Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6-10 years of age.
Ontology highlight
ABSTRACT: Background
There is concern over potential neurobehavioral effects of prenatal phthalate exposures, but available data are inconsistent.Objectives
We examined associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral scores among children.Methods
We measured phthalate metabolite concentrations in urine samples from 153 pregnant participants in the Study for Future Families, a multicenter cohort study. Mothers completed the Child Behavior Checklist when the children were 6-10 years of age. We estimated overall and sex-specific associations between phthalate concentrations and behavior using adjusted multiple regression interaction models.Results
In boys, concentrations of monoisobutyl phthalate were associated with higher scores for inattention (? = 0.27; 95% CI: 0.04, 0.50), rule-breaking behavior (? = 0.20; 95% CI: 0.01, 0.38), aggression (? = 0.34; 95% CI: 0.09, 0.59), and conduct problems (? = 0.39; 95% CI: 0.20, 0.58), whereas the molar sum of di(2-ethylhexyl) phthalate metabolites was associated with higher scores for somatic problems (? = 0.15; 95% CI: 0.03, 0.28). Higher monobenzyl phthalate concentrations were associated with higher scores for oppositional behavior (? = 0.16; 95% CI: 0.01, 0.32) and conduct problems (? = 0.21; 95% CI: 0.06, 0.37) in boys, but with reduced anxiety scores in girls (? = -0.20; 95% CI: -0.39, -0.01). In general, the associations reported above were close to the null among girls. Model coefficients represent the difference in the square root-transformed outcome score associated with a 1-unit increase in log-transformed metabolites.Conclusions
Our results suggest associations between exposure to certain phthalates in late pregnancy and behavioral problems in boys. Given the few studies on this topic and methodological and population differences among studies, additional research is warranted.
SUBMITTER: Kobrosly RW
PROVIDER: S-EPMC4014764 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
Publications
Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6-10 years of age.
Kobrosly Roni W RW Evans Sarah S Miodovnik Amir A Barrett Emily S ES Thurston Sally W SW Calafat Antonia M AM Swan Shanna H SH
Environmental health perspectives 20140221 5
<h4>Background</h4>There is concern over potential neurobehavioral effects of prenatal phthalate exposures, but available data are inconsistent.<h4>Objectives</h4>We examined associations between prenatal urinary concentrations of phthalate metabolites and neurobehavioral scores among children.<h4>Methods</h4>We measured phthalate metabolite concentrations in urine samples from 153 pregnant participants in the Study for Future Families, a multicenter cohort study. Mothers completed the Child Beh ...[more]
Similar Datasets
Project description:We used data from the 2016 Nepal National Micronutrient Status Survey to evaluate factors associated with anaemia (World Health Organization cut-points using altitude- and smoking-adjusted haemoglobin [Hb]) among nationally representative samples of adolescents 10-19 years. Hb, biomarkers of micronutrients, infection and inflammation were assessed from venous blood. Sociodemographic and household characteristics, dietary diversity, pica and recent morbidity were ascertained by interview. We explored bivariate relationships between candidate predictors and anaemia among boys (N = 967) and girls (N = 1,680). Candidate predictors with P < 0.05 in bivariate analyses were included in sex-specific multivariable logistic regression models. Anaemia prevalence was 20.6% (95% confidence interval [CI] [17.1, 24.1]) among girls and 10.9% (95% CI [8.2, 13.6]) among boys. Among girls, living in the Mountain and Hill ecological zones relative to the Terai (adjusted odds ratio [AOR] 0.28, 95% CI [0.15, 0.52] and AOR 0.42, 95% CI [0.25, 0.73], respectively), ln ferritin (μg/L) (AOR 0.53, 95% CI [0.42, 0.68]) and ln retinol binding protein (RBP) (μmol/L) (AOR 0.08, 95% CI [0.04, 0.16]) were associated with reduced anaemia odds. Older age (age in years AOR 1.19, 95% CI [1.12, 1.27]) and Janajati ethnicity relative to the Muslim ethnicity (AOR 3.04, 95% CI [1.10, 8.36]) were associated with higher anaemia odds. Among boys, ln RBP [μmol/L] (AOR 0.25, 95% CI [0.10, 0.65]) and having consumed flesh foods (AOR 0.57, 95% CI [0.33, 0.99]) were associated with lower anaemia odds. Open defecation (AOR 2.36, 95% CI [1.15, 4.84]) and ln transferrin receptor [mg/L] (AOR 3.21, 95% CI [1.25, 8.23]) were associated with increased anaemia odds. Anaemia among adolescents might be addressed through effective public health policy and programs targeting micronutrient status, diet and sanitation.
| S-EPMC8770652 | biostudies-literature
Project description:BackgroundPrenatal phthalate exposure has been linked with altered neurodevelopment, including externalizing behaviors and attention-deficit hyperactivity disorder (ADHD). However, the implicated metabolite, neurobehavioral endpoint, and child sex have not always been consistent across studies, possibly due to heterogeneity in neurodevelopmental instruments. The complex set of findings may be synthesized using executive function (EF), a construct of complex cognitive processes that facilitate ongoing goal-directed behaviors. Impaired EF can be presented with various phenotypes of poor neurodevelopment, differently across structured conditions, home/community, or preschool/school. We evaluated the relationship between prenatal phthalate exposure and comprehensive assessment of preschool EF.MethodsOur study comprised 262 children with clinically significant/subthreshold ADHD symptoms and 78 typically developing children who were born between 2003 and 2008 and participated in the Preschool ADHD Substudy, which is nested within a population-based prospective cohort study, the Norwegian Mother, Father, and Child Cohort (MoBa). Twelve phthalate metabolites were measured from urine samples that their mothers had provided during pregnancy, at 17 weeks' gestation. All children, at approximately 3.5-years, took part in a detailed clinical assessment that included parent-and teacher-rated inventories and administered tests. We used instruments that measured constructs related to EF, which include a parent-and teacher-reported Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and three performance-based tests: A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet intelligence test V (SB5), and the cookie delay task (CDT). The standard deviation change in test score per interquartile range (IQR) increase in phthalate metabolite was estimated with multivariable linear regression. We applied weighting in all models to account for the oversampling of children with clinically significant or subthreshold symptoms of ADHD. Additionally, we assessed modification by child sex and potential co-pollutant confounding.ResultsElevated exposure to mono-benzyl phthalate (MBzP) during pregnancy was associated with poorer EF, across all domains and instruments, in both sex. For example, an IQR increase in MBzP was associated with poorer working memory rated by parent (1.23 [95% CI: 0.20, 2.26]) and teacher (1.13 [0.14, 2.13]) using BRIEF-P, and administered tests such as SB5 (no-verbal: 0.19 [0.09, 0.28]; verbal: 0.13 [0.01, 0.25]). Adverse associations were also observed for mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), although results varied by instruments. EF domains reported by parents using BRIEF-P were most apparently implicated, with stronger associations among boys (e.g., MnBP and inhibition: 2.74 [1.77, 3.72]; MiBP and inhibition: 1.88 [0.84, 2.92]) than among girls (e.g., MnBP and inhibition: -0.63 [-2.08, 0.83], interaction p-value: 0.04; MiBP and inhibition: -0.15 [-1.04, 0.74], interaction p-value: 0.3). Differences by sex, however, were not found for the teacher-rated BRIEF-P or administered tests including NEPSY, SB5, and CDT.Conclusion and relevanceElevated mid-pregnancy MBzP, MiBP, and MnBP were associated with more adverse profiles of EF among preschool-aged children across a range of instruments and raters, with some associations found only among boys. Given our findings and accumulating evidence of the prenatal period as a critical window for phthalate exposure, there is a timely need to expand the current phthalate regulations focused on baby products to include pregnancy exposures.
| S-EPMC7945722 | biostudies-literature
Project description:Study questionIs the age of onset of pubertal markers related to subsequent changes in DNA methylation (DNAm)?Summary answerWe identified 273 cytosine-phosphate-guanine (CpG) dinucleotides in girls and 67 CpGs in boys that were related to puberty and that were replicable in two other investigations.What is known alreadyPreviously, 457 CpGs (not gender-specific) and 347 (in girls) and 50 (in boys), respectively, were found to be associated with puberty, according to investigations of studies from Denmark (20 girls and 31 boys) and North America (30 girls and 25 boys).Study design size durationThe study was based on a birth cohort of 1456 participants born in 1989/90, with follow-up at age 10 and 18 years.Participants/materials setting methodsThe follow-up included 470 participants with information on DNAm and age of pubertal onset (244 girls and 226 boys). Age of pubertal onset was ascertained retrospectively at age 18 years. Using the Pubertal Development Scale, both genders were asked about ages of onset of growth spurt, body hair growth and skin changes. Ages at voice deepening and growth of facial hair were inquired from boys; ages at breast development and menarche from girls. Blood samples were collected at 10 and 18 years of age. DNA was extracted using a standard salting out procedure. The methylation level for each CpG site was assessed using one of two different platforms. DNAm was measured by a ratio of intensities denoted as β values for each CpG site. After quality control, 349 455 CpG sites were available for analysis. M values were calculated (log2(β/(1-β)) to approximate a normal distribution, and their levels were adjusted for blood cell proportions. Linear mixed models were applied to test the association between age of pubertal markers and repeated measurement of DNAm at 10 and 18 years.Main results and the role of chanceIn girls, a total of 63 019 CpGs statistically significantly changed after occurrence of any of the five pubertal events and 13 487 were changed subsequent to all five events: the respective number is boys were 3072 and 301. To further exclude false-positive findings, we investigated which CpGs were replicable in prior studies from Denmark or North America, resulting in 273 replicable CpG in girls and 67 CpGs in boys (236 and 68 genes, respectively). Most identified genes are known to be related to biological processes of puberty; however, genetic polymorphisms of only four of these genes were previously linked to pubertal markers in humans.Limitations reasons for cautionThe relative age of pubertal onset to the age of DNAm measurements does not allow causal inference, since DNAm at an earlier age may have affected the pubertal age or pubertal age may have altered later DNAm. This investigation concentrates on autosomes. CpGs on X and Y chromosomes are not included in the current study.Wider implications of the findingsAssessment of biological processes involved in pubertal transitions should include epigenetic information. Differential DNAm related to puberty needs to be investigated to determine whether it can act as an early marker for adult diseases known to be associated with puberty.Study funding/competing interestsThis work was supported by NIH grants R03HD092776 (Epigenetic characterization of pubertal transitions) and R01AI121226. The 10-year follow-up of this study was funded by National Asthma Campaign, UK (Grant No 364), and the 18-year follow-up by a grant from the National Heart and Blood Institute (R01 HL082925). The authors have no conflicts to report.
| S-EPMC7067683 | biostudies-literature
Project description:BackgroundEvidence on anemia and associated factors among young adolescent girls and boys in rural western China is limited.MethodsWe used data from a follow-up study of adolescents (10-14?years) born to women who participated in a randomized trial of antenatal micronutrient supplementation in western China. Anemia was defined by World Health Organization standards. Logistic regression was used to examine the factors associated with anemia.ResultsThe overall prevalence of anemia was 11.7% (178/1517). Female adolescents were 1.73 (95% CI 1.21, 2.48) times more likely to have anemia as compared to males. Adolescents whose mothers had completed high school were 0.35 (95% CI 0.13, 0.93) times less likely to be anemic, compared to those of whom had <?3?years of formal education. Household wealth was also inversely associated with anemia. The association of puberty status with anemia was modified by adolescent sex (P-value for interaction was 0.04); males with greater than mild pubertal development had reduced odds (OR 0.35, 95% CI 0.15, 0.83) of anemia while there was no association among females (OR 0.72, 95% CI 0.29, 1.78). Consumption of flesh foods (OR 0.58, 95% CI 0.38, 0.89), eggs (OR 0.60, 95% CI 0.38, 0.93), and having a meal frequency of three times or more per day (OR 0.68, 95% CI 0.48, 0.96) were also associated with a lower likelihood of anemia.ConclusionsAnemia was a mild public health problem among young adolescents in rural western China. Nutritional and social determinants were identified as predictors, warranting interventions to reduce the risk of anemia among this critical age group.
| S-EPMC7836596 | biostudies-literature
Project description:Gestational phthalate exposures have been adversely associated with attention, externalizing, and internalizing behaviors in childhood. Early childhood temperament may be a marker of later behavioral patterns. We therefore sought to determine whether gestational phthalate exposures were associated with infant and toddler temperament.The Mount Sinai Children's Environmental Health Study is a prospective cohort study of children born between May 1998 and July 2001 in New York City (N=404). Phthalate metabolites were measured in spot urine samples collected from pregnant women in their third trimester. Child temperament was assessed by parental report at 12-months using the Infant Behavior Questionnaire (IBQ) (N=204) and at 24-months using the Toddler Behavior Assessment Questionnaire (TBAQ) (N=279). We used multiple linear regression to evaluate associations between urinary phthalate metabolites and eleven temperament domains.Phthalate biomarker concentrations were weakly associated with lower gross motor activity levels as well as higher duration of orienting at the 12-month assessment. Mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP) and the sum of metabolites of di(2-ethylhexyl) phthalate (?DEHP) were associated with lower levels of smiling and laughing at 12 months. At 24-months, social fear and lower pleasure was linked to higher concentrations of MCPP and MBzP, and higher ?DEHP was weakly associated with increased anger levels at 24-months.Though we observed some weak associations between biomarkers of prenatal exposure to phthalates and temperament at 12- and 24-months, overall phthalates biomarkers were not strongly associated with alterations in temperament.
| S-EPMC5623642 | biostudies-literature
Project description:Prenatal exposure to gonadal hormones plays a major role in the normal development of the male and female brain and sexually dimorphic behaviors. Hormone-dependent differences in brain structure and function suggest that exposure to exogenous endocrine disrupting chemicals may be associated with sex-specific alterations in behavior. Bisphenol A (BPA) is an environmental chemical that has been shown to alter estrogen, androgen, and thyroid hormone signaling pathways. Epidemiological and experimental studies suggest associations between prenatal exposure to BPA and child behavior, however data are inconsistent, and few studies have examined school age children. We examined BPA concentration in spot urine samples from women at mean 27 weeks of pregnancy in relation to child behavior assessed at age 6-10 years using the parent-completed Child Behavior Checklist (CBCL). We report associations between maternal BPA urinary concentrations and several CBCL scores in 153 children (77 boys and 76 girls). We observed a significant interaction between maternal urinary BPA and sex for several behaviors (externalizing, aggression, Anxiety Disorder, Oppositional/Defiant Disorder and Conduct Disorder traits), but no significant associations between BPA and scores on any CBCL scales. However in analyses restricted to children of mothers with detectable prenatal urinary BPA (n=125), BPA was associated with moderately increased internalizing and externalizing behaviors, withdrawn/depressed behavior, somatic problems, and Oppositional/Defiant Disorder traits in boys. In addition we observed a significant interaction between BPA and sex for several behaviors (externalizing, withdrawn/depressed, rule-breaking, Oppositional/Defiant Disorder traits, and Conduct Disorder traits). These results suggest that prenatal exposure to BPA may be related to increased behavior problems in school age boys, but not girls.
| S-EPMC4362616 | biostudies-literature
Project description:During fetal development, sex steroids influence sexually dimorphic behaviors, such as visual-spatial abilities. Thus, endocrine disrupting chemicals that impact sex steroids during gestation may affect these behaviors.We investigated the relationship between prenatal urinary phthalate metabolite, triclosan, and BPA concentrations and visual-spatial abilities in a prospective cohort of 198 mother-child dyads.Data are from a prospective cohort in Cincinnati, OH (HOME Study). We measured nine phthalate metabolites, triclosan, and BPA in maternal urine samples collected at 16 and 26 weeks of gestation. We assessed children's visual-spatial abilities at 8 years of age using the Virtual Morris Water Maze (VMWM), a computerized version of the rodent Morris Water Maze. We quantified the covariate-adjusted change in the time or distance to complete the VMWM and time spent in the correct quadrant during a probe trial with an interquartile range increase in chemical concentrations using linear mixed models and linear regression, respectively.Boys completed the VMWM faster (4.1s; 95% CI:-7.1, -1.2) and in less distance (1.4 units; 95% CI:-2.8, 0) than girls. Overall, children with higher mono-n-butyl (MnBP), mono-benzyl (MBzP), and mono-carboxypropyl phthalate concentrations completed the VMWM in less time and distance than children with lower concentrations. For example, children with higher MnBP concentrations completed the VMWM in 0.9 less distance units (95% CI:-1.8, -0.0). Child sex modified the association between MnBP and VMWM performance. In girls, higher MnBP concentrations were associated with longer time (1.7s; 95% CI: -0.7, 4.1) and shorter distance (-1.7 units; 95% CI: -2.8, -0.5), whereas in boys, it was associated with shorter time (-3.0s; 95% CI:-5.6, -0.4), but not distance (-0.1 units; 95% CI:1.4, 1.0). Other phthalate metabolites, triclosan, and BPA were not associated with VMWM performance, and sex did not consistently modify these associations.In this cohort, greater prenatal urinary concentrations of some phthalate metabolites were associated with improved VMWM performance, particularly among boys. Future studies should confirm these findings and determine if phthalates affect other hormonally sensitive aspects of child neurobehavior.
| S-EPMC5303542 | biostudies-literature
Project description:BACKGROUND:Phthalates are environmental chemicals that may play a role in the development of obesity. Few studies have investigated longitudinal associations between postnatal phthalate exposures and subsequent anthropometric measurements in children. METHODS:We collected data as part of The Breast Cancer and Environment Research Program at three US sites. A total of 1,239 girls, aged 6-8 years, were enrolled in 2004-2007. We categorized baseline phthalate exposures, assessed from creatinine-corrected urinary concentrations of low-molecular weight phthalate metabolites, as low, <78; medium, 78 to <194; and high, ?194 ?g/g creatinine and of high-molecular weight phthalates as low, <111; medium, 111-278; and high, ?278 ?g/g creatinine. Anthropometric measurements were collected through 2012 (n = 1,017). Linear mixed effects regression estimated how baseline low and high-molecular weight phthalate concentrations related to changes in girls' body mass index (BMI), height, and waist circumference at ages 7-13 years. RESULTS:Low-molecular weight phthalates were positively associated with gains in BMI and waist circumference. Predicted differences in BMI and waist circumference between girls with high versus low concentrations of low-molecular weight phthalates increased from 0.56 (95% confidence interval [CI]: -0.02, 1.1) to 1.2?kg/m (95% CI: 0.28, 2.1) and from 1.5 (95% CI: -0.38, 3.3) to 3.9?cm (95% CI: 1.3, 6.5), respectively. High-molecular weight phthalates were negatively associated with height but only among girls who were normal weight at baseline (BMI ? 85th percentile). CONCLUSION:Phthalates, specifically low-molecular weight phthalates, have small but detectable associations with girls' anthropometric outcomes. Low-molecular weight phthalates showed stronger associations than other types of phthalates.
| S-EPMC5524128 | biostudies-literature
Project description:Phthalates are ubiquitous endocrine-disrupting chemicals, and research indicates that prenatal exposure to some phthalates may affect neurodevelopment. In a prospective birth cohort study, five first-morning urine samples collected across pregnancy were pooled and the following phthalate biomarkers assessed: sum of di-(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of diisononyl phthalate metabolites (ΣDINP), sum of dibutyl phthalate metabolites (ΣDBP), sum of anti-androgenic metabolites (ΣAA), monoethyl phthalate (MEP), and sum of all phthalate metabolites (ΣAll). The Ages & Stages Questionnaires® (ASQ), a standardized parent-reported, age-adapted screening tool, measured communication, personal-social, problem solving, and motor domains in infants at 4.5 and 7.5 months (n = 123). Adjusting for maternal age, annual household income, gestational age at birth, infant age at assessment, and sex, repeated-measures generalized linear regression models were used to examine associations between prenatal phthalate urine biomarker concentrations and domain scores (assuming a Poisson distribution). Beta estimates were exponentiated back to the domain scale for ease of interpretation. Mothers were mostly white and college-educated, and most reported an annual household income of ≥$60,000. Associations of phthalate concentrations with ASQ outcomes are presented as follows: (1) anti-androgenic phthalate metabolites (ΣDEHP, ΣDINP, ΣDBP, and ΣAA), (2) MEP, which is not anti-androgenic, and (3) ΣAll. Overall, anti-androgenic phthalates were associated with higher (i.e., better) scores. However, there were exceptions, including the finding that a one-unit increase in ΣDBP was associated with a 12% increase in problem solving scores in 4.5-month-old females (β = 1.12; 95% CI: 0.99, 1.28; p = 0.067) but a 85% decrease for 7.5-month-old females (β = 0.54; 95% CI: 0.3, 0.99; p = 0.047). In contrast, MEP was associated with poorer scores on several outcomes. Sex- and timepoint-specific estimates demonstrated a one-unit increase in MEP was associated with: a 52% decrease in personal-social scores in 7.5-month-old males (β = 0.66; 95% CI: 0.46, 0.95; p = 0.02), a 39% decrease in fine motor scores in 7.5-month-old males (β = 0.72; 95% CI: 0.52, 0.98; p = 0.035), and a 6% decrease in fine motor scores in 4.5-month-old females (β = 0.94; 95% CI: 0.88, 0.99; p = 0.03). A one-unit increase in ΣAll was associated with a 4% increase in personal-social scores in 4.5-month-old males (β = 1.04; 95% CI: 0.99, 1.1; p = 0.08) but a 17% decrease in 7.5-month-old males (β = 0.85; 95% CI: 0.73, 0.99; p = 0.03). These data suggest age- and sex-specific associations of prenatal phthalates with infant neurobehavior. The current findings should be confirmed by longitudinal studies with larger sample sizes.
| S-EPMC9271634 | biostudies-literature
Project description:BackgroundExperimental animal studies and limited epidemiologic evidence suggest that prenatal exposure to phthalates may be obesogenic, with potential sex-specific effects of phthalates having anti-androgenic activity.ObjectivesWe aimed to assess associations between prenatal phthalate exposures and childhood fat mass in a prospective cohort study.MethodsWe measured phthalate metabolite concentrations in third-trimester maternal urine in a cohort of women enrolled in New York City between 1998 and 2002 (n = 404). Among 180 children (82 girls and 98 boys), we evaluated body composition using a Tanita scale at multiple follow-up visits between ages 4 and 9 years (363 total visits). We estimated associations of standard deviation differences or tertiles of natural log phthalate metabolite concentrations with percent fat mass using linear mixed-effects regression models with random intercepts for repeated outcome measurements. We assessed associations in multiple metabolite models and adjusted for covariates including prepregnancy body mass index, gestational weight gain, maternal smoking during pregnancy, and breastfeeding.ResultsWe did not observe associations between maternal urinary phthalate concentrations and percent body fat in models examining continuous exposures. Fat mass was 3.06% (95% CI: -5.99, -0.09%) lower among children in the highest tertile of maternal urinary concentrations of summed di(2-ethylhexyl) phthalate (ΣDEHP) metabolites than in children in the lowest tertile. Though estimates were imprecise, there was little evidence that associations between maternal urinary phthalate concentrations and percent fat mass were modified by child's sex.ConclusionsPrenatal phthalate exposures were not associated with increased body fat among children 4-9 years of age, though high prenatal DEHP exposure may be associated with lower fat mass in childhood.CitationBuckley JP, Engel SM, Mendez MA, Richardson DB, Daniels JL, Calafat AM, Wolff MS, Herring AH. 2016. Prenatal phthalate exposures and childhood fat mass in a New York City cohort. Environ Health Perspect 124:507-513; http://dx.doi.org/10.1289/ehp.1509788.
| S-EPMC4829985 | biostudies-literature