Faculty Bibliography

OBJECTIVE:Both psychosocial stress and gestational weight gain are independently associated with adverse maternal and fetal outcomes. Studies of the association between psychosocial stress and gestational weight gain (GWG) have yielded mixed results. The objective of this study was to evaluate the association between psychosocial stress and GWG in a large population-based cohort. METHODS:Data from the nationally representative Pregnancy Risk Assessment Monitoring System (PRAMS) Phase 7 questionnaire 2012-2015 was utilized. Maternal psychosocial stress was assessed through response to questions designed to examine four domains of psychosocial stress (i.e., traumatic, financial, emotional, partner-related) three months prior to or during pregnancy. GWG was categorized using pre-pregnancy BMI and total GWG into inadequate, adequate, or excessive according to the Institute of Medicine's GWG guidelines. Multinomial logistic regression was used to evaluate the association between psychosocial stressors and adequacy of GWG. Analyses took into account complex survey design. RESULTS:All respondents who delivered ≥ 37 weeks gestation with GWG information available were included in the analysis (n = 119,183). After adjusting for confounders, patients who reported financial stress were more likely to experience excessive versus adequate GWG (RRR 1.09 [95%CI: 1.02-1.17]). Exposure to any of the stressor groups did not significantly increase the risk of inadequate GWG. CONCLUSIONS:This large, population-based study revealed that among pregnant people in the US, exposure to financial stress is associated with higher risk of excessive GWG. Understanding the role stress plays in GWG will help to inform initiatives targeting this important aspect of prenatal care.

BACKGROUND:Biologically active cervical glands provide a mucous barrier while influencing the composition and biomechanical strength of the cervical extracellular matrix. Cervical remodeling during ripening may be reflected as loss of the sonographic cervical gland area. As sonographic cervical length remains suboptimal for universal screening, adjunctive evaluation of other facets of the mid-trimester cervix may impart additional screening benefit. OBJECTIVE:To sonographically assess the cervical gland area at universal cervical length screening for preterm birth. STUDY DESIGN/METHODS:We performed a retrospective cohort study of singletons with transvaginal cervical length screening universally performed during anatomic survey between 18 0/7 and 23 6/7 weeks and subsequent live delivery at a single institution in 2018. Uterine anomalies, cerclage, suboptimal imaging, or medically indicated preterm birth were excluded. Ultrasound images were assessed for cervical length and cervical gland area (with quantitative measurements when present). The primary outcome was spontaneous preterm birth <37 weeks. Absent and present gland groups were compared using χ2, Fisher's exact, T-test, and multivariate logistic regression (adjusting for parity and progesterone use, as well as the gestational age, cervical length, and gland absence at screening ultrasound). Gland measurements were evaluated using the Mann-Whitney-U Test and Spearman's correlation. RESULTS:Among the cohort of 772 patients, absent and present CGA groups were overall similar. Patients were on average 33 years old, ∼20 weeks gestation at screening ultrasound, and overall, 2.5% had history of prior spontaneous preterm birth. The absent gland group was more likely to have been taking progesterone (17% vs 4%, p=0.04). Overall rate of preterm birth was 2.6%. However, the 2.3% of patients with absent cervical gland area were significantly more likely to deliver <37 weeks (aOR 23.9, 95% CI 6.4-89, p<0.001). Multivariate logistic regression demonstrated better performance of a cervical length screening model for preterm birth prediction with the addition of qualitative gland evaluation (p<0.001). Qualitative gland assessment was reproducible (PABAK 0.89), but quantitative gland measurements did not correlate with preterm birth. CONCLUSION/CONCLUSIONS:Qualitative gland absence at mid-gestation cervical length screening was associated with subsequent spontaneous preterm birth, whereas quantitative gland measurements were not. Multifaceted ultrasound screening may be needed to adequately evaluate the multiple biologic functions of the cervix.

BACKGROUND:Phthalate exposure may contribute to hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PE/E), but epidemiologic studies are lacking. OBJECTIVES/OBJECTIVE:To evaluate associations of pregnancy phthalate exposure with development of PE/E and HDP. METHODS:Using data from 3,430 participants in eight Environmental influences on Child Health Outcomes (ECHO) Program cohorts (enrolled from 1999 to 2019), we quantified concentrations of 13 phthalate metabolites (8 measured in all cohorts, 13 in a subset of four cohorts) in urine samples collected at least once during pregnancy. We operationalized outcomes as PE/E and composite HDP (PE/E and/or gestational hypertension). After correcting phthalate metabolite concentrations for urinary dilution, we evaluated covariate-adjusted associations of individual phthalates with odds of PE/E or composite HDP via generalized estimating equations, and the phthalate mixture via quantile-based g-computation. We also explored effect measure modification by fetal sex using stratified models. Effect estimates are reported as odds ratios (OR) with 95% confidence intervals (95% CIs). RESULTS:In adjusted analyses, a doubling of mono-benzyl phthalate (MBzP) and of mono (3-carboxypropyl) phthalate (MCPP) concentrations was associated with higher odds of PE/E as well as composite HDP, with somewhat larger associations for PE/E. For example, a doubling of MCPP was associated with 1.12 times the odds of PE/E (95%CI 1.00, 1.24) and 1.02 times the odds of composite HDP (95%CI 1.00, 1.05). A quartile increase in the phthalate mixture was associated with 1.27 times the odds of PE/E (95%CI 0.94, 1.70). A doubling of mono-carboxy isononyl phthalate (MCiNP) and of mono-carboxy isooctyl phthalate (MCiOP) concentrations were associated with 1.08 (95%CI 1.00, 1.17) and 1.11 (95%CI 1.03, 1.19) times the odds of PE/E. Effect estimates for PE/E were generally larger among pregnancies carrying female fetuses. DISCUSSION/CONCLUSIONS:In this study, multiple phthalates were associated with higher odds of PE/E and HDP. Estimates were precise and some were low in magnitude. Interventions to reduce phthalate exposures during pregnancy may help mitigate risk of these conditions.

BACKGROUND:Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS:Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS:57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS:In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT/CONCLUSIONS:First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

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.

STUDY QUESTION:How did the first two coronavirus disease 2019 (COVID-19) waves affect fertility rates in the USA? SUMMARY ANSWER:States differed widely in how their fertility rates changed following the COVID-19 outbreak and these changes were influenced more by state-level economic, racial, political, and social factors than by COVID-19 wave severity. WHAT IS KNOWN ALREADY:The outbreak of the COVID-19 pandemic contributed to already declining fertility rates in the USA, but not equally across states. Identifying drivers of differential changes in fertility rates can help explain variations in demographic shifts across states in the USA and motivate policies that support families in general, not only during crises. STUDY DESIGN, SIZE, DURATION:This is an ecological study using state-level data from 50 US states and the District of Columbia (n = 51). The study period extends from 2020 to 2021 with historical data from 2016 to 2019. We identified Wave 1 as the first apex for each state after February 2020 and Wave 2 as the second apex, during Fall/Winter 2020-2021. PARTICIPANTS/MATERIALS, SETTING, METHODS:State-level COVID-19 wave severity, defined as case acceleration during each 3-month COVID-19 wave (cases/100 000 population/month), was derived from 7-day weekly moving average COVID-19 case rates from the US Centers for Disease Control and Prevention (CDC). State-level fertility rate changes (change in average monthly fertility rate/100 000 women of reproductive age (WRA)/year) were derived from the CDC Bureau of Vital Statistics and from 2020 US Census and University of Virginia 2021 population estimates 9 months after each COVID-19 wave. We performed univariate analyses to describe national and state-level fertility rate changes following each wave, and simple and multivariable linear regression analyses to assess the relation of COVID-19 wave severity and other state-level characteristics with fertility rate changes. MAIN RESULTS AND THE ROLE OF CHANCE:Nationwide, fertility dropped by 17.5 births/month/100 000 WRA/year following Wave 1 and 9.2 births/month/100 000 WRA/year following Wave 2. The declines following Wave 1 were largest among majority-Democrat, more non-White states where people practiced greater social distancing. Greater COVID-19 wave severity was associated with steeper fertility rate decline post-Wave 1 in simple regression, but the association was attenuated when adjusted for other covariates. Adjusting for the economic impact of the pandemic (hypothesized mediator) also attenuated the effect. There was no relation between COVID-19 wave severity and fertility rate change following Wave 2. LIMITATIONS, REASONS FOR CAUTION:Our study harnesses state-level data so individual-level conclusions cannot be inferred. There may be residual confounding in our multivariable regression and we were underpowered to detect some effects. WIDER IMPLICATIONS OF THE FINDINGS:The COVID-19 pandemic initially impacted the national fertility rate but, overall, the fertility rate rebounded to the pre-pandemic level following Wave 2. Consistent with prior literature, COVID-19 wave severity did not appear to predict fertility rate change. Economic, racial, political, and social factors influenced state-specific fertility rates during the pandemic more than the severity of the outbreak alone. Future studies in other countries should also consider whether these factors account for internal heterogeneity when examining the impact of the COVID-19 pandemic and other crises on fertility. STUDY FUNDING/COMPETING INTEREST(S):L.G.K. received funding from the National Institute of Environmental Health Sciences (R00ES030403), M.C. from the National Science Foundation Graduate Research Fellowship Program (20-A0-00-1005789), and M.L. and E.S. from the National Institute of Environmental Health Sciences (R01ES032808). None of the authors have competing interests. TRIAL REGISTRATION NUMBER:N/A.

BACKGROUND:Haemophilus influenzae (Hi) is an emerging cause of early onset neonatal sepsis, but mechanisms of transmission are not well understood. We aimed to determine the prevalence of vaginal carriage of Hi in reproductive age women and to examine behavioral and demographic characteristics associated with its carriage. METHODS:) value < 35 were defined as positive. Sanger sequencing confirmed the presence of hpd. Behavioral and demographic characteristics associated with vaginal carriage of Hi were examined. RESULTS:415 samples were available. 315 (75.9%) had sufficient bacterial DNA and were included. 14 (4.4%) were positive for hpd. There were no demographic or behavioral differences between the women with Hi vaginal carriage and those without. There was no difference in history of bacterial vaginosis, vaginal microbiome community state type, or presence of Group B Streptococcus in women with and without vaginal carriage of Hi. CONCLUSION:Hi was present in vaginal lavage specimens of 4.4% of this cohort. Hi presence was unrelated to clinical or demographic characteristics, though the relatively small number of positive samples may have limited power to detect such differences.

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.

Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of inflammation associated with autoimmune renal and cardiovascular disease that may be associated with preeclampsia. We aimed to evaluate plasma suPAR levels throughout pregnancy in women with and without hypertensive disorders of pregnancy (HDP), including preeclampsia, eclampsia, and gestational hypertension.
Study Design: This was a secondary analysis of the NYU Children's Health and Environment Study (CHES), a prospective birth cohort designed to assess the impact of prenatal exposure to environmental chemicals on maternal and child health. CHES participants with suPAR data in any trimester and information about HDP were included (n=329). We regressed suPAR levels on the gestational age at time of sample collection to assess change over the course of gestation. Wilcoxon signed-rank tests were used to assess whether suPAR levels in each trimester and averaged over pregnancy were different among participants with and without HDP. Among a subset of participants with repeated measures, we utilized paired Wilcoxon tests to assess the within-person change in suPAR across trimesters in both groups.
Result(s): Participants with HDP (n=44) were older and had higher body mass index. In the overall population, suPAR decreased by 1.1% per week of advancing gestation (p< 0.001). suPAR levels did not significantly differ between those with and without HDP at any sampling timepoint. However, among the subset with repeated measures, suPAR values significantly decreased across pregnancy among those without HDP (p< 0.001), but remained stable among those with HDP (p=0.58) (Figure 1).
Conclusion(s): Although HDP is a primary cause of morbidity and mortality in pregnancy, predictive biomarkers are lacking. suPAR levels decrease with advancing gestation among healthy women, but remain stable in women with HDP, which may reflect a heightened inflammatory state. Additional research is needed to understand if stable suPAR levels can predict HDP accurately in clinical practice. [Formula presented] [Formula presented]
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Objective: The SARS-CoV-2 (COVID-19) pandemic has led to reductions in pregnancy intention and subsequent births in the United States (US). We sought to describe how fluctuations in COVID-19 case rates impacted numbers of births at NYU Langone Health (NYULH) to better understand the impact of the ongoing pandemic on New York City (NYC) births.
Study Design: Beginning in March 2020, three COVID-19 "waves'' and two "dips'' were identified using the US Centers for Disease Control and Prevention seven-day moving average of cases per 100,000 in NYC. We compared the number of births at two NYULH hospitals (Manhattan and Brooklyn) nine months following a COVID-19 wave or dip with births during the same window (to account for seasonality) two years prior (pre-COVID). We also performed a sensitivity analysis to account for post-COVID population movement using change-of-address request data from the US Postal Service.
Result(s): Table 1 shows numbers of births recorded in the periods of interest. Compared with pre-COVID, the largest reduction in births followed Wave 1 (-29.28%); as the pandemic went on, the difference vs. pre-COVID diminished. By Wave 2, the percent change was -6.38% and by Wave 3, there was a net increase (5.34%). Manhattan had a steeper decrease in live births following Wave 1; births rebounded in Brooklyn after Dip 2; and both sites reported increases following Wave 3, with a greater increase in Brooklyn (Figure 1). These trends were slightly attenuated after accounting for migration.
Conclusion(s): Births initially decreased during the pandemic; however, this decline attenuated as time passed and then reversed by Wave 3, when the number of births surpassed pre-COVID. This reversal may have resulted from delayed pregnancy intention or other factors. Changes in the number of births during the pandemic varied by hospital site, with a greater rebound in Brooklyn. Future studies are warranted that focus on the interplay between secular events, such the COVID-19 pandemic, and individual-level factors, including sociodemographics, in shaping pregnancy intention. [Formula presented] [Formula presented]
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