Faculty Bibliography

Electronic health records (EHRs) present opportunities to study uterine fibroids uterine fibroids and endometriosis within diverse populations. When using EHR data, it is important to validate outcome classification via diagnosis codes. We performed a validation study of three approaches (1: ICD-10 code alone, 2: ICD-10 code + diagnostic procedure, and 3: ICD-10 code + all diagnostic information) to identify incident uterine fibroids and endometriosis patients among n=750 NYU Langone Health 2016-2023. Chart review was used to determine the true diagnosis status. When using a binary classification system (incident vs. non-incident patient), Approaches 2 and 3 had higher positive predictive values (PPVs) for uterine fibroids (0.86 and 0.87 vs. 0.78) and for endometriosis (0.70 and 0.73 vs. 0.66), but Approach 1 outperformed the other two in negative predictive values (NPVs) for both outcomes. When using a three-level classification system (incident vs. prevalent vs. disease free patients), PPV for prevalent patients was low for all approaches, while PPV/NPV of disease-free patients was generally above 0.8. Using ICD-10 codes alone yielded higher NPVs but resulted in lower PPVs compared with the other approaches. Continued validation of uterine fibroids/endometriosis EHR studies is warranted to increase research into these understudied gynecologic conditions.

Characterizing the chemical composition of semen can provide valuable insights into the exposome and environmental factors that directly affect seminal and overall health. In this study, we compared molecular profiles of 45 donated semen samples from general population New York City participants and examined the correlation between the chemical profiles in semen and fertility parameters, i.e., sperm concentration, sperm motility, sperm morphology, and semen volume. Samples were prepared using a protein precipitation procedure and analyzed using liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS). Non-targeted analysis (NTA) revealed 18 chemicals not previously reported in human exposome studies, with 3-hydroxyoctanedioic acid, a cosmetic additive, emerging as a plausible candidate found to be at higher levels in cases vs controls (p < 0.01) and associated with adverse sperm motility and morphology. Four level 1 identified compounds were found to have associations with semen health parameters; dibutyl phthalate and 2-aminophenol negatively impacted motility, 4-nitrophenol was associated with low morphology, while palmitic acid was found to be associated with both low morphology and low volume. This study aims to utilize NTA to understand the association of contaminants of emerging concern (CECs) along with a full chemical profile to find trends separating poor and normal semen health parameters from each other chemically. Our results suggest that the collective effects of many CECs could adversely affect semen quality.

Many phthalates have been identified as endocrine-disrupting chemicals because they alter hormone functions throughout the lifespan. Nationally representative biomonitoring data are available from the United States, Canada, and Europe, but data elsewhere are sparse, making extrapolations of related disease and disability burdens difficult. We therefore examined trends in urinary phthalate metabolite concentrations in non-occupationally exposed populations in countries other than the United States, Canada, and Europe, where representative data are already available at the country level. We systematically reviewed studies published between 2000 and 2023 and analyzed changes in urinary phthalate metabolite concentrations across time using mixed-effects meta-regression models with and without a quadratic term for time. We controlled for region, age, and pregnancy status, and identified heterogeneity using Cochran's Q-statistic and I² index. Our final analysis consisted of 216 studies. Non-pregnant and youth populations exhibited nearly 2.0-fold or greater difference in concentration compared to pregnant and adult populations. Phthalates with significant regional differences had 10-fold higher concentrations in the Middle East and South Asia than in other regions. Our meta-regressions identified an exponential increase in DBP exposure through MnBP concentration internationally (beta: 0.65 ng/mL/year²) and in Eastern and Pacific Asia (EPA) (beta: 0.78 ng/mL/year²). Most DEHP and DnOP metabolites significantly declined internationally and in EPA, while MEP concentration declined by 10.62 ng/mL in Latin America and 8.98 ng/mL in Africa over time. Our findings fill gaps in phthalate exposure data and set the stage for further analysis of the attributable disease burden and cost at regional and international levels, especially in low- and middle-income countries.

BACKGROUND:While the striking impact of the COVID-19 pandemic on mental health, heath care access and lifestyle behaviors, including perceived health, diet, physical activity, and sleep has been reported, few studies have examined these domains jointly among pregnant and postpartum people in the early stages of the COVID-19 pandemic. METHODS:This mixed methods study was conducted among a subset of participants (n = 22) in a cohort study in Austin, Texas, who were pregnant or had recently delivered when the outbreak occurred. Measures were from the early second trimester up to 6 months postpartum. Findings from questionnaires were complemented by qualitative interviews during Spring/Summer 2020 regarding experiences during the early pandemic. RESULTS:From our quantitative data (n = 22), most participants reported that the pandemic generally had a negative impact on their lives (81%), that they shifted to eating more at home (71%), and that they were less physically active (62%). Five major themes emerged in our qualitative interviews (n = 22): (1) adaptation to pandemic restrictions; (2) psychosocial experiences, such as feelings of anxiety, guilt, sadness, isolation, and frustration; (3) health behavior changes; (4) health care experiences; and (5) where they obtained general and perinatal related pandemic information. Of those who completed both pregnancy and postpartum interviews (n = 8), all reported anxiety during both periods; however, those who delivered in Spring 2020 experienced more anxiety surrounding delivery and less social support than those who delivered in Summer 2020, who reported less anxiety surrounding hospital birth and greater social support, particularly after delivery. CONCLUSIONS:Overall, our findings confirm prior evidence that the COVID-19 pandemic had a marked impact on stress, anxiety, and worries, as well as lifestyle behaviors among pregnant and postpartum people. Our work provides lessons for health care practitioners about support need for pregnant and postpartum persons amid societal disruption.

Human-made chemicals are ubiquitous, leading to chronic exposure to complex mixtures of potentially harmful substances. We investigated chemical exposures in pregnant women in New York City by applying a non-targeted analysis (NTA) workflow to 95 paired prenatal urine and serum samples (35 pairs of preterm birth) collected as part of the New York University Children's Health and Environment Study. We analyzed all samples using liquid chromatography coupled with Orbitrap high-resolution mass spectrometry in both positive and negative electrospray ionization modes, employing full scan and data-dependent MS/MS fragmentation scans. We detected a total of 1524 chemical features for annotation, with 12 chemicals confirmed by authentic standards. Two confirmed chemicals dodecyltrimethylammonium and N,N-dimethyldecylamine N-oxide appear to not have been previously reported in human blood samples. We observed a statistically significant differential enrichment between urine and serum samples, as well as between preterm and term birth (p < 0.0001) in serum samples. When comparing between preterm and term births, an exogenous contaminant, 1,4-cyclohexanedicarboxylic acid (tentative), showed a statistical significance difference (p = 0.003) with more abundance in preterm birth in serum. An example of chemical associations (12 associations in total) observed was between surfactants (tertiary amines) and endogenous metabolites (fatty acid amides).

This study aimed to investigate whether fetal growth trajectories (FGTs) could predict early childhood development, indicate intrauterine metabolic changes, and explore potential optimal and suboptimal FGTs. FGTs were developed by using an unsupervised machine-learning approach. Children's neurodevelopment, anthropometry, and respiratory outcomes in the first 6 years of life were assessed at different ages. In a subgroup of participants, we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs. We identified 6 FGTs: early decelerating, early decelerating with late catch-up growth, early accelerating, early accelerating with late medium growth, late decelerating, and late accelerating. The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development, mental development, intelligence quotient, and lung function and a lower risk of behaviour and respiratory problems. Compared with the optimal FGT, early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function, while early accelerating FGT was associated with more severe autistic symptoms, poor lung function, and increased risks of overweight/obesity. Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs, whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT. These findings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism. The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease, but further research on related mechanisms is still needed.

INTRODUCTION/BACKGROUND:Bisphenols are endocrine-disrupting chemicals known to contribute to chronic disease across the lifespan. With increased awareness of their health effects, changes in regulation and health behaviors have contributed to reductions in urinary bisphenol A (BPA) levels in the United States, Canada, and Europe. However, global trends in bisphenols outside these regions, especially bisphenol S (BPS) exposure, have been less studied. AIM/OBJECTIVE:We examine trends in urinary BPA and BPS concentration in non-occupationally exposed populations, where representative data at a country level is unavailable. METHODS:index, and funnel plots. RESULTS:, 95% CI: [-0.50, -0.08], respectively). In the sensitivity analyses excluding studies with geometric or arithmetic mean values, each displayed significant shifts from the main findings with some consistent outcomes occurring internationally and/or in specific regions. Heterogeneity was high across studies, suggesting possible bias in our estimations. CONCLUSIONS:Our findings provide evidence for concern about increasing population exposure to BPA and BPS. Further studies estimating attributable disease burden and costs at regional and global levels are warranted to show these chemicals' impact on population health and economies.

IMPORTANCE/OBJECTIVE:Existing research suggests the impact of infertility on the risk of neurodevelopmental disorders in children, however, studies to date have failed to separate the impact of male and female infertility, often blurring the lines with proxies that encompass all forms of infertility. Moreover, while both health conditions co-occurring with infertility and genetic factors operating upstream have been suggested to influence the association between infertility and child outcomes, their roles and potential impact on observed associations remain unclear. OBJECTIVE:The objectives of this study are to investigate the relationship between female infertility and autism in the child, differentiating it from the effects of male and the couple infertility; consider the role of various maternal and birth factors in the association; and examine the effects of shared familial confounders on the association. DESIGN SETTING AND PARTICIPANTS/METHODS:Danish population-based cohort study, including all singleton live births in Denmark 1998-2015, their parents and parents' siblings. The cohort was followed up until December 31, 2016. EXPOSURES/METHODS:The exposure was a history of female infertility in the mother and the mother's sister. We examined four definitions of female infertility based on the ICD-10 codes derived from the Danish National Patient Register - any female infertility; specified female infertility; female exclusive infertility; and female or male infertility. MAIN OUTCOME AND MEASURES/METHODS:The outcome was diagnosis of autism spectrum disorder (ASD) in the Danish Psychiatric Central Research Register or the national patient register. A multivariable Cox regression model was used to estimate the associations between female infertility and autism, accounting for child's sex, year of birth, maternal age, education level, chronic comorbidities, and pregnancy and birth complications. The effects of shared familial factors on the association were analyzed using exposure information from the child's maternal aunt. RESULTS:=1.10 (95% CI, 1.00-1.20). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:in This population-based birth cohort study, we found a slightly higher risk of autism in children born to mothers with a history of infertility, with the association remaining consistent across various definitions of female infertility and robust to adjustments for demographic, child, and maternal factors. The study suggests for the first time that shared familial factors, possibly both genetic and non-genetic, could be influencing both female infertility and the risk of autism in children, indicating a need for further investigation into these familial effects.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at three time points. Fetal biometrics were obtained from ultrasounds in the second (n=773) and third (n=535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z-scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (-0.15 SD; 95% CI: -0.29, -0.01), head circumference (-0.11 SD; CI: -0.22, 0.01), biparietal diameter (-0.14 SD; CI: -0.27, -0.01), and abdominal circumference (-0.12 SD; CI: -0.26, 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (-0.14 SD; CI: -0.28, 0.00) and biparietal diameter (-0.12 SD; CI: -0.26, 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation.

OBJECTIVE:Although some studies have observed an association between birthweight and cardiovascular disease in adulthood, fewer have investigated whether birthweight is linked to cardiovascular health in early childhood. This study assesses the association between birthweight and cardiovascular outcomes in children 6 years of age. STUDY DESIGN/METHODS:Birthweight, blood pressure (BP), and markers of arterial stiffness in children, including brachial artery distensibility and carotid-femoral pulse wave velocity (cfPWV), were obtained from 324 participants in The Infant Development and the Environment Study, a prospective multisite pregnancy cohort. Birthweight was converted into sex-specific birthweight-for-gestational-age (bw/ga) z -scores based on the INTERGROWTH-21st standard. Following 2017 American Academy of Pediatrics guidelines, SBP and DBP were transformed into sex, age, and height-specific z -scores. Associations between birthweight and cardiovascular outcomes were assessed using nested multivariable linear regression models among the overall and sex-stratified samples. RESULTS:Among the overall sample, bw/ga z -score was positively associated with cfPWV [b = 0.11 m/s, 95% confidence interval (CI): 0.01 m/s, 0.21 m/s] in crude and adjusted models. No associations between birthweight and cardiovascular outcomes were detected among the sex-stratified analyses. CONCLUSION/CONCLUSIONS:Overall, birthweight was not related to cardiovascular outcomes in children 6 years old. However, infants born with a higher birthweight may be at risk for higher cfPWV in childhood. Early intervention in pregnant people at risk of delivering high birthweight infants may be warranted if results are replicated.