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Abstract Background Hypertensive disorders of pregnancy are a main cause of maternal morbidity and mortality in the United States and worldwide, and it is estimated that approximately 60% of maternal deaths in the United States occur during the postpartum period. The utilization of telehealth modalities such as home blood pressure monitoring has shown improvement in blood pressure control and adherence with follow up visits. Our study sought to determine if standardized education improved patient hypertension knowledge and if this when combined with home blood pressure telemonitoring increased participants’ postpartum self-blood pressure monitoring and postpartum visit attendance. Methods This is an Institutional Review Board approved prospective cohort study conducted at the University of Mississippi Medical Center. Women with a hypertensive disorder of pregnancy who met the inclusion criteria and provided written informed consent to participate were enrolled. Participants received a baseline pre-education questionnaire designed to assess their knowledge of their hypertensive diagnosis, hypertension management, and postpartum preeclampsia (PreE). Participants then received standard education, a blood pressure monitor, and were scheduled a follow-up visit during the first 10 days following discharge. Remote home blood pressure monitoring was performed via text messages and voice calls for 6-weeks postpartum. At the conclusion of the study, participants repeated their original questionnaire. Results 250 women provided informed consent to participate in the study and were included in this analysis. Relative to the baseline survey, there was a significant increase (p = 0.0001) in the percentage of correct responses. There was not an association between study engagement and percentage of correct responses on end of study questionnaire (p = 0.33) or postpartum visit attendance (p = 0.69). Maternal age was found to drive study engagement, even when adjusted for community-level distress (p = 0.03) and maternal race (p = 0.0002). Conclusion Implementing a standardized postpartum education session was associated with improvement in patient’s knowledge. Further studies are needed with more longitudinal follow up to assess if this program would also result in improved long-term outcomes and decreased hospital readmission rates. Trial registration NCT04570124.

BACKGROUND: In high-resource settings, biomarkers of angiogenic balance, such as the soluble fms-like tyrosine kinase-1 (sFlt1)/placental growth factor (PlGF) ratio, have been studied extensively to aid in evaluation of patients with suspected preeclampsia (PE), and have been incorporated into the 2021 International Society for the Study of Hypertension in Pregnancy definition of PE. The utility in under-resourced settings has not been as well characterized. OBJECTIVE: This analysis sought to identify the role of the sFlt1/PlGF ratio in the evaluation of patients with or without hypertension who are suspected of having PE without other diagnostic information. STUDY DESIGN: This is a secondary analysis of a prior prospective study of patients who were presented with suspected PE at ≥20+0 weeks’ gestation at a single academic tertiary care center. Patients were recruited in the parent study from July 2009 to June 2012. In the original study, clinicians were masked to biomarker results, and patients were followed by chart review. In this analysis, the performance of the sFlt1/PlGF ratio (≤38, >38, or >85) was assessed alone in identifying both hypertensive and non-hypertensive patients at risk of evolving into PE with severe features (PE-SF; American College of Obstetricians and Gynecologists’ definition) within two weeks of the triage visit (PE-SF2). Hypertension was defined as a blood pressure (BP)≥140/90 mmHg. RESULTS: There were 1043 patients included in the analysis; of whom, 579 (55.5%) and 464 (44.5%) presented with or without hypertension, respectively. In triage, 332 (75.4%) of hypertensive patients presented due to BP concerns, and the remainder were evaluated due to other features (new-onset headache, proteinuria, or edema). On triage evaluation, 66.8% of all patients had a normal sFlt1/PlGF ratio ≤38, and 17.0% had an elevated ratio >85. Among hypertensive patients, a sFlt1/PlGF ratio ≤38 was a good rule-out test for PE-SF2 (negative likelihood ratio [LR-] of 0.15), and a ratio >85 was a good rule-in test (positive likelihood ratio [LR+] of 5.75). Among normotensive patients, sFlt1/PlGF was useful as a rule-in test for ratio >38 (LR+ 5.13) and >85 (LR+ 12.80). Stratified by gestational age, sFlt1/PlGF continued to be a good rule in and good rule out test at 85 regardless of gestational age. In triage, 4.3% (30/693) of patients with sFlt1/PlGF ratio 85. CONCLUSION: These findings support the potential for the use of sFlt1/PlGF and BP measurement alone in resource-limited settings where other laboratory tests or clinical expertise are unavailable for risk stratification. Performance of the biomarker varied by the presence of hypertension and gestational age.

Abstract The mechanisms that underlie the timing of labor in humans are largely unknown. In most pregnancies, labor is initiated at term (≥ 37 weeks gestation), but in a signifiicant number of women spontaneous labor occurs preterm and is associated with increased perinatal mortality and morbidity. The objective of this study was to characterize the cells at the maternal–fetal interface (MFI) in term and preterm pregnancies in both the laboring and non-laboring state in Black women, who have among the highest preterm birth rates in the U.S. Using mass cytometry to obtain high-dimensional single-cell resolution, we identified 31 cell populations at the MFI, including 25 immune cell types and six non-immune cell types. Among the immune cells, maternal PD1+ CD8 T cell subsets were less abundant in term laboring compared to term non-laboring women. Among the non-immune cells, PD-L1+ maternal (stromal) and fetal (extravillous trophoblast) cells were less abundant in preterm laboring compared to term laboring women. Consistent with these observations, the expression of CD274, the gene encoding PD-L1, was significantly depressed and less responsive to fetal signaling molecules in cultured mesenchymal stromal cells from the decidua of preterm compared to term women. Overall, these results suggest that the PD1/PD-L1 pathway at the MFI may perturb the delicate balance between immune tolerance and rejection and contribute to the onset of spontaneous preterm labor.

BackgroundPreeclampsia is a disease with far-reaching consequences that extend beyond the immediate postpartum period and have a significant impact later in life. Preeclampsia exerts an effect on most organ systems in the body. These sequelae are mediated in part by the incompletely elucidated pathophysiology of preeclampsia and the associated vascular changes.ContentCurrent research focuses on unraveling the pathophysiology of preeclampsia with the goal of implementing accurate screening and treatment modalities based on disease development and progression. Preeclampsia causes significant short- and long-term maternal morbidity and mortality, not only in the cardiovascular system but also in other organ systems throughout the body. This impact persists beyond pregnancy and the immediate postpartum period.SummaryThe goal of this review is to discuss the current understanding of the pathophysiology of preeclampsia as it relates to the adverse health consequences in patients impacted by this disease, along with a brief discussion of ways to improve overall outcomes.

Background Preeclampsia is a prominent risk factor for long‐term development of cardiovascular disease. Although existing studies report a strong correlation between preeclampsia and heart failure, the underlying mechanisms are poorly understood. One possibility is the glycoprotein growth factor activin A. During pregnancy, elevated activin A levels are associated with impaired cardiac global longitudinal strain at 1 year, but whether these changes persist beyond 1 year is not known. We hypothesized that activin A levels would remain increased more than 1 year after a preeclamptic pregnancy and correlate with impaired cardiac function. Methods and Results To test our hypothesis, we performed echocardiograms and measured activin A levels in women approximately 10 years after an uncomplicated pregnancy (n=25) or a pregnancy complicated by preeclampsia (n=21). Compared with women with a previously normal pregnancy, women with preeclampsia had worse global longitudinal strain (−18.3% versus −21.3%, P=0.001), left ventricular posterior wall thickness (0.91 mm versus 0.80 mm, P=0.003), and interventricular septal thickness (0.96 mm versus 0.81 mm, P=0.0002). Women with preeclampsia also had higher levels of activin A (0.52 versus 0.37 ng/mL, P=0.02) and activin/follistatin‐like 3 ratio (0.03 versus 0.02, P=0.04). In a multivariable model, the relationship between activin A levels and worsening global longitudinal strain persisted after adjusting for age at enrollment, mean arterial pressure, race, and body mass index (P=0.003). Conclusions Our findings suggest that both activin A levels and global longitudinal strain are elevated 10 years after a pregnancy complicated by preeclampsia. Future studies are needed to better understand the relationship between preeclampsia, activin A, and long‐term cardiac function.

Background Approximately 60% of women have Stage B heart failure 1 year after a preeclamptic delivery. Emerging evidence suggests that the profibrotic growth factor activin A, which has been shown to induce cardiac fibrosis and hypertrophy, is elevated in preeclampsia and may be inhibited by aspirin therapy. We hypothesized that preeclamptic women receiving aspirin would have lower activin A levels and reduced global longitudinal strain (GLS), a sensitive measure of cardiac dysfunction, than women who do not receive aspirin. To test our hypothesis, we performed a cohort study of women with preeclampsia or superimposed preeclampsia and compared activin A levels and GLS in parturients who did or did not receive aspirin. Methods and Results Ninety‐two parturients were enrolled, of whom 25 (27%) received aspirin (81 mg/day) therapy. GLS, plasma activin A, and follistatin, which inactivates activin A, were measured. Women receiving aspirin therapy had lower median (interquartile range) levels of activin A (8.17 [3.70, 10.36] versus 12.77 [8.37, 31.25] ng/mL; P=0.001) and lower activin/follistatin ratio (0.59 [0.31, 0.93] versus 1.01 [0.64, 2.60] P=0.002) than women who did not receive aspirin, which also remained significant after multivariable analysis. Furthermore, GLS was worse in patients who did not receive aspirin (−19.84±2.50 versus −17.77±2.60%; P=0.03) despite no differences in blood pressure between groups. Conclusions Our study suggests that antepartum aspirin therapy reduced serum activin A levels and improved GLS in preeclamptic patients, suggesting that aspirin may mitigate the postpartum cardiac dysfunction seen in women with preeclampsia.

Objective: To study the association between cardiac function measured by myocardial performance index (MPI), blood pressures and angiogenic factors measured at the time of echocardiography in patients with and without hypertensive disorders of pregnancy (HDP). Methods: We prospectively studied 189 pregnant women and evaluated whether changes in cardiac function observed on echocardiography were correlated with higher blood pressures and whether higher blood pressures were associated with antiangiogenic proteins (soluble fms-like tyrosine kinase, sFlt1; soluble endoglin, sEng). Comprehensive echocardiograms, including measurement of MPI, were performed on all patients. sFlt1 and sEng levels were measured using enzyme-linked immunosorbent assay. Results: Overall, 189 patients were divided into tertiles based on mean arterial pressure (MAP). The MPI was worst in tertile 3 (0.50 ± 0.15) compared to tertile 1 (0.42 ± 0.10), p = 0.0004. sFlt1 (pg/ml) and sEng (ng/ml) were highest in tertile 3 compared to tertile 1: 15055.37 vs. 1623.01 and 33.06 vs. 8.15, respectively, with p-value

Objective: Cardiogenic shock (CS) may occur during pregnancy and dramatically worsen peripartum outcomes. Methods: We analyzed the National Inpatient Sample from 2002 to 2013 to describe the incidence of, risk factors for and outcomes of CS during pregnancy. Results: Of the 53,794,192 hospitalizations analyzed, 2044 were complicated by CS. The mortality rate in peripartum women with CS was 18.81% versus 0.02% without. It occurs more often during postpartum (58.83%) as compared with delivery (23.47%) or antepartum (17.70%) hospitalizations. Factors associated with CS -related death included cardiac arrest, renal failure, and sepsis. Conclusions: CS during pregnancy occurs more commonly in the postpartum period and is associated with a high mortality.

Angiogenic factors are strongly associated with adverse maternal and fetal outcomes among women with preterm preeclampsia (PE) in developed countries. We evaluated the role of angiogenic factors and their relationship to adverse outcomes among Haitian women with PE.We measured plasma antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) levels in women with PE (n=35) compared to controls with no hypertensive disorders (NHD) (n=43) among subjects with singleton pregnancies that delivered at Hospital Albert Schweitzer (HAS) in Haiti. We divided the preeclamptic women into two groups, early onset (≤ 34 weeks) and late onset (>34 weeks) and examined relationships between sFlt1/PlGF ratios on admission and adverse outcomes (abruption, respiratory complications, stroke, renal insufficiency, eclampsia, maternal death, birth weight 34 weeks with no adverse outcome.PE-related adverse outcomes are common in women in Haiti and are associated with profound angiogenic imbalance regardless of gestational age at presentation.

The purpose of this study was to compare plasma soluble endoglin (sEng) levels with standard clinical evaluation or plasma levels of other angiogenic proteins [soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF)] in predicting short-term adverse maternal and perinatal outcomes in women with suspected preeclampsia presenting prior to 34 weeks.Data from all women presenting at

Background. Preeclampsia is difficult to diagnose in patients with underlying renal disease and proteinuria. Prior studies show that there is an angiogenic factor imbalance with elevated levels of antiangiogenic proteins soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) and reduced levels of the proangiogenic protein, placental growth factor (PlGF) in women with preeclampsia. These angiogenic biomarkers may be useful in distinguishing preeclampsia from other conditions of pregnancy, which may present with overlapping clinical characteristics. Cases. Case 1: A multiparous woman at 18 weeks gestation with nephrotic syndrome presented with hypertensive emergency and worsening renal insufficiency. She underwent induction of labor for severe preeclampsia. Her sFlt1 and sEng levels were at the 97 percentile while her PlGF level was undetectable (less than the 1st percentile). Case 2: A nulliparous woman with lupus nephritis at 22 weeks gestation presented with fetal demise and heart failure. Three weeks previously, the patient had developed thrombocytopenia and hypertensive urgency. She underwent dilation and evacuation. Her angiogenic profile was consistent with severe preeclampsia. Conclusion. Angiogenic factors may provide evidence to support a diagnosis of preeclampsia in patients with preexisting renal disease and proteinuria, conditions in which the classical definition of hypertension and proteinuria cannot be used.