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Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health.

ABSTRACT: Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.The Strengths and Difficulties Questionnaire (SDQ) was used to assess behavioral problems at 5 years of age. BPA and phthalate metabolite levels in the first trimester maternal serum was determined by LC-MS/MS for 458 children. Variables used for adjustment were parental ages, maternal cotinine levels, family income during pregnancy, child sex, birth order, and age at SDQ completed.The median concentrations of BPA, MnBP, MiBP, MEHP, and MECPP, primary and secondary metabolites of phthalates, were 0.062, 26.0, 7.0, 1.40, and 0.20 ng/ml, respectively. MECPP level was associated with increase conduct problem risk (OR?=?2.78, 95% CI 1.36-5.68) overall and the association remained after child sex stratification, and odds ratios were increased with wider confidence interval (OR?=?2.85, 95% CI 1.07-7.57 for boys, OR?=?4.04, 95% CI 1.31-12.5 for girls, respectively). BPA, ?DBPm (MnBP + MiBP), and ?DEHPm (MEHP+MECPP) levels were not associated with any of the child behavioral problems.Our analyses found no significant association between BPA or summation of phthalate metabolite levels and any of the behavioral problems at 5 years of age but suggested possible association between MECPP levels and increased risk of conduct problems.

SUBMITTER: Minatoya M

PROVIDER: S-EPMC6129008 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health.

Minatoya Machiko M Itoh Sachiko S Yamazaki Keiko K Araki Atsuko A Miyashita Chihiro C Tamura Naomi N Yamamoto Jun J Onoda Yu Y Ogasawara Kazuki K Matsumura Toru T Kishi Reiko R

Environmental health and preventive medicine 20180907 1

<h4>Background</h4>Studies reported adverse behavioral development including internalizing and externalizing problems in association with prenatal exposure to bisphenol A (BPA) and phthalates; however, findings were not sufficient due to using different assessment tools and child ages among studies. This study aimed to examine associations between maternal serum levels of BPA and phthalate metabolites and behavioral problems at preschool age.<h4>Methods</h4>The Strengths and Difficulties Questio ...[more]

PMID: 30193567

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Project description:BackgroundPrevious research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored.ObjectiveThis study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children.MethodsData 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.ResultsMaternal 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.DiscussionThis 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.

Project description:BackgroundEnvironmental health research has reported mixed findings on the associations between prenatal exposure to phthalates and parent-ratings of child behavioral problems.ObjectiveWe 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.MethodA 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.ResultsPrimary 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 (β's = 0.16), Internalizing Problems (β's from 0.16 to 0.20), and Behavioral Symptoms Index (β'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.ConclusionPrenatal 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.

Project description:BackgroundBisphenol A (BPA) is a ubiquitous endocrine disrupting compound. Several experimental and epidemiological studies suggest that gestational BPA exposure can lead to neurodevelopmental and behavioral problems in early-life, but results have been inconsistent. We previously reported that prenatal BPA exposure may affect child behavior and differently among boys and girls at ages 3-5 years.ObjectivesWe investigated the association of prenatal and early childhood BPA exposure with behavioral outcomes in 7-9 year old minority children and hypothesized that we would observe the same sex-specific pattern observed at earlier ages.MethodsAfrican-American and Dominican women enrolled in an inner-city prospective cohort study and their children were followed from mother's pregnancy through children's age 7-9 years. Women during the third trimester of pregnancy and children at ages 3 and 5 years provided spot urine samples. BPA exposure was categorized by tertiles of BPA urinary concentrations. The Child Behavioral Checklist (CBCL) was administered at ages 7 and 9 to assess multiple child behavior domains. Associations between behavior and prenatal (maternal) BPA concentrations and behavior and postnatal (child) BPA concentration were assessed via Poisson regression in models stratified by sex. These models accounted for potential confounders including prenatal or postnatal urinary BPA concentrations, child age at CBCL assessment, ethnicity, gestational age, maternal intelligence, maternal education and demoralization, quality of child's home environment, prenatal environmental tobacco smoke exposure, and prenatal mono-n-butyl phthalate concentration.ResultsThe direction of the associations differed between boys and girls. Among boys (n=115), high prenatal BPA concentration (upper tertile vs. lower two tertiles) was associated with increased internalizing (β=0.41, p<0.0001) and externalizing composite scores (β=0.40, p<0.0001) and with their corresponding individual syndrome scales. There was a general decrease in scores among girls that was significant for the internalizing composite score (β=-0.17, p=0.04) (n=135). After accounting for possible selection bias, the results remained consistent for boys. Conversely, high postnatal BPA concentration was associated with increased behaviors on both the internalizing composite (β=0.30, p=0.0002) and externalizing composite scores (β=0.33, p<0.0001) and individual subscores in girls but fewer symptoms in boys. These results remained significant in girls after accounting for selection bias.ConclusionThese results suggest BPA exposure may affect childhood behavioral outcomes in a sex-specific manner and differently depending on timing of exposure.

Project description:BackgroundPrevious reports suggest that prenatal phthalate exposure is associated with lower scores on measures of motor skills in infants and toddlers. Whether these associations persist into later childhood or preadolescence has not been studied.MethodsIn a follow up study of 209 inner-city mothers and their children the concentrations of mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monomethyl phthalate (MEP), mono-carboxy-isooctyl phthalate (MCOP), and four di-2-ethylhexyl phthalate metabolites (ΣDEHP) were measured in spot urine sample collected from the women in late pregnancy and from their children at ages 3, 5, and 7 years. The Bruininks-Oseretsky Test of Motor Proficiency short form (BOT-2) was administered at child age 11 to assess gross and fine motor skills.ResultsThe total number of children included in the study was 209. Of the 209 children, 116(55.5%) were girls and 93 were (45%) boys. Among girls, prenatal MnBP(b=-2.09; 95%CI: [-3.43, -0.75]), MBzP (b=-1.14; [95%CI: -2.13, -0.14]), and MiBP(b=-1.36; 95%CI: [-2.51, -0.21] and MEP(b=-1.23 [95%CI: -2.36, -0.11]) were associated with lower total BOT-2 composite score. MnBP (b= -1.43; 95% CI: [-2.44, -0.42]) was associated with lower fine motor scores and MiBP(b = -0.56; 95% CI: [-1.12, -0.01]) and MEP (b = -0.60; 95% CI: [-1.14, -0.06])was associated with lower gross motor scores. Among boys, prenatal MBzP (b = -0.79; 95% CI: [-1.40, -0.19]) was associated with lower fine motor composite score. The associations between MEP measured at age 3 and the BOT-2 gross motor, fine motor and total motor score differed by sex. In boys, there was an inverse association between ΣDEHP metabolites measured in childhood at ages 3 (b = -1.30; 95% CI: [-2.34, -0.26]) and 7 years (b = -0.96; 95% CI: [-1.79, -0.13]), and BOT-2 fine motor composite scores.ConclusionsHigher prenatal exposure to specific phthalates was associated with lower motor function among 11- year old girls while higher postnatal exposure to ΣDEHP metabolites was associated with lower scores among boys. As lower scores on measures of motor development have been associated with more problems in cognitive, socioemotional functioning and behavior, the findings of this study have implications related to overall child development.

Project description:BackgroundEmerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific.MethodsIn a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately.ResultsAmong boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations.ConclusionConcentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific.

Project description:BackgroundStudies suggest that phthalate exposures may adversely affect child respiratory health.ObjectivesWe evaluated associations between asthma diagnosed in children between 5 and 11 years of age and prenatal exposures to butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), di(2-ethylhexyl) phthalate (DEHP), and diethyl phthalate (DEP).MethodsPhthalate metabolites were measured in spot urine collected from 300 pregnant inner-city women. Children were examined by an allergist or pulmonologist based on the first parental report of wheeze, other respiratory symptoms, and/or use of asthma rescue/controller medication in the preceding 12 months on repeat follow-up questionnaires. Standardized diagnostic criteria were used to classify these children as either having or not having current asthma at the time of the physician examination. Children without any report of wheeze or the other asthma-like symptoms were classified as nonasthmatics at the time of the last negative questionnaire. Modified Poisson regression analyses were used to estimate relative risks (RR) controlling for specific gravity and potential confounders.ResultsOf 300 children, 154 (51%) were examined by a physician because of reports of wheeze, other asthma-like symptoms, and/or medication use; 94 were diagnosed with current asthma and 60 without current asthma. The remaining 146 children were classified as nonasthmatic. Compared with levels in nonasthmatics, prenatal metabolites of BBzP and DnBP were associated with a history of asthma-like symptoms (p < 0.05) and with the diagnosis of current asthma: RR = 1.17 (95% CI: 1.01, 1.35) and RR = 1.25 (95% CI: 1.04, 1.51) per natural log-unit increase, respectively. Risk of current asthma was > 70% higher among children with maternal prenatal BBzP and DnBP metabolite concentrations in the third versus the first tertile.ConclusionPrenatal exposure to BBzP and DnBP may increase the risk of asthma among inner-city children. However, because this is the first such finding, results require replication.

Dataset Information

Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health.

Publications

Prenatal exposure to bisphenol A and phthalates and behavioral problems in children at preschool age: the Hokkaido Study on Environment and Children's Health.

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