Are fetal microchimerism and circulating fetal extracellular vesicles important links between spontaneous preterm delivery and maternal cardiovascular disease risk?

Trafficking and persistence of fetal microchimeric cells (fMCs) and circulating extracellular vesicles (EVs) have been observed in animals and humans, but their consequences in the maternal body and their mechanistic contributions to maternal physiology and pathophysiology are not yet fully defined. Fetal cells and EVs may help remodel maternal organs after pregnancy-associated changes, but the cell types and EV cargos reaching the mother in preterm pregnancies after exposure to various risk factors can be distinct from term pregnancies. As preterm delivery-associated maternal complications are rising, revisiting this topic and formulating scientific questions for future research to reduce the risk of maternal morbidities are timely. Epidemiological studies report maternal cardiovascular risk as one of the major complications after preterm delivery. This paper suggests a potential link between fMCs and circulating EVs and adverse maternal cardiovascular outcomes post-pregnancies, the underlying mechanisms, consequences, and methods for and how this link might be assessed.

Point of care maternal ultrasound in obstetrics.

Ultrasound is the hallmark imaging modality traditionally used by obstetricians for fetal diagnosis and surveillance. The COVID-19 pandemic highlighted the role of point of care ultrasound for expeditious assessment of the maternal cardiopulmonary status. The familiarity of obstetricians with ultrasound, coupled with the availability of ultrasound equipment without the need to transport the patient, make point of care ultrasound particularly valuable in the labor and delivery unit. The rising contribution of cardiopulmonary disorders to maternal morbidity and mortality carves out many potential applications for point of care ultrasound during labor and delivery. Obstetricians have access to the technology and the skills to obtain the basic views required to assess for the presence of pulmonary edema, ventricular dysfunction, or intra-abdominal free fluid. Point of care ultrasound can be used routinely for the evaluation of pulmonary complaints or in the assessment of hypotension and may play an essential role in the diagnosis and management of life-threatening emergencies such as shock, an amniotic fluid embolism, or cardiac arrest. We reviewed the currently established point of care ultrasound protocols for the evaluation of cardiopulmonary complaints through the lens of the obstetrician. We call on educators and academic leaders to incorporate maternal point of care ultrasound teachings into existing curricula. Point of care ultrasound is of enormous value for providers with limited access to diagnostic imaging or subspecialty providers. With the growing complexity of the obstetrical population, acquiring the clinical skills to meet these evolving needs is a requisite step in the ongoing efforts to reduce maternal morbidity and mortality.

Imaging the Uterus in Placenta Accreta Spectrum Disorder.

Antenatal diagnosis of placenta accreta spectrum (PAS) improves maternal and neonatal outcomes by allowing for multidisciplinary planning and preparedness. Ultrasound is the primary imaging tool. Simplification and standardization of placental evaluation and reporting terminology allows improved communication and understanding between teams. Prior to 10 weeks of gestation, gestational sac position and least myometrial thickness surrounding the gestational sac help PAS diagnosis very early in pregnancy. Late first-, second-, and third-trimester evaluation includes comprehensive evaluation of the placenta, transabdominal and transvaginal with partially full maternal urinary bladder, and by color Doppler. Subsequently, the sonologist should indicate whether the evaluation was optimal or suboptimal; the level of suspicion as low, moderate, or high; and the extent as focal, global, or extending beyond the uterus. Other complementary imaging modalities such as 3D-power Doppler ultrasound, magnetic resonance imaging (MRI), and vascular topography mapping strive to improve antenatal placental evaluation but remain investigational at present. KEY POINTS: · Antenatal imaging, primarily using ultrasound with partially full maternal urinary bladder, is an essential means of evaluation of those at risk for PAS.. · Simplification and standardization of placental evaluation and reporting will allow improved communication between the multidisciplinary teams.. · Gestational sac location prior to 10 weeks of gestation and four markers after that (placental lacunae and echostructure, myometrial thinning, hypoechoic zone with or without bulging between placenta and myometrium, and increased flow on color Doppler)..

Cardiac arrest during pregnancy: ongoing clinical conundrum.

While global maternal mortality has decreased in the last 25 years, the maternal mortality ratio in the United States has actually increased. Maternal mortality is a complex phenomenon involving multifaceted socioeconomic and clinical parameters including inequalities in access to health care, racial and ethnic disparities, maternal comorbidities, and epidemiologic ascertainment bias. Escalating maternal mortality underscores the importance of clinician preparedness to respond to maternal cardiac arrest that may occur in any maternal health care setting. Management of maternal cardiac arrest requires an interdisciplinary team familiar with the physiologic changes of pregnancy and the maternal resuscitation algorithm. Interventions intended to mitigate obstacles such as aortocaval compression, which may undermine the success of resuscitation interventions, must be performed concurrent to standard basic and advanced cardiac life support maneuvers. High-quality chest compressions and oxygenation must be performed along with manual left lateral uterine displacement when the uterine size is ≥20 weeks. While deciphering the etiology of maternal cardiac arrest, diagnoses unique to pregnancy and those of the nonpregnant state should be considered at the same time. If initial basic life support and advanced cardiac life support interventions fail to restore maternal circulation within 4 minutes of cardiac arrest, perimortem delivery is advised provided the uterus is ≥20 weeks' size. Preparations for perimortem delivery are best anticipated by the resuscitation team for the procedure to be executed opportunely. Following delivery, intraabdominal examination may reveal a vascular catastrophe, hematoma, or both. If return of spontaneous circulation has not been achieved, additional interventions may include cardiopulmonary bypass and/or extracorporeal membrane oxygenation. Simulation and team training enhance institution readiness for maternal cardiac arrest. Knowledge gaps are significant in the science of maternal resuscitation. Further research is required to fully optimize: relief of aortocaval compression during the resuscitation process, gestational age and timing of perimortem delivery, and other interventions that deviate from nonpregnant standard resuscitation protocol to achieve successful maternal resuscitation. A robust detailed national and international prospective database was recommended by the International Liaison Committee on Resuscitation in 2015 to facilitate further research unique to cardiac arrest during pregnancy that will produce optimal resuscitation techniques for maternal cardiac arrest.

Cardiac Arrest in Pregnancy: A Scientific Statement From the American Heart Association.

This is the first scientific statement from the American Heart Association on maternal resuscitation. This document will provide readers with up-to-date and comprehensive information, guidelines, and recommendations for all aspects of maternal resuscitation. Maternal resuscitation is an acute event that involves many subspecialties and allied health providers; this document will be relevant to all healthcare providers who are involved in resuscitation and specifically maternal resuscitation.

MRI evaluation of maternal cardiac displacement in pregnancy: implications for cardiopulmonary resuscitation.

OBJECTIVE: The purpose of this study was to determine, with the use of cardiac magnetic resonance imaging, whether there is vertical displacement of the heart during pregnancy. Cardiopulmonary resuscitation guidelines during pregnancy recommend placing the hands 2-3 cm higher on the sternum than in nonpregnant individuals. This recommendation is based on the presumption that the heart is displaced superiorly by the diaphragm during the third trimester. Whether there is true cardiac displacement because of the expanding uterus in pregnancy remains unknown. STUDY DESIGN: A total of 34 healthy female volunteers 18-35 years old were enrolled prospectively from 2010-2012 at 2 tertiary care centers. The conditions of all participants were evaluated with cardiac magnetic resonance imaging in the one-half left lateral decubitus position during the third trimester of pregnancy and again at a minimum of 3 months after delivery (surrogate for the nonpregnant state). Superior displacement of the heart was determined by measurement of the distance between the inferior aspect of the clavicular heads and the coronary sinus at both time points. RESULTS: The study population included 34 women (mean age, 29 ± 3 years; body mass index, 24 ± 4 kg/m(2)). The mean gestational age at third-trimester imaging was 237 ± 16 days (34 weeks ± 16 days); the mean number of days for postpartum imaging (baseline) was 107 ± 25 days (16 weeks ± 25 days). There was no statistical difference between the cardiac position at baseline (10.1 ± 1.2 cm) and during the third trimester (10.3 ± 1.1 cm; P = .22). CONCLUSION: Contrary to popular assumption, there is no significant vertical displacement of the heart in the third trimester of pregnancy relative to the nonpregnant state. Accordingly, there is no need to alter hand placement for chest compressions during cardiopulmonary resuscitation in pregnancy.

Efficacy of the genetic sonogram in a stepwise sequential protocol for down syndrome screening.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of the genetic sonogram in Down syndrome screening for women who have received the stepwise sequential test. METHODS: This retrospective cohort study included women with singleton pregnancies who underwent stepwise sequential (first-trimester combined and second-trimester serum) screening and then had a genetic sonogram between March 2005 and January 2010. Stepwise sequential Down syndrome risks were multiplied by either a positive or negative likelihood ratio based on the second-trimester sonographic findings to determine the final Down syndrome risk. A final Down syndrome risk of 1:270 or higher was considered screen positive. RESULTS: A total of 6286 women fulfilled our criteria, including 17 with Down syndrome-affected fetuses. After stepwise sequential testing, the Down syndrome detection rate was 88.2% (15 of 17), and after the genetic sonogram, there was a non-significant reduction in detection to 82.4% (14 of 17; P > .05). For the 6269 unaffected pregnancies, the genetic sonogram converted 58 screen-negative results (1%) to positive and 183 screen-positive results (3.1%) to negative. The net effect was a change in the false-positive rate from 6.2% (390 of 6269) after stepwise sequential screening to 4.2% (266 of 6269) after the genetic sonogram. CONCLUSIONS: The genetic sonogram should be applied cautiously for women who have received prior prenatal screening tests. Women with screen-positive results need to be counseled that a negative sonographic result can be falsely reassuring. Conversely, for women with screen-negative results who have a risk close to the cutoff, a sonographic examination could assist in the decision of whether to accept or reject amniocentesis.

2023 HRS expert consensus statement on the management of arrhythmias during pregnancy.

This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac electrophysiologists, cardiologists, and other health care professionals, on the management of cardiac arrhythmias in pregnant patients and in fetuses. This document covers general concepts related to arrhythmias, including both brady- and tachyarrhythmias, in both the patient and the fetus during pregnancy. Recommendations are provided for optimal approaches to diagnosis and evaluation of arrhythmias; selection of invasive and noninvasive options for treatment of arrhythmias; and disease- and patient-specific considerations when risk stratifying, diagnosing, and treating arrhythmias in pregnant patients and fetuses. Gaps in knowledge and new directions for future research are also identified.

Morbidity following primary cesarean delivery in the Danish National Birth Cohort.

OBJECTIVE: Cesarean delivery rates are on the rise in many countries, including the United States. There is mounting evidence that cesarean delivery is associated with adverse reproductive outcomes in subsequent pregnancies. The purpose of this article is to review those outcomes in a well-defined cohort of pregnant women. STUDY DESIGN: In a cohort of primigravid women from the Danish National Birth Cohort with known baseline exposure characteristics, we stratified women by method of first delivery, vaginal or cesarean, and evaluated for appearance of adverse reproductive events in subsequent pregnancies. RESULTS: After adjusting for age, body mass index, alcohol, smoking, and socioeconomic status, women who underwent cesarean delivery at first birth were at increased risk in their subsequent pregnancy for anemia (odds ratio [OR], 2.8; 95% confidence interval [CI], 2.3-3.4), placental abruption (OR, 2.3; 95% CI, 1.5-3.6), uterine rupture (OR, 268; 95% CI, 65.6-999), and hysterectomy (OR, 28.8; 95% CI, 3.1-263.8). CONCLUSION: Women who deliver their first baby with a cesarean are at increased risk of adverse reproductive outcomes in subsequent pregnancies and should be counseled accordingly.

COVID-19 in pregnancy: possible mechanisms not to be discounted.

SARS-CoV-2 has infected more than 16 million people worldwide. Related complications and death from COVID-19 disease and their underlying pathophysiology are intensely investigated. Pregnant women are among the affected. Although the severity of disease in pregnancy does not appear to be increased, the effects of infection on pregnancy should not escape careful examination. The currently known receptor for the virus, ACE2, regulates the renin-angiotensin system and is increased during pregnancy. Virus-receptor interactions may have significant effects on placental function, fetal development, and maternal immunity. The manifestation of cardiovascular complications of infection produces the hypothesis that a significant effect of the virus may be its influence on the maternal vascular system. Interference with the vascular adaptations to pregnancy and the post-partum may have implications for concurrent and future pregnancies as well as for long-term cardiovascular health. We should not miss the opportunity to learn from this virus about the physiology of pregnancy.

Guidance for Cardiopulmonary Resuscitation of Children With Suspected or Confirmed COVID-19.

This article aims to provide guidance to health care workers for the provision of basic and advanced life support to children and neonates with suspected or confirmed coronavirus disease 2019 (COVID-19). It aligns with the 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular care while providing strategies for reducing risk of transmission of severe acute respiratory syndrome coronavirus 2 to health care providers. Patients with suspected or confirmed COVID-19 and cardiac arrest should receive chest compressions and defibrillation, when indicated, as soon as possible. Because of the importance of ventilation during pediatric and neonatal resuscitation, oxygenation and ventilation should be prioritized. All CPR events should therefore be considered aerosol-generating procedures. Thus, personal protective equipment (PPE) appropriate for aerosol-generating procedures (including N95 respirators or an equivalent) should be donned before resuscitation, and high-efficiency particulate air filters should be used. Any personnel without appropriate PPE should be immediately excused by providers wearing appropriate PPE. Neonatal resuscitation guidance is unchanged from standard algorithms, except for specific attention to infection prevention and control. In summary, health care personnel should continue to reduce the risk of severe acute respiratory syndrome coronavirus 2 transmission through vaccination and use of appropriate PPE during pediatric resuscitations. Health care organizations should ensure the availability and appropriate use of PPE. Because delays or withheld CPR increases the risk to patients for poor clinical outcomes, children and neonates with suspected or confirmed COVID-19 should receive prompt, high-quality CPR in accordance with evidence-based guidelines.

Does antidepressant use attenuate the risk of a major depressive episode in pregnancy?

BACKGROUND: Many women become pregnant while undergoing antidepressant treatment and are concerned about continuing antidepressant medication. However, antidepressant discontinuation may increase the risk of a new episode of major depressive disorder. We sought to estimate differences in the risk of developing a new major depressive episode among pregnant and postpartum women with recurrent illness who either did or did not use antidepressants. METHODS: Participants were recruited from obstetrical settings; we analyzed a subgroup of 778 women with a history of a depressive disorder. Diagnoses were determined by the Composite International Diagnostic Interview administered twice in pregnancy and once after delivery. We used Cox Regression to model onset of a major depressive episode with a time-dependent predictor of antidepressant use. RESULTS: There was no clear difference in risk of a major depressive episode between women who took antidepressants and women who did not (hazard ratio [HR] = 0.88; 95% CI = 0.51-1.50). After accounting for antidepressant use, clearly hazardous factors included 4 or more depressive episodes before pregnancy (HR = 1.97; 95% CI = 1.09-3.57), black race (HR = 3.69; 95% CI = 2.16-6.30), and Hispanic ethnicity (HR = 2.33; 95% CI = 1.47-3.69). CONCLUSIONS: Failure to use or discontinuation of antidepressants in pregnancy did not have a strong effect on the development of a major depressive episode. Women with 4 or more episodes before pregnancy were at high risk of a major depressive episode, independent of antidepressant use. Black and Hispanic women also were at high risk of a major depressive episode, but it is possible that this effect is attributable to unmeasured factors.

Factors associated with non-survival from in-hospital maternal cardiac arrest: An analysis of Get With The Guidelines® (GWTG) data.

INTRODUCTION: Maternal mortality has risen in the United States during the 21st century. Factors influencing outcome of maternal cardiac arrest (MCA) remain largely unexplored. OBJECTIVE: We sought to further elucidate the factors affecting maternal death from in-hospital (IH) MCA. METHODS: Our query of the American Heart Association's GWTG®-Resuscitation voluntary registry from 2000-2017 revealed 561 index cases of IH MCA with complete outcome data. Logistic regression was performed using hospital death as the primary outcome and included variables with a p value = 0.1 or less based upon univariate analysis. Age, race, year of arrest, pre-existing conditions, first documented pulseless rhythm and location of arrest were used in the model. Sensitivity analyses and assessment of variable interaction were also performed to test model stability. Institutional review deemed this research exempt from ethical approval. RESULTS: Among 561 cases of MCA, 57.2% (321/561) did not survive to hospital discharge. IH death was not associated with maternal age, race and year of event. In the final model, IH death was significantly associated with pre-arrest hypotension/hypoperfusion (OR = 1.80 (95% CI, 1.16-2.79); p = 0.009). The occurrence of MCA outside of the delivery suite (referent group) or operating room was associated with a significantly higher risk of death: ICU/Post-Anesthesia Care Unit (PACU) (OR = 3.32 (95% CI, 2.00-5.52); p < 0.001) and ER/other (OR = 1.89 (95% CI, 1.15-3.11); p = 0.012). While MCA cases with a shockable vs. non-shockable first documented pulseless rhythm had similar outcomes, those with an indeterminate rhythm were less likely to die, (OR = 0.41(95% CI, 0.20-0.84); p = 0.014). In a sensitivity analysis, removal of the indeterminate group did not alter outcomes regarding first documented pulseless rhythm or arrest location. Area under the curve for the final model was 0.715 (95% CI 0.673-0.757). CONCLUSIONS: Our study identified several novel factors associated with IH death of our MCA cohort. More research is required to further understand the pathophysiologic dynamics affecting outcomes of IH MCA in this unique population.

Cardiovascular Health After Preeclampsia: Patient and Provider Perspective.

Background: Preeclampsia predicts future cardiovascular disease (CVD) yet few programs exist for post-preeclampsia care. Methods: The Health after Preeclampsia Patient and Provider Engagement Network workshop was convened at the Radcliffe Institute for Advanced Study in June 2018. The workshop sought to identify: 1) patient perspectives on barriers and facilitators to CVD risk reduction; 2) clinical programs specialized in post-preeclampsia care; 3) recommendations by national organizations for risk reduction; and 4) next steps. Stakeholders included the Preeclampsia Foundation, patients, clinicians who had initiated CVD risk reduction programs for women with prior preeclampsia, researchers, and national task force members. Results: Participants agreed there is insufficient awareness and action to prevent CVD after preeclampsia. Patients suggested a clinician checklist to ensure communication of CVD risks, enhanced training for clinicians on the link between preeclampsia and CVD, and a post-delivery appointment with a clinician knowledgeable about this link. Clinical programs primarily served patients in the first postpartum year, bridging obstetrical and primary care. They recommended CVD risk modification with periodic blood pressure, weight, lipid and diabetes screening. Barriers included the paucity of programs designed for this population and gaps in insurance coverage after delivery. The American Heart Association, the American College of Obstetricians and Gynecologists, and the Preeclampsia Foundation have developed guidelines and materials for patients and providers to guide management of women with prior preeclampsia. Conclusions: Integrated efforts of patients, caregivers, researchers, and national organizations are needed to improve CVD prevention after preeclampsia. This meeting's recommendations can serve as a resource and catalyst for this effort.

ACR Appropriateness Criteria® Second and Third Trimester Screening for Fetal Anomaly.

The Appropriateness Criteria for the imaging screening of second and third trimester fetuses for anomalies are presented for fetuses that are low risk, high risk, have had soft markers detected on ultrasound, and have had major anomalies detected on ultrasound. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

ACR Appropriateness Criteria® Nuchal Translucency Evaluation at 11 to 14 Weeks of Gestation.

A fetus with an increased nuchal translucency at 11 to 14 weeks gestation is at risk for aneuploidy, genetic syndromes, structural anomalies, and intrauterine fetal demise in both single and twin gestations. In addition to referral to genetics for counseling and consideration of diagnostic genetic testing, a detailed anatomic survey and fetal echocardiogram are indicated in the second trimester to screen for congenital malformations and major heart defects. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

A comparison of reasons for choosing obstetrician/gynecologist subspecialty training.

Recently, applications for subspecialty fellowship positions in obstetrics and gynecology have increased dramatically. A survey completed by fellows in Maternal-Fetal Medicine (MFM), Reproductive Endocrinology (REI), Gynecologic Oncology (Gyn Onc), and Urogynecology (Urogyn) training programs in the United States between January and March 2006 was aimed at determining why this trend was occuring. Of 449 fellows in 2006, 192 (42.8%) responded. The two most influential factors in all four subspecialties were interest and lifestyle (P < .001). Although these factors were similar throughout all subspecialties, variations exist in how fellows rated each factor by subspecialty. An overwhelming majority (99%) of fellows were either "very satisfied" or "satisfied" with their decisions to pursue fellowship training. The majority of fellows believe that when compared to a generalist Obstetrician/Gynecologist (OB/GYN) they will have a reduced workload, decreased liability, and a higher salary. The recent increase in the number of fellowship applicants is most likely due to a complex interplay of multiple factors.

ACR Appropriateness Criteria® Growth Disturbances-Risk of Fetal Growth Restriction.

Fetal growth restriction, or an estimated fetal weight of less than the 10th percentile, is associated with adverse perinatal outcome. Optimizing management for obtaining the most favorable outcome for mother and fetus is largely based on detailed ultrasound findings. Identifying and performing those ultrasound procedures that are most associated with adverse outcome is necessary for proper patient management. Transabdominal ultrasound is the mainstay of initial management and assessment of fetal growth. For those fetuses that are identified as small for gestational age, assessment of fetal well-being with biophysical profile and Doppler velocimetry provide vital information for differentiating those fetuses that may be compromised and may require delivery and those that are well compensated. Delivery of the pregnancy is primarily based upon the gestational age of the pregnancy and the ultrasound findings. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.