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With the incorporation of angiogenic biomarkers into clinical practice, identification of potential modifiers of the angiogenic profile, including fetal sex, is essential.In this retrospective cohort analysis, patients with hypertensive disorders of pregnancy (HDP) and normotensive pregnancies were enrolled upon admission to Labor and Delivery. Blood samples for angiogenic factors were assessed using an automated platform. Clinical and demographic information was abstracted from each patient's medical records.Soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) levels and their ratio in relation to fetal sex in patients with normotensive pregnancies compared to those with HDP were evaluated.A total of 617 patients were analyzed (299 normotensive, 113 gestational hypertensive, 71 chronic hypertensive, and 134 preeclamptic patients). There was no difference between the number of patients who had a male fetus among preeclampsia and normotensive parturients (56.0 % vs 50.2 %, p = 0.26). Normotensive patients carrying a male fetus had significantly higher sFlt1 (pg/ml) (3168 [IQR: 2160-4945] vs 2678 [IQR: 1752-4271]; p = 0.01) and sFlt1/PlGF ratios (18 [IQR: 7-44] vs 12 [IQR: 5-30]; p = 0.01) in comparison to pregnant patients carrying a female fetus. This difference between fetal sexes was not observed in the angiogenic profile of patients with HDP.Our study of primarily Black, obese patients demonstrates that normotensive patients carrying a male fetus have a significantly higher sFlt1 and sFlt1/PlGF ratio as compared to those carrying a female fetus at term gestation. Fetal sex should be considered as a covariate when studying angiogenic factors in normotensive pregnant patients.

Preeclampsia (PE) is a pregnancy disease characterized by maternal hypertension and vascular dysfunction. PE is believed to originate from the ischemic/hypoxic placenta that activate local HIF-1α-mediated release of anti-angiogenic sFlt-1 and release of inflammatory cytokines, such as TNF-α. Signaling from both sFlt-1 and TNF-α-induced NF-κB activation result in upregulation of the potent vasoconstrictor ET-1. Antagonism of ET-1 signaling has been shown to relieve symptoms in animal models of PE, but these treatments are contraindicated in pregnancy. Luteolin is a naturally occurring bioflavonoid that has been studied for its use as an anti-inflammatory and anti-hypertensive agent but has never been studied in PE. In this in vitro study, we tested the hypothesis that luteolin may attenuate pathways involved in vascular dysfunction by attenuating HIF-1α increase (via upstream PI3K and ERK) as well as TNF-α-induced NF-κB activation. To study HIF-1α inhibition by luteolin, placental explants from normotensive patients were treated under normoxic (20%) and hypoxic (2%) conditions with luteolin (10μM) for 72 hours, in the presence and absence of relevant inhibitors; PI3K inhibitor (LY294002, 50μM) and ERK inhibitor (U0126, 20μM). Western blots were used to measure HIF-1α protein changes. HUVEC cells were stimulated by TNF-α in the presence or absence of luteolin to determine NF-κB nuclearization by immunofluorescence.Hypoxic incubations significantly increased HIF-1α compared to normoxia (1.44 + 0.43 vs 0.55 + 0.21 arbitrary units (AU); p This work was supported by NIH 1R56HL157579-01. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Hypertensive disorders of pregnancy (HDP) remain one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Affected women are also at increased risk for cardiovascular disease later in life, independently of traditional cardiovascular disease risks. Despite the immediate and long-term cardiovascular disease risks, recommendations for diagnosis and treatment of HDP in the United States have changed little, if at all, over past decades, unlike hypertension guidelines for the general population. The reasons for this approach include the question of benefit from normalization of blood pressure treatment for pregnant women, coupled with theoretical concerns for fetal well-being from a reduction in utero-placental perfusion and in utero exposure to antihypertensive medication. This report is based on a review of current literature and includes normal physiological changes in pregnancy that may affect clinical presentation of HDP; HDP epidemiology and the immediate and long-term sequelae of HDP; the pathophysiology of preeclampsia, an HDP commonly associated with proteinuria and increasingly recognized as a heterogeneous disease with different clinical phenotypes and likely distinct pathological mechanisms; a critical overview of current national and international HDP guidelines; emerging evidence that reducing blood pressure treatment goals in pregnancy may reduce maternal severe hypertension without increasing the risk of pregnancy loss, high-level neonatal care, or overall maternal complications; and the increasingly recognized morbidity associated with postpartum hypertension/preeclampsia. Finally, we discuss the future of research in the field and the pressing need to study socioeconomic and biological factors that may contribute to racial and ethnic maternal health care disparities.

Racial disparities are prevalent in many aspects of obstetric care in the USA. Non-Hispanic black women have a higher prevalence of the diagnosis of hypertensive disorders of pregnancy in addition to associated morbidity and mortality. The purpose of this review is to review current data regarding racial disparities in the diagnosis and management of hypertensive disorders of pregnancy.Diagnosis of hypertensive disorders of pregnancy is more common among non-Hispanic black women even after adjustment for comorbidities. Furthermore, prevalence of severe morbidity among those with hypertensive disorders of pregnancy is increased in non-Hispanic black women, including cardiovascular events related. Proposed management solutions include quality improvement initiatives, telehealth, and strategies to reduce both structural racism and implicit bias. Racial disparities exist in both diagnosis and management of hypertensive disorders of pregnancy; further innovative work is needed to reduce these disparities.

All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes. The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies.

Preeclampsia is associated with significant morbidity and mortality for mother and baby. Although around 30% of all pregnancies are evaluated for preeclampsia, diagnosis is difficult, especially in patients who have overlying symptoms from other diseases. Discovery of circulating angiogenic factors in the pathogenesis of preeclampsia has been a major advance for both diagnosis and prognosis. The anti-angiogenic factor, soluble fms-like tyrosine kinase 1 (sFlt-1) and the pro-angiogenic factor, placental growth factor (PlGF), can be measured in plasma and serum and are usually reported as a ratio, which specifically relates to the onset and severity of preeclampsia. The sFlt-1/PlGF ratio has a very high negative predictive value in ruling out the development of preeclampsia within 7 days among women with suspected preeclampsia. Currently, there is no clear consensus on the practical use of angiogenic biomarkers in the detection and management of preeclampsia in routine clinical practice. While major international clinical guidelines exist, they do not define which specific parameters signal patient admission, or outpatient evaluation of suspected preeclampsia, and most clinicians follow local practices. Better guidance is needed on risk stratification among women with suspected preeclampsia, as well as among women at high risk for preeclampsia. Prediction of adverse outcomes in women, after the clinical diagnosis of preeclampsia, is also important. This report has been developed following a meeting of international experts and aims to guide clinicians in the management of pregnant women at risk of preeclampsia using the sFlt-1/PlGF ratio test.

Preeclampsia is a devastating medical complication of pregnancy that can lead to significant maternal and fetal morbidity and mortality. It is currently believed that there is abnormal placentation in as early as the first trimester in women destined to develop preeclampsia. Although the etiology of the abnormal placentation is being debated, numerous epidemiologic and experimental studies suggest that imbalances in circulating angiogenic factors released from the placenta are responsible for the maternal signs and symptoms of preeclampsia. In particular, circulating levels of soluble fms-like tyrosine kinase 1, an antiangiogenic factor, are markedly increased in women with preeclampsia, whereas free levels of its ligand, placental, growth factor are markedly diminished. Alterations in these angiogenic factors precede the onset of clinical signs of preeclampsia and correlate with disease severity. Recently, the availability of automated assays for the measurement of angiogenic biomarkers in the plasma, serum, and urine has helped investigators worldwide to demonstrate a key role for these factors in the clinical diagnosis and prediction of preeclampsia. Numerous studies have reported that circulating angiogenic biomarkers have a very high negative predictive value to rule out clinical disease among women with suspected preeclampsia. These blood-based biomarkers have provided a valuable tool to clinicians to accelerate the time to clinical diagnosis and minimize maternal adverse outcomes in women with preeclampsia. Angiogenic biomarkers have also been useful to elucidate the pathogenesis of related disorders of abnormal placentation such as intrauterine growth restriction, intrauterine fetal death, twin-to-twin transfusion syndrome, and fetal hydrops. In summary, the discovery and characterization of angiogenic proteins of placental origin have provided clinicians a noninvasive blood-based tool to monitor placental function and health and for early detection of disorders of placentation. Uncovering the mechanisms of altered angiogenic factors in preeclampsia and related disorders of placentation may provide insights into novel preventive and therapeutic options.

Background Preeclampsia is a leading cause of maternal and neonatal mortality and morbidity worldwide. Diagnosis of the condition is currently limited to utilization of nonspecific signs and symptoms. However, identification of potential pathogenic biomarkers may support earlier diagnosis and ultimately improved prognosis. Content The current models of preeclampsia suggest that the disease has components of abnormal placentation, a degree of angiogenic imbalance and endothelial dysfunction. Angiogenic factors such as soluble fms-like tyrosine kinase-1 and soluble endoglin increase while placental growth factor concentrations decrease in the circulation weeks before the onset of the disease. Multiple studies have looked at the capacity of angiogenic factors for the prediction of preeclampsia and adverse pregnancy outcomes. Summary The goal of this review is to focus on the role of angiogenic factors in the pathogenesis of preeclampsia and use of angiogenic biomarkers for risk stratification, diagnosis, and prognosis of the disease.

Patients with a history of hypertensive disorders of pregnancy (HDP) suffer higher rates of long-term cardiovascular events including heart failure, coronary artery disease, and stroke. Cardiovascular changes during pregnancy can act as a natural stress test, subsequently unmasking latent cardiovascular disease in the form of HDP. Because HDP now affect 10% of pregnancies in the United States, the American Heart Association has called for physicians who provide peripartum care to promote early identification and cardiovascular risk reduction. In this review, we discuss the epidemiology, pathophysiology, and outcomes of HDP-associated cardiovascular disease. In addition, we propose a multi-pronged approach to support cardiovascular risk reduction for women with a history of HDP. Additional research is warranted to define appropriate blood pressure targets in the postpartum period, optimize the use of pregnancy history in risk stratification tools, and clarify the effectiveness of preventive interventions. The highest rates of HDP are in populations with poor access to resources and quality health care, making it a major risk for inequity of care. Interventions to decrease long-term cardiovascular disease risk in women following HDP must also target disparity reduction.

Introduction Women with a history of preeclampsia have a higher risk of recurrent preeclampsia. This study sought to ascertain the relationship between the interbirth interval and the risk of recurrent preeclampsia and difference in angiogenic markers between the two groups. Methods Data was collected from an ongoing cohort study of women with hypertensive disorders of pregnancy (HDP) enrolled at the admission to the labor and delivery floor. From this dataset, multigravida women with a prior diagnosis of preeclampsia were identified and compared to women with no prior history of preeclampsia. Results Of the 375 women with HDP who were predominantly African American, 245 were multigravida and 44 (18.0%) had a prior history of preeclampsia. Women with prior preeclampsia had an earlier gestational age of delivery, higher rates of preterm delivery and a higher incidence of preeclampsia with severe features (56.8% vs 29.8%) in the index pregnancy (p-values ≤ 0.001) than those without. The median number of years between history of preeclampsia in previous pregnancy and current pregnancy was 6 years (IQR 3, 8). Among patients with a prior history of preeclampsia, the interbirth interval was not associated with severe preeclampsia (p = 0.60) and there was no difference in angiogenic factors between patients with a prior history of preeclampsia compared to those without. Conclusions In this study, the duration of the interbirth interval was not identified as a risk factor of developing severe preeclampsia in a subsequent pregnancy and angiogenic factors are not a reflection of maternal predisposition to recurrent preeclampsia.

Supplemental Digital Content is available in the text., This study evaluated whether planned early delivery would ameliorate cardiovascular dysfunction 6 months postpartum, compared with usual care with expectant management, in women with late preterm preeclampsia. We conducted a mechanistic observational study in women with preterm preeclampsia between 34+0 and 36+6 weeks’ gestation, nested within a randomized controlled trial of planned early delivery versus expectant management (usual care), in 28 maternity hospitals in England and Wales. Women were followed up 6 months postpartum with cardiovascular assessments. The primary outcome was a composite of systolic and diastolic dysfunction (by 2009 and 2016 definitions of diastolic dysfunction). Between April 27, 2016, and November 30, 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited. One hundred thirty-three women were randomized to planned delivery, 137 women were randomized to expectant management within the trial, while 150 women received expectant management outside of the trial. 321 (76.4%) completed their 6 month echocardiography assessment. 10% (31/321) had a left ventricular ejection fraction

Maternal mortality is a worldwide epidemic, with rates in the United States far surpassing those in similar high-income countries, and years of implicit bias and systemic racism have impacted outcomes for individuals belonging to racial and ethnic minorities. Structural racism must be dismantled to ensure better care for all.

Hypertension complicates 2% to 8% of all pregnancies and is a leading cause of maternal and perinatal morbidity and mortality globally. Given the prognostic role that angiogenic markers play in evaluation of patients with "suspected preeclampsia," the International Society for the Study of Hypertension in Pregnancy incorporated angiogenic imbalance into the 2021 definition of preeclampsia. As women with "suspected preeclampsia" are a heterogeneous group, with some already meeting the diagnostic criteria for preeclampsia, we evaluated whether the soluble fms-like tyrosine kinase-1/placental growth factor ratio adds prognostic value among these women.This study aimed to assess the additive value of soluble fms-like tyrosine kinase-1/placental growth factor ratio when the diagnostic criteria for preeclampsia have already been met.This was a secondary analysis of a prospective cohort study of patients presenting to obstetrical triage with suspected preeclampsia at ≥20Of 1043 patients included, 459 presented at 20Our findings support the prognostic value of the soluble fms-like tyrosine kinase-1/placental growth factor ratio among patients with confirmed preeclampsia, particularly to identify those both likely and unlikely to progress toward the development of severe features in the next 2 weeks and those who may be most appropriate for expectant and potentially outpatient care. Our findings support the incorporation of angiogenic imbalance into the definition of preeclampsia, particularly at 20-34

Background The flavonoid, luteolin, promotes vasorelaxation in various arteries through endothelial-dependent and independent mechanisms. Although there is growing interest in the vasoactive effects of flavonoids on maternal vascular function during pregnancy, it is unknown whether luteolin elicits vasorelaxation in the uterine circulation. We tested the hypothesis that luteolin induces vasorelaxation via endothelial-dependent mechanisms in uterine arteries from normal pregnant rats during late gestation. Methods Uterine arteries and aortas were isolated from Sprague-Dawley rats at gestational day 19 and prepared for wire myography. Results The potency of luteolin-induced vasorelaxation was examined between uterine arteries and the aortas. By 50 µM of luteolin, there was complete relaxation (100.5 ± 5.2%) in uterine arteries as compared to aortas (27.5 ± 10.0%). Even the highest concentration of 100 µM luteolin produced less than half relaxation (43.6 ± 8.6%) in aortas compared to uterine arteries. We then explored if luteolin-induced vasorelaxation in uterine arteries from pregnant rats was mediated by endothelial-dependent vasorelaxation pathways, including nitric oxide synthase (NOS), cyclooxygenase (COX), or potassium (K+) channels. Blocking these pathways with N(G)-Nitro- l -arginine methyl ester hydrochloride (L-NAME), indomethacin, or tetraethylammonium (TEA)/high potassium chloride (KCl), respectively, did not alter luteolin responses in uterine arteries from pregnant rats. These findings suggested that endothelial factors may not mediate luteolin-induced vasorelaxation in uterine arteries during pregnancy. Indeed, experiments where the endothelium was removed did not alter luteolin-induced vasorelaxation in uterine arteries during pregnancy. Conclusions Luteolin directly promotes vasorelaxation in the medial smooth muscle layer of uterine arteries during normal pregnancy.

To compare outcomes, specifically development of preeclampsia with severe features (sPE), between angiogenic biomarker-based admission and admission based on routine clinical care.This secondary analysis of a prospective study evaluated soluble fms-like tyrosine kinase-1 (sFlt1)/placental growth factor (PlGF) ratio in women presenting to triage for preeclampsia evaluation. Biomarkers levels were measured in samples collected from triage and analyzed retrospectively after outcomes were achieved. For this analysis patients would be hypothetically assigned to 'discharged' with a sFlt1/PlGF ratio ≤ 38 and 'admitted' with a sFlt1/PlGF ratio 85. Development of sPE and other outcomes were then compared using the biomarker and clinical criteria for admission.459 patients were included in this analysis. Using biomarker criteria, a larger proportion of patients were hypothetically discharged (67.8% vs 51.0%, p 0.0001). A larger proportion of patients 'admitted' with a high biomarker level developed sPE (69.5% vs 40.9%, p 0.0001). A sFlt1/PlGF ratio ≤ 38 had a negative predictive value of 96.8% for development of sPE within two weeks.Assessment of angiogenic biomarkes that 'discharges' patients with a low sFlt1/PlGF ratio and 'admits' patients with high ratio could result in reduced admissions and increased admission of patients at risk for developing sPE. Randomized trials are needed to determine the effectiveness of angiogenic biomarker use in decision making in a triage setting among women with suspected preeclampsia.

To compare characteristics and outcomes of women with chronic hypertension (cHTN) between those with normal and abnormal plasma angiogenic profiles.This secondary analysis explored associations between angiogenic markers soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) drawn prior to delivery among women with history of cHTN who were enrolled between 22 and 41 weeks. Patients were divided into two groups based on sFlt1/PlGF ratio, namely low sFlt1/PlGF (85) and high sFlt1/PlGF (≥85) ratio.Of the 115 patients, 76% were African American. Compared to women with low sFlt1/PlGF (n = 78), patients with high sFlt1/PlGF (n = 37) had higher median antenatal blood pressures (systolic mmHg 179 vs 155; diastolic 106 vs 91), lower gestational age at delivery (34.7 vs 38.2 weeks), lower birthweight (1940 vs 3103 g), and a higher prevalence of preterm delivery 34 (40.5% vs 7.7%) and 37 weeks (64.9% vs 20.5%), all p 0.001. Importantly, more women with high sFlt1/PlGF had a diagnosis of superimposed preeclampsia (62.2% vs 26.9%, p = 0.003), preeclampsia with severe features (59.5% vs 20.5%, p 0.0001), maternal adverse outcomes (24.3% vs 3.9%, p = 0.002), neonatal intensive care unit admissions (71.9% vs 40.8%; p = 0.003), severe postpartum hypertension (67.6% vs 38.5%, p = 0.01) and longer hospital stays (median 6.0 vs 4.5 days, p = 0.003).In contrast to patients with a low ratio, high sFlt1/PlGF is characterized by an increased risk of maternal adverse outcomes and prematurity. Incorporation of angiogenic biomarkers while managing cHTN may improve accuracy of early identification of adverse outcomes to improve outcomes.

Introduction: Peripartum cardiomyopathy (PPCM) is a rare form of pregnancy-related heart failure associated with preeclampsia. Our understanding of their shared pathophysiology is limited as are treatment options. Hypothesis: We hypothesized that plasma proteomic profiling would identify deleterious circulating proteins and provide insights into shared mechanisms driving preeclampsia and PPCM. Methods: We performed serum proteomic case-control studies in women with preeclampsia or PPCM to identify biological processes common to both conditions. The top candidate was validated in independent preeclampsia (n=58) and PPCM (n=114) cohorts. Preeclamptic placenta was examined as a potential source of circulating proteins. Therapeutic targeting the top candidate was examined in an animal model of PPCM. Results: Paradoxically, we found the senescence-associated secretory phenotype (SASP), a marker of biological aging, to be the most upregulated process in relatively young women with preeclampsia (normalized enrichment score [NES]=3.3;p adj =4.0x10 -6 ) or PPCM (NES=3.2;p adj =1.9x10 -5 ). 28 circulating proteins contributed to this common signal, and were strongly enriched in preeclamptic placenta, which expressed markers of increased senescence. The TGFb family member, Activin-A, was the most highly upregulated SASP gene in preeclamptic placentas (5-fold;p Conclusions: These data implicate placental senescence in the increased deleterious circulating proteins seen in preeclampsia and PPCM. We identify multiple new circulating factors associated with these diseases and demonstrate that targeting SASP proteins, such as Activin-A, can mitigate PPCM in mice.

Hypertensive disorders of pregnancy (HDP) are associated with maternal and neonatal morbidity as well as postpartum hospital readmission. This study seeks to characterize differences among patients with postpartum readmissions related to HDP. This is a retrospective study of patients with HDP admitted at an urban tertiary care center from January 2019 to November 2019 following the implementation of a standardized readmission workflow for patients with HDP at a single institution. Medical information up to 6 weeks postpartum was collected by chart review. The primary outcome was readmission. Secondary outcomes included reason for readmission, location of initial evaluation, and blood pressure values at time of readmission. A total of 729 patients with HDP delivered over the study period, 79.7% (N = 581) of whom were Black and 11.0% (N = 80) of all patients were readmitted within 6 weeks of delivery. Patients who were older, privately insured, and with chronic hypertension/cardiac disease were more likely to be readmitted. There was no difference in readmission rate by race. However, Black patients were more likely to be readmitted for preeclampsia with severe features (43.3% vs 10.0% non-Black, p = 0.01). Black patients who were readmitted were more likely to be initially evaluated in the emergency room compared to non-Black patients (43.3% vs 15.0%, p = 0.03). Our results suggest although readmission rates did not differ by race, there are significant differences at the patient and system level between Black and non-Black patients readmitted to the hospital after a pregnancy affected by HDP.

This study aimed to evaluate womens' perspectives about current and novel preeclampsia testing methods at an urban tertiary medical center.This was an observational survey study conducted between October 1, 2020 and December 31, 2020. Subjects were eligible if they were ≥ 18 years of age and had a diagnosis of gestational hypertension, preeclampsia, or superimposed preeclampsia at the time of delivery. Informed consent was obtained, and the 26-question survey was administered after delivery. A detailed medical record review was completed for respondents (patients) and their neonates.A total of 100 women were included in the study. The majority of participants were Black (78%) and/or on Medicaid (51%). Most respondents agreed that they fully trust their doctor and medical team (96%) and that the newest medical tests, treatments, and technologies should always be used (91%). Most women (80%) at least somewhat agreed they have enough knowledge about preeclampsia and its complications. Over 90% of women agreed a test to predict complications of preeclampsia would be useful to them. Most women reported a rule out test would be useful to them because it would help them worry less (68%), reduce hospitalizations (32%) and reduce interventions (17%).There was majority support for novel methods such as biomarker testing among this cohort. Most patients reported the test would decrease worry associated with preeclampsia development and complications.

Objective Preeclampsia is a major obstetric disorder that can lead to severe maternal, fetal and infant outcomes. In women with suspected preeclampsia, measurement of the soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) ratio has been shown to have a high negative predictive value (>97%). Our aim was to estimate the value to the US healthcare system of adopting this test into clinical practice. Study design: An economic model was developed for the evaluation of suspected preeclampsia from a US payer perspective using data from a US observational study of 459 women evaluated between 23 and 34.6 weeks. Test results were not available to clinicians. The model compares two strategies for managing suspected preeclampsia: standard care versus a biomarker-informed pathway utilizing the sFlt1/PlGF ratio. Results Utilization of the sFlt1/PlGF ratio test reduced the number of women admitted for suspected preeclampsia by 34–49%. Despite fewer admissions, a higher proportion of women admitted to hospital subsequently developed preeclampsia, and the proportion of women not admitted who would subsequently develop preeclampsia remained low (3.2%–6.7%). Cost savings arising from a reduction in admissions are estimated to be $1050 in the base case; varying the hospitalization cost ±25% would lead to savings in the range $771 to $1330 per patient at 2020 prices. Conclusion Adopting the sFlt1/PlGF ratio test as an adjunct to clinical criteria improves the assessment of risk in women presenting with suspicion of preeclampsia and has the potential to safely reduce unnecessary admissions and save costs.

To test the ability of a hospital-wide, bundled quality-improvement initiative to improve postpartum maternal blood pressure control and adherence to postpartum follow-up among patients with hypertensive disorders of pregnancy.This quality-improvement initiative consisted of a bundle of clinical interventions including health care professional and patient education, a dedicated nurse educator, and protocols for postpartum hypertensive disorders of pregnancy care in the inpatient, outpatient and readmission setting. We implemented this initiative in patients with hypertensive disorders of pregnancy starting in January 2019 at the University of Chicago. The study period was divided into four periods, which correspond to preintervention, distinct bundle roll outs, and postintervention. Our primary outcome was postpartum hypertension visit adherence. Secondary outcomes included blood pressure values and antihypertensive medication use in the immediate postpartum and outpatient postpartum time periods. We then stratified our outcomes by race to assess whether the effect size differed.A total of 926 patients who delivered between September 2018 and November 2019 were included. Postpartum hypertension visit adherence improved from preintervention period compared with the full implementation period (33.5% vs 59.4%, P.001). Blood pressure in the first 24 hours postpartum decreased from preintervention compared with full implementation (preintervention median [interquartile range] systolic blood pressure 149 mm Hg [138, 159] vs 137 [131, 146] in postimplementation; P.001). After implementation, fewer patients experienced a blood pressure of 140/90 mm Hg or higher at the first postpartum blood pressure check, when compared with preintervention (39.1% vs 18.5%, P=.004). The effect size did not differ by race.A bundled quality-improvement initiative for patients with hypertensive disorders of pregnancy was associated with improved postpartum visit adherence and blood pressure control in the postpartum period.

Background: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. Methods: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN , and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. Results: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [ P *]=1.2×10 –46 ). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P *=7.0×10 –8 ), DSP (odds ratio=14.9, P *=1.0×10 –8 ), and BAG3 (odds ratio=53.1, P *=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P =2.5×10 –4 ), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. Conclusions: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Persistent postpartum hypertension is a significant cause of maternal morbidity. Our objective was to study the effect of furosemide on postpartum blood pressure recovery in women with hypertensive disorders of pregnancy. We performed a randomized, double-blind, placebo controlled trial of a 5-day course of 20mg oral furosemide versus placebo in women with gestational hypertension and preeclampsia with/without severe features from June 2018 to October 2019. Primary outcomes were persistent hypertension at 7-days postpartum (using generalized linear models to calculate adjusted relative risk) and days to resolution of hypertension (Kaplan Meier curves), stratified by severe/non-severe hypertensive disease. Secondary outcomes included readmissions and need for additional hypertensive medication.We randomized 384 women (192/group). Baseline characteristics were similar except cesarean delivery rate was higher in the furosemide group (29% vs. 20%, p=0.04). In women randomized to furosemide, there was a 60% reduction in the prevalence of persistently elevated blood pressure at 7-days when controlling for cesarean (aRR 0.40, 95%CI 0.20–0.81). The magnitude of reduction was greater in women with non-severe disease (aRR 0.26, 95% CI 0.10–0.67). Days to blood pressure resolution was significantly shorter among women with non-severe disease randomized to furosemide (8.5 vs. 10.5, p=0.001). There were no significant differences in readmissions or need for additional antihypertensive medication postpartum between groups. In this double-blinded randomized trial, a short course of postpartum furosemide significantly improved blood pressure control in women with hypertensive disorders of pregnancy, mostly among women without severe disease.

Objectives To describe patient outcomes, management of hypertensive disorders of pregnancy, and evaluate provider knowledge of practice guidelines at a tertiary care center in urban China. Study design Retrospective chart review of patients admitted between September 2017 and March 2018 with a diagnosis of any hypertensive disorder at Zhongnan Hospital of Wuhan University Medical Center in China. Healthcare providers including physicians, midwives, nurses and medical students were surveyed. Patient outcomes were compared to those at the University of Chicago, USA. Main outcome measures Prevalence of hypertensive disorders of pregnancy, comparative rates of medication administration, mode of delivery, and other pregnancy characteristics were abstracted. Responses regarding definitions, treatment and outcomes of hypertension were analyzed using survey data. Results Among 2834 patients, the prevalence of hypertensive disorders at the Zhongnan Hospital was 7.1%, with a 6.4% prevalence of preeclampsia. Compared to hypertensive women from the University of Chicago, hypertensive patients at Zhongnan Hospital were more likely to be older and weigh less but had higher rates of antihypertensive drug administration and delivery via cesarean section. Infants born at Zhongnan Hospital were less likely to be admitted to the neonatal intensive care unit. Survey respondents demonstrated poor knowledge of preeclampsia diagnoses and first line treatments for severe hypertension in pregnancy. Conclusions Although several clinical characteristics of preeclampsia were similar between hospitals, the rates of cesarean section were higher in China. Provider knowledge was most lacking in areas about diagnostic criteria and medication use for preeclampsia. Future studies are needed to explore these differences.

Objective To study the association between hypertensive diseases of pregnancy and immediate postpartum development of heart failure in a large national database. Patients and Methods Using the 2013 to 2014 National Readmissions Database, which covered admissions from January 1 through September 30 in years 2013 and 2014, we examined 90-day readmission rates in parturients with a diagnosis of hypertensive disease of pregnancy who were discharged after delivery. The primary outcome was the association between the presence of hypertensive disease of pregnancy and readmission with heart failure within 90 days of delivery discharge. Secondary outcomes included readmission mortality, time between delivery discharge and readmission, length of stay, and costs of readmission. Results Women with hypertensive disease of pregnancy were more likely to be readmitted with heart failure (1809 of 25,908 readmissions (7.0%) vs 2622 of 89,660 readmissions (2.9%); P Conclusion Parturients with hypertensive disease of pregnancy were more likely to be readmitted with heart failure within 90 days of delivery. Most patients readmitted with heart failure were readmitted within 2 weeks of discharge after delivery. Patients readmitted with heart failure had substantial health care expenditures.

Hypertensive disorders of pregnancy—chronic hypertension, gestational hypertension, and preeclampsia—are uniquely challenging as the pathology and its therapeutic management simultaneously affect mother and fetus, sometimes putting their well-being at odds with each other. Preeclampsia, in particular, is one of the most feared complications of pregnancy. Often presenting as new-onset hypertension and proteinuria during the third trimester, preeclampsia can progress rapidly to serious complications, including death of both mother and fetus. While the cause of preeclampsia is still debated, clinical and pathological studies suggest that the placenta is central to the pathogenesis of this syndrome. In this review, we will discuss the current evidence for the role of abnormal placentation and the role of placental factors such as the antiangiogenic factor, sFLT1 (soluble fms-like tyrosine kinase 1) in the pathogenesis of the maternal syndrome of preeclampsia. We will discuss angiogenic biomarker assays for disease-risk stratification and for the development of therapeutic strategies targeting the angiogenic pathway. Finally, we will review the substantial long-term cardiovascular and metabolic risks to mothers and children associated with gestational hypertensive disorders, in particular, preterm preeclampsia, and the need for an increased focus on interventional studies during the asymptomatic phase to delay the onset of cardiovascular disease in women.

Black people have a disproportionately higher risk of hypertensive disorders of pregnancy and postpartum complications than White people but historically lower rates of postpartum follow-up. Few studies have investigated telehealth in the postpartum population.This study aimed to investigate whether rapid switch to telehealth with audio-based visits during the COVID-19 pandemic decreased racial disparities in postpartum hypertension follow-up adherence.This retrospective cohort study included all the patients with hypertensive disorders of pregnancy who delivered between December 2019 and June 2020 at an urban tertiary care center. A preexisting postpartum hypertension quality improvement initiative was in place at this institution. Follow-up adherence within 6 weeks postpartum and at the 6-week visit were compared before February 15, 2020 (pretelehealth period) and following March 14, 2020 (post-telehealth period), with a 1-month implementation or washout period. The blood pressures at these visits were compared between time periods as a secondary outcome.A total of 473 patients were included in this analysis, of whom 76.3% were non-Hispanic Black. There were 215 and 258 patients in the pre- and post-telehealth cohorts, respectively. Among those who attended follow-up, the proportion of visits done over telehealth went from 0% pretelehealth to 98.0% post-telehealth. The proportion of postpartum hypertension follow-up attendance changed from 48.5% to 76.3% among non-Hispanic Black people (P.0001) and from 73.1% to 76.7% among non-Hispanic White people (P=.76), leaving only a 0.4% racial gap (P=.97). This resulted in an elimination of the racial disparities in the post-telehealth period.Transition to telehealth with audio-based visits at the onset of the COVID-19 pandemic improved attendance at postpartum hypertension visits among non-Hispanic Black people. This, therefore, led to significant decreases in the racial disparities in follow-up rates at our institution in the setting of an existing quality improvement initiative. Further research should focus on the intentional use of telehealth in improving maternal outcomes, especially among the non-Hispanic Black people.

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.

The utility of angiogenic biomarkers in a low resource outpatient setting is not well known. This study evaluates the clinical utility of angiogenic biomarkers, soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) among patients at risk for preeclampsia in a low resource outpatient setting.This was a prospective pilot study among high risk third trimester outpatients conducted in Bengaluru, India. Serum sFlt1/PlGF was measured between 28 and 37 weeks. Patients with high risk ratio were managed with close observation, intermediate risk had serum redrawn in one week, and those with low risk ratio received routine care. Delivery decisions were made based on local protocols.Maternal complication rate, development of preeclampsia with severe features, and latency to delivery was examined by sFlt1/PlGF ratio.The study included 50 patients. Compared to women with a low risk ratio, women with a high-risk ratio were more likely to have preeclampsia with severe features (90.91% vs 8.00%, p 0.0001), a higher composite maternal complication rate (18.18% vs 0%, p = 0.04) and deliver at earlier gestational ages (32.57 [30.43, 34.71] vs 37.43 [36.86, 38.14] weeks, p = 0.0001).Angiogenic factors may have utility in the low resource outpatient setting for women with a hypertensive disease. Low sFlt1/PlGF levels were associated with a longer latency to delivery and no maternal complications. This study confirms the broad clinical utility of biomarkers in the real world.

Objectives Ischemic placental disease (IPD), including preeclampsia, abruption, and fetal growth restriction, often recurs in subsequent pregnancies. Angiogenic factors of placental origin have been implicated in the pathogenesis of preeclampsia, but have not been studied as predictors of IPD in subsequent pregnancies. We hypothesized that elevated angiogenic factors in an index pregnancy would be associated with recurrence of IPD. Study design We conducted a retrospective cohort study of patients undergoing evaluation for preeclampsia who had angiogenic factors measured in an index pregnancy and experienced a subsequent pregnancy at the same institution. Patients with IPD in the index pregnancy were included. A high ratio of soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF) was defined as greater than or equal to 85. Main outcome measures The primary outcome was IPD in a subsequent pregnancy. Results We included 109 patients in the analysis. The sFlt1/PlGF ratio was elevated in 30% of participants. Those with an elevated ratio were more likely to be nulliparous in the index pregnancy, and less likely to have chronic hypertension. The recurrence of IPD in the study was 27%, with a non-significant difference in risk based on a high sFlt-1/P1GF ratio RR 0.58 (95% CI 0.21 – 1.6) compared to a low ratio. Conclusions A high sFlt1/P1GF ratio in an index pregnancy is not associated with a higher risk of IPD in a subsequent pregnancy. These data suggest placental angiogenic biomarkers are specific to the pregnancy and not a reflection of maternal predisposition to IPD.