Faculty Bibliography

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.

Importance/UNASSIGNED:Air pollutants interact with estrogen nuclear receptors, but their effect on thyroid signaling is less clear. Thyroid function is of particular importance for pregnant women because of the thyroid's role in fetal brain development. Objective/UNASSIGNED:To determine the short-term association of exposure to air pollution in the first trimester with thyroid function throughout pregnancy. Design, Setting, and Participants/UNASSIGNED:In this cohort study, 9931 pregnant women from 4 European cohorts (the Amsterdam Born Children and Their Development Study, the Generation R Study, Infancia y Medio Ambiente, and Rhea) and 1 US cohort (Project Viva) with data on air pollution exposure and thyroid function during pregnancy were included. The recruitment period for the Amsterdam Born Children and Their Development Study was January 2003 to March 2004; for Generation R, April 2002 to January 2006; for Infancia y Medio Ambiente, November 2003 to January 2008; for Rhea, February 2007 to February 2008; and for Project Viva, April 1999 to November 2002. Statistical analyses were conducted from January 2018 to April 2019. Main Outcomes and Measures/UNASSIGNED:Residential air pollution concentrations (ie, nitrogen oxide and particulate matter [PM]) during the first trimester of pregnancy were estimated using land-use regression and satellite-derived aerosol optical depth models. Free thyroxine, thyrotropin, and thyroid peroxidase antibody levels were measured across gestation. Hypothyroxinemia was defined as free thyroxine below the fifth percentile of the cohort distribution with normal thyrotropin levels, following the American Thyroid Association guidelines. Results/UNASSIGNED:Among 9931 participants, the mean (SD) age was 31.2 (4.8) years, 4853 (48.9%) had more than secondary educational levels, 5616 (56.6%) were nulliparous, 404 (4.2%) had hypothyroxinemia, and 506 (6.7%) tested positive for thyroid peroxidase antibodies. Concentrations of nitrogen dioxide and PM with an aerodynamic diameter of 2.5 μm or less (PM2.5) were lower and had less variation in women in the US cohort than those in European cohorts. No associations of nitrogen oxide with thyroid function were found. Higher exposures to PM2.5 were associated with higher odds of hypothyroxinemia in pregnant women (odds ratio per 5-μg/m3 change, 1.21; 95% CI, 1.00-1.47). Although exposure to PM with an aerodynamic diameter of 10 μm or less was not significantly associated with hypothyroxinemia, the coefficient was similar to that for the association of PM2.5 with hypothyroxinemia (odds ratio per 10-μg/m3 change, 1.18; 95% CI, 0.93-1.48). Absorbances of PM2.5 and PM with aerodynamic diameter from 2.5 to 10 μg and were not associated with hypothyroxinemia. There was substantial heterogeneity among cohorts with respect to thyroid peroxidase antibodies (P for heterogeneity, <.001), showing associations of nitrogen oxide and PM with thyroid autoimmunity only in the women in the Generation R Study. Conclusions and Relevance/UNASSIGNED:The findings of this study suggest that first-trimester exposures to PM2.5 were associated with mild thyroid dysfunction throughout pregnancy. The association of PM2.5 exposure with thyroid function during pregnancy is of global health importance because air pollution exposure is widespread and hypothyroxinemia may adversely influence the brain development of offspring.

BACKGROUND:) are linked to poor fetal outcomes but their relationship with childhood development is unclear. OBJECTIVES/OBJECTIVE:increase the risk of early developmental delays. STUDY DESIGN/METHODS:Prospective cohort. SETTINGS/METHODS:New York State excluding New York City. PARTICIPANTS/METHODS:4089 singletons and 1016 twins born between 2008 and 2010. EXPOSURES/UNASSIGNED:estimated by the Environmental Protection Agency Downscaler models were spatiotemporally linked to each child's prenatal and early-life addresses incorporating residential history, and locations of maternal work and day-care. OUTCOMES/RESULTS:, and for those living <1000 m away from a major roadway compared to those living further. Models adjusted for potential confounders. RESULTS:exposures. CONCLUSIONS:were associated with developmental delays. While awaiting larger studies with personal air pollution assessment, efforts to minimize air pollution exposures during critical developmental windows may be warranted.

OBJECTIVE:The goal of this study was to determine whether newborn concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) are associated with early childhood growth. METHODS:A total of 1,954 singletons and 966 twins from the Upstate KIDS Study (born 2008-2010) were included in this study. Newborn dried blood spot concentrations of PFOS, PFOA, and BPA were quantified by liquid chromatography tandem mass spectrometry. Children's weight and height were reported from birth through 3 years of age. Repeated measures were modeled using generalized linear mixed models. RESULTS:[-0.17 to -0.051] per 1 standard deviation increase in log PFOS and PFOA, respectively) and not with early obesity among singletons. Inconsistent associations were observed for twins. BPA levels were higher among neonates with a neonatal intensive care unit stay (P < 0.001), making associations difficult to interpret. CONCLUSIONS:Perfluorinated alkyl substances did not exhibit obesogenic associations with early measures of childhood growth. Blood-based BPA measures are limited by the nonpersistent nature of the chemical, and unknown sources from hospital settings may present only transient exposures.

Experimental studies suggest that prenatal exposure to endocrine disrupting chemicals interferes with developmental processes in the fetal brain. Yet, epidemiological evidence is inconclusive. In a birth cohort (2008-2010, upstate New York), we quantified concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) in stored newborn dried blood spots using liquid chromatography/tandem mass spectrometry. Mothers reported on children's behavior using the Strengths and Difficulties Questionnaire at age 7 (650 singletons and 138 twins). Difficulties in total behavior (i.e., emotional, conduct, hyperactivity, and peer problems) and prosocial behavior were classified using validated cut-offs. We used logistic regression with generalized estimating equations to estimate the odds of having difficulties per exposure category. In total, 111 children (12.1%) had total behavioral difficulties and 60 (6.5%) had difficulties in prosocial behavior. The median (interquartile range) of PFOS, PFOA, and BPA were 1.74 ng/ml (1.33), 1.12 ng/ml (0.96), and 7.93 ng/ml (10.79), respectively. Higher PFOS levels were associated with increased odds of having behavioral difficulties (OR per SD of log PFOS = 1.30, 95%CI: 1.03-1.65). We observed associations between PFOS in the highest relative to the lowest quartile and behavioral difficulties (OR for PFOS_1.14-1.74 = 1.65, 95%CI: 0.84-3.34; PFOS_1.75-2.47 = 1.73, 95%CI: 0.87-3.43; and PFOS_>2.47 = 2.47, 95%CI: 1.29-4.72 compared to PFOS_<1.41). The associations between higher concentrations of PFOS and behavioral difficulties at age 7 years were driven by problems in conduct and emotional symptoms. Higher PFOA levels were associated with difficulties in prosocial behavior (OR = 1.35, 95%CI: 1.03-1.75). There was an inverse association between BPA concentrations and difficulties in prosocial behavior but only in the 2nd and 4th quartiles. We found no interactions between sex and chemical concentrations. Increasing prenatal exposure to PFOS and PFOA, as reflected in neonatal concentrations, may pose risk for child behavioral difficulties.