Faculty Bibliography

Vasa previa is a rare but potentially catastrophic obstetric condition characterized by unprotected fetal blood vessels over or adjacent to the internal cervical os. Although advances in prenatal ultrasound have dramatically improved neonatal survival through planned cesarean delivery, many aspects of vasa previa remain poorly understood. Existing studies are limited by small sample sizes, single-center designs, heterogeneous diagnostic criteria, and inconsistent reporting of clinical outcomes, highlighting the need for large, systematically collected multicenter datasets. Here we describe, to our knowledge, the first United States multicenter registry of pregnancies complicated by vasa previa without concurrent placenta previa, the U.S. Vasa Previa Registry (US-VPR). This report outlines the rationale, design, and implementation of a large, multicenter, retrospective registry developed to characterize patient demographics, risk factors, placental pathology, natural history, antenatal management, maternal outcomes, neonatal outcomes, and healthcare utilization associated with vasa previa. The US-VPR includes contributions from 15 tertiary referral centers and represents the largest multicenter cohort of pregnancies complicated by vasa previa without concurrent placenta previa reported to date. By leveraging multicenter collaboration and standardized data collection, the registry provides a unique opportunity to characterize variation in clinical practice and outcomes across referral centers, strengthen the evidence base for this rare condition, and inform future prospective studies and evidence-based patient counseling.

INTRODUCTION/UNASSIGNED:There is uncertainty about the benefits of cerclage in patients with transvaginal cervical length (TVCL) ≤10 mm and no prior spontaneous preterm birth. Our aim was to assess whether cervical cerclage in these patients was associated with prolonged pregnancy latency. METHODS/UNASSIGNED:This was an observational study of asymptomatic singleton pregnancies without a history of spontaneous preterm birth with extremely short cervix (TVCL ≤10 mm) in the second trimester. Exposure and outcome data were extracted manually from medical charts by obstetric providers, with all outcomes occurring prior to study initiation. All patients were prescribed vaginal progesterone and those with a cervical dilation >1.5 cm were excluded. The primary outcome was time interval from diagnosis to delivery (or 37 weeks' gestation, whichever occurred first). Secondary outcomes included gestational age at delivery, mode of delivery, and neonatal outcomes. We adjusted for parity and used log-binomial regression to estimate the relative risk for categorical variables and linear regression to estimate mean differences for continuous variables. RESULTS/UNASSIGNED:There were 247 patients with TVCL ≤10 mm during anatomy scan. After exclusions, 87 remained, of which 55 (63.2%) received cervical cerclage. At the time of diagnosis, the mean cervical length was 5.8 mm (cerclage group) versus 7.4mm (no cerclage group, difference: -1.6, 95% CI -0.6, -2.6) and the gestational age was 21.0 weeks (cerclage group) versus 22.1 weeks (no cerclage group, -1.1, 95% CI -1.8, -0.3). Mean pregnancy latency was longer in the cerclage group compared to the no cerclage group (13.4 vs 11.1 weeks, 2.2, 95% CI -0.3, 4.9), though there was a high level of uncertainty in the estimate. Term delivery occurred 30% more often in the cerclage group compared to the no cerclage group (RR 1.31, 95% CI 0.96, 1.79). CONCLUSION/UNASSIGNED:In our cohort, patients with extremely short cervix who received a cerclage had longer pregnancy latency than those who did not receive cerclage and more patients achieved term gestation, suggesting a potential benefit of cerclage in this population. However, given the high level of uncertainty of our estimates, additional research is needed to investigate these findings.

INTRODUCTION/UNASSIGNED:Platelet hyperreactivity is linked to inflammation and cardiovascular risk in nonpregnant populations, but its relationship to placentally mediated pregnancy outcomes is undefined. We prospectively evaluated platelet hyperreactivity in pregnancy and subsequent ischemic placental disease (IPD), and examined aspirin's (ASA) effect on platelet activity by baseline platelet phenotype. METHODS/UNASSIGNED: RESULTS/UNASSIGNED:Of 66 pregnant participants recruited, 61 had first-trimester LTA; 20 (32.8%) had platelet hyperreactivity. Participants with hyperreactivity were more likely to develop IPD than those without (55% versus 24%, adjusted odds ratio [aOR] 3.77 (95% CI [1.05-13.53]), with consistent directionality across individual components despite low event frequencies. Participants with platelet hyperreactivity showed greater platelet aggregation to ADP, collagen, and low-dose AA. Platelet transcriptomic profiling distinguished participants with versus without platelet hyperreactivity and revealed differential expression of pathways related to platelet activity, energy metabolism, and immune regulation. Among 45 high-risk participants recommended ASA, those with hyperreactivity exhibited higher AA-induced aggregation (24% vs 12.5% platelet aggregation, p=0.01) despite similar serum TxB2 levels. CONCLUSION/UNASSIGNED:First-trimester platelet hyperreactivity was present in approximately one-third of participants and was independently associated with increased risk of IPD. Participants with platelet hyperreactivity demonstrated distinct transcriptomic signatures and greater platelet aggregation despite ASA use. Together, these findings support a contributory role for platelets in placental ischemic pathology and highlight the need to elucidate mechanisms and develop platelet-targeted preventive strategies.

BACKGROUND:Patent foramen ovale (PFO) is a common finding that occurs in approximately 25% of the population and, in the absence of clinical sequelae, is considered benign. However, PFO can potentially become clinically significant and result in systemic embolization, strokes, or hypoxemia. During pregnancy, hemodynamic cardiovascular changes may unmask previously undetected congenital heart anomalies or exacerbate existing ones, affecting both mother and fetus. CASE SUMMARY/METHODS:A healthy 33-year-old woman developed symptomatic hypoxemia on minimal exertion during pregnancy secondary to newly diagnosed right-to-left intracardiac shunting through a PFO. We posit that the physiological changes of pregnancy enhanced this abnormal streaming through the PFO without evidence of pulmonary hypertension. The patient had a successful percutaneous occlusion of the PFO with a 25-mm Amplatzer cribriform septal occluder device at 18 weeks' gestation, with appropriate fetal protection. CONCLUSIONS:Pregnancy may produce or accentuate acute hypoxemia due to right-to-left shunting through a PFO. The PFO may be safely treated with percutaneous device closure to resolve hypoxemia-related symptoms and avert risks of hypoxia to the developing fetus.

BACKGROUND/UNASSIGNED:Although infective endocarditis during pregnancy is rare, it carries significant morbidity and mortality for both mother and foetus. While professional societies provide recommendations for the treatment of infective endocarditis, there are no specific guidelines for the management of pregnancy-associated infective endocarditis. In this report, we present two cases of infective endocarditis presenting during the second trimester of pregnancy that required surgical intervention, focusing on the unique considerations when caring for pregnant individuals. CASE SUMMARIES/UNASSIGNED:Two patients in the second trimester of pregnancy presented with fevers and malaise. Both were found to have positive blood cultures and mitral valve vegetations, leading to diagnoses of mitral valve endocarditis. Their hospital courses were complicated by embolic strokes, and one patient required transcatheter embolization of a mycotic aneurysm. Both patients underwent surgical valve replacements with bioprosthetic valves. Ultimately, both patients delivered at term without complication. DISCUSSION/UNASSIGNED:In addition to the standard management of infective endocarditis, pregnancy-associated infective endocarditis requires multidisciplinary collaboration regarding the relative timing of cardiac surgery and delivery, the use of intraoperative foetal monitoring, and the choice of valve replacement and anticoagulation. Each of these decisions requires balancing the risk of morbidity and mortality to the patient, the risk of neonatal prematurity and associated complications and disability, and the risk of foetal death during cardiopulmonary bypass. We discuss our teams' decision-making processes with a focus on the relevant considerations for each of these challenging decisions.

BACKGROUND:Perinatal ovarian cysts may spontaneously resolve or cause ovarian torsion. Cyst size and appearance often guide surgical decision making. The natural history of these cysts and impact of perinatal interventions on ovarian outcomes remain unclear. We investigated the association of various clinical parameters with operative intervention and ovarian loss. METHODS:Infants with ovarian cysts meeting our definition of perinatal (diagnosed between 15 weeks gestational age and 1 year) from November 2006-January 2022 were identified. Cysts were characterized by size, morphology, laterality, and evolution. Outcome measures included resolution, ovarian loss, and operative intervention. Mann-Whitney U and Fisher exact tests were used. Optimal maximal size cutoffs were obtained using ROC curves. RESULTS:Sixty-two female patients with perinatal ovarian cysts were identified. Spontaneous resolution occurred in 35, prenatally and postnatally, with follow-up length averaging 186 days. Of 18 undergoing cystectomies, 9 revealed non-viable ovaries. Overall ovarian loss rate was 29%. Loss occurred more frequently with large, complex, and right-sided cysts (P < 0.05) but some complex cysts also resolved spontaneously. Operative intervention occurred more frequently with larger cysts (P=<0.001) and was associated with ovarian salvage when performed earlier (P = 0.008) on larger cysts (P = 0.02). Maximal cyst diameter > 4.05 cm predicted ovarian loss with 78% sensitivity, 64% specificity (AUC = 0.67,95%CI = 0.54-0.81, P = 0.04). Maximal cyst diameter > 4.55 cm predicted surgery with 83% sensitivity, 82% specificity (AUC = 0.86,95%CI = 0.77-0.96, P < 0.001). CONCLUSIONS:29% of perinatal ovarian cysts resulted in ovarian loss. 56% resolved spontaneously (prenatal and postnatal resolution) including some complex cysts. Cysts that were postnatally complex and maximally > 4 cm had higher rates of ovarian loss and operative intervention. Earlier postnatal operative intervention was associated with ovarian preservation. Standardized imaging (such as the IOTA terminology) and management protocols are needed to better understand behavior and improve treatment of these cysts.

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:Social determinants of health (SDOH) may impact the incidence of Respiratory Syncytial Virus (RSV) infection and the uptake of vaccinations in pregnancy. The objective of this study is to identify contributors to disparities in RSV vaccination in pregnancy. DESIGN/METHODS:This is a retrospective cohort study of patients delivering at term within three hospitals during February and March 2024, comparing pregnant patients identified as receiving vs not receiving RSV vaccinations. This period and gestational age were chosen to include patients who would have qualified for RSV vaccination administration. Vaccination status was extracted from standardized admission templates where these variables were recorded as discrete fields. Patients without RSV vaccination information were excluded. Sociodemographic factors, COVID vaccination status, and delivery campus were evaluated. Outcomes were analyzed using chi-squared, t-test, and McNemar test. RESULT/RESULTS:2181 patients met inclusion criteria and RSV vaccination information was available for 1548 patients (71%) with a 14% vaccination rate. Compared to those not vaccinated (n=1332), RSV vaccinated patients (n=216) were more likely to be older (30.7 vs 34.8, p<0.001), have private insurance (42% vs 85%, p<0.001), speak English (82% vs 95%, p<0.001), and deliver at our regional perinatal center (26% vs 77%, p<0.001). 50% of RSV vaccinated patients had a history of COVID vaccination compared to 33% of those not vaccinated against RSV (p<0.001). CONCLUSIONS:SDOH were associated with differences in RSV vaccination status. In addition, patients without RSV vaccination were less likely to have had COVID vaccination. These findings highlight the need to address SDOH to increase vaccination rates for vulnerable populations.