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.

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.

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.

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.

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.

Polymorphisms in the Apolipoprotein L1 (APOL1) gene are common in ancestrally African populations, and associate with kidney injury and cardiovascular disease. These risk variants (RV) provide an advantage in resisting Trypanosoma brucei, the causal agent of African trypanosomiasis, and are largely absent from non-African genomes. Clinical associations between the APOL1 high risk genotype (HRG) and disease are stronger in those with comorbid infectious or immune disease. To understand the interaction between cytokine exposure and APOL1 cytotoxicity, we established human umbilical vein endothelial cell (HUVEC) cultures representing each APOL1 genotype. Untreated HUVECs were compared to IFNÉ£-exposed; and APOL1 expression, mitochondrial function, lysosome integrity, and autophagic flux were measured. IFNÉ£ increased median APOL1 expression across all genotypes 22.1 (8.3 to 29.8) fold (p=0.02). Compared to zero risk variant-carrying HUVECs (0RV), HUVECs carrying 2 risk variant copies (2RV) showed both depressed baseline and maximum mitochondrial oxygen consumption (p<0.01), and impaired mitochondrial networking on MitoTracker assays. These cells also demonstrated a contracted lysosomal compartment, and an accumulation of autophagosomes suggesting a defect in autophagic flux. Upon blocking autophagy with non-selective lysosome inhibitor, hydroxychloroquine, autophagosome accumulation between 0RV HUVECs and untreated 2RV HUVECs was similar, implicating lysosomal dysfunction in the HRG-associated autophagy defect. Compared to 0RV and 2RV HUVECs, HUVECs carrying 1 risk variant copy (1RV) demonstrated intermediate mitochondrial respiration and autophagic flux phenotypes, which were exacerbated with IFNÉ£ exposure. Taken together, our data reveal that IFNÉ£ induces APOL1 expression, and that each additional RV associates with mitochondrial dysfunction and autophagy inhibition. IFNÉ£ amplifies this phenotype even in 1RV HUVECs, representing the first description of APOL1 pathobiology in variant heterozygous cell cultures.