Personal care product use and urinary phthalate metabolite and paraben concentrations during pregnancy among women from a fertility clinic.

Parabens and phthalates are potential endocrine disruptors frequently used in personal care/beauty products, and the developing fetus may be sensitive to these chemicals. We measured urinary butyl-paraben (BP), methyl-paraben, propyl-paraben, mono-n-butyl phthalate (MBP), and monoethyl phthalate (MEP) concentrations up to three times in 177 pregnant women from a fertility clinic in Boston, MA. Using linear mixed models, we examined the relationship between self-reported personal care product use in the previous 24 h and urinary paraben and phthalate metabolite concentrations. Lotion, cosmetic, and cologne/perfume use were associated with the greatest increases in the molar sum of phthalate metabolite and paraben concentrations, although the magnitude of individual biomarker increases varied by product used. For example, women who used lotion had BP concentrations 111% higher (95% confidence interval (CI): 41%, 216%) than non-users, whereas their MBP concentrations were only 28% higher (CI: 2%, 62%). Women using cologne/perfume had MEP concentrations 167% (CI: 98%, 261%) higher than non-users, but BP concentrations were similar. We observed a monotonic dose-response relationship between the total number of products used and urinary paraben and phthalate metabolite concentrations. These results suggest that questionnaire data may be useful for assessing exposure to a mixture of chemicals from personal care products during pregnancy.

Association between birth weight and DNA methylation of IGF2, glucocorticoid receptor and repetitive elements LINE-1 and Alu.

AIM: We examined the association between birth weight and methylation in the imprinted IGF/H19 loci, the nonimprinted gene NR3C1 and repetitive element DNA (LINE-1 and Alu). MATERIALS & METHODS: We collected umbilical cord venous blood from 219 infants born in Mexico City (Mexico) as part of a prospective birth cohort study and analyzed DNA methylation using pyrosequencing. RESULTS: Birth weight was not associated with DNA methylation of the regions studied. One of the CpG dinucleotides in the IGF2 imprinting control region (ICR)1 includes a potential C-T SNP. Among individuals with an absence of methylation at this site, probably due to a paternally inherited T allele, birth weight was associated with mean methylation status of both IGF2 ICR1 and ICR2. However, this association would not have survived adjustment for multiple testing. CONCLUSION: While we did not detect an association between DNA methylation and birth weight, our study suggests a potential gene-epigene interaction between a T allele in the IGF2 ICR1 and methylation of ICRs of IGF2, and fetal growth.

Predictors of virtual radial arm maze performance in adolescent Italian children.

BACKGROUND: Comparisons between animal and human neurotoxicology studies are a foundation of risk assessment, but are hindered by differences in measured behaviors. The radial arm maze (RAM), a rodent visuospatial learning and memory task, has a computerized version for use in children, which may help improve comparisons between animal and human studies. OBJECTIVE: To describe the characteristics and correlates of the virtual radial arm maze (VRAM) in 255 children age 10-15 years from Italy. METHODS: We administered the VRAM using a laptop computer and measured children's performance using the latency, distance, and working/reference memory errors during eight trials. Using generalized linear mixed models, we described VRAM performance in relation to demographic factors, child activities, and several standard neuropsychologic tests (Italian translations), including the Conners Parent Rating Scales-Short Version (CPRS), California Verbal Learning Test (CVLT), Wechsler Intelligence Scales for Children, finger tapping speed, reaction time, and motor skills. RESULTS: Children's VRAM performance tended to improve between trials 1 and 6 and then plateaued between trials 6 and 8. Males finished the task 14 s faster (95% confidence interval [CI]: -20, -9) than females. Children who played 2+h of video games per day finished 16 s faster (CI: -26, -6) and with 34% (CI: 5, 54%) fewer working memory errors than children who reported not playing video games. Higher IQ and better CVLT scores were associated with better VRAM performance. Higher cognitive/inattention CPRS scores were associated with more working (11%; CI: 1, 22) and reference memory errors (7%; CI: 1, 12). CONCLUSIONS: Consistent with animal studies, VRAM performance improved over the course of test trials and males performed better than females. Better VRAM performance was related to higher IQ, fewer inattentive behaviors, and better verbal memory. The VRAM may help to improve the integration and comparison between animal and epidemiological studies of environmental neurotoxicants.

Predictors and variability of urinary paraben concentrations in men and women, including before and during pregnancy.

BACKGROUND: Parabens are suspected endocrine disruptors and ubiquitous preservatives used in personal care products, pharmaceuticals, and foods. No studies have assessed the variability of parabens in women, including during pregnancy. OBJECTIVE: We evaluated predictors and variability of urinary paraben concentrations. METHODS: We measured urinary concentrations of methyl (MP), propyl (PP), and butyl paraben (BP) among couples from a fertility center. Mixed-effects regression models were fit to examine demographic predictors of paraben concentrations and to calculate intraclass correlation coefficients (ICCs). RESULTS: Between 2005 and 2010, we collected 2,721 spot urine samples from 245 men and 408 women. The median concentrations were 112 µg/L (MP), 24.2 µg/L (PP), and 0.70 µg/L (BP). Urinary MP and PP concentrations were 4.6 and 7.8 times higher in women than men, respectively, and concentrations of both MP and PP were 3.8 times higher in African Americans than Caucasians. MP and PP concentrations were slightly more variable in women (ICC = 0.42, 0.43) than men (ICC = 0.54, 0.51), and were weakly correlated between partners (r = 0.27-0.32). Among 129 pregnant women, urinary paraben concentrations were 25-45% lower during pregnancy than before pregnancy, and MP and PP concentrations were more variable (ICCs of 0.38 and 0.36 compared with 0.46 and 0.44, respectively). CONCLUSIONS: Urinary paraben concentrations were more variable in women compared with men, and during pregnancy compared with before pregnancy. However, results for this study population suggest that a single urine sample may reasonably represent an individual's exposure over several months, and that a single sample collected during pregnancy may reasonably classify gestational exposure.

Assessing windows of susceptibility to lead-induced cognitive deficits in Mexican children.

BACKGROUND: The identification of susceptible periods to Pb-induced decrements in childhood cognitive abilities remains elusive. OBJECTIVE: To draw inferences about windows of susceptibility using the pattern of associations between serial childhood blood lead (BPb) concentrations and children's cognitive abilities at 4 years of age among 1035 mother-child pairs enrolled in 4 prospective birth cohorts from Mexico City. METHODS: Multiple longitudinally collected BPb measurements were obtained from children (1, 2, 3, and 4 years) between 1994 and 2007. Child cognitive abilities were assessed at 4 years using the general cognitive index (GCI) of the McCarthy Scales of Children's Abilities. We used multivariable linear regression to estimate the change in cognitive abilities at 4 years of age with a 10 µg/dL increase in childhood BPb concentrations adjusting for maternal IQ, education, marital status, child sex, breastfeeding duration, and cohort. RESULTS: In separate models for each BPb measurement, 2 year BPb concentrations were most strongly associated with reduced GCI scores at 4 years after adjusting for confounders (ß: -3.8; 95% confidence interval CI: -6.3, -1.4). Mutual adjustment for other BPb concentrations in a single model resulted in larger, but less precise estimate between 2 year BPb concentrations and GCI scores at 4 years of age (ß: -7.1; 95% CI: -12, -2.0). The association between 2 year BPb and GCI was not heterogeneous (p=0.89), but some BPb and GCI associations varied in magnitude and direction across the cohorts. Additional adjustment for child hemoglobin, birth weight, gestational age, gestational BPb concentrations, or test examiner did not change the pattern of associations. CONCLUSIONS: Higher BPb concentrations at 2 years of age were most predictive of decreased cognitive abilities among these Mexico City children; however, the observed pattern may be due to exposure, outcome, or cohort related factors. These results may help developing countries more efficiently implement childhood Pb prevention strategies.

Associations of prenatal exposure to organophosphate pesticide metabolites with gestational age and birth weight.

BACKGROUND: Prenatal exposure to organophosphate (OP) insecticides, a widely used class of pesticides, may be associated with decreased gestational age and lower birth weight. Single nucleotide polymorphisms in paroxanase (PON1) enzyme genotypes may modify the relationships between OP exposure and perinatal outcomes. OBJECTIVE: We examined the relationship of prenatal OP insecticide exposure, measured using urinary dialkyl phosphate (DAP) metabolite concentrations, with gestational age and birth weight. METHODS: We measured the concentrations of six nonspecific DAP metabolites of OP insecticides in two maternal spot urine samples collected in a prospective birth cohort. We performed multivariable regression to examine associations between the sum of six DAP concentrations (ΣDAP) with gestational age and birth weight. We also examined whether these associations differed according to infant PON1(192) and PON1(-108) genotypes. RESULTS: Among 306 mother-infant dyads, a 10-fold increase in ΣDAP concentrations was associated with a decrease in covariate-adjusted gestational age [-0.5 weeks; 95% confidence interval (CI): -0.8, -0.1] and birth weight (-151 g; CI: -287, -16); the decrements in birth weight were attenuated after adjusting for gestational age. The relationship between ΣDAP concentrations and gestational age was stronger for white (-0.7 weeks; CI: -1.1, -0.3) than for black (-0.1 weeks; 95% CI: -0.9, 0.6) newborns. In contrast, there was a greater decrease in birth weight with increasing urinary ΣDAP concentrations for black (-188 g; CI: -395, 19) than for white (-118 g; CI: -296, 60) newborns. Decrements in birth weight and gestational age associated with ΣDAP concentrations were greatest among infants with PON1(192QR) and PON(-108CT) genotypes. CONCLUSIONS: Prenatal urinary ΣDAP concentrations were associated with shortened gestation and reduced birth weight in this cohort, but the effects differed by race/ethnicity and PON1(192/108) genotypes.

Maternal smoking during pregnancy and the prevalence of autism spectrum disorders, using data from the autism and developmental disabilities monitoring network.

BACKGROUND: Reported associations between gestational tobacco exposure and autism spectrum disorders (ASDs) have been inconsistent. OBJECTIVE: We estimated the association between maternal smoking during pregnancy and ASDs among children 8 years of age. METHODS: This population-based case-cohort study included 633,989 children, identified using publicly available birth certificate data, born in 1992, 1994, 1996, and 1998 from parts of 11 U.S. states subsequently under ASD surveillance. Of these children, 3,315 were identified as having an ASD by the active, records-based surveillance of the Autism and Developmental Disabilities Monitoring Network. We estimated prevalence ratios (PRs) of maternal smoking from birth certificate report and ASDs using logistic regression, adjusting for maternal education, race/ethnicity, marital status, and maternal age; separately examining higher- and lower-functioning case subgroups; and correcting for assumed under-ascertainment of autism by level of maternal education. RESULTS: About 13% of the source population and 11% of children with an ASD had a report of maternal smoking in pregnancy: adjusted PR (95% confidence interval) of 0.90 (0.80, 1.01). The association for the case subgroup autistic disorder (1,310 cases) was similar: 0.88 (0.72, 1.08), whereas that for ASD not otherwise specified (ASD-NOS) (375 cases) was positive, albeit including the null: 1.26 (0.91, 1.75). Unadjusted associations corrected for assumed under-ascertainment were 1.06 (0.98, 1.14) for all ASDs, 1.12 (0.97, 1.30) for autistic disorder, and 1.63 (1.30, 2.04) for ASD-NOS. CONCLUSIONS: After accounting for the potential of under-ascertainment bias, we found a null association between maternal smoking in pregnancy and ASDs, generally. The possibility of an association with a higher-functioning ASD subgroup was suggested, and warrants further study.

Variability of urinary phthalate metabolite and bisphenol A concentrations before and during pregnancy.

BACKGROUND: Gestational phthalate and bisphenol A (BPA) exposure may increase the risk of adverse maternal/child health outcomes, but there are few data on the variability of urinary biomarkers before and during pregnancy. OBJECTIVE: We characterized the variability of urinary phthalate metabolite and BPA concentrations before and during pregnancy and the ability of a single spot urine sample to classify average gestational exposure. METHODS: We collected 1,001 urine samples before and during pregnancy from 137 women who were partners in couples attending a Boston fertility clinic and who had a live birth. Women provided spot urine samples before (n ≥ 2) and during (n ≥ 2) pregnancy. We measured urinary concentrations of monoethyl phthalate (MEP), mono-n-butyl phthalate (MBP), mono-iso-butyl phthalate, monobenzyl phthalate (MBzP), four metabolites of di-(2-ethylhexyl) phthalate (DEHP), and BPA. After adjusting for specific gravity, we characterized biomarker variability using intraclass correlation coefficients (ICCs) and conducted several surrogate category analyses to determine whether a single spot urine sample could adequately classify average gestational exposure. RESULTS: Absolute concentrations of phthalate metabolites and BPA were similar before and during pregnancy. Variability was higher during pregnancy than before pregnancy for BPA and MBzP, but similar during and before pregnancy for MBP, MEP, and ΣDEHP. During pregnancy, MEP (ICC = 0.50) and MBP (ICC = 0.45) were less variable than BPA (ICC = 0.12), MBzP (ICC = 0.25), and ΣDEHP metabolites (ICC = 0.08). Surrogate analyses suggested that a single spot urine sample may reasonably classify MEP and MBP concentrations during pregnancy, but more than one sample may be necessary for MBzP, DEHP, and BPA. CONCLUSIONS: Urinary phthalate metabolites and BPA concentrations were variable before and during pregnancy, but the magnitude of variability was biomarker specific. A single spot urine sample adequately classified MBP and MEP concentrations during pregnancy. The present results may be related to unique features of the women studied, and replication in other pregnancy cohorts is recommended.

Impact of early-life bisphenol A exposure on behavior and executive function in children.

OBJECTIVES: To estimate the impact of gestational and childhood bisphenol A (BPA) exposures on behavior and executive function at 3 years of age and to determine whether child gender modified those associations. METHODS: We used a prospective birth cohort of 244 mothers and their 3-year-old children from the greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of gestation and birth) and child (1, 2, and 3 years of age) urine samples, respectively. Behavior and executive function were measured by using the Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). RESULTS: BPA was detected in >97% of the gestational (median: 2.0 µg/L) and childhood (median: 4.1 µg/L) urine samples. With adjustment for confounders, each 10-fold increase in gestational BPA concentrations was associated with more anxious and depressed behavior on the BASC-2 and poorer emotional control and inhibition on the BRIEF-P. The magnitude of the gestational BPA associations differed according to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among girls, but changes were null or negative among boys. Associations between childhood BPA exposure and neurobehavior were largely null and not modified by child gender. CONCLUSIONS: In this study, gestational BPA exposure affected behavioral and emotional regulation domains at 3 years of age, especially among girls. Clinicians may advise concerned patients to reduce their exposure to certain consumer products, but the benefits of such reductions are unclear.

Case report: high prenatal bisphenol a exposure and infant neonatal neurobehavior.

CONTEXT: Most of the U.S. population is exposed to the high-production-volume chemical bisphenol A (BPA), but targetable sources of exposure remain to be determined. Animal studies and one human study suggest that BPA is a neurotoxicant. CASE PRESENTATION: A mother in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort examining prenatal and postnatal environmental toxicants and childhood health outcomes, had a urinary BPA concentration of 583 µg/g creatinine at 27 weeks of pregnancy, which was the highest concentration observed in this cohort (median, 2.0 µg/g creatinine) and the general population. We used prenatal questionnaire data and a follow-up interview to identify potential sources of exposure that included daily plastic use and consumption of canned beverages and foods. Her male infant had a normal newborn neurobehavioral assessment but presented with abnormalities at the 1-month examination that prompted physician referral. Subsequently, the child had normal neurobehavioral testing results at annual evaluations from 1 to 5 years of age. DISCUSSION: Investigations into sources of high gestational urinary BPA concentrations provide an opportunity to identify potential targets for reduction of BPA exposure. This case highlights a potential link between gestational BPA exposure and transient neurobehavioral changes that is hypothesis generating and can serve to alert researchers to potential areas for examination in future studies. RELEVANCE TO CLINICAL PRACTICE: It is important to educate health care practitioners regarding potential sources of BPA exposure and anticipatory guidance on minimization of exposures during vulnerable periods of development.

Bisphenol A and children's health.

PURPOSE OF REVIEW: Bisphenol A (BPA) is a widely used chemical that has been shown to adversely affect health outcomes in experimental animal studies, particularly following fetal or early life exposure. Despite widespread human exposure in the United States and developed countries, there are limited epidemiological studies on the association of BPA with adverse health outcomes. This review briefly summarizes the epidemiological literature with special emphasis on childhood health outcomes. RECENT FINDINGS: Several studies report correlations between urinary BPA and serum sex steroid hormone concentrations in adults. Two studies report weak associations between urinary BPA concentrations and delayed onset of breast development in girls. One study found a relationship between prenatal BPA exposure and increased hyperactivity and aggression in 2-year-old female children. SUMMARY: Additional large prospective cohort studies are needed to confirm and validate findings from animal studies. Even in the absence of epidemiological studies, concern over adverse effects of BPA is warranted given the unique vulnerability of the developing fetus and child. Healthcare providers are encouraged to practice primary prevention and counsel patients to reduce BPA exposures.

Variability and predictors of urinary bisphenol A concentrations during pregnancy.

BACKGROUND: Prenatal bisphenol A (BPA) exposure may be associated with developmental toxicity, but few studies have examined the variability and predictors of urinary BPA concentrations during pregnancy. OBJECTIVE: Our goal was to estimate the variability and predictors of serial urinary BPA concentrations taken during pregnancy. METHODS: We measured BPA concentrations during pregnancy and at birth in three spot urine samples from 389 women. We calculated the intraclass correlation coefficient (ICC) to assess BPA variability and estimated associations between log10-transformed urinary BPA concentrations and demographic, occupational, dietary, and environmental factors, using mixed models. RESULTS: Geometric mean (GM) creatinine-standardized concentrations (micrograms per gram) were 1.7 (16 weeks), 2.0 (26 weeks), and 2.0 (birth). Creatinine-standardized BPA concentrations exhibited low reproducibility (ICC = 0.11). By occupation, cashiers had the highest BPA concentrations (GM: 2.8 µg/g). Consuming canned vegetables at least once a day was associated with higher BPA concentrations (GM = 2.3 µg/g) compared with those consuming no canned vegetables (GM = 1.6 µg/g). BPA concentrations did not vary by consumption of fresh fruits and vegetables, canned fruit, or store-bought fresh and frozen fish. Urinary high-molecular-weight phthalate and serum tobacco smoke metabolite concentrations were positively associated with BPA concentrations. CONCLUSIONS: These results suggest numerous sources of BPA exposure during pregnancy. Etiological studies may need to measure urinary BPA concentrations more than once during pregnancy and adjust for phthalates and tobacco smoke exposures.

Prenatal environmental tobacco smoke exposure and early childhood body mass index.

Maternal smoking during pregnancy is associated with increased risk of childhood overweight body mass index (BMI). Less is known about the association between prenatal secondhand tobacco smoke (SHS) exposure and childhood BMI. We followed 292 mother-child dyads from early pregnancy to 3 years of age. Prenatal tobacco smoke exposure during pregnancy was quantified using self-report and serum cotinine biomarkers. We used linear mixed models to estimate the association between tobacco smoke exposure and BMI at birth, 4 weeks, and 1, 2 and 3 years. During pregnancy, 15% of women reported SHS exposure and 12% reported active smoking, but 51% of women had cotinine levels consistent with SHS exposure and 10% had cotinine concentrations indicative of active smoking. After adjustment for confounders, children born to active smokers (self-report or serum cotinine) had higher BMI at 2 and 3 years of age, compared with unexposed children. Children born to women with prenatal serum cotinine concentrations indicative of SHS exposure had higher BMI at 2 (mean difference [MD] 0.3 [95% confidence interval -0.1, 0.7]) and 3 (MD 0.4 [0, 0.8]) years compared with unexposed children. Using self-reported prenatal exposure resulted in non-differential exposure misclassification of SHS exposures that attenuated the association between SHS exposure and BMI compared with serum cotinine concentrations. These findings suggest active and secondhand prenatal tobacco smoke exposure may be related to an important public health problem in childhood and later life. In addition, accurate quantification of prenatal secondhand tobacco smoke exposures is essential to obtaining valid estimates.

A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight.

BACKGROUND: The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure. METHODS: We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations) and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression. RESULTS: We detected nicotine (80%), cotinine (69%), and trans-3'-hydroxycotinine (57%) in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight. CONCLUSIONS: Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

Determinants of serum cotinine and hair cotinine as biomarkers of childhood secondhand smoke exposure.

Understanding the determinants of childhood secondhand smoke (SHS) exposure is important in measuring and preventing exposure to this widespread environmental contaminant. We evaluated the ability of a broad set of factors to explain variability in serum cotinine, reflecting recent exposure, and hair cotinine, reflecting longer-term exposure. We included repeated measures from 223 elementary-school-age asthmatic children residing with a smoker. We used a manual model-building approach and likelihood ratio tests to select a model predicting each biomarker, and also compared the predictive ability of determinants using Akaike Information Criteria. Potential determinants included a comprehensive parent questionnaire, household nicotine, home ventilation characteristics, exposure in vehicles and others' homes, child demographics, and family social class. Variables in each of these categories remained in the final model for both serum (R(2) of 0.61) and hair cotinine (R(2) of 0.45). A comprehensive set of factors was required to best predict cotinine. Studies should use biomarkers for the best quantitative assessment of SHS exposure. Hair cotinine may be a problematic measure because it was highly influenced by racial differences that were unexplained by SHS exposure. When biospecimen collection is not possible, a household nicotine measurement is warranted. If only questionnaires are available, multiple questions are required to best characterize exposure, such as number of cigarettes, hours spent in a room with concurrent smoking, maternal smoking, and approximate home size.

The effect of maternal smoking during pregnancy on intellectual disabilities among 8-year-old children.

Prenatal tobacco smoke exposure has been implicated as a risk factor for cognitive deficits in children. The purpose of this study is to examine the association between prenatal tobacco smoke exposure and diagnosis of intellectual disabilities (ID) among 8-year-old children living in Arkansas, Georgia, North Carolina and Utah. In 2002 and 2004, 965 ID case children were identified through a surveillance network and compared with the population of children born in the surveillance region during the same period (n = 104 607). Prenatal tobacco smoke exposure was determined from birth certificates. We estimated the effect of prenatal tobacco smoke exposure (none, <10, 10-19 and > or =20 cigarettes per day) on ID using logistic regression. Generally, the risk of ID was mildly elevated among children whose mothers smoked > or =20 cigarettes per day during pregnancy [RR 1.34; 95% (confidence interval) CI 0.96, 1.87] after adjustment for maternal education, maternal race, maternal age, marital status, child sex, birth year and study site. However, the effect of exposure to > or =20 cigarettes per day significantly differed for males [RR 1.77, 95% CI 1.20, 2.62] compared with females [RR 0.81, 95% CI 0.44, 1.50]. Supplemental analyses reveal substantial confounding of this relationship by socio-economic indicators. A differential effect of tobacco smoke exposure on the risk of ID is suggested for males and females and deserves further investigation; however, the interpretation is tempered by the potential for residual confounding.

Prenatal bisphenol A exposure and early childhood behavior.

BACKGROUND: Prenatal exposure to bisphenol A (BPA) increases offspring aggression and diminishes differences in sexually dimorphic behaviors in rodents. OBJECTIVE: We examined the association between prenatal BPA exposure and behavior in 2-year-old children. METHODS: 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. RESULTS: 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