Faculty Bibliography

Infant exposure to per/polyfluoroalkyl compounds is associated with immune disruption. We examined associations between neonatal concentrations of perflurooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) and immunoglobulin (Ig) isotype profiles in a prospective cohort of infants. We measured Ig isotypes, including IgA, IgE, IgM and the IgG subclasses IgG₁, IgG₂, IgG₃, and IgG_4, and PFOA and PFOS in newborn dried bloodspots from N = 3175 infants in the Upstate KIDS Study (2008-2010). We examined the association between newborn Ig isotype levels and individual PFOS and PFOA concentrations using mixed effects regression models with a random intercept to account for twins among study participants. We assessed the joint effect PFOA and PFOS with quantile-based g-computation on all singletons and one randomly selected twin (N = 2901), with Ig categorized as above or below median value. Models were adjusted for infant sex, and maternal pre-pregnancy body mass index, race, parity, age and infertility treatment. In adjusted models, PFOA was inversely associated with IgE (coefficient = -0.12 per unit increase in PFOA, 95% CI: -0.065, -0.17), whereas IgG₂, IgM, and IgA were positively associated with PFOA (coefficient for IgG₂ = 0.22, 95% CI: 0.15, 0.27; coefficient for IgM = 0.11, 95% CI: 0.08, 0.15; and coefficient for IgA = 0.15, 95% CI: 0.07, 0.18). There was no relation between PFOS and Ig isotypes. Analysis of the joint effect of PFOA and PFOS showed an OR of 1.2 (95% CI: 1.04, 1.36) for IgA and OR of 1.12 (95% CI: 1.00, 1.24) for IgG₂ levels above the median for every quartile increase. PFOA levels were significantly associated with elevated IgA, IgM, IgG₂, and reduced levels of IgE in single-pollutant models. A small but significant joint effect of PFOA and PFOS was observed. Our results suggest that early exposure to PFOA and PFOS may disrupt neonatal immunoglobulin levels.

While racial/ethnic differences in fetal growth have been documented, few studies have examined whether they vary by exogenous factors, which could elucidate underlying causes. The purpose of this study was to characterize longitudinal fetal growth patterns by maternal sociodemographic, behavioral, and clinical factors and examine whether associations with maternal race/ethnicity varied by these other predictors. Between 2016-2019, pregnant women receiving prenatal care at NYU Langone were invited to participate in a birth cohort study. Women completed questionnaires and clinical data were abstracted from ultrasound examinations. Maternal characteristics were assessed in relation to fetal biometric measures throughout pregnancy using linear mixed models. Maternal race/ethnicity was consistently associated with fetal biometry: Black, Hispanic, and Asian women had fetuses with smaller head circumference, abdominal circumference, and biparietal diameter than White women. The associations between race/ethnicity and fetal growth varied by nativity for Asian women, such that the disparity between Asian and White women was much greater for US-born than foreign-born women. However, associations for Black and Hispanic women did not vary by nativity. While racial/ethnic-specific fetal growth standards have been proposed, work is needed to elucidate what could be driving these differences, including factors that occur in parallel and differentially affect fetal growth.

BACKGROUND:Young children's digital media use may adversely affect child development, but the mechanisms of this association are unclear. We evaluated whether screen time displaces reading and peer play time, which are subsequently associated with child development. METHODS:When children were 12, 18, 24, 30, and 36 months, mothers (n = 3894) reported the time their children spent on screens, being read to by an adult, and playing with other children. At 36 months, mothers completed the Ages and Stages Questionnaire©, an assessment of their child's developmental status. RESULTS:In unadjusted models, screen time from 12 to 36 months was not associated with reading but was associated with less time engaging in play with peers. In adjusted models accounting for developmental delay at 12 months, family and child characteristics, screen time was not directly associated with developmental delay. More peer play time was associated with a lower likelihood of developmental delay, and having higher screen time increased the likelihood of developmental delay indirectly through reduced peer play time. Results were similar for developmental delays in fine and gross motor, communication, and personal-social domains. CONCLUSIONS:Screen time in early childhood did not displace reported time spent reading, but did displace reported peer play time. IMPACT/CONCLUSIONS:Among children 1-3 years of age, more screen time was associated with less time engaged in peer play but not less reading with an adult. Having higher screen time from 1 to 3 years increased the odds of developmental delay indirectly through reduced peer play time. Ensuring that children engage in adequate time playing with peers may offset the negative associations between screen time and child development.

OBJECTIVE:To evaluate whether children conceived using assisted reproductive technology (ART) or ovulation induction (OI) have greater cardiometabolic risk than children conceived without treatment. DESIGN/METHODS:Clinical assessments in 2018-2019 in the Upstate KIDS cohort. SETTING/METHODS:Clinical sites in New York. PATIENT(S)/METHODS:Three hundred thirty-three singletons and 226 twins from 448 families. INTERVENTION(S)/METHODS:Mothers reported their use of fertility treatment and its specific type at baseline and approximately 4 months after delivery. High validity of the self-reported use of ART was previously confirmed. The children were followed up from infancy through 8-10 years of age. A subgroup was invited to participate in clinic visits. MAIN OUTCOME MEASURE(S)/METHODS:The measurements of blood pressure (BP), arterial stiffness using pulse wave velocity, anthropometric measures, and body fat using bioelectrical impedance analysis were performed (n = 559). The levels of plasma lipids, C-reactive protein, and hemoglobin A1c were measured using blood samples obtained from 263 children. RESULT(S)/RESULTS:The average age of the children was 9.4 years at the time of the clinic visits Approximately 39% were conceived using fertility treatment (18% using ART and 21% using OI). Singletons conceived using fertility treatment (any type or using ART or OI specifically) did not statistically differ in systolic or diastolic BP, heart rate, or pulse wave velocity. Singletons conceived using OI were smaller than singletons conceived without treatment, but the average body mass index of the latter was higher (z-score: 0.41 [SD, 1.24]) than the national norms. Twins conceived using either treatment had lower BP than twins conceived without treatment. However, twins conceived using OI had significantly higher arterial stiffness (0.59; 95% CI, 0.03-1.15 m/s), which was attenuated after accounting for maternal BP (0.29; 95% CI, -0.03 to 0.46 m/s). Twins did not significantly differ in size or fat measures across the groups. The mode of conception was not associated with the levels of lipids, C-reactive protein, or glycosylated hemoglobin. CONCLUSION(S)/CONCLUSIONS:Clinical measures at the age of 9 years did not indicate greater cardiometabolic risk in children conceived using ART or OI compared with that in children conceived without treatment. CLINICAL TRIAL REGISTRATION NUMBER/BACKGROUND:ClinicalTrials.gov #NCT03106493.

Fetal exposure to environmental chemicals has been associated with adverse health outcomes in children and later into adulthood. While several studies have examined correlations and variability of non-persistent chemical exposures throughout pregnancy, many do not capture more recent exposures, particularly in New York City. Our goal was to characterize exposure to phthalates, bisphenols, polycyclic aromatic hydrocarbons, and organophosphate pesticides among pregnant women residing in New York City who enrolled in the New York University Children's Health and Environment Study (NYU CHES) between 2016 and 2018. We measured urinary chemical metabolite concentrations in 671 women at early, mid, and late pregnancy (median 10.8, 20.8, and 29.3 weeks, respectively). We calculated Spearman correlation coefficients among chemical concentrations at each measurement time point. We compared changes in population-level urinary metabolites at each stage using paired Wilcoxon signed-rank tests and calculated intraclass correlation coefficients (ICCs) to quantify intra-individual variability of metabolites across pregnancy. Geometric means and ICCs were compared to nine other pregnancy cohorts that recruited women in 2011 or later as well as nationally reported levels from women of child-bearing age. Compared with existing cohorts, women in NYU CHES had higher geometric means of organophosphate pesticides (Σdiethylphosphates = 28.7 nmol/g cr, Σdimethylphosphates = 57.3 nmol/g cr, Σdialkyl phosphates = 95.9 nmol/g cr), bisphenol S (0.56 μg/g cr), and 2-naphthalene (8.98 μg/g cr). Five PAH metabolites and two phthalate metabolites increased between early to mid and early to late pregnancy at the population level. Spearman correlation coefficients for chemical metabolites were generally below 0.50. Intra-individual exposures varied over time, as indicated by low ICCs (0.22-0.88, median = 0.38). However, these ICCs were often higher than those observed in other pregnancy cohorts. These results provide a general overview of the chemical metabolites measured in NYU CHES in comparison to other contemporary pregnancy cohorts and highlight directions for future studies.

OBJECTIVE:To estimate the prevalence of perinatal cannabis use (ie, before and/or during pregnancy); document the frequency, modes, and motivations for use; and identify predictors of perinatal cannabis use. METHODS:Six states in the Pregnancy Risk Assessment Monitoring System, a state-specific, population-based surveillance system, administered a supplemental questionnaire on perinatal cannabis use in 2016-2018. Women with live births were surveyed 2-6 months postpartum about behaviors ≤3 months preconception and during pregnancy. Demographic, psychosocial, and behavioral characteristics were examined in relation to perinatal cannabis use using multinomial regression models. Those who: (1) never used cannabis, (2) only used in preconception period, and (3) used in both preconception and prenatal periods were compared. RESULTS:Among 6428 respondents, 379 (5.8%) used cannabis preconceptionally only and 466 (4.4%) used in both the preconception and prenatal periods. Among those using prenatally, most reported smoking as their single mode (87.1%), with the two most common reasons being stress (83.8%) and nausea/vomiting (79.2%). Marital status, race/ethnicity, socioeconomic status, parity, and cigarette and alcohol use were significantly associated with perinatal cannabis use. Single (vs partnered) women were more likely to use cannabis prenatally (odds ratio = 2.4, 95% confidence interval: 1.5, 3.9) and non-Hispanic Black (vs White) women were less likely to use prenatally (odds ratio = 0.4, 95% confidence interval: 0.2, 0.8). CONCLUSIONS:Using a population-based sample of US births in six states, several demographic, psychosocial, and behavioral characteristics were identified in relation to perinatal cannabis use. These data are valuable for counseling in prenatal care and investigations of health effects.

OBJECTIVES/OBJECTIVE:To assess the association between age of juice introduction and child anthropometry after the American Academy of Pediatrics changed their guidelines in 2017 to recommend delaying juice introduction until at least 12 months of age (previously 6 months), citing concerns of weight gain. STUDY DESIGN/METHODS:percentiles. Controlling for sociodemographic characteristics and parental BMI, we assessed the associations of age of juice introduction with child anthropometry. RESULTS:Prevalence of childhood obesity was 16.4% at 2-3 (n=1713) and 22.8% at 7-9 years (n=1283). Juice introduction at <6 versus ≥12 months was associated with higher weight-for-age Z score at 2-3 years (mean difference=0.21; 95% confidence interval 0.04-0.37). At 7-9 years, juice introduction at <6 versus ≥12 months was related to higher BMI-for-age (0.38; 0.12-0.64) and weight-for-age Z scores (0.27; 0.06-0.49). Risk of developing overweight/obesity and obesity was 1.54 (0.99-2.38) and 2.17 (1.11-4.23) times higher among children with juice introduced at <6 months. No associations were found with juice introduced at 6-<12 vs ≥12 months. CONCLUSIONS:Risk of developing overweight/obesity or obesity is higher among children introduced to juice before 6 months of age compared with ≥12 months.

Previous studies have provided data on determinants of phthalates in pregnant women, but results were disparate across regions. We aimed to identify the food groups and demographic factors that predict phthalate exposure in an urban contemporary pregnancy cohort in the US. The study included 450 pregnant women from the New York University Children's Health and Environment Study in New York City. Urinary concentrations of 22 phthalate metabolites, including metabolites of di-2-ethylhexylphthalate (DEHP), were determined at three time points across pregnancy by liquid chromatography coupled with tandem mass spectrometry. The Diet History Questionnaire II was completed by pregnant women at mid-pregnancy to assess dietary information. Linear mixed models were fitted to examine determinants of urinary phthalate metabolite concentrations. Using partial-linear single-index (PLSI) models, we assessed the major contributors, among ten food groups, to phthalate exposure. Metabolites of DEHP and its ortho-phthalate replacement, diisononyl phthalate (DiNP), were found in >90% of the samples. The sum of creatinine-adjusted DiNP metabolite concentrations was higher in older and single women and in samples collected in summer. Hispanic and non-Hispanic Black women had lower urinary concentrations of summed metabolites of di-n-octyl phthalate (DnOP), but higher concentrations of low molecular weight phthalates compared with non-Hispanic White women. Each doubling of grain products consumed was associated with a 20.9% increase in ∑DiNP concentrations (95%CI: 4.5, 39.9). PLSI models revealed that intake of dried beans and peas was the main dietary factor contributing to urinary ∑DEHP, ∑DiNP, and ∑DnOP levels, with contribution proportions of 76.3%, 35.8%, and 27.4%, respectively. Urinary metabolite levels of phthalates in pregnant women in NYC varied by age, marital status, seasonality, race/ethnicity, and diet. These results lend insight into the major determinants of phthalates levels, and may be used to identify exposure sources and guide interventions to reduce exposures in susceptible populations.

OBJECTIVE:To determine if feeding problems are an indicator of developmental delay. STUDY DESIGN/METHODS:percentile across time. The Battelle Developmental Inventory (BDI-2) assessed development in 5 domains for a subset of children at 4 years. RESULTS:In adjusted analyses, feeding problems (per point increase) were increasingly associated with six ASQ domains from 18 months (Odds Ratios (ORs) ranged from 1.30 to 1.98) to 24 months (ORs = 2.07 - 2.69) to 30 months (ORs = 3.90 - 5.64). Compared with children who never experienced feeding problems, children who experienced high feeding problems at one or two time points were more than twice as likely to fail all ASQ domains (ORs = 2.10 - 2.50), and children who experienced high feeding problems at all three time points were four or more times as likely to fail all ASQ domains (ORs = 3.94 - 5.05). Children with one-point higher feeding problems at 30 months scored 3-4 points lower on all BDI-2 domains at 4 years. CONCLUSIONS:Frequent feeding problems, especially those that persist into the third year, could be used to identify children at risk for developmental delay for more targeted screening.

While definitions vary, endocrine-disrupting chemicals (EDCs) have two fundamental features: their disruption of hormone function and their contribution to disease and disability. The unique vulnerability of children to low-level EDC exposures has eroded the notion that only the dose makes the thing a poison, requiring a paradigm shift in scientific and policy practice. In this review, we discuss the unique vulnerability of children as early as fetal life and provide an overview of epidemiological studies on programming effects of EDCs on neuronal, metabolic, and immune pathways as well as on endocrine, reproductive, and renal systems. Building on this accumulating evidence, we dispel and address existing myths about the health effects of EDCs with examples from child health research. Finally, we provide a list of effective actions to reduce exposure, and subsequent harm that are applicable to individuals, communities, and policy-makers. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.