Faculty Bibliography

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.

Accumulating evidence suggests that maternal exposure to objectively stressful events and subjective distress during pregnancy may have intergenerational impacts on children's mental health, yet evidence is limited. In a multisite longitudinal cohort (N = 454), we used multi-variable linear regression models to evaluate the predictive value of exposure to stressful events and perceived distress in pregnancy for children's internalizing problems, externalizing problems, and adaptive skills at age 4. We also explored two- and three-way interactions between stressful events, distress, and child sex. Both objective and subjective maternal stress independently predicted children's behavior, with more stressful events and higher distress predicting more internalizing and externalizing problems and worse adaptability; stress types did not significantly interact. There was some evidence that more stressful events predicted higher externalizing behaviors only for girls. Three-way interactions were not significant. The current findings highlight the importance of considering the type of stress measurement being used (e.g., counts of objective event exposure or subjective perceptions), suggest prenatal stress effects may be transdiagnostic, and meet calls for rigor and reproducibility by confirming these independent main effects in a relatively large group of families across multiple U.S. regions. Results point to adversity prevention having a two-generation impact and that pre- and postnatal family-focused intervention targets may help curb the rising rates of children's mental health problems.

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.

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture exposure was associated with earlier pubic hair development in both sexes. In conclusion, higher maternal gestational urinary bisphenol and phthalate concentrations were associated with alterations in offspring reproductive development, mainly in boys.

BACKGROUND/OBJECTIVES/OBJECTIVE:Excessive gestational weight gain (GWG) and pre-pregnancy obesity affect a significant portion of the US pregnant population and are linked with negative maternal and child health outcomes. The objective of this study was to explore associations of pre-pregnancy body mass index (pBMI) and GWG with longitudinally measured maternal urinary metabolites throughout pregnancy. SUBJECTS/METHODS/METHODS:Among 652 participants in the New York University Children's Health and Environment Study, a longitudinal pregnancy cohort, targeted metabolomics were measured in serially collected urine samples throughout pregnancy. Metabolites were measured at median 10 (T1), 21 (T2), and 29 (T3) weeks gestation using the Biocrates AbsoluteIDQ® p180 Urine Extension kit. Acylcarnitine, amino acid, biogenic amine, phosphatidylcholine, lysophosphatidylcholine, sphingolipid, and sugar levels were quantified. Pregnant people 18 years or older, without type 1 or 2 diabetes and with singleton live births and valid pBMI and metabolomics data were included. GWG and pBMI were calculated using weight and height data obtained from electronic health records. Linear mixed effects models with interactions with time were fit to determine the gestational age-specific associations of categorical pBMI and continuous interval-specific GWG with urinary metabolites. All analyses were corrected for false discovery rate. RESULTS:Participants with obesity had lower long-chain acylcarnitine levels throughout pregnancy and lower phosphatidylcholine and glucogenic amino acids and higher phenylethylamine concentrations in T2 and T3 compared with participants with normal/underweight pBMI. GWG was associated with taurine in T2 and T3 and C5 acylcarnitine species, C5:1, C5-DC, and C5-M-DC, in T2. CONCLUSIONS:pBMI and GWG were associated with the metabolic environment of pregnant individuals, particularly in relation to mid-pregnancy. These results highlight the importance of both preconception and prenatal maternal health.

Background/UNASSIGNED:Air pollution, which results in the formation of polycyclic aromatic hydrocarbons (PAHs), has been identified as a cause of renal function decline and a contributor to CKD. However, the results of cross-sectional studies investigating personal, integrated biomarkers of PAHs have been mixed. Longitudinal studies may be better suited to evaluate environmental drivers of kidney decline. The purpose of this study was to examine associations of serially measured urinary PAH metabolites with clinical and subclinical measures of kidney function over time among children with CKD. Methods/UNASSIGNED:-isoprostane) were assayed in urine samples. Results/UNASSIGNED:Children were followed over an average (SD) of 3.0 (1.6) years and 2469 study visits (mean±SD, 4.0±1.6). Hydroxynaphthalene (NAP) or hydroxyphenanthrene (PHEN) metabolites were detected in >99% of samples and NAP concentrations were greater than PHEN concentrations. PHEN metabolites, driven by 3-PHEN, were associated with increased eGFR and reduced proteinuria, diastolic BP z-score, and NGAL concentrations over time. However, PAH metabolites were consistently associated with increased KIM-1 and 8-OHdG concentrations. Conclusions/UNASSIGNED:Among children with CKD, these findings provoke the potential explanation of reverse causation, where renal function affects measured biomarker concentrations, even in the setting of a longitudinal study. Additional work is needed to determine if elevated KIM-1 and 8-OHdG excretion reflects site-specific injury to the proximal tubule mediated by low-grade oxidant stress.

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.