Faculty Bibliography

Objective: To compare pregnancy latency achieved with oral labetalol versus extended-release nifedipine during expectant management of preterm preeclampsia with severe features (PEC-SF).
Study Design: This is a retrospective cohort study of patients initiated on antihypertensive therapy with oral labetalol or extended-release nifedipine during admission for expectant management of PEC-SF < 34 weeks between 1/2013 and 4/2022. Those on antihypertensive therapy prior to admission or with another indication for delivery < 34 weeks were excluded (monochorionic-monoamniotic twins, higher order multiples, absent or reversed umbilical artery Dopplers). Pregnancy latency (from oral agent initiation to delivery decision) was compared between groups. Secondary outcomes included need for initial agent dose uptitration, addition of second oral agent, acute antihypertensive therapy, and delivery for refractory hypertension. Linear and modified Poisson regression models were used to estimate adjusted mean differences (AMD) with 95% confidence intervals.
Result(s): The cohort included 78 patients (Table 1). Comparing those initiated on labetalol versus extended-release nifedipine (Table 2), there was no difference in latency (6.2 (7.5) vs 5.4 (7.4) days, AMD 1.1 days, 95% CI [-2.1, 4.4]), nor in the proportion of patients achieving 1 week latency (25.0% vs 23.8%, respectively, AMD 2.9%, 95% CI [-16.5, 22.3]). Those initiated on labetalol were less likely to require a second agent (16.7% vs 38.1% for nifedipine, AMD -18.4, 95% CI [-37.3, 0.5]). There were no differences in need for initial agent uptitration, acute antihypertensive therapy, or delivery for refractory hypertension.
Conclusion(s): There was no difference in pregnancy latency among patients with PEC-SF initiated on oral labetalol versus extended-release nifedipine. Patients on labetalol may be less likely to require a second antihypertensive agent, but comparative outcome estimates may be limited by small cohort size. Further investigations with a larger cohort should be performed to evaluate for any relative advantages of the two oral agents. [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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Objective: To determine whether a machine learning model can predict patients at risk for shoulder dystocia (SD) better than estimations of birthweight (BW) alone.
Study Design: This was a retrospective analysis of 17,731 pregnant individuals from 7/2013 to 10/2018. Utilizing a machine learning model, a total of 122 binary and continuous variables were included. Baseline models were built with different sets of variables during 3 time periods: 57 in antepartum period, 96 in stage 1 and 119 in stage 2 of labor. BW was used as a proxy for estimated fetal weight (EFW) because documented assessment of EFW was not available in all cases. Two decision tree-based models, Random Forest and XGBoost, were used as predictive models and performance was evaluated with 5-fold cross validation. Area under the receiver operating characteristic curve (AUROC) and area under precision/recall curve (AUPR) were used as metrics for evaluating model performance. Mean and standard error of performance metrics were calculated.
Result(s): The cohort included 21,232 vaginal deliveries. There were 415 (1.95%) vaginal deliveries complicated by SD that occurred in 406 patients. An AUROC of 0.73 +/- 0.01 (mean +/- standard error) was achieved for RandomForest model and 0.78 +/- 0.01 for XGBoost model for BW. BW was then added as a variable to variable sets from the antepartum period and each labor stage to assess performance change. The RandomForest model predicted patients at risk for SD better than BW alone, but only the AUROC was statistically significant at all stages (p < 0.05). (Figure 1) This finding was not demonstrated in the XGBoost model.
Conclusion(s): Our machine learning model performed better in predicting SD than EFW alone (using BW as a proxy) at each time period evaluated - the antepartum period, 1st stage and 2nd stage of labor. While our results indicate that our model may enhance the prediction of SD, these findings should be validated using a more robust data set that includes documented EFW to account for the margin of error between BW and EFW. [Formula presented] [Formula presented]
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PURPOSE/OBJECTIVE:To assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCA) in an unselected obstetrical population with genetic confirmation. METHODS:This was a planned secondary analysis of the multicenter, prospective SMART study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCTs; 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. RESULTS:17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs and fetal sex was determined in 17,297, 10,333 and 14,486 pregnancies, respectively. Sensitivity, specificity, and PPV of cfDNA were 83.3%, 99.9%, and 22.7% for MX, and 70.4%, 99.9%, and 82.6% for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. CONCLUSION/CONCLUSIONS:Screening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, while the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.

Objective: Iron deficiency is the most common cause of anemia in pregnancy, which is associated with maternal and neonatal complications. The objective of this study was to identify the frequency and risk factors for isolated iron deficiency (iID) in the 1^st trimester.
Study Design: This was a secondary analysis of a prospective cohort study to identify risk factors for iID of non-anemic pregnant individuals presenting for prenatal care in the 1^st trimester from February 2022 to June 2022 at NYU Langone Health. iID was defined as serum ferritin level of <= 29 ng/mL. Inclusion criteria included pregnant individuals ages 18-60 years with a singleton gestation enrolled in the 1^st trimester (prior to 14 weeks 0 days gestation) and were non-anemic (hemoglobin >=11.0 g/dl). Patients were excluded if they had 1^st trimester anemia or history of blood transfusion 3 months prior to pregnancy. Univariate analyses were followed by multiple logistic regression (OR [95% CI]) with statistical significance defined at p< 0.05.
Result(s): Of 600 patients enrolled in the study, 89 (14.8%) had 1^st trimester iID. Black/African American patients (19.1% vs. 8.2%, p=0.003), those with uterine fibroids (20.2% vs. 9.4%, p=0.003), and those with higher median BMI (25.2 kg/m² (IQR 22.7-29.6) vs. 23.6 kg/m² (IQR 21.4-27.3), p=0.01) were more likely have to 1^st trimester iID. White patients (41.6% vs. 56.6%, p=0.01) and those with a normal BMI (44.9% vs. 57.3%, p=0.04) were less likely to have 1^st trimester iID. After adjusting for confounders in regression models, Black/African American patients had the strongest association with 1^st trimester iID (aOR 2.18 [1.12-4.11], p=0.02), followed by uterine fibroids (aOR 2.02 [1.05-3.72], p=0.03). Overweight or obese BMIs were not identified as risk factors for 1^st trimester iID.
Conclusion(s): Based on our findings, Black/African American pregnant individuals and those with uterine fibroids are at highest risk for 1^st trimester iID. Future studies should investigate perinatal outcomes for pregnant individuals with 1^st trimester iID. [Formula presented]
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BACKGROUND:The clinical implications of nonreportable cell-free DNA screening results are uncertain, but such results may indicate poor placental implantation in some cases and be associated with adverse obstetrical and perinatal outcomes. OBJECTIVE:This study aimed to assess the outcomes of pregnancies with nonreportable cell-free DNA screening in a cohort of patients with complete genetic and obstetrical outcomes. STUDY DESIGN/METHODS:This was a prespecified secondary analysis of a multicenter prospective observational study of prenatal cell-free DNA screening for fetal aneuploidy and 22q11.2 deletion syndrome. Participants who underwent cell-free DNA screening from April 2015 through January 2019 were offered participation. Obstetrical outcomes and neonatal genetic testing results were collected from 21 primary-care and referral centers in the United States, Europe, and Australia. The primary outcome was risk for adverse obstetrical and perinatal outcomes (aneuploidy, preterm birth at <28, <34, and <37 weeks' gestation, preeclampsia, small for gestational age or birthweight <10th percentile for gestational week, and a composite outcome that included preterm birth at <37 weeks, preeclampsia, small for gestational age, and stillbirth at >20 weeks) after nonreportable cell-free DNA screening because of low fetal fraction or other causes. Multivariable analyses were performed, adjusting for variables known to be associated with obstetrical and perinatal outcomes, nonreportable results, or fetal fraction. RESULTS:In total, 25,199 pregnant individuals were screened, and 20,194 were enrolled. Genetic confirmation was missing in 1165 (5.8%), 1085 (5.4%) were lost to follow-up, and 93 (0.5%) withdrew; the final study cohort included 17,851 (88.4%) participants who had cell-free DNA, fetal or newborn genetic confirmatory testing, and obstetrical and perinatal outcomes collected. Results were nonreportable in 602 (3.4%) participants. A sample was redrawn and testing attempted again in 427; in 112 (26.2%) participants, results were again nonreportable. Nonreportable results were associated with higher body mass index, chronic hypertension, later gestational age, lower fetal fraction, and Black race. Trisomy 13, 18, or 21 was confirmed in 1.6% with nonreportable tests vs 0.7% with reported results (P=.013). Rates of preterm birth at <28, 34, and 37 weeks, preeclampsia, and the composite outcome were higher among participants with nonreportable results, and further increased among those with a second nonreportable test, whereas the rate of small for gestational age infants was not increased. After adjustment for confounders, the adjusted odds ratios were 2.2 (95% confidence interval, 1.1-4.4) and 2.6 (95% confidence interval, 0.6-10.8) for aneuploidy, and 1.5 (95% confidence interval, 1.2-1.8) and 2.1 (95% confidence interval, 1.4-3.2) for the composite outcome after a first and second nonreportable test, respectively. Of the patients with nonreportable tests, 94.9% had a live birth, as opposed to 98.8% of those with reported test results (adjusted odds ratio for livebirth, 0.20 [95% confidence interval, 0.13-0.30]). CONCLUSION/CONCLUSIONS:Patients with nonreportable cell-free DNA results are at increased risk for a number of adverse outcomes, including aneuploidy, preeclampsia, and preterm birth. They should be offered diagnostic genetic testing, and clinicians should be aware of the increased risk of pregnancy complications.

BACKGROUND:Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE:This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN/METHODS:This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS:A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION/CONCLUSIONS:Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.

Introduction Fetal cardiac disease is strongly associated with maternal anti-SSA/Ro antibodies, but gaps in our knowledge include the influence of antibody specificity and titer, maternal diagnosis, overall non-cardiac adverse pregnancy outcomes (APOs), optimal surveillance protocols, and efficacy of rapid treatment. Methods The multi-center Surveillance and Treatment To Prevent Fetal AV Block Likely to Occur Quickly (STOP BLOQ) study recruited pregnant women with commercially positive anti-Ro antibodies and stratified them into high and low titers of anti-Ro60 and Ro52 based on a research ELISA, using a cutoff defined by that obtained for 50 mothers with previous AVB offspring. Mothers with anti-Ro60 and/or 52 antibodies at or above 1,000 I.U. were trained to perform FHRM. From 17-25 weeks of gestation, FHRM was completed 3x/day in addition to weekly or biweekly fetal echocardiograms (echo). Mothers texted all audio sounds to the coordinating center. Texts deemed abnormal by mothers were immediately sent to an on call pediatric cardiologist who either reassured if FHRM was normal or referred for emergency fetal echo in < 6 hours if abnormal. Results 250 anti-Ro pregnant women (22% Hispanic, 50% white, 12% Black, 12% Asian, 4% other) have been consented, including 28 whose previous child had AVB. Of mothers tested to date, 153 were provided home monitors given high titer anti-Ro60 and/or 52 antibodies (26 high titer anti-Ro60 alone, 21 high titer anti-Ro52 alone,105 high titer antibodies to both antigens). The 83 patients with low titers were surveilled with echos per local standard of care. Regarding maternal diagnosis, of 161 assessed to date, 39% were asym/UAS, 11% RA, 31% SS, 19% SLE. Antibody titers did not significantly differ by ethnicity, race or diagnosis (table 1). Non-AVB APOs occurred in 18% and were not predicted by Ro60 or 52 titers but rather SLE diagnosis (table 2). In total, 24,759 FHRM audiotexts were received from 131 patients (90 of whom have delivered) during the monitoring period. Of these, 22 were evaluated by the on-call pediatric cardiologist, who prompted an emergency echo (all completed in < 6 hrs). In 11 cases, the emergency echo was normal. In 9, there were premature atrial contractions, confirming the mother's perception. In 2 with 2degree block on urgent echo (both treated per protocol with IVIG and dexamethasone), 1 reverted to normal sinus rhythm and the other progressed to 3degree block. In 2 others, the mother did not perceive abnormal FHRM for > 24 hrs, echo identified 3degree block, and retrospective cardiology review of FHRM audio captures identified an abnormality prior to obtaining the echo. All 4 AVB developed in fetuses of mothers with high titer antibodies to both Ro60 and 52 (mean 32,451 and 34,991 respectively). Of the 18 mothers with a previous AVB child who followed the 400mg hydroxychloroquine PATCH protocol, 1 developed AVB in accord with the results of Step 1 in that study. Conclusion These data support that APOs in this clinically diverse group of mothers are not influenced by anti-Ro titer or specificity, but rather SLE diagnosis. All conduction defects were initially identified by FHRM and in mothers with high titer anti-Ro60 and 52. Hydroxychloroquine continues to show efficacy in reducing the AVB recurrence rate with rapid intervention of emergent block being promising