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Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants.

ABSTRACT: The association of prenatal phthalate exposure with physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants from a prospective cohort. Phthalate metabolites were quantified in urine from 16-18 gestational weeks and a pool of five urines from across pregnancy. Infants' looking times to physically impossible and possible events were recorded via infrared eye-tracking. Infants that recognize that one of the events is impossible will look at that event longer. Associations of phthalate biomarkers with looking time differences (impossible-possible) were adjusted for maternal age, infant sex, and order of event presentation, and effect modification by infant sex was assessed. Each interquartile range (IQR) increase of monoethyl phthalate in the pooled sample was associated with females' increased looking time (? = 1.0; 95%CI = 0.3, 1.7 s) to the impossible event. However, for males, an IQR increase in monoethyl phthalate at 16-18 weeks (? = -2.5; 95%CI = -4.4,-0.6 s), the sum of di(isononyl) phthalate metabolites in the pooled sample (? = -1.0; 95%CI = -1.8, -0.1 s), and the sum of all phthalate metabolites in both samples (? = -2.3; 95%CI = -4.4, -0.2 s) were associated with increased looking to the possible event, suggesting that higher prenatal phthalate exposure is associated with poorer physical reasoning in male infants.

SUBMITTER: Merced-Nieves FM

PROVIDER: S-EPMC7917638 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants.

Merced-Nieves Francheska M FM Dzwilewski Kelsey L C KLC Aguiar Andrea A Musaad Salma S Korrick Susan A SA Schantz Susan L SL

International journal of environmental research and public health 20210213 4

The association of prenatal phthalate exposure with physical reasoning was assessed in 159 (78 female; 81 male) 4.5-month-old infants from a prospective cohort. Phthalate metabolites were quantified in urine from 16-18 gestational weeks and a pool of five urines from across pregnancy. Infants' looking times to physically impossible and possible events were recorded via infrared eye-tracking. Infants that recognize that one of the events is impossible will look at that event longer. Associations ...[more]

PMID: 33668677

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Project description:BackgroundPhthalates are endocrine disrupting chemicals that have been associated with adverse neurobehavior, but little is known about their influence on infant cognition.MethodsA visual recognition memory task was used to assess cognition in 244 7-8-month-old infants (121 females; 123 males) from a prospective cohort study. Phthalate metabolites were quantified in maternal urines pooled from across pregnancy. The task included familiarization trials (infant shown 2 identical faces) and test trials (infant shown the now familiar face paired with a novel one). Half of the infants saw one set of faces as familiar (set 1) and half saw the other set as familiar (set 2). During familiarization trials, average run duration (time looking at stimuli before looking away, measure of processing speed), and time to familiarization (time to reach 20 s looking at the stimuli, measure of attention) were assessed. During test trials, novelty preference (proportion of time looking at the novel face, measure of recognition memory) was assessed. Multivariable generalized linear models were used to assess associations of monoethyl phthalate (MEP), sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), sum of di(isononyl) phthalate metabolites (ΣDINP), and sum of anti-androgenic phthalate metabolites (ΣAA) with each outcome.ResultsMothers were mostly white and college educated, and urine phthalate concentrations were similar to those in reproductive age women in the U.S.PopulationAll phthalate exposure biomarkers, except MEP, were associated with increases in average run duration. However, depending on the phthalate, associations were only in males or infants who saw the set 2 stimuli as familiar. Unexpectedly, ΣAA was associated with a shorter time to reach familiarization. Phthalate biomarkers also were associated with modest decrements in novelty preference, but these associations were nonsignificant.ConclusionPrenatal exposure to phthalates may be related to slower information processing and poorer recognition memory in infants.

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.

Project description:Maternal prenatal stress can adversely impact subsequent child neurodevelopment, but little is known about its effect on cognitive development in infancy. This analysis of 107 infants from a prospective birth cohort assessed whether prenatal stress disrupts sexually dimorphic performance typically observed on a physical reasoning task. Maternal stress was assessed at 8-14 and 33-37 gestational weeks using the Perceived Stress Scale. Stress was defined as: low (scores below the median at both times), medium (scores above the median at one of the two times), and high (scores above the median at both times). At 4.5 months infants saw videos of two events: one impossible and the other possible. In the impossible event a box was placed against a wall without support underneath. In the possible event the box was placed against the wall, supported by the floor. Looking time at each event was recorded via infrared eye-tracking. Previous literature has shown that, at 4.5 months of age, girls typically look significantly longer at the impossible than at the possible event, suggesting that they expect the unsupported box to fall and are surprised when it does not. Boys tend to look equally at the two events suggesting that they do not share this expectation. This sex difference was replicated in the current study. General linear models stratified by sex and adjusted for household income, maternal education, mother's age at birth, infant's age at exam, and order of event presentation revealed that girls whose mothers reported high perceived stress during pregnancy had shorter looking time differences between the impossible and possible events than girls whose mothers reported low perceived stress (β = -7.1; 95% CI: -12.0, -2.2 s; p = 0.006). Similar to boys, girls in the highest stress category spent about the same amount of time looking at each event. For boys, there were no significant looking time differences by maternal stress level. This finding suggests prenatal stress is associated with a delay in the development of physical reasoning in girls.

Project description:BACKGROUND:Previous studies suggest that prenatal exposure to phthalates, ubiquitous synthetic chemicals, may adversely affect neurodevelopment. However, data are limited on how phthalates affect cognition, executive function, and behavioral function into adolescence. OBJECTIVE:We aimed to investigate associations of prenatal phthalate exposure with neurodevelopment in childhood and adolescence in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study. METHODS:We examined associations between maternal urinary phthalate metabolite concentrations measured twice during pregnancy and a range of neurodevelopmental outcomes from ages 7 through 16 y in the CHAMACOS birth cohort (n=334). We used age-specific linear regression models and generalized estimating equation models to assess longitudinal effects and examined differences by sex. RESULTS:Phthalate metabolites were detected in 88%-100% of samples, depending on the metabolite. Associations of phthalates with neurodevelopmental outcomes were largely null with some noteworthy patterns. Higher prenatal concentrations of metabolites of low-molecular weight phthalates (?LMW) were associated with more self-reported hyperactivity [?=0.8, 95% confidence interval (CI): 0.1, 1.4 per 2-fold increase in ?LMW phthalates], attention problems (?=1.5, 95% CI: 0.7, 2.2), and anxiety (?=0.9, 95% CI: 0.0, 1.8) at age 16. We observed sex-specific differences for the sums of high-molecular-weight and di(2-ethylhexyl) metabolites and cognitive outcomes (e.g., ? for Full-Scale IQ for boys=-1.9, 95% CI: -4.1, 0.3 and -1.7, 95% CI: -3.8, 0.3, respectively; ? for girls=1.8, 95% CI: 0.1, 3.4 and 1.6, 95% CI: 0.0, 3.2, respectively; p-int=0.01 for both). CONCLUSION:We found predominantly null associations of prenatal phthalates with neurodevelopment in CHAMACOS, and weak associations of ?LMW phthalates with internalizing and externalizing behaviors in adolescence. No previous studies have examined associations of prenatal phthalate exposure with neurodevelopment into adolescence, an important time for manifestations of effects. https://doi.org/10.1289/EHP5165.

Dataset Information

Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants.

Publications

Associations of Prenatal Exposure to Phthalates with Measures of Cognition in 4.5-Month-Old Infants.

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