Faculty Bibliography

BACKGROUND/UNASSIGNED:Sleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age. METHODS/UNASSIGNED:Participants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist. FINDINGS/UNASSIGNED: = 0.026). We did not document substantial offspring sex moderation. INTERPRETATION/UNASSIGNED:Poor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment. FUNDING/UNASSIGNED:NIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

Silicone wristbands were utilized as personal passive samplers in a sub-cohort of 92 women, who participated in New York University Children's Health and Environment Study, to assess exposure to semi-volatile organic compounds (SVOCs). Wristbands were analyzed for 77 SVOCs, including halogenated and non-halogenated organophosphate esters (OPEs), polychlorinated biphenyls (PCBs), pesticides, phthalates, and brominated flame retardants (BFRs) (e.g. polybrominated diphenyl ethers (PBDEs)). This study aimed to look for patterns in chemical exposure utilizing participant demographics gathered from a questionnaire, and chemical exposure data across multiple timepoints during pregnancy. Analysis focused on 27 compounds detected in at least 80% of the wristbands examined. The chemicals detected most frequently included two pesticides, eight phthalates, one phthalate alternative, seven BFRs, and nine OPEs, including isopropylated and tert-butylated triarylphosphate esters (ITPs and TBPPs). Co-exposure to different SVOCs was most prominent in compounds that were within the same chemical class or were used in similar consumer applications such as phthalates and OPEs, which are often used as plasticizers. Pre-pregnancy BMI was positively associated with multiple compounds, and there were both positive and negative associations between women's parity and SVOC exposure. Outdoor temperature was not correlated with the wristband concentrations over a five-day sampling period. Lastly, significant and moderately high Intraclass Correlation Coefficient (ICC) (0.66-0.84) values for phthalate measurementsacross pregnancy indicate chronic exposure and suggest that using wristbands during one sampling period may reliably predict exposure. However, multiple sampling periods may be necessary to accurately determine indoor exposure to other SVOCs including OPEs and BFRs.

Studying time-dependent exposure mixtures has gained increasing attentions in environmental health research. When a scalar outcome is of interest, distributed lag (DL) models have been employed to characterize the exposures effects distributed over time on the mean of final outcome. However, there is a methodological gap on investigating time-dependent exposure mixtures with different quantiles of outcome. In this article, we introduce semiparametric partial-linear single-index (PLSI) DL quantile regression, which can describe the DL effects of time-dependent exposure mixtures on different quantiles of outcome and identify susceptible periods of exposures. We consider two time-dependent exposure settings: discrete and functional, when exposures are measured in a small number of time points and at dense time grids, respectively. Spline techniques are used to approximate the nonparametric DL function and single-index link function, and a profile estimation algorithm is proposed. Through extensive simulations, we demonstrate the performance and value of our proposed models and inference procedures. We further apply the proposed methods to study the effects of maternal exposures to ambient air pollutants of fine particulate and nitrogen dioxide on birth weight in New York University Children's Health and Environment Study (NYU CHES). This article is protected by copyright. All rights reserved.

STUDY OBJECTIVE:To study associations between nighttime sleep characteristics and time to pregnancy. METHODS:Pregnant people age ≥18 years and<18 weeks' gestation were recruited from 3 New York University Grossman School of Medicine affiliated hospitals in Manhattan and Brooklyn (n = 1428) and enrolled into the New York University Children's Health and Environment Study. Participants in the first trimester of pregnancy were asked to recall their time to pregnancy and their sleep characteristics in the 3 months before conception. RESULTS:Participants who reported sleeping<7 hours per night tended to have shorter time to pregnancy than those who slept 7-9 hours per night (adjusted fecundability odds ratio = 1.16, 95% confidence interval: 0.94, 1.41). Participants with a sleep midpoint of 4 AM or later tended to have longer time to pregnancy compared with those with earlier sleep midpoints (before 4 AM) (adjusted fecundability odds ratio = 0.88, 95% confidence interval: 0.74, 1.04). When stratified by sleep midpoint, sleeping<7 hours was significantly associated with shorter time to pregnancy only among those whose sleep midpoint was before 4 AM (adjusted fecundability odds ratio = 1.33, 95% confidence interval: 1.07, 1.67). CONCLUSIONS:The association of sleep duration with time to pregnancy was modified by chronotype, suggesting that both biological and behavioral aspects of sleep may influence fecundability.

BACKGROUND:Air pollution is a health risk in pregnant women and children. Despite the importance of refined exposure assessment, the characterisation of personalised air pollution exposure remains a challenge in paediatric and perinatal epidemiology. OBJECTIVE:We used portable personal air monitors to characterise personalised exposure to air pollutants in pregnant women. METHODS:), and volatile organic compounds (average use = 14 days). Data were stored in real-time on a secure database via synchronisation with a smartphone application. Of 497 women who agreed to use air monitors, 273 women (55%) were successful in using air monitors for longer than a day. For these participants, we identified daily patterns of exposure to air pollutants using functional principal component analysis (3827 days of air monitoring). RESULTS:had higher daily variations compared to PM. CONCLUSIONS:Small wearables are useful for the measurement of personalised air pollution exposure in birth cohorts and identify daily patterns that cannot be captured otherwise. Successful participation, however, depends on certain individual characteristics. Future studies should consider strategies in design and analysis to account for selective participation.

BACKGROUND AND OBJECTIVES:Infant weight patterns predict subsequent weight outcomes. Rapid infant weight gain, defined as a >0.67 increase in weight-for-age z-score (WAZ) between two time points in infancy, increases obesity risk. Higher oxidative stress, an imbalance between antioxidants and reactive oxygen species, has been associated with low birthweight and paradoxically also with later obesity. We hypothesized that prenatal oxidative stress may also be associated with rapid infant weight gain, an early weight pattern associated with future obesity. METHODS:Within the NYU Children's Health and Environment Study prospective pregnancy cohort, we analyzed associations between prenatal lipid, protein, and DNA urinary oxidative stress biomarkers and infant weight data. Primary outcome was rapid infant weight gain (>0.67 increase in WAZ) between birth and later infancy at the 8 or 12 month visit. Secondary outcomes included: very rapid weight gain (>1.34 increase in WAZ), low (<2500 g) or high (≥4000 g) birthweight, and low (< -1 WAZ) or high (>1 WAZ) 12 month weight. RESULTS:Pregnant participants consented to the postnatal study (n = 541); 425 participants had weight data both at birth and in later infancy. In an adjusted binary model, prenatal 8-iso-PGF2α, a lipid oxidative stress biomarker, was associated with rapid infant weight gain (aOR 1.44; 95% CI: 1.16, 1.78, p = 0.001). In a multinomial model using ≤0.67 change in WAZ as a reference group, 8-iso-PGF2α was associated with rapid infant weight gain (defined as >0.67 but ≤1.34 WAZ; aOR 1.57, 95% CI: 1.19, 2.05, p = 0.001) and very rapid infant weight gain (defined as >1.34 WAZ; aOR 1.33; 95% CI: 1.02, 1.72, p < 0.05) Secondary analyses detected associations between 8-iso-PGF2α and low birthweight outcomes. CONCLUSIONS:We found an association between 8-iso-PGF2α, a lipid prenatal oxidative stress biomarker, and rapid infant weight gain, expanding our understanding of the developmental origins of obesity and cardiometabolic disease.

PURPOSE/OBJECTIVE:To evaluate whether underlying infertility and mode of conception are associated with childhood behavioral disorders. METHODS:Oversampling on fertility treatment exposure using vital records, the Upstate KIDS Study followed 2057 children (of 1754 mothers) from birth to 11 years. Type of fertility treatment and time to pregnancy (TTP) were self-reported. Mothers completed annual questionnaires reporting symptomology, diagnoses, and medications at 7-11 years of age. The information identified children with probable attention-deficit/hyperactivity disorder, anxiety or depression, and conduct or oppositional defiant disorders. We estimated adjusted relative risks (aRR) for disorders by underlying infertility (TTP > 12 months) or treatment exposure groups compared to children born to parents with TTP ≤ 12 months. RESULTS:Children conceived with fertility treatment (34%) did not have an increased risk of attention-deficit/hyperactivity disorder (aRR): 1.21; 95% CI: 0.88, 1.65), or conduct or oppositional defiant disorders (aRR: 1.31; 0.91, 1.86), but did have an increased risk of anxiety or depression (aRR: 1.63; 1.18, 2.24), which remained elevated even after adjusting for parental mood disorders (aRR: 1.40; 0.99, 1.96). Underlying infertility without the use of treatment was also associated with a risk of anxiety or depression (aRR: 1.82; 95% CI: 0.96, 3.43). CONCLUSIONS:Underlying infertility or its treatment was not associated with risk of attention-deficit/hyperactivity disorder. Observations of increased anxiety or depression require replication.

IMPORTANCE:Gender-diverse youths have higher rates of mental health problems compared with the general population, as shown in both clinical and nonclinical populations. Brain correlates of gender diversity, however, have been reported only among youths with gender dysphoria or in transgender individuals. OBJECTIVE:To examine brain morphologic correlates of gender diversity among adolescents from a general pediatric population who were assigned male or female at birth, separately. DESIGN, SETTING, AND PARTICIPANTS:This cross-sectional study was embedded in Generation R, a multiethnic population-based study conducted in Rotterdam, the Netherlands. Adolescents who were born between April 1, 2002, and January 31, 2006, and had information on self-reported or parent-reported gender diversity and structural neuroimaging at ages 13 to 15 years were included. Data analysis was performed from April 1 to July 31, 2022. EXPOSURES:Gender-diverse experiences among adolescents were measured with selected items from the Achenbach System of Empirically Based Assessment forms and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults, as reported by adolescents and/or their parents. MAIN OUTCOMES AND MEASURES:High-resolution structural neuroimaging data were collected using a 3-T magnetic resonance imaging scanner (at a single site). We used linear regression models to examine differences in global brain volumetric measures between adolescents who reported gender diversity and those who did not. RESULTS:This study included 2165 participants, with a mean (SD) age of 13.8 (0.6) years at scanning. A total of 1159 participants (53.5%) were assigned female at birth and 1006 (46.5%) were assigned male at birth. With regard to maternal country of origin, 1217 mothers (57.6%) were from the Netherlands and 896 (42.4%) were from outside the Netherlands. Adolescents who reported gender diversity did not differ in global brain volumetric measures from adolescents who did not report gender diversity. In whole-brain, vertexwise analyses among adolescents assigned male at birth, thicker cortices in the left inferior temporal gyrus were observed among youths who reported gender diversity compared with those who did not. No associations were observed between gender diversity and surface area in vertexwise analyses. CONCLUSIONS AND RELEVANCE:The findings of this cross-sectional study suggest that global brain volumetric measures did not differ between adolescents who reported gender diversity and those who did not. However, these findings further suggest that gender diversity in the general population correlates with specific brain morphologic features in the inferior temporal gyrus among youths who are assigned male at birth. Replication of these findings is necessary to elucidate the potential neurobiological basis of gender diversity in the general population. Future longitudinal studies should also investigate the directionality of these associations.

CONTEXT/BACKGROUND:Manganese (Mn) exposure is prevalent, as it is found naturally as ionized trace elements and released into the environment as a byproduct of manufacturing and waste disposal. Animal and human studies have suggested variable effects on thyroid function, but the association of Mn exposure with thyroid function has not been evaluated in a national sample. OBJECTIVE:To investigate the associations between serum and urinary Mn levels and serum thyroid hormone concentrations in a nationally representative sample. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION/METHODS:This was a cross-sectional analysis of data from the 2011-2012 National Health and Nutrition Examination Survey among 1360 participants. MAIN OUTCOME MEASURES/METHODS:Serum thyroid stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), free T3, and free T4. RESULTS:Serum Mn levels were positively associated with increasing total T4, free T3, and total T3 in the whole cohort (p < 0.01). Urinary Mn levels were not associated with thyroid hormone levels. When subgroup analyses were performed by gender, only males had total T4 associated with serum Mn [β = 0.01, p < 0.01, confidence interval (CI): 0.004-0.018]. In individuals under 22 years old, serum Mn was significantly associated with total T4 (β = 0.02, p = 0.002, CI: 0.008-0.029). Serum Mn was positively associated with Free T3 in both genders (β = 0.07, p < 0.001). CONCLUSION/CONCLUSIONS:While our findings do not suggest clinical thyroid dysfunction, there is an association between serum Mn and subclinical changes in thyroid function that warrant further studies. Regulatory action should be considered as Mn-based organometallic compounds are being considered as replacements for lead in gasoline and may pose future risks to human health.

BACKGROUND:Bisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth. METHODS:Participants included 855 mother-fetal pairs enrolled in the population-based New York University Children's Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models. RESULTS:Few statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution. CONCLUSION/CONCLUSIONS:In this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.