Mode of Delivery in Antepartum Singleton Stillbirths and Associated Risk Factors.

OBJECTIVE: This study was aimed to investigate delivery management of patients with antepartum stillbirth. STUDY DESIGN: Using data from fetal death certificates and linked maternal hospital discharge records, we identified a population-based sample of patients with singleton antepartum stillbirth at 20 to 42 weeks of gestation in California in 2007 to 2011. Primary outcomes were intended mode of delivery and actual mode of delivery. We used multivariable regressions to examine the association between patient demographic, clinical, and hospital characteristics and their mode of delivery. Separate analysis was performed for patients who had prior cesarean delivery versus those who did not. RESULTS: Of 7,813 patients with singleton antepartum stillbirth, 1,356 had prior cesarean, while 6,457 had no prior cesarean. Labor was attempted in 51.8% of patients with prior cesarean and 93.7% of patients without prior cesarean, with 76.2 and 95.8% of these patients, respectively, delivered vaginally. Overall, 18.9% of patients underwent a cesarean delivery (60.5% among those with prior cesarean and 10.2% among those without prior cesarean). Multivariable regression analysis identified several factors associated with the risk of cesarean delivery that were not medically indicated. For instance, among patients without prior cesarean, malpresentation (of which the vast majority was breech presentation) was associated with an increased likelihood of planned cesarean (adjusted odds ratio [OR] = 3.26, 95% confidence interval [CI]: 2.53-4.22) and cesarean delivery after attempting labor (adjusted OR = 3.09, 95% CI: 2.25-4.25). For both patients with and without prior cesarean, delivery at an urban teaching hospital was associated with a lower likelihood of planned cesarean and a lower likelihood of cesarean delivery after attempting labor (adjusted ORs ranged from 0.28 to 0.56, p < 0.001 for all). CONCLUSION: Over one in six patients with antepartum stillbirth underwent cesarean delivery. Among patients who attempted labor, rate of vaginal delivery was generally high, suggesting a potential opportunity to increase vaginal delivery in this population. KEY POINTS: · In singleton antepartum stillbirths, 18.9% underwent cesarean delivery.. · Rate of vaginal delivery was high when labor was attempted.. · Both clinical and non-clinical factors were associated with risk of cesarean delivery..

Noonan syndrome and pregnancy outcomes.

BACKGROUND: Noonan syndrome is a genetic disorder with high prevalence of congenital heart defects, such as pulmonary stenosis, atrial septal defect and hypertrophic cardiomyopathy. Scarce data exists regarding the safety of pregnancy in patients with Noonan syndrome, particularly in the context of maternal cardiac disease. STUDY DESIGN: We performed a retrospective chart review of patients at Yale-New Haven Hospital from 2012 to 2020 with diagnoses of Noonan syndrome and pregnancy. We analysed medical records for pregnancy details and cardiac health, including echocardiograms to quantify maternal cardiac dysfunction through measurements of pulmonary valve peak gradient, structural heart defects and interventricular septal thickness. RESULTS: We identified five women with Noonan syndrome (10 pregnancies). Three of five patients had pulmonary valve stenosis at the time of pregnancy, two of which had undergone cardiac procedures. 50% of pregnancies (5/10) resulted in pre-term birth. 80% (8/10) of all deliveries were converted to caesarean section after a trial of labour. One pregnancy resulted in intra-uterine fetal demise while nine pregnancies resulted in the birth of a living infant. 60% (6/10) of livebirths required care in the neonatal intensive care unit. One infant passed away at 5 weeks of age. CONCLUSIONS: The majority of mothers had pre-existing, though mild, heart disease. We found high rates of prematurity, conversion to caesarean section, and elevated level of care. No maternal complications resulted in long-term morbidity. Our study suggests that women with Noonan syndrome and low-risk cardiac lesions can become pregnant and deliver a healthy infant with counselling and risk evaluation.

Coronary Disease in Pregnancy: Myocardial Infarction and Spontaneous Coronary Artery Dissection.

Pregnancy-related maternal mortality and morbidity rates continue to increase in the United States despite global improvements in maternal outcomes. The unique hemodynamic and physiological changes of pregnancy results in a 3- to 4-fold increased risk of acute myocardial infarction (AMI) which causes a substantial proportion of all maternal cardiac deaths. In addition to atherosclerosis, pregnancy-associated AMI is commonly caused by nonatherosclerotic etiologies such as spontaneous coronary artery dissection, embolus to the coronary artery, and coronary vasospasm. Herein, the epidemiology, etiologies, presentation, diagnosis, and management of AMI in pregnancy is discussed along with future directions for multidisciplinary care.

Severe cardiovascular morbidity in women with hypertensive diseases during delivery hospitalization.

BACKGROUND: Cardiovascular disease is the leading cause of pregnancy-related death in the United States. Identification of short-term indicators of cardiovascular morbidity has the potential to alter the course of this devastating disease among women. It has been established that hypertensive disorders of pregnancy are associated with increased risk of cardiovascular disease 10-30 years after delivery; however, little is known about the association of hypertensive disorders of pregnancy with cardiovascular morbidity during the delivery hospitalization. OBJECTIVE: We aimed to identify the immediate risk of cardiovascular morbidity during the delivery hospitalization among women who experienced a hypertensive disorder of pregnancy. MATERIALS AND METHODS: This retrospective cohort study of women, 15-55 years old with a singleton gestation between 2008 and 2012 in New York City, examined the risk of severe cardiovascular morbidity in women with hypertensive disorders of pregnancy compared with normotensive women during their delivery hospitalization. Women with a history of chronic hypertension, diabetes mellitus, or cardiovascular disease were excluded. Mortality and severe cardiovascular morbidity (myocardial infarction, cerebrovascular disease, acute heart failure, heart failure or arrest during labor or procedure, cardiomyopathy, cardiac arrest and ventricular fibrillation, or conversion of cardiac rhythm) during the delivery hospitalization were identified using birth certificates and discharge record coding. Using multivariable logistic regression, we assessed the association between hypertensive disorders of pregnancy and severe cardiovascular morbidity, adjusting for relevant sociodemographic and pregnancy-specific clinical risk factors. RESULTS: A total of 569,900 women met inclusion criteria. Of those women, 39,624 (6.9%) had a hypertensive disorder of pregnancy: 11,301 (1.9%) gestational hypertension; 16,117 (2.8%) preeclampsia without severe features; and 12,206 (2.1%) preeclampsia with severe features, of whom 319 (0.06%) had eclampsia. Among women with a hypertensive disorder of pregnancy, 431 experienced severe cardiovascular morbidity (10.9 per 1000 deliveries; 95% confidence interval, 9.9-11.9). Among normotensive women, 1780 women experienced severe cardiovascular morbidity (3.4 per 1000 deliveries; 95% confidence interval, 3.2-3.5). Compared with normotensive women, there was a progressively increased risk of cardiovascular morbidity with gestational hypertension (adjusted odds ratio, 1.18; 95% confidence interval, 0.92-1.52), preeclampsia without severe features (adjusted odds ratio, 1.96; 95% confidence interval, 1.66-2.32), preeclampsia with severe features (adjusted odds ratio, 3.46; 95% confidence interval, 2.99-4.00), and eclampsia (adjusted odds ratio, 12.46; 95% confidence interval, 7.69-20.22). Of the 39,624 women with hypertensive disorders of pregnancy, there were 15 maternal deaths, 14 of which involved 1 or more cases of severe cardiovascular morbidity. CONCLUSION: Hypertensive disorders of pregnancy, particularly preeclampsia with severe features and eclampsia, are significantly associated with cardiovascular morbidity during the delivery hospitalization. Increased vigilance, including diligent screening for cardiac pathology in patients with hypertensive disorders of pregnancy, may lead to decreased morbidity for mothers.

Hospital variation in utilization and success of trial of labor after a prior cesarean.

BACKGROUND: Trial of labor after cesarean delivery is an effective and safe option for women without contraindications. OBJECTIVES: The objective of the study was to examine hospital variation in utilization and success of trial of labor after cesarean delivery and identify associated institutional characteristics and patient outcomes. STUDY DESIGN: Using linked maternal and newborn hospital discharge records and birth certificate data in 2010-2012 from the state of California, we identified 146,185 term singleton mothers with 1 prior cesarean delivery and no congenital anomalies or clear contraindications for trial of labor at 249 hospitals. Risk-standardized utilization and success rates of trial of labor after cesarean delivery were estimated for each hospital after accounting for differences in patient case mix. Risk for severe maternal and newborn morbidities, as well as maternal and newborn length of stay, were compared between hospitals with high utilization and high success rates of trial of labor after cesarean delivery and other hospitals. Bivariate analysis was also conducted to examine the association of various institutional characteristics with hospitals' utilization and success rates of trial of labor after cesarean delivery. RESULTS: In the overall sample, 12.5% of women delivered vaginally. After adjusting for patient clinical risk factors, utilization and success rates of trial of labor after cesarean delivery varied considerably across hospitals, with a median of 35.2% (10th to 90th percentile range: 10.2-67.1%) and 40.5% (10th to 90th percentile range: 8.5-81.1%), respectively. Risk-standardized utilization and success rates of trial of labor after cesarean delivery demonstrated an inverted U-shaped relationship such that low or excessively high use of trial of labor after cesarean delivery was associated with lower success rate. Compared with other births, those delivered at hospitals with above-the-median utilization and success rates of trial of labor after cesarean delivery had a higher risk for uterine rupture (adjusted risk ratio, 2.74, P < .001), severe newborn respiratory complications (adjusted risk ratio, 1.46, P < .001), and severe newborn neurological complications/trauma (adjusted risk ratio, 2.48, P < .001), but they had a lower risk for severe newborn infection (adjusted risk ratio, 0.80, P = .003) and overall severe unexpected newborn complications (adjusted risk ratio, 0.86, P < .001) as well as shorter length of stays (adjusted mean ratio, 0.948 for mothers and 0.924 for newborns, P < .001 for both). Teaching status, system affiliation, larger volume, higher neonatal care capacity, anesthesia availability, higher proportion of midwife-attended births, and lower proportion of Medicaid or uninsured patients were positively associated with both utilization and success of trial of labor after cesarean delivery. However, rural location and higher local malpractice insurance premium were negatively associated with the utilization of trial of labor after cesarean delivery, whereas for-profit ownership was associated with lower success rate. CONCLUSION: Utilization and success rates of trial of labor after cesarean delivery varied considerably across hospitals. Strategies to promote vaginal birth should be tailored to hospital needs and characteristics (eg, increase availability of trial of labor after cesarean delivery at hospitals with low utilization rates while being more selective at hospitals with high utilization rates, and targeted support for lower capacity hospitals).

Optimal maternal and neonatal outcomes and associated hospital characteristics.

BACKGROUND: This study aims to examine hospital variation in both maternal and neonatal morbidities and identify institutional characteristics associated with hospital performance in a combined measure of maternal and neonatal outcomes. METHODS: Using the California Linked Birth File containing data from birth certificate and hospital discharge records, we identified 1 322 713 term births delivered at 248 hospitals during 2010-2012. For each hospital, a risk-standardized rate of severe maternal morbidities and a risk-standardized rate of severe newborn morbidities were calculated after adjusting for patient clinical risk factors. Hospitals were ranked based on combined information on their maternal and newborn morbidity rates. RESULTS: Risk-standardized severe maternal and severe newborn morbidity rates varied substantially across hospitals (10th to 90th percentile range = 67.5-148.2 and 141.8-508.0 per 10 000 term births, respectively), although there was no significant association between the two (P = 0.15). Government hospitals (non-Federal) were more likely than other hospitals to be in worse rank quartiles (P value for trend = 0.004), whereas larger volume was associated with better rank among hospitals in the first three quartiles (P = 0.004). The most prevalent morbidities that differed progressively across hospital rank quartiles were severe hemorrhage, disseminated intravascular coagulation, and heart failure during procedure/surgery for mothers, and severe infection, respiratory complication, and shock/resuscitation for neonates. CONCLUSIONS: Hospitals with low maternal morbidity rates may not have low neonatal morbidity rates and vice versa, highlighting the importance of assessing joint maternal-newborn outcomes in order to fully characterize a hospital's obstetrical performance. Hospitals with smaller volume and government ownership tend to have less desirable outcomes and warrant additional attention in future quality improvement efforts.

Estimated Placental Volume and Gestational Age.

OBJECTIVE: The objective of this study was to validate estimated placental volume (EPV) across a range of gestational ages (GAs). STUDY DESIGN: Three hundred sixty-six patients from 2009 to 2011 received ultrasound scans between 11 + 0 and 38 + 6 weeks GA to assess EPV. An EPV versus GA best fit curve was generated and compared with published normative curves of EPV versus GA in a different population. A subanalysis was performed to explore the relationship between EPV and birth weight (BW). RESULTS: Analysis of EPV versus GA revealed a parabolic curve with the following best fit equation: EPV = (0.372 GA - 0.00364 GA2)3. EPV was weakly correlated with BW, and patients with an EPV in the bottom 50th percentile had 2.42 times the odds of having a newborn with a BW in the bottom 50th percentile (95% confidence interval: 1.27-4.68). Microscopic evaluation of two placentas corresponding to the smallest EPV outliers revealed significant placental pathology. CONCLUSION: Placental volume increases throughout gestation and follows a predictable parabolic curve, in agreement with the existing literature. Further validation is required, but EPV may have the potential for clinical utility as a screening tool in a variety of settings.

Developing an interactive reproductive health equity session for pre-clerkship medical students.

In the United States, sexual, reproductive, and perinatal health inequities are well documented and known to be caused by a history of systemic oppression along many axes, including but not limited to race, ethnicity, gender, socioeconomic position, sexual orientation, and disability. Medical schools are responsible for educating students on systems of oppression and their impact on health. Reproductive justice advocates, including lay persons, medical students, and teaching faculty, have urged for integrating the reproductive justice framework into medical education and clinical practice. In response to medical student advocacy, we developed introductory didactic sessions on social and reproductive justice for preclinical medical students. These were created in a team-based learning format and include pre-course primer materials on reproductive justice. During the sessions, students engaged with hypothetical clinical vignettes in small groups to identify oppressive structures that may have contributed to the health outcomes described and potential avenues for contextually relevant and level-appropriate advocacy. The sessions took place in November 2019 (in-person) and 2020 (virtually) and were well attended by students. We highlight our experience, student feedback, and next steps, including further integration of reproductive health equity into medical school curricula in concert with department-wide education for faculty, residents, nursing, and allied health professionals. This introduction to social and reproductive justice can be adapted and scaled across different medical school curricula, enhancing the training of a new generation of physicians to become critically aware of how oppressive structures create health inequities and able to mitigate their impact through their roles as clinicians, researchers, and advocates.

Adherence to Labor Arrest and Failed Induction of Labor Guidelines: The Impact of a Quality-Improvement Educational Intervention.

Background/Objective: To evaluate adherence to labor arrest and failed induction of labor (IOL) criteria in nulliparous, term, singleton, and vertex (NTSV) cesarean deliveries at an academic medical center and to measure the impact of a quality-improvement educational initiative that focused on obstetric provider education of modern labor arrest and failed IOL criteria. Methods: This is a retrospective cohort study using electronic health record (EHR) data with a pre- (1 September 2018-30 September 2019) and post-intervention (1 October 2019-31 March 2020) study design of all NTSV cesarean deliveries for labor arrest or failed IOL performed at an academic medical center in the northeastern United States. The quality-improvement educational intervention consisted of the distribution of educational pocket cards outlining modern labor arrest and failed IOL criteria to obstetric providers. Outcomes included adherence to labor arrest and failed IOL criteria pre- and post-intervention with secondary outcomes evaluating adherence by provider type (Maternal-Fetal Medicine (MFM) or generalist obstetrician). Descriptive and bivariate statistics were used in the analysis. Results: Pre-intervention, 272 NTSV cesarean deliveries were performed for labor arrest or failed IOL versus 92 post-intervention. Adherence improved post-intervention amongst failed IOL (OR 6.5, CI 1.8-23.8), first-stage arrest (OR 4.5, CI 2.2-10.8) and second-stage arrest (OR 3.7, CI 1.5-9.4). When comparing provider type, MFM physicians were more likely to be adherent to labor arrest and failed IOL criteria compared to generalist obstetricians pre-intervention (OR 3.1, CI 1.7-5.5); however, post-intervention, there was no longer a difference in adherence (OR 3.3, CI 0.9-12.3). Conclusions: Adherence to labor arrest criteria was suboptimal in the pre-intervention period; however, a targeted quality-improvement educational intervention improved adherence rates to labor arrest and failed IOL criteria among obstetric providers.

Severe Maternal Morbidity Review and Preventability Assessment in a Large Academic Center.

With the goal of identifying factors contributing to severe maternal morbidity (SMM) at our institution, we established a formal SMM review process. We performed a retrospective cohort study including all SMM cases as defined by American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine consensus criteria that were managed at Yale-New Haven Hospital over a 4-year period. Overall, 156 cases were reviewed. The SMM rate was 0.49% (95% CI 0.40-0.58). The leading causes of SMM were hemorrhage (44.9%) and nonintrauterine infection (14.1%). Two thirds of the cases were deemed to be preventable. Preventability was mostly associated with health care professional-level (79.4%) and system-level (58.8%) factors that could coexist. Detailed case review allowed for identification of preventable causes of SMM, revealed gaps in care, and allowed for implementation of practice changes targeting health care professional-level and system-level factors.

Comparative analysis of 2-D versus 3-D ultrasound estimation of the fetal adrenal gland volume and prediction of preterm birth.

OBJECTIVE: We aim to test the hypothesis that two-dimensional (2-D) fetal adrenal gland volume (AGV) measurements offer similar volume estimates as volume calculations based on 3-D technique. METHODS: Fetal AGV was estimated by three-dimensional (3-D) ultrasound (VOCAL) in 93 women with signs/symptoms of preterm labor and 73 controls. Fetal AGV was calculated using an ellipsoid formula derived from 2-D measurements of the same blocks (0.523 × length × width × depth). Comparisons were performed by intraclass correlation coefficient (ICC), coefficient of repeatability, and Bland-Altman method. The corrected AGV (cAGV; AGV/fetal weight) was calculated for both methods and compared for prediction of preterm birth (PTB) within 7 days. RESULTS: Among 168 volumes, there was a significant correlation between 3-D and 2-D methods (ICC = 0.979; 95% confidence interval [CI]: 0.971 to 0.984). The coefficient of repeatability for the 3-D was superior to the 2-D method (intraobserver 3-D: 30.8, 2-D:57.6; interobserver 3-D:12.2, 2-D: 15.6). Based on 2-D calculations, cAGV ≥ 433 mm3/kg was best for prediction of PTB (sensitivity: 75%, 95% CI = 59 to 87; specificity: 89%, 95% CI = 82 to 94). Sensitivity and specificity for the 3-D cAGV (cutoff ≥ 420 mm3/kg) was 85% (95% CI = 70 to 94) and 95% (95% CI = 90 to 98), respectively. In receiver-operating-curve curve analysis, 3-D cAGV was superior to 2-D cAGV for prediction of PTB (z = 1.99, p = 0.047). CONCLUSION: 2-D volume estimation of fetal adrenal gland using ellipsoid formula cannot replace 3-D AGV calculations for prediction of PTB.

Racial and ethnic differences in severe maternal morbidity among singleton stillbirth deliveries.

BACKGROUND: Despite growing evidence suggesting racial or ethnic disparities in the risk of severe maternal morbidity among live births, there is little research investigating potential differences in severe maternal morbidity risk among stillbirths across race and ethnicity. OBJECTIVE: This study aimed to compare the risk of severe maternal morbidity by race and ethnicity among patients with singleton stillbirth pregnancies. STUDY DESIGN: We used the California Linked Birth File database to perform a retrospective analysis of singleton stillbirth pregnancies delivered at 20 to 42 weeks' gestation between 2007 and 2011. The database contained information from fetal death certificates linked to maternal hospital discharge records. We defined severe maternal morbidity using the Centers for Disease Control and Prevention composite severe maternal morbidity indicator and compared rates of severe maternal morbidity across racial and ethnic groups. Multivariable regression analysis was used to examine how race and ethnicity were associated with severe maternal morbidity risk after accounting for the influence of patients' clinical risk factors, socioeconomic characteristics, and attributes of the delivery hospital. RESULTS: Of the 9198 patients with singleton stillbirths, 533 (5.8%) experienced severe maternal morbidity. Non-Hispanic Black patients had a significantly higher risk of severe maternal morbidity (10.6% vs 5.2% in non-Hispanic White patients, 5.2% in Hispanic patients, and 5.1% in patients with other race or ethnicity; P<.001). The higher risk of severe maternal morbidity among non-Hispanic Black patients persisted even after adjusting for patients' clinical, socioeconomic, and hospital characteristics (adjusted odds ratio for non-Hispanic Black vs non-Hispanic White patients, 1.74; 95% confidence interval, 1.21-2.50). Further analysis separating blood-transfusion and nontransfusion severe maternal morbidity showed a higher risk of blood transfusion in non-Hispanic Black patients, which remained significant after adjusting for patients' clinical, socioeconomic, and hospital characteristics (adjusted odds ratio for non-Hispanic Black vs non-Hispanic White patients, 1.64; 95% confidence interval, 1.11-2.43). However, the higher risk of nontransfusion severe maternal morbidity in non-Hispanic Black patients was no longer significant after adjusting for patients' clinical risk factors (adjusted odds ratio for non-Hispanic Black vs non-Hispanic White patients, 1.38; 95% confidence interval, 0.83-2.30). CONCLUSION: Severe maternal morbidity occurred in 5.8% of patients with a singleton stillbirth. Risk of severe maternal morbidity in stillbirth was higher in patients with non-Hispanic Black race, which was likely owing to a higher risk of hemorrhage, as evidenced by increased rate of blood transfusion.

Unrepaired Maternal Vein of Galen Malformation in Pregnancy: A Case Report.

We present a case of a pregnant patient with an unrepaired vein of Galen malformation (VGAM) and left ventricular (LV) dilation. Patients with VGAM lesions typically present during childhood with cardiac failure or developmental delay prompting embolization. Therefore, it is highly unusual for an adult to present with an unrepaired lesion.1 It poses challenges for obstetric and anesthetic management during pregnancy and delivery to reduce the risk of heart failure, arrhythmia, and intracranial hemorrhage. Our patient safely delivered a term neonate by cesarean delivery with neuraxial analgesia at a Level IV Maternal Care Center.

Accreta complicating complete placenta previa is characterized by reduced systemic levels of vascular endothelial growth factor and by epithelial-to-mesenchymal transition of the invasive trophoblast.

OBJECTIVE: We sought to characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta, or percreta shares features of epithelial-to-mesenchymal transition. STUDY DESIGN: We analyzed gestational age-matched serum samples from 90 pregnant women with either complete placenta previa (n = 45) or uncomplicated pregnancies (n = 45). Vascular endothelial growth factor (VEGF), placental growth factor, and soluble form of fms-like-tyrosine-kinase-1 were immunoassayed. VEGF and phosphotyrosine immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. RESULTS: Women with previa and invasive placentation (accreta, n = 5; increta, n = 6; percreta, n = 2) had lower systemic VEGF (invasive previa: median 0.8 [0.02-3.4] vs control 6.5 [2.7-10.5] pg/mL, P = .02). VEGF and phosphotyrosine immunostaining predominated in the invasive extravillous trophoblasts that coexpressed vimentin and cytokeratin-7, an epithelial-to-mesenchymal transition feature and tumorlike cell phenotype. CONCLUSION: Lower systemic free VEGF and a switch of the interstitial extravillous trophoblasts to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion.

Maternal respiratory SARS-CoV-2 infection in pregnancy is associated with a robust inflammatory response at the maternal-fetal interface.

BACKGROUND: Pregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this increased morbidity and its potential effect on the developing fetus is not well understood. METHODS: We assessed placental histology, ACE2 expression, and viral and immune dynamics at the term placenta in pregnant women with and without respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FINDINGS: The majority (13 of 15) of placentas analyzed had no detectable viral RNA. ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term, suggesting that low ACE2 expression may protect the term placenta from viral infection. Using immortalized cell lines and primary isolated placental cells, we found that cytotrophoblasts, the trophoblast stem cells and precursors to syncytiotrophoblasts, rather than syncytiotrophoblasts or Hofbauer cells, are most vulnerable to SARS-CoV-2 infection in vitro. To better understand potential immune mechanisms shielding placental cells from infection in vivo, we performed bulk and single-cell transcriptomics analyses and found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited robust immune responses, including increased activation of natural killer (NK) and T cells, increased expression of interferon-related genes, as well as markers associated with pregnancy complications such as preeclampsia. CONCLUSIONS: SARS-CoV-2 infection in late pregnancy is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. FUNDING: NIH (T32GM007205, F30HD093350, K23MH118999, R01AI157488, U01DA040588) and Fast Grant funding support from Emergent Ventures at the Mercatus Center.

SARS-CoV-2 infection in pregnancy is associated with robust inflammatory response at the maternal-fetal interface.

Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Amongst uninfected women, ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term. Term placentas from women infected with SARS-CoV-2, however, displayed a significant increase in ACE2 levels. Using immortalized cell lines and primary isolated placental cells, we determined the vulnerability of various placental cell types to direct infection by SARS-CoV-2 in vitro. Yet, despite the susceptibility of placental cells to SARS-CoV-2 infection, viral RNA was detected in the placentas of only a subset (~13%) of women in this cohort. Through single cell transcriptomic analyses, we found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited markers associated with pregnancy complications, such as preeclampsia, and robust immune responses, including increased activation of placental NK and T cells and increased expression of interferon-related genes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.

Acceleration/ejection time ratio in the fetal pulmonary artery predicts fetal lung maturity.

OBJECTIVE: The aim of this study was to determine whether sonographic fetal pulmonary artery flow velocity waveforms correlate with amniotic fluid biomarkers of fetal lung maturity. STUDY DESIGN: We studied women with singleton pregnancies undergoing clinically indicated amniocentesis for fetal lung maturity at Yale-New Haven Hospital. Fetal pulmonary artery flow velocity measurements, including systolic/diastolic ratio, pulsatility index, resistance index, and acceleration-time/ejection-time ratio were obtained using spectral Doppler ultrasound. Pearson's correlation coefficient was used to determine the association between fetal pulmonary artery flow velocity parameters and the lecithin/sphingomyelin ratio. RESULTS: Twenty-nine subjects met study criteria. The acceleration-time/ejection-time ratio was inversely correlated with the lecithin/sphingomyelin ratio (r = -0.76; P < or = .001). This relationship was maintained after controlling for potential confounders. Other fetal pulmonary artery flow velocity measurements were not associated with the lecithin/sphingomyelin ratio. CONCLUSION: There is an inverse correlation between the acceleration-time/ejection-time ratio in the fetal pulmonary artery and the amniotic fluid lecithin/sphingomyelin ratio. This suggests that ultrasound evaluation of fetal pulmonary artery blood flow may be a promising new noninvasive technique to evaluate fetal lung maturity.

Cesarean scar ectopic pregnancy: case series and review of the literature.

Cesarean scar ectopic pregnancy is becoming increasingly common at tertiary care hospitals around the world. It is a condition in which the embryo implants within the myometrium at the site of a previous cesarean hysterotomy, and it can occur in women with only one prior cesarean delivery. We present four cases of cesarean scar ectopic pregnancy diagnosed within a 6-month period between 2007 and 2008. Their initial presentations and management are discussed, followed by a review of the published literature summarizing both diagnostic and management recommendations.

Consolidation of obstetric services in a public health emergency.

Though much of routine healthcare pauses in a public health emergency, childbirth continues uninterrupted. Crises like COVID-19 put incredible strains on healthcare systems and require strategic planning, flexible adaptability, clear communication, and judicious resource allocation. Experiences from obstetric units affected by COVID-19 highlight the importance of developing new teams and workflows to ensure patient and healthcare worker safety. Additionally, adapting a strategy that combines units and staff from different areas and hospitals can allow for synergistic opportunities to provision care appropriately to manage a structure and workforce at maximum capacity.