Faculty Bibliography

OBJECTIVE:The aim of this study was to evaluate the incidence of congenital anomalies in dichorionic-diamniotic twins conceived with in-vitro fertilization (IVF) versus unassisted conception pregnancies in a large geographically diverse population. DESIGN/METHODS:This is a secondary analysis of data from a retrospective cohort study of twin pregnancies seen at 17 centers between 12/2011-2/2020. SUBJECTS/METHODS:This study included dichorionic-diamniotic twins conceived unassisted, or by in-vitro fertilization. EXPOSURE/METHODS:The exposure group is dichorionic-diamniotic twins conceived with IVF. MAIN OUTCOME MEASURE/METHODS:The primary outcome was presence of a congenital anomaly. Neonates with an abnormal newborn exam were evaluated for having a major or minor congenital anomaly and the major anomalies were further classified by organ system (cardiac, renal/genitourinary, gastrointestinal, and musculoskeletal). RESULTS:Of the 968 dichorionic-diamniotic twin pregnancies included, 521 (53.8%) were conceived with IVF and 447 (46.2%) were conceived unassisted. Congenital anomalies were found in 70 pregnancies (7.23%). Of those, 37 were found in pregnancies conceived by IVF (52.9%) versus 33 unassisted conception pregnancies (47.1) (p=0.87). There were no significant differences between IVF and unassisted conception pregnancies for major anomalies (p=0.65) or minor anomalies (p=0.94). CONCLUSION/CONCLUSIONS:In this large cohort of twin pregnancies, there is no significant difference in the incidence of anomalies for dichorionic-diamniotic twin pregnancies conceived by IVF versus unassisted conception pregnancies.

OBJECTIVE:To determine whether administration of antenatal corticosteroids to patients with twin gestations at risk for late preterm delivery is associated with reduced risk for neonatal respiratory morbidity compared with unexposed twins. METHODS:This was a multicenter, retrospective cohort study in a large, urban health network (2013-2022) of patients with twin gestations at risk for preterm delivery between 34 0/7 and 36 6/7 weeks of gestation. Patients were excluded if they received antenatal corticosteroids before 34 weeks of gestation or had pregestational diabetes, single-twin death before 34 weeks, or oral steroid exposure during pregnancy. Neonates were excluded if they had major congenital anomalies. The primary outcome was a composite of neonatal respiratory morbidity requiring respiratory support within 72 hours of birth, including continuous positive airway pressure (CPAP) or high-flow nasal cannula for 2 hours or more, supplemental oxygen of 30% for 2 hours or more, extracorporeal membrane oxygenation, mechanical ventilation, and fetal or neonatal death. Secondary outcomes included neonatal hypoglycemia and indications for neonatal intensive care unit (NICU) admission. Adjusted and unadjusted relative risks with 95% CIs were calculated. RESULTS:During the study period, 366 twin gestations and 722 patient-neonate dyads were included: 162 gestations (321 neonates) in the exposed group and 204 (401 neonates) in the unexposed group. There was no difference in the composite outcome of respiratory morbidity in those exposed to antenatal corticosteroids (23.4% vs 20.4%, P=.40, adjusted relative risk [RR] 1.00, 95% CI, 0.71-1.42). The composite was driven mostly by rates of CPAP use (21.2% vs 18.5%, P=.41, adjusted RR 1.05, 95% CI, 0.73-1.53) and high-flow nasal cannula use (6.2% vs 2.2%, P=.02, RR 2.77, 95% CI, 1.16-6.66). Antenatal corticosteroid exposure was associated with a lower risk of need for supplemental oxygen (0.6% vs 3.5%, P=.02, RR 0.18, 95% CI, 0.04-0.79) and mechanical ventilation (0.6% vs 3.2%, P=.03, RR 0.19, 95% CI, 0.04-0.87). Although antenatal corticosteroids exposure was not associated with higher rates of hypoglycemia (44.2% vs 41.7%, P=.57, adjusted RR 0.99, 95% CI, 0.82-1.19), exposure was associated with a higher risk of having hypoglycemia as the only indication for NICU admission (10.3% vs 5.2%, P=.03, RR 1.96, 95% CI, 1.07-3.59). CONCLUSION/CONCLUSIONS:In a large, multicenter, network-wide retrospective cohort study of patients with twin gestations at risk for late preterm birth, antenatal corticosteroid use was not associated with a decrease in overall respiratory morbidity but was associated with a decreased risk of need for supplemental oxygen and mechanical ventilation, as well as a higher risk of NICU admission for hypoglycemia. These results underscore the ongoing need to elucidate the risks and benefits of late preterm antenatal corticosteroids for patients with twin gestations at risk for late preterm birth.

OBJECTIVE: We sought to create a machine learning (ML) model to identify variables that would aid in the prediction of surgical morbidity in cases of placenta accreta spectrum (PAS). STUDY DESIGN/METHODS: A multicenter analysis including all cases of PAS identified by pathology specimen confirmation, across five tertiary care perinatal centers in New York City from 2013 to 2022. We developed models to predict operative morbidity using 213 variables including demographics, obstetrical information, and limited prenatal imaging findings detailing placental location. Our primary outcome was prediction of a surgical morbidity composite defined as including any of the following: blood loss (>1,500 mL), transfusion, intensive care unit admission, vasopressor use, mechanical ventilation/intubation, and organ injury. A nested, stratified, cross-validation approach was used to tune model hyperparameters and estimate generalizability. Gradient boosted tree classifier models incorporated preprocessing steps of standard scaling for numerical variables and one-hot encoding for categorical variables. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), positive and negative predictive values (PPV, NPV), and F1 score. Variable importance ranking was also determined. RESULTS: Among 401 PAS cases, 326 (81%) underwent hysterectomy. Of the 401 cases of PAS, 309 (77%) had at least one event defined as surgical morbidity. Our predictive model had an AUC of 0.79 (95% confidence interval: 0.69, 0.89), PPV 0.79, NPV 0.76, and F1 score of 0.88. The variables most predictive of surgical morbidity were completion of a hysterectomy, prepregnancy body mass index (BMI), absence of a second trimester ultrasound, socioeconomic status zip code, BMI at delivery, number of prenatal visits, and delivery time of day. CONCLUSION/CONCLUSIONS: By identifying social and obstetrical characteristics that increase patients' risk, ML models are useful in predicting PAS-related surgical morbidity. Utilizing ML could serve as a foundation for risk and complexity stratification in cases of PAS to optimize surgical planning. KEY POINTS/CONCLUSIONS:· ML models are useful models are useful in predicting PAS-related surgical morbidity.. · Optimal management for PAS remains unclear.. · Utilizing ML can serve as a foundation for risk and complexity stratification in cases of PAS..

BACKGROUND:The relationship between fetal fraction and birth weight in twin gestations is poorly understood. OBJECTIVE:To investigate the relationship between first trimester cfDNA fetal fraction and birth weight < 10th percentile in twin gestations. STUDY DESIGN/METHODS:This is a planned secondary analysis of the Twin cfDNA Study, a 17-center retrospective cohort of twin pregnancies screened for aneuploidy using cfDNA in the first trimester from 12/2011 - 2/2022, excluding those with positive screen results for chromosomal aneuploidy. CfDNA testing was performed by a single lab using massively parallel sequencing (MPSS). Baseline characteristics and birth weight of pregnancies with normal fetal fraction were compared to those with low (<5%) and high (>95%) fetal fraction using univariable analyses and multivariable regression. RESULTS:A total of 1041 twin pregnancies were included. Chronic hypertension, elevated BMI, and self-identified Black race were associated with fetal fraction <5th percentile. There was no difference in median fetal fraction between those with birth weight <10th percentile in at least one twin (median [IQR] fetal fraction 12.2% [9.8, 14.8] versus those with normal birth weight (10th percentile) in both twins (median [IQR] fetal fraction 12.3% [9.7, 15.2] for normal birth weight, p = 0.49). There was no association between high or low fetal fraction and birth weight <10th percentile for one (p=0.45) or both (p=0.81) twins, and there was no association between high or low fetal fraction and birth weight <5th percentile for one (p=0.44) or both (p=0.74) twins. The results were unchanged after adjustment for potential confounders. CONCLUSION/CONCLUSIONS:In this large cohort, there was no association between the extremes of cfDNA fetal fraction and birthweight < 10th percentile, suggesting that first trimester fetal fraction may not predict impaired fetal growth in twin gestations.

BACKGROUND/UNASSIGNED:Placenta accreta spectrum (PAS) disorder is a source of severe obstetric morbidity and mortality worldwide. The objective of this paper was to evaluate the potential relationship between social vulnerability and severe maternal morbidity in a cohort of patients delivering a pregnancy complicated by PAS. METHODS/UNASSIGNED:A retrospective review of 323 deliveries at three academic medical institutions between January 2013 and June 2022 was included in the analyses. Patients were those with a histopathologically confirmed case of PAS. The composite morbidity outcome included such maternal complications as mechanical ventilation, injury to organs and transfusion of 4+units of red blood cells. Social vulnerability was measured by assigning subjects a value of the Childhood Opportunity Index based on their home zip code. Logistic regression models were employed and adjusted for potential confounders. RESULTS/UNASSIGNED:73% of our sample experienced composite severe maternal morbidity at the time of their delivery. There were no statistically significant associations between social vulnerability and severe surgical morbidity, either as a composite or individually, within the multivariate regression models. CONCLUSION/UNASSIGNED:Our results do not support the hypothesis that social vulnerability is associated with severe maternal morbidity in deliveries complicated by PAS. The present study suggests that the relationship between social vulnerability and obstetrical surgical morbidity is more complicated than can be assessed by the present linear regression models.

We present a case of a vein of Galen aneurysmal malformation (VGAM), a rare congenital arteriovenous malformation, in one fetus of a monochorionic-diamniotic twin pregnancy. The diagnosis was made with color Doppler ultrasonography at 28 weeks and the affected fetus was found to have worsening cardiomegaly on subsequent fetal echocardiograms. She was emergently delivered at 32 weeks for abnormal fetal heart rate tracing of the affected twin. Magnetic resonance imaging of the brain findings after delivery demonstrated severe neurological injury; therefore, postnatal embolization was not performed. The neonate died on day of life 9. The cotwin survived without neurological complications. This is the first case in the literature of a VGAM diagnosed prenatally in a monochorionic-diamniotic twin pregnancy and demonstrates the challenge of delivery timing with prenatal diagnosis in a twin pregnancy.

BACKGROUND:Placenta accreta spectrum is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in the outcomes of patients with placenta accreta spectrum. OBJECTIVE:This study aimed to investigate health inequities in maternal and neonatal outcomes of pregnancies with placenta accreta spectrum. STUDY DESIGN:This multicentered retrospective cohort study included patients with a histopathological diagnosis of placenta accreta spectrum at 4 regional perinatal centers between January 1, 2013, and June 30, 2022. Maternal race and ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. The primary outcome was a composite adverse maternal outcome: transfusion of ≥4 units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury, or mortality. The secondary outcomes were a composite adverse neonatal outcome (Apgar score of <7 at 1 minute, morbidity, or mortality), gestational age at placenta accreta spectrum diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race and ethnicity with maternal and neonatal outcomes. RESULTS:A total of 408 pregnancies with placenta accreta spectrum were included. In 218 patients (53.0%), the diagnosis of placenta accreta spectrum was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, body mass index, income, and parity, there was no difference in composite adverse maternal outcomes among the racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team, and cesarean hysterectomy were similar among groups. CONCLUSION:In our multicentered placenta accreta spectrum cohort, race and ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis, or planned multidisciplinary care. This study hypothesized that a comparable incidence of individual risk factors for perinatal morbidity and geographic proximity reduces potential inequities that may exist in a larger population.

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:Crown-rump length discordance, defined as ≥10% discordance, has been investigated as an early sonographic marker of subsequent growth abnormalities and is associated with an increased risk of fetal loss in twin pregnancies. Previous studies have not investigated the prevalence of fetal aneuploidy or structural anomalies in twins with discordance or the independent association of crown-rump length discordance with adverse perinatal outcomes. Moreover, data are limited on cell-free DNA screening for aneuploidy in dichorionic twins with discordance. OBJECTIVE:This study aimed to evaluate whether crown-rump length discordance in dichorionic twins between 11 and 14 weeks of gestation is associated with a higher risk of aneuploidy, structural anomalies, or adverse perinatal outcomes and to assess the performance of cell-free DNA screening in dichorionic twin pregnancies with crown-rump length discordance. STUDY DESIGN/METHODS:This was a secondary analysis of a multicenter retrospective cohort study that evaluated the performance of cell-free DNA screening for the common trisomies in twin pregnancies from December 2011 to February 2020. For this secondary analysis, we included live dichorionic pregnancies with crown-rump length measurements between 11 and 14 weeks of gestation. First, we compared twin pregnancies with discordant crown-rump lengths with twin pregnancies with concordant crown-rump lengths and analyzed the prevalence of aneuploidy and fetal structural anomalies in either twin. Second, we compared the prevalence of a composite adverse perinatal outcome, which included preterm birth at <34 weeks of gestation, hypertensive disorders of pregnancy, stillbirth or miscarriage, small-for-gestational-age birthweight, and birthweight discordance. Moreover, we assessed the performance of cell-free DNA screening in pregnancies with and without crown-rump length discordance. Outcomes were compared with multivariable regression to adjust for confounders. RESULTS:Of 987 dichorionic twins, 142 (14%) had crown-rump length discordance. The prevalence of aneuploidy was higher in twins with crown-rump length discordance than in twins with concordance (9.9% vs 3.9%, respectively; adjusted relative risk, 2.7; 95% confidence interval, 1.4-4.9). Similarly, structural anomalies (adjusted relative risk, 2.5; 95% confidence interval, 1.4-4.4]) and composite adverse perinatal outcomes (adjusted relative risk, 1.2; 95% confidence interval, 1.04-1.3) were significantly higher in twins with discordance. A stratified analysis demonstrated that even without other ultrasound markers, there were increased risks of aneuploidy (adjusted relative risk, 3.5; 95% confidence interval, 1.5-8.4) and structural anomalies (adjusted relative risk, 2.7; 95% confidence interval, 1.5-4.8) in twins with CRL discordance. Cell-free DNA screening had high negative predictive values for trisomy 21, trisomy 18, and trisomy 13, regardless of crown-rump length discordance, with 1 false-negative for trisomy 21 in a twin pregnancy with discordance. CONCLUSION/CONCLUSIONS:Crown-rump length discordance in dichorionic twins is associated with an increased risk of aneuploidy, structural anomalies, and adverse perinatal outcomes, even without other sonographic abnormalities. Cell-free DNA screening demonstrated high sensitivity and negative predictive values irrespective of crown-rump length discordance; however, 1 false-negative result illustrated that there is a role for diagnostic testing. These data may prove useful in identifying twin pregnancies that may benefit from increased screening and surveillance and are not ascertained by other early sonographic markers.