Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children.

BACKGROUND: The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. METHODS: We enrolled 2,001 women>18 years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3-4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale-II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 T-scores with a doubling in phthalate concentrations in 510 children with complete data. RESULTS: Mean total SRS T-score was 45.3 (SD=6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3-carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS T-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS T-scores. Associations were consistently and significantly stronger in boys (ßMBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (ßMBP=0.1; 95% CI: -0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400µg/d) (ßMBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (≥400µg/d) (ßMBP=0.4; 95% CI: -0.1, 0.8; n=451). CONCLUSIONS: Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. https://doi.org/10.1289/EHP5621.

Associations of cord blood leptin and adiponectin with children's cognitive abilities.

Background Adipocytokines may play a role in fetal programming of neurodevelopment. We aimed to investigate the associations between cord blood adipocytokine concentrations and children's intelligence test scores. Methods We used data from two ongoing pregnancy cohorts in North America: the Maternal-Infant Research on Environmental Chemicals (MIREC, n = 429) and Health Outcomes and Measures of the Environment (HOME, n = 183) Studies. Umbilical cord blood adipocytokine concentrations were measured using enzyme-linked immunosorbent assays. We assessed children's Intelligence Quotient (IQ) and its components using the Wechsler Preschool and Primary Scales of Intelligence-III or Wechsler Intelligence Scale for Children-IV. We used linear regression and linear mixed models to estimate associations between log2-transformed adipocytokine concentrations and children's IQ after adjusting for sociodemographic, perinatal, and child factors. Results After adjusting for covariates, cord blood adiponectin was positively associated with children's full-scale IQ scores at age 3 years in the MIREC Study (ß = 1.4, 95% confidence interval [CI]: 0.2, 2.5) and at ages 5 and 8 years in the HOME Study (ß = 1.7, CI: -0.1, 3.5). Adiponectin was positively associated with performance IQ in both studies (MIREC: ß = 2.0, CI: 0.7, 3.3; HOME: ß = 2.2, CI: 0.5, 3.9). Adiponectin was positively associated with working memory composite scores at age 8 in the HOME Study (ß = 3.1, CI: 1.0, 5.2). Leptin was not associated with children's IQ in either study. Conclusions Cord blood adiponectin was associated with higher full-scale and performance IQ and working memory composite scores in children. Future studies are needed to explore the mechanisms underlying these associations.

Prenatal, concurrent, and sex-specific associations between blood lead concentrations and IQ in preschool Canadian children.

BACKGROUND: Lead exposure predicts altered neurodevelopment and lower intelligence quotient (IQ) in children, but few studies have examined this association in children who have relatively low blood lead concentrations. OBJECTIVES: To test the associations between blood lead concentrations and cognitive function in Canadian preschoolers, with a possible moderation by sex. METHODS: The data were gathered from 609 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study. Lead was measured in umbilical and maternal blood, and in children's venous blood at age 3-4 years. Cognitive function was measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) at 3-4 years. We tested the relationship between WPPSI-III scores and blood lead concentrations with multiple linear regression, adding child sex as a moderator. RESULTS: Median blood lead concentrations for the mother at 1st trimester and 3rd trimester of pregnancy, and for cord and child blood were 0.60 µg/dL, 0.58 µg/dL, 0.79 µg/dL and 0.67 µg/dL, respectively. We found no association between cord blood lead concentrations and WPPSI-III scores in multivariable analyses. However, cord blood lead concentrations showed a negative association with Performance IQ in boys but not in girls (B = 3.44; SE = 1.62; 95% CI: 0.82, 5.98). No associations were found between WPPSI-III scores and prenatal maternal blood or concurrent child blood lead concentrations. CONCLUSIONS: Prenatal blood lead concentrations below 5 µg/dL were still associated with a decline in cognitive function in this Canadian cohort, but only for boys.

Prenatal exposure to polybrominated diphenyl ethers and predisposition to frustration at 7 months: Results from the MIREC study.

BACKGROUND: Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with cognitive deficits and behavioral problems in children. To date, no study has examined this exposure in association with neurobehavioral development in infants younger than 12 months assessed with observational tasks. OBJECTIVES: This study examined the relation between prenatal PBDE concentrations and predisposition to frustration, assessed by the arm restraint task (ART), in Canadian infants. METHODS: In a prospective longitudinal study conducted in Canada, exposure to nine PBDE congeners was measured in maternal plasma during the first trimester of pregnancy. The ART was used to measure predisposition to frustration in infancy (N = 333; mean age = 6.9 months), as assessed by negative vocalizations (crying and screaming) and physical reactivity (discomfort movements). RESULTS: Maternal plasma PBDE-47 concentrations collected during pregnancy were associated with negative vocalizations using the ART (adjusted Relative Risk [aRR] = 1.04, 95% CI: 1.00, 1.09). Prenatal PBDE-99 concentrations during pregnancy were also related to a shift to the left in the tail of the distribution of onset of negative vocalizations as measured by a decrease of 38 s (95% CI: -78.1, 1.3) in the 75th quantile of the distribution for infants whose mothers had detectable levels of PBDE-99 compared to infants of mothers with undetectable levels. Similarly, infants whose mothers had detectable levels of PBDE-100 showed an increase of 24.1 s (95% CI: 4.1, 44.1) in the 75th quantile of the distribution of proportion of time in negative vocalizations compared with infants of mothers with undetectable levels. Finally, the association between PBDE-47 and PBDE-153, and physical reactivity was significantly modified by sex (p < 0.1), with opposite patterns in girls and boys. CONCLUSIONS: Prenatal exposure to PBDEs was associated with increased incidence of crying and screaming with delayed onset of discomfort movement, which may indicate a predisposition to frustration and lack of habituation in infants younger than 12 months from the general population.

Prenatal urinary triclosan concentrations and child neurobehavior.

BACKGROUND: Exposure to triclosan, an antimicrobial chemical, is ubiquitous among pregnant women and may reduce thyroid hormone levels that are important for fetal neurodevelopment. Few studies have examined the association between prenatal triclosan exposure and children's neurobehavior. OBJECTIVE: We investigated the relationship of prenatal urinary triclosan concentrations with children's behavior and cognitive abilities at age three years in a prospective pregnancy and birth cohort in Canada. METHODS: We measured triclosan in urine samples collected at ~12 weeks of gestation in 794 Canadian women enrolled in a prospective pregnancy and birth cohort study (MIREC) from 2008 to 2011. Around age 3 years, we assessed children's cognitive abilities using the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III), and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's problem and reciprocal social behaviors using the Behavior Assessment System for Children-2 (BASC-2) and Social Responsiveness Scale-2 (SRS-2), respectively. RESULTS: After adjusting for confounders using multivariable linear regression, triclosan was not associated with most of the 30 examined neurobehavioral scales. Each 10-fold increase in triclosan was associated with better WPPSI-III picture completion scores (ß: 0.2; 95% CI: 0,0.5) and BASC-2 externalizing (ß: -0.5; 95% CI: -1.1, 0) and hyperactivity (ß: -0.6; 95% CI: -1.2, -0.1) scores, suggesting less externalizing and hyperactive behaviors. Child sex did not modify these associations. CONCLUSIONS: In this cohort, urinary triclosan concentrations measured once in early pregnancy were not associated with most assessed aspects of neurobehavior and weakly associated with a few others, but not in the hypothesized direction.

Associations of Prenatal Urinary Bisphenol A Concentrations with Child Behaviors and Cognitive Abilities.

BACKGROUND: Prenatal bisphenol A (BPA) exposure has been associated with adverse neurodevelopment in epidemiological studies. However, prior studies had limited statistical power to examine sex-specific effects, and few examined child cognition. OBJECTIVES: We estimated the association between prenatal BPA exposure and child neurobehavior at 3 y of age in a prospective cohort of 812 mothers and their children. METHODS: We measured BPA concentration in urine samples collected at ∼12 wk gestation among women enrolled in a 10-city Canadian cohort study. At approximately 3 y of age, we assessed children's cognitive abilities with the Wechsler Primary and Preschool Scale of IntelligenceTM­III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function­Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children­2 (BASC-2) and the Social Responsiveness ScaleTM­2 (SRS-2). We estimated covariate-adjusted differences in neurobehavioral outcomes with a doubling in BPA concentration and sex-specific associations. RESULTS: BPA was not associated with WPPSI-III scores; child sex did not modify these associations. The association between BPA and BRIEF-P scores was modified by child sex (BPA×sex p-values≤0.03). For example, a doubling of BPA concentration was associated with 1-point (95% CI: 0.3, 1.7) poorer working memory in boys and 0.5-point (95% CI: −1.1, 0.1) better scores in girls. BPA was not associated with most BASC-2 scales; however, it was associated with more internalizing and somatizing behaviors in boys, but not in girls (BPA×sex p&-values≤0.08). A doubling of BPA concentration was associated with poorer SRS-2 scores [ß=0.3 ( 95% CI: 0, 0.7)]; this association was not modified by sex. CONCLUSION: Prenatal urinary BPA concentration was associated with some aspects of child behavior in this cohort, and some associations were stronger among boys. https://doi.org/10.1289/EHP984.

Similarities and differences between behavioral and electrophysiological visual acuity thresholds in healthy infants during the second half of the first year of life.

PURPOSE: Behavioral and electrophysiological methods for visual acuity estimation typically correlate well in children and adult populations, but this relationship remains unclear in infants, particularly during the second half of the first year of life. It has been suggested that the agreement between both methods mostly relies on age and/or subjective acuity factors. The present study aimed at comparing acuity thresholds obtained with both approaches in a sample of healthy infants in a relatively narrow age range, that is 6-10 months old. METHODS: Acuity thresholds were assessed in 61 healthy infants aged between 6 and 10 months using the Teller acuity cards (TAC) and sweep visual evoked potentials (sVEP). The TAC stimuli (stationary vertical gratings displayed on laminated cards) ranged from 0.31 to 38 cycles per degree (cpd). The TAC acuity threshold was estimated according to the highest spatial frequency scored by the experimenter as seen by the infant. The sVEP stimuli (high-contrast vertical gratings counter-phased at 12 reversals/s) ranged from 13.5 to 1 cpd. sVEP were recorded at Oz and acuity threshold was estimated using regression linear fitting. RESULTS: Considering the entire sample, sVEP acuity thresholds (8.97 ± 2.52 cpd) were significantly better than TAC scores (5.58 ± 2.95 cpd), although the difference was within 1 octave for 64% of the infants. Neither Pearson nor intra-class correlations between the two methods were significant (0.18 and 0.03, respectively). While age at assessment was not related to any dependent variable (TAC, sVEP, sVEP-TAC difference score), subjective (behavioral) acuity was found to underlie the difference between the two methods. The difference between sVEP and TAC scores decreased as a function of subjective acuity, and at the highest subjective acuity level (>10 cpd), TAC acuity slightly exceeded sVEP acuity. CONCLUSIONS: The superiority of sVEP acuity often reported in the literature was evident in our infant sample when subjective acuity (TAC) was low or moderate, but not when it was high (>10 cpd). The relationship between the two estimation methods was not dependent on age, but on subjective acuity.