Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years.
Ontology highlight
ABSTRACT: Background
Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.Methods
In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ).Results
Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b?=?-2.69 (95% confidence interval [CI]?=?-4.33, -1.05) and b?=?-2.69 (95% CI?=?-4.22, -1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI?=?1.9, 11.4) and 7.6 (95% CI?=?3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.Conclusion
Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.
SUBMITTER: Factor-Litvak P
PROVIDER: S-EPMC4262205 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years.
Factor-Litvak Pam P Insel Beverly B Calafat Antonia M AM Liu Xinhua X Perera Frederica F Rauh Virginia A VA Whyatt Robin M RM
PloS one 20141210 12
<h4>Background</h4>Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.<h4>Methods</h4>In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl ...[more]
Similar Datasets
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.
| S-EPMC6814270 | biostudies-literature
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.
| S-EPMC7867029 | biostudies-literature
Project description:We examined whether prenatal exposure to two classes of endocrine-disrupting chemicals (EDCs) was associated with infant epigenetic age acceleration (EAA), a DNA methylation biomarker of aging. Participants included 224 maternal-infant pairs from a Canadian pregnancy cohort study. Two bisphenols and 12 phthalate metabolites were measured in maternal second trimester urines. Buccal epithelial cell cheek swabs were collected from 3 month old infants and DNA methylation was profiled using the Infinium MethylationEPIC BeadChip. The Pediatric-Buccal-Epigenetic tool was used to estimate EAA. Sex-stratified robust regressions examined individual chemical associations with EAA, and Bayesian kernel machine regression (BKMR) examined chemical mixture effects. Adjusted robust models showed that in female infants, prenatal exposure to total bisphenol A (BPA) was positively associated with EAA (B = 0.72, 95% CI: 0.21, 1.24), and multiple phthalate metabolites were inversely associated with EAA (Bs from -0.36 to -0.66, 95% CIs from -1.28 to -0.02). BKMR showed that prenatal BPA was the most important chemical in the mixture and was positively associated with EAA in both sexes. No overall chemical mixture effects or male-specific associations were noted. These findings indicate that prenatal EDC exposures are associated with sex-specific deviations in biological aging, which may have lasting implications for child health and development.
| S-EPMC11348373 | biostudies-literature
Project description:BackgroundAfrican Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards.ObjectiveWe examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs.MethodsFirst-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86).ResultsUsing quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations.SignifanceWe conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs.ImpactAfrican Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.
| S-EPMC10450095 | biostudies-literature
Project description:Although banned in most countries, dichlorodiphenyl-trichloroethane (DDT) continues to be used for vector control in some malaria endemic areas. Previous findings from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort study found increased prenatal levels of DDT and its breakdown product dichlorodiphenyl-dichloroethylene (DDE) to be associated with altered neurodevelopment in children at 1 and 2years of age. In this study, we combined the measured maternal DDT/E concentrations during pregnancy obtained for the prospective birth cohort with predicted prenatal DDT and DDE levels estimated for a retrospective birth cohort. Using generalized estimating equation (GEE) and linear regression models, we evaluated the relationship of prenatal maternal DDT and DDE serum concentrations with children's cognition at ages 7 and 10.5years as assessed using the Full Scale Intelligence Quotient (IQ) and 4 subtest scores (Working Memory, Perceptual Reasoning, Verbal Comprehension, and Processing Speed) of the Wechsler Intelligence Scale for Children (WISC). In GEE analyses incorporating both age 7 and 10.5 scores (n=619), we found prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales (p-value>0.05). In linear regression analyses assessing each time point separately, prenatal DDT levels were inversely associated with Processing Speed at age 7years (n=316), but prenatal DDT and DDE levels were not associated with Full Scale IQ or any of the WISC subscales at age 10.5years (n=595). We found evidence for effect modification by sex. In girls, but not boys, prenatal DDE levels were inversely associated with Full Scale IQ and Processing Speed at age 7years. We conclude that prenatal DDT levels may be associated with delayed Processing Speed in children at age 7years and the relationship between prenatal DDE levels and children's cognitive development may be modified by sex, with girls being more adversely affected.
| S-EPMC5152618 | biostudies-literature
Project description:High levels of persistent organic pollutants (POPs) and heavy metals are found in Arctic populations. POP and heavy metals are linked to impaired cognitive development. This study examined associations between prenatal POP and metals exposure and problematic child behavior using the Strength and Difficulties Questionnaire (SDQ). POPs and metals were measured in 102 pregnant Greenlandic women. During follow-up at 3-5 years, parents answered an assisted questionnaire including children's SDQ scores. Associations were analyzed using linear and logistic regression analyses and adjusted for maternal plasma cotinine, educational level and age at delivery. In the adjusted analyses, the medium tertile of hexachlorobenzene (β = 3.06, p = 0.010), β-hexachlorocyclohexane (β = 3.58, p = 0.004) and trans-nonachlor (β = 2.06, p = 0.082) were positively associated with SDQ scores. The continuous cis-nonachlor (OR = 1.09, p = 0.079), dichloro-diphenyl-dichloroethylene (OR = 1.01, p = 0.077), trans-nonachlor (OR = 1.01, p = 0.091), and sum Organochlorine-Pesticides (OR = 1.00, p = 0.094) were positively associated with abnormal SDQ score and the continuous mirex (OR = 1.28, p = 0.096), oxychlordane (OR = 1.04, p = 0.066), and trans-nonachlor (OR = 1.02, p = 0.071) with abnormal hyperactivity score. We found no consistent evidence of associations between polychlorinated biphenyls, perfluoroalkylated substances and heavy metals and problematic behavior. Prenatal organochlorine pesticide exposure associated significantly with problematic behavior in 3-5 year old children.
| S-EPMC8589846 | biostudies-literature
Project description:Importance:Although antibiotics are associated with obesity in animal models, the evidence in humans is conflicting. Objective:To assess whether antibiotic exposure during pregnancy and/or early childhood is associated with the development of childhood obesity, focusing particularly on siblings and twins. Design, Setting, and Participants:This cross-sectional national study included 284 211 participants (132 852 mothers and 151 359 children) in New Zealand. Data analyses were performed for 150 699 children for whom data were available, 30 696 siblings, and 4188 twins using covariate-adjusted analyses, and for 6249 siblings and 522 twins with discordant outcomes using fixed-effects analyses. Data analysis was performed November 2017 to March 2019. Exposure:Exposure to antibiotics during pregnancy and/or early childhood. Main Outcomes and Measures:The main outcome is odds of obesity at age 4 years. Anthropometric data from children born between July 2008 and June 2011 were obtained from the B4 School Check, a national health screening program that records the height and weight of 4-year-old children in New Zealand. These data were linked to antibiotics (pharmaceutical records) dispensed to women before conception and during all 3 trimesters of pregnancy and to their children from birth until age 2 years. Results:The overall study population consisted of 132 852 mothers and 151 359 children (77 610 [51.3%] boys) who were aged 4 to 5 years when their anthropometrical measurements were assessed. Antibiotic exposure was common, with at least 1 course dispensed to 35.7% of mothers during pregnancy and 82.3% of children during the first 2 years of life. Results from covariate-adjusted analyses showed that both prenatal and early childhood exposures to antibiotics were independently associated with obesity at age 4 years, in a dose-dependent manner. Every additional course of antibiotics dispensed to the mothers yielded an adjusted odds ratio (aOR) of obesity in their children (siblings) of 1.02 (95% CI, 0.99-1.06), which was similar to the odds across pregnancy for the whole population (aOR, 1.06; 95% CI, 1.04-1.07). For the child's exposure, the aOR for the association between antibiotic exposure and obesity was 1.04 (95% CI, 1.03-1.05) among siblings and 1.05 (95% CI, 1.02-1.09) among twins. However, fixed-effects analyses of siblings and twins showed no associations between antibiotic exposure and obesity, with aORs of 0.95 (95% CI, 0.90-1.00) for maternal exposure, 1.02 (95% CI, 0.99-1.04) for child's exposure, and 0.91 (95% CI, 0.81-1.02) for twins' exposure. Conclusions and Relevance:Although covariate-adjusted analyses demonstrated an association between antibiotic exposure and odds of obesity, further analyses of siblings and twins with discordant outcomes showed no associations. Thus, these discordant results likely reflect unmeasured confounding factors.
| S-EPMC6991276 | biostudies-literature
Project description:BackgroundAirborne polycyclic aromatic hydrocarbons (PAH) are widespread urban air pollutants from fossil fuel burning and other combustion sources. We previously reported that a broad spectrum of combustion-related DNA adducts in cord blood was associated with attention problems at 6-7 years of age in the Columbia Center for Children's Environmental Health (CCCEH) longitudinal cohort study.ObjectivesWe evaluated the relationship between behavioral problems and two different measures of prenatal exposure--both specific to PAH--in the same cohort.MethodsChildren of nonsmoking African-American and Dominican women in New York City (NYC) were followed from in utero to 6-7 years. Prenatal PAH exposure was estimated by personal air monitoring of the mothers during pregnancy as well as by the measurement of DNA adducts specific to benzo[a]pyrene (BaP), a representative PAH, in maternal and cord blood. At 6-7 years of age, child behavior was assessed using the Child Behavior Checklist (CBCL) (n = 253). Generalized linear models were used to test the association between prenatal PAH exposure and behavioral outcomes.ResultsIn multivariate analyses, high prenatal PAH exposure, whether characterized by personal air monitoring (greater than the median of 2.27 ng/m³) or maternal and cord adducts (detectable or higher), was positively associated with symptoms of Anxious/Depressed and Attention Problems (p ? 0.05).ConclusionThese results provide additional evidence that environmental levels of PAH encountered in NYC air can adversely affect child behavior.
| S-EPMC3385432 | biostudies-literature
Project description:The aim of this study was to determine if prenatal or recent postnatal methylmercury (MeHg) exposure from consuming ocean fish and seafood is associated with auditory deficits in young adults. Some investigators have reported adverse associations while others have found no associations. Ocean fish is an important nutrient source for billions of people around the world. Consequently, determining if there is an adverse association with objective auditory measures is important in assessing whether a risk is present or not.The peripheral and central auditory function of 534 subjects in the Seychelles Child Development Study (SCDS) Main Cohort was examined at age of 19 years. The auditory test battery included standard pure-tone audiometry, tympanometry, auditory brainstem response (ABR) latencies, and both click-evoked and distortion product otoacoustic emissions (OAE). Associations with MeHg were evaluated with multiple linear regression models, adjusting for sex, recent postnatal MeHg exposure, and hearing loss.Bilateral hearing loss (defined as a mean pure-tone threshold of greater than 25 dB) was present in 1.1%of the subjects and was not associated with prenatal or recent postnatal MeHg exposure. As expected, absolute and interwave ABR latencies were shorter for women as compared to men, as the stimulus presentation rate decreased from 69.9 to 19.9 clicks/s and as the stimulus intensity increased from 60 to 80 dBnHL. Similarly, larger OAE amplitudes were elicited in women as compared to men and in the right ears as compared to the left. There was no association of prenatal MeHg exposure with hearing loss, ABR absolute and interwave latencies or OAE amplitudes. As recent postnatal MeHg increased, some associations were found with a few ABR absolute and interwave latencies and a few OAE amplitudes. However, the direction of these associations was inconsistent. As recent postnatal MeHg levels increased the wave I absolute latencies were shorter at 80 dBnHL for all three click rates, but the interwave I–V latency was longer for males for the 80 dBnHL 19 clicks/s and for the III–V interwave latencies for males and females for the dBnHL 69 clicks/s. Similarly, smaller OAE amplitudes were found at 1500, 2000, and 4000 Hz for males while larger OAE amplitudes were found for females at 1500 and 2000 Hz as the recent postnatal MeHg levels increased.No consistent associations were present in this study between prenatal MeHg exposure from consumption of oceanic fish and seafood during pregnancy and auditory functions at 19 years of age. Given the level of prenatal exposure to MeHg, the number of audiologic measures tested, and the presence of the expected sex, click rate, and level dependent findings, it seems unlikely that an association was present and not detected. As recent postnatal MeHg exposure increased, a few associations with ABR latencies and OAE amplitudes were found. The direction of these associations was inconsistent as some showed improved performance as MeHg exposure levels increased while others showed poorer performance. The presence of the inconsistent postnatal MeHg exposure findings are intriguing and deserve further clarification.
| S-EPMC4293315 | biostudies-literature
Project description:BackgroundFish is a primary source of protein and n-3 PUFA but also contains methylmercury (MeHg), a naturally occurring neurotoxicant to which, at sufficient exposure levels, the developing fetal brain is particularly sensitive.ObjectivesTo examine the association between prenatal MeHg and maternal status of n-3 and n-6 PUFA with neurodevelopment, and to determine whether PUFA might modify prenatal MeHg associations with neurodevelopment.MethodsWe examined the Seychelles Child Development Study Nutrition Cohort 2 (NC2) at age 7 y. We used a sophisticated and extensive neurodevelopmental test battery that addressed 17 specific outcomes in multiple neurodevelopmental domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Analyses were undertaken on 1237 mother-child pairs with complete covariate data (after exclusions) and a measure of at least 1 outcome. We examined the main and interactive associations of prenatal MeHg exposure (measured as maternal hair mercury) and prenatal PUFA status (measured in maternal serum at 28 weeks' gestation) on child neurodevelopmental outcomes using linear regression models. We applied the Bonferroni correction to account for multiple comparisons and considered P values <0.0029 to be statistically significant.ResultsPrenatal MeHg exposure and maternal DHA and arachidonic acid (20:4n-6) (AA) status were not significantly associated with any neurodevelopmental outcomes. Findings for 4 outcomes encompassing executive function, cognition, and linguistic skills suggested better performance with an increasing maternal n-6:n-3 PUFA ratio (P values ranging from 0.004 to 0.05), but none of these associations were significant after adjusting for multiple comparisons. No significant interaction between MeHg exposure and PUFA status was present.ConclusionsOur findings do not support an association between prenatal MeHg exposure or maternal DHA and AA status with neurodevelopmental outcomes at age 7 y. The roles of n-6 and n-3 PUFA in child neurodevelopment need further research.
| S-EPMC7851824 | biostudies-literature