined the consistency of the associations between prenatal urinary phthalate concentrations and child behavior scores across two standardized instruments - the Behavior Assessment System for Children-Second Edition (BASC-2) and the Child Behavior Checklist (CBCL) - using two analytical approaches used to correct for urine dilution.Method: A sample of 351 mother-child pairs were selected from a prospective birth cohort of pregnant women enrolled between 2009 and 2012. Women provided spot urine samples during the second trimester of pregnancy, which were analyzed for levels of nine urinary phthalate metabolites. When their typically developing children were 3-4 years of age, mothers completed the BASC-2 and CBCL on the same day. Adjusted regression analyses examined the associations between maternal prenatal phthalate concentrations and child behavior scores on the BASC-2 and CBCL. To correct for urine dilution, primary regression analyses included urinary creatinine concentration as a separate independent variable (i.e., covariate). In the secondary regression analyses, creatinine-adjusted phthalate concentrations were used.Results: Primary logistic regression analyses that included urinary creatinine as a covariate showed that higher prenatal phthalate concentrations were related to increased odds of scores falling into the borderline or clinical range on the Hyperactivity, Aggression, Anxiety, Depression, Withdrawal, Externalizing Problems, Internalizing Problems, and Behavioral Symptoms Index scales on the BASC-2 (ORs from 1.39 to 2.07), but only the Anxious/ Depressed and Externalizing Problems scales on the CBCL (ORs from 1.80 to 3.28). Primary linear regression analyses showed that higher prenatal phthalate concentrations were related to higher scores on the Externalizing Problems (beta's = 0.16), Internalizing Problems (beta's from 0.16 to 0.20), and Behavioral Symptoms Index (beta's from 0.18 to 0.21) scales on the BASC-2, but not related to any CBCL scales. Sex-stratified analyses found that many associations were only significant for male children. Secondary analyses using creatinine-adjusted phthalate concentrations revealed that some of the associations from the primary analyses remained significant; however, a number of unique associations were observed.Conclusion: Prenatal phthalate exposure was associated with preschool behavioral development; however, findings were not consistent for the BASC-2 and CBCL, especially related to the clinical/syndrome scales and Internalizing Problems scale. Further, many findings differed based on the analytical approach used to correct for urine dilution. Future work is needed to delineate the similarities and differences between similarly named child behavior constructs assessed by different neurodevelopmental assessments. Also, research is needed to better understand why and how different analytical approaches influence the reported associations between maternal prenatal phthalate concentrations and children's behavior problems.
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| 6. |
- England-Mason, Gillian, et al.
(författare)
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White matter microstructure mediates the association between prenatal exposure to phthalates and behavior problems in preschool children
- 2020
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 182
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored. Objective: This study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children. Methods: Data are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated. Results: Maternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI.95 = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI.95 = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI.95 = 0.01, 0.23) through MD of the right pyramidal fibers. Discussion: This study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems.
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| 7. |
- Grohs, Melody N., et al.
(författare)
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Prenatal maternal and childhood bisphenol a exposure and brain structure and behavior of young children
- 2019
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Ingår i: Environmental Health. - : Springer Science and Business Media LLC. - 1476-069X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- 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: beta = 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.
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| 8. |
- Irvine, Nathalie, et al.
(författare)
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Associations between maternal folate status and choline intake during pregnancy and neurodevelopment at 3–4 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) study
- 2023
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Ingår i: Journal of Developmental Origins of Health and Disease. - 2040-1744 .- 2040-1752. ; 14:3, s. 402-414
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Tidskriftsartikel (refereegranskat)abstract
- Folate and choline are methyl donor nutrients that may play a role in fetal brain development. Animal studies have reported that prenatal folate and choline supplementation are associated with better cognitive outcomes in offspring and that these nutrients may interact and affect brain development. Human studies that have investigated associations between maternal prenatal folate or choline levels and neurodevelopmental outcomes have reported contradictory findings and no human studies have examined the potential interactive effect of folate and choline on children’s neurodevelopment. During the second trimester of pregnancy, maternal red blood cell folate was measured from blood samples and choline intake was estimated using a 24-h dietary recall in 309 women in the APrON cohort. At 3–5 years of age, their children’s neurodevelopment was assessed using the Wechsler Preschool and Primary Scales of Intelligence – Fourth EditionCND, NEPSY-II language and memory subtests, four behavioral executive function tasks, and the Movement Assessment Battery for Children – Second Edition. Adjusted regressions revealed no associations between maternal folate and choline levels during pregnancy and most of the child outcomes. On the Dimensional Change Card Sort, an executive function task, there was an interaction effect; at high levels of choline intake (i.e., 1 SD above the mean; 223.03 mg/day), higher maternal folate status was associated with decreased odds of receiving a passing score (β = −0.44; 95%CI −0.81, −0.06). In conclusion, maternal folate status and choline intake during the second trimester of pregnancy were not associated with children’s intelligence, language, memory, or motor outcomes at 3–4 years of age; however, their interaction may have an influence children’s executive functions.
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| 9. |
- Liu, Jiaying, et al.
(författare)
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Exposure and dietary sources of bisphenol A (BPA) and BPA-alternatives among mothers in the APrON cohort study
- 2018
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 119, s. 319-326
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Tidskriftsartikel (refereegranskat)abstract
- Diet is regarded as the main source of bisphenol A (BPA) exposure, but comparatively little is known about dietary sources of BPA-alternatives. Here we measured exposure of BPA and BPA-alternatives among pregnant women in Canada, estimated their 24-h intakes and examined the importance of various dietary sources. Free and total BPA, bisphenol S (BPS) and bisphenol F (BPF) were measured in 467 second trimester maternal urine samples, and in 455 paired samples collected M three months postpartum. Linear regression was used to evaluate associations between urinary concentrations of bisphenols and 24-h dietary recall data. The geometric means of total BPA in second trimester and postpartum urine (1.2 and 0.95 ng/mL, respectively) were 5-7 times higher than corresponding total BPS (0.16 and 0.17 ng/mL). The detection frequency of BPF was only 9% (i.e. > 1.0 ng/mL). However, M both time points 95th percentiles of total BPF (7.3 and 4.2 ng/mL, respectively) were similar to total BPA (8.2 and 5.0 ng/mL). Free BPS and BPF were detected in < 2% of samples, but were detectable when total BPS or BPF concentrations were highest, always M < 1% of the total concentration. The tolerable daily intake for total BPA (i.e. 18 nmol/kg BW/d) was not exceeded, but for BPS the estimated 24-h intake was as high as 14 nmol/kg BW/d (95th percentile: 0.12 nmol/kg BW/d), and for BPF was even higher among the highest centile of exposure (maximum and 95th percentile: 30, 0.81 nmol/kg BW/d). Canned food consumption was associated with higher total BPA, but was not associated with BPS. For BPF, mustard consumption may be an important exposure source, particularly among the highest exposed. Relatively high exposure to BPS and BPF in a minority of pregnant women highlights the need to better understand the associated health risks and exposure sources of BPA-alternatives.
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| 10. |
- Liu, Jiaying, et al.
(författare)
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Interaction of prenatal bisphenols, maternal nutrients, and toxic metal exposures on neurodevelopment of 2-year-olds in the APrON cohort
- 2021
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies suggest that Bisphenol-A (BPA) is a developmental neurotoxicant, but the modifying effects of maternal nutrient status or neurotoxicant metal co-exposures have not been reported. Bisphenol-S (BPS) is being used as a BPA-alternative, but few epidemiological studies have evaluated its effects.Objectives: To examine if prenatal maternal BPA or BPS exposure are associated with children's neurodevelopment at two years of age while adjusting for effect-measure modification by sex, maternal nutrients, and co-exposure to neurotoxic metals.Methods: Total BPA and BPS concentrations were analyzed in spot maternal urine from the second trimester; metals and maternal nutrient status were analyzed in blood. Child neurodevelopment was evaluated with the Bayley Scales of Infant Development-III (Bayley-III) at age 2 (394 maternal-child pairs) and linear regression was used to investigate associations.Results: Among nutrients and neurotoxic metals, selenium (Se) and cadmium (Cd) were the most significant predictors of Bayley-III scale scores. Higher maternal Cd was significantly correlated with poorer motor performance (p < 0.01), and higher levels of maternal Se were significantly associated with poorer performance on the cognitive, motor, and adaptive behavior scales (p < 0.05). While maternal Cd did not modify relationships between bisphenol exposures and Bayley-III scores, both maternal Se and child sex were significant effectmeasure modifiers. Associations between BPA exposure and social emotional scores were negative for boys (p = 0.056) but positive for girls (p = 0.046). Higher exposure to bisphenols was associated with lower motor scores among children with lower levels of maternal Se.Conclusion: Higher maternal Cd was associated with poorer motor development, but it was not an effect-measure modifier of bisphenols' effects on motor development. Maternal Se may be protective against adverse effects of bisphenols, and additional nutrient-bisphenol interaction studies examining sex-specific effects of BPA and BPS on child development are warranted.
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