Faculty Bibliography

Experimental studies suggested per- and polyfluoroalkyl substances (PFASs) may disrupt estrogens in animals, however, the epidemiological evidence on the associations of PFASs with estrogens is sparse. We investigated the associations of legacy PFASs and their alternatives, including F-53B, the perfluorooctane sulfonate (PFOS) replacement that is specifically and commonly used in China, with estrogen concentrations in newborns. We quantified six PFASs and three estrogens in the cord sera of 942 newborns from a birth cohort in Wuhan, China, between 2013 and 2014. After adjusting for confounders and correcting for multiple comparisons, we observed that both legacy PFASs and their alternatives were associated with higher serum levels of estradiol (E2). Some of the PFASs were associated with increasing levels of estrone (E1) and estriol (E3). Analysis of PFASs in mixture using weighted quantile sum regressions showed that F-53B contributed 20.1% and 48.5% to the associations between PFASs and E1 and E2, respectively. This study provided epidemiological data on the associations between common PFAS exposures and estrogens in newborns. Additional toxicology studies are needed to fully understand the effects of PFASs on estrogens and the mechanisms.

BACKGROUND:Most pregnant women are exposed to bisphenols, a group of chemicals that can interfere with various components of the thyroid system. OBJECTIVES/OBJECTIVE:To investigate the association of maternal urinary bisphenol concentrations during pregnancy with maternal, newborn and early childhood thyroid function. METHODS:This study was embedded in Generation R, a prospective, population-based birth cohort (Rotterdam, the Netherlands). Maternal urine samples were analyzed for eight bisphenols at early (<18), mid (18-25) and late (>25 weeks) pregnancy. Maternal serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and total thyroxine (TT4) were measured in early pregnancy and child TSH and FT4 were measured in cord blood and childhood. RESULTS: = 0.08). DISCUSSION/CONCLUSIONS:Our findings show that exposure to bisphenols may interfere with the thyroid system during pregnancy. Furthermore, the potential developmental toxicity of exposure to bisphenols during pregnancy could affect the thyroid system in the offspring in a sex-specific manner.

BACKGROUND:Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester. OBJECTIVE:We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age. METHOD/METHODS: RESULTS: CONCLUSIONS:We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.

OBJECTIVES/OBJECTIVE:To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study. STUDY DESIGN/METHODS:Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression. RESULTS:had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes. CONCLUSIONS:Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy.

The aims of the NYU Children's Health and Environment Study (CHES) are to evaluate influences of prenatal non-persistent chemical exposures on fetal and postnatal growth and pool our data with the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program to answer collaborative research questions on the impact of the preconceptual, prenatal, and postnatal environment on childhood obesity, neurodevelopment, pre/peri/postnatal outcomes, upper and lower airway outcomes, and positive health. Eligible women were ≥ 18 years old, < 18 weeks pregnant, had a pregnancy that is not medically threatened, and planned to deliver at NYU Langone Hospital-Manhattan, Bellevue Hospital, or NYU Langone Hospital-Brooklyn. Between March 22, 2016 and April 15, 2019, we recruited 2469 pregnant women, from whom 2193 completed an initial questionnaire and continued into NYU CHES. Of the 2193, 88 miscarried, 28 terminated, and 20 experienced stillbirth, while 57 were lost to follow up. We report here demographic and other characteristics of the 2000 live deliveries (2037 children), from whom 1624 (80%) consented to postnatal follow-up. Data collection in pregnancy was nested in clinical care, with questionnaire and specimen collection conducted during routine prenatal visits at < 18, 18-25, and > 25 weeks gestation. These have been followed by questionnaire and specimen collection at birth and regular postpartum intervals.

OBJECTIVE:To study the associations between maternal polycystic ovary syndrome (PCOS) and hirsutism with offspring attention-deficit/hyperactivity disorder (ADHD), anxiety, conduct disorder, and behavioral problems. DESIGN/METHODS:Prospective birth cohort study. SETTING/METHODS:Not applicable. PATIENT(S)/METHODS:A total of 1,915 mother-child dyads. INTERVENTION(S)/METHODS:None. MAIN OUTCOME MEASURE(S)/METHODS:Maternal report of offspring ADHD, anxiety, or conduct disorder diagnosis at 7 to 8 years; emotional symptoms, behavioral problems (including peer relationship, conduct, hyperactivity/inattention), and prosocial problems measured with the Strengths and Difficulties Questionnaire (SDQ) at 7 years. RESULT(S)/RESULTS:Prevalence of PCOS and hirsutism were 12.0% and 3.9%; 84% of women with hirsutism had PCOS. After adjustment for sociodemographic covariates, prepregnancy body mass index, and parental history of affective disorders, children born to mothers with PCOS had higher risk of anxiety (adjusted risk ratio [aRR] 1.62; 95% confidence interval [CI], 1.02-2.57) and borderline emotional symptoms (aRR 1.66; 95% CI, 1.18-2.33) compared with children born to mothers without PCOS. The associations between maternal PCOS and offspring ADHD were positive but imprecise. Maternal hirsutism was related to a higher risk of children's ADHD (aRR 2.33; 95% CI, 1.28-4.24), conduct disorder (aRR 2.54; 95% CI 1.18-5.47), borderline emotional symptoms, peer relationship problems, and conduct problems (aRRs 2.61; 95% CI, 1.69-4.05; 1.92; 95% CI, 1.16-3.17; and 2.22; 95% CI, 1.30-3.79, respectively). CONCLUSION(S)/CONCLUSIONS:Maternal PCOS was associated with offspring anxiety, and hirsutism was related to other offspring behavioral problems. These findings should be interpreted with caution as replication is needed in prospective cohort studies that assess PCOS and hirsutism diagnoses using medical records.

BACKGROUND:Impaired neuromotor development is often one of the earliest observations in children with autism spectrum disorder (ASD). We investigated whether a genetic predisposition to developmental disorders was associated with nonoptimal neuromotor development during infancy and examined the genetic correlation between nonoptimal neuromotor development and autistic traits in the general population. METHODS:In a population-based cohort in The Netherlands (2002-2006), we calculated polygenic risk scores (PRSs) for ASD and attention-deficit/hyperactivity disorder (ADHD) using genome-wide association study summary statistics. In 1921 children with genetic data, parents rated autistic traits at 6 years of age. Among them, 1174 children (61.1%) underwent neuromotor examinations (tone, responses, senses, and other observations) during infancy (9-20 weeks of age). We used linear regressions to examine associations of PRSs with neuromotor scores and autistic traits. We performed a bivariate genome-based restricted maximum likelihood analysis to explore whether genetic susceptibility underlies the association between neuromotor development and autistic traits. RESULTS:Higher PRSs for ASD were associated with less optimal overall infant neuromotor development, in particular low muscle tone. Higher PRSs for ADHD were associated with less optimal senses. PRSs for ASD and those for ADHD both were associated with autistic traits. The single nucleotide polymorphism-based heritability of overall motor development was 20% (SE = .21) and of autistic traits was 68% (SE = .26). The genetic correlation between overall motor development and autistic traits was .35 (SE = .21, p < .001). CONCLUSIONS:We found that genetic liabilities for ASD and ADHD covary with neuromotor development during infancy. Shared genetic liability might partly explain the association between nonoptimal neuromotor development during infancy and autistic traits in childhood.

Importance/UNASSIGNED:Many children begin interacting with screen media as early as infancy. Although screen time is associated with negative developmental consequences, few longitudinal studies in the United States have examined covariates of screen time among children under 3 years of age. Objectives/UNASSIGNED:To identify trajectories of screen time among children aged 1 to 3 years, to examine their association with screen use at 8 years of age, and to assess potential determinants of screen time. Design, Setting, and Participants/UNASSIGNED:This prospective birth cohort study included 3895 children (3083 singletons and 812 unrelated multiples) in New York State who had screen time data available for at least 1 time point from 1 to 3 years of age; 1156 children had data at 8 years. The study spanned September 4, 2007, through June 12, 2014, in the first phase, and August 29, 2014, through November 15, 2019, in the second phase. Data analysis for the present study was conducted from September 28, 2018, to July 15, 2019. Main Outcomes and Measures/UNASSIGNED:Maternal reports of children's television, movie, and computer game times were summed for total daily screen time at 12, 18, 24, 30, and 36 months of age. Two screen time trajectories (low and increasing use) were classified by cluster analysis, and logistic regression was used to model risk factors for the increasing trajectory. Children exhibiting the highest 10th percentile of screen use at each point were examined, and linear mixed models were used to identify risk factors of this high exposure category. Results/UNASSIGNED:Among the 3895 children included in the analysis (2031 boys [52.1%] and 1864 girls [47.9%]), median daily screen time increased from 30 (interquartile range, 0-60) minutes at 12 months of age to 120 (interquartile range, 75-200) minutes at 36 months of age. Of 1045 children with complete data at all 5 time points, 279 (26.7%) had an increasing screen time trajectory. Female child sex (adjusted odds ratio [aOR], 0.90; 95% CI, 0.81-0.99) and graduate school levels of paternal (aOR, 0.73; 95% CI, 0.56-0.95) and maternal (aOR, 0.60; 95% CI, 0.47-0.77) education, compared with having completed college, were associated with lower risk of increasing trajectory. Maternal nulliparity was associated with higher risk of increasing trajectory (aOR, 1.14; 95% CI, 1.00-1.30). Children with an increasing trajectory from 1 to 3 years of age had an additional 22 (95% CI, 11-33) minutes per day of screen time at 8 years of age. Covariates associated with the highest 10th percentile of screen exposure included paterman graduate school education compared with college (aOR, 0.63; 95% CI, 0.39-0.99), maternal graduate school education compared with college (aOR, 0.55; 95% CI, 0.37-0.82), maternal nulliparity (aOR, 1.98; 95% CI, 1.50-2.61), twins compared with singletons (aOR, 1.41; 95% CI, 1.05-1.91), non-Hispanic black compared with non-Hispanic white race/ethnicity (aOR, 4.77; 95% CI, 2.25-10.10), and type of care (home-based care aOR, 2.17 [95% CI, 1.38-3.41]; parental care aOR, 2.11 [95% CI, 1.41-3.15]) compared with center-based care. Conclusions and Relevance/UNASSIGNED:These findings suggest that a range of parental and child characteristics are associated with screen time. Screen time habits appear to track from as early as infancy, emphasizing the need for earlier interventions.

Endocrine disrupting chemicals are known to cause neurodevelopmental toxicity through direct and indirect pathways. In this study we used data from the National Health and Nutrition Examination Surveys, along with known exposure-disease relationships, to quantify the intellectual disability burden attributable to in utero exposure to polybrominated diphenyl ethers (PBDEs), organophosphates, and methylmercury and early life exposure to lead. We also estimated the cost of the IQ points lost and cases of intellectual disability. PBDE exposure was the greatest contributor to intellectual disability burden, resulting in a total of 162 million IQ points lost and over 738,000 cases of intellectual disability. This was followed by lead, organophosphates, and methylmercury. From 2001 to 2016, IQ loss from PBDEs, methylmercury, and lead have decreased or remained stagnant. Organophosphate exposure measurements were only available up to 2008 but did show an increase in organophosphate-attributable IQ loss. Although most of these trends show benefit for children's neurodevelopmental health, they may also point towards the use of potentially harmful substitutions for chemicals that are being phased out.