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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 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.

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

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.

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.

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.

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.

Chronic hypertension (cHTN) affects 3-5% of all pregnancies and is twice as prevalent in African American (AA) women. AA women develop more severe HTN at an earlier onset and have higher rates of adverse pregnancy outcomes. Blood pressure control during pregnancy is controversial.This retrospective cohort included AA women with cHTN and singleton pregnancies delivering between January 2013 and December 2016. Patients were classified as not receiving antihypertensives in the first 20 weeks (Group A), on antihypertensives in the first 20 weeks but with an average BP140/90 during pregnancy (Group B) and on antihypertensives in the first 20 weeks but with average BP during pregnancy ≥140/90 (Group C). Adverse outcomes including severe HTN and preterm delivery35 weeks was compared between groups.Of the 198 patients included, 68 received at least one AHT before 20 weeks including 45 patients with average BP140/90 and 23 with average BP ≥140/90 during pregnancy. The incidence of superimposed PE and preterm birth was significantly higher among women with elevated BPs on AHT (39.1% vs 8.9% vs 17.7%, p = 0.01; preterm birth 52.2%, 8.9% and 9.2%, p 0.001 for Groups C, B and A, respectively). A significantly higher proportion of adverse neonatal outcomes were observed in Group C (78.3%) as opposed to those in Group B (53.3%) or Group A (50.0%; p = 0.04).Among AA women with cHTN, use of antihypertensives prior to 20 weeks and lower antenatal BP was associated with a decreased risk of adverse maternal and neonatal outcomes.

There is an urgent need for biomarkers that can help stratify women with suspected preeclampsia (PE) for the subsequent appearance of PE with severe features (sPE), to improve risk assessment and direct monitoring related to complications of sPE. Elevated levels of circulating anti-angiogenic factors like soluble fms-like tyrosine kinase 1 (sFlt1) and decreased free levels of pro-angiogenic factors such as placental growth factor (PlGF) are associated with adverse outcomes related to preeclampsia (PE). Here, we report in a single-center prospective study (N = 402) that plasma levels of these circulating angiogenic markers predict sPE within two weeks among women presenting with suspected PE in the preterm period (37 weeks). sFlt1/PlGF ratio of 38 at the triage visit had a positive predictive value (PPV) of 47% and a negative predictive value (NPV) of 98% for the presence of sPE within 2 weeks. Among patients presenting 34 weeks, the PPV for sPE improved to 65% with NPV of 98%. sFlt1/PlGF ratio 85, had a PPV of 59% in all patients and 74% among patients presenting 34 weeks for the presence of sPE within 2 weeks. When we restricted the analysis to hospitalized patients, PPVs were 58% and 63% in all patients and 73% and 77% for patients presenting 34 weeks for plasma sFlt1/PlGF cutoff 38 and 85 respectively. Clinical trials are needed to evaluate whether risk stratification with angiogenic biomarkers in patients with suspected PE will lead to improved maternal and fetal outcomes among women at risk for severe disease.

Women with hypertensive disorders of pregnancy have an increased risk of subsequent heart failure and cardiovascular disease when compared with women with normotensive pregnancies. Although the mechanisms underlying these findings are unclear, elevated levels of the biomarker activin A are associated with myocardial dysfunction and may have predictive value. We hypothesized that elevated levels of antepartum activin A levels would correlate with postpartum cardiac dysfunction in women with hypertensive disorders of pregnancy. We prospectively studied 85 women to determine whether increased antepartum activin A levels were associated with cardiac dysfunction at 1 year postpartum as measured by global longitudinal strain. Thirty-two patients were diagnosed with preeclampsia, 28 were diagnosed with gestational or chronic hypertension, and the remainder were nonhypertensive controls. Activin A levels were measured with ELISA both in the third antepartum trimester and at 1 year postpartum. Comprehensive echocardiograms including measurement of global longitudinal strain were also performed at enrollment and at 1 year postpartum. Antepartum activin A levels correlated with worsening antepartum global longitudinal strain ( r =0.70; P =0.0001). Across the entire cohort, elevated antepartum activin A levels were associated with the development of abnormal global longitudinal strain at 1 year (C statistic 0.74; P =0.004). This association remained significant after multivariable adjustment for clinically relevant confounders (C statistic 0.93; P =0.01). Postpartum activin A levels also correlated with increasing left ventricular mass index ( P =0.02), increasing mean arterial pressures ( P =0.02), and decreasing E′ values ( P =0.01). Activin A may be a useful tool for identifying and monitoring patients at risk for postpartum development of cardiovascular disease.

Chronic hypertension (cHTN) affects 7% of all pregnancies. We hypothesized that cHTN during pregnancy would be associated with abnormal myocardial strain patterns and adverse perinatal outcomes.This was a retrospective cohort study of patients seen in a high-risk obstetrics clinic with cHTN. Parturients with a singleton pregnancy who had undergone an echocardiogram as part of routine clinical care were eligible. Clinical and demographic information was collected from medical records. Global peak longitudinal strain (GLS) was measured using automated software from stored echocardiographic images.60 patients were included in this analysis, of which 48 (80.0%) were African American. The median BMI was 40.6, age was 34 years, and the gestational age was 20.4 weeks at the time of the echo and 37.9 weeks at delivery. Thirty-four patients (56.7%) demonstrated abnormal strain, defined as a GLS = -19%. Patients with abnormal strain were similar in age and BMI to patients with normal cardiac function. When compared to women with normal strain, those with abnormal strain had lower stroke volume (69.0 ml vs 81.5 ml; p = .001) and ejection fraction (49.6% vs 57.5%; p .0001). Rates of superimposed preeclampsia were higher (38.2% vs 11.5%, p-value = .02) and a higher proportion of patients in the abnormal strain group delivered before 37 weeks (44.1% vs 19.2%; p = .04).In a population of parturients with cHTN, we found that more than one-half demonstrated subclinical abnormal cardiac function. The presence of abnormal cardiac strain predates superimposed preeclampsia and preterm delivery. Further studies are needed to validate these findings.

Novel angiogenic biomarker profiles have demonstrated emerging evidence for predicting preeclampsia onset, severity, and adverse outcomes. Limited data exist in screening patients with fetal growth restriction for preeclampsia development using angiogenic biomarkers.The objective of this study was to risk stratify patients with fetal growth restriction using a soluble fms-like tyrosine kinase-1 to placental growth factor ratio. Previously published cutoff of 38 was used to predict preeclampsia development and severity as well as adverse maternal or neonatal outcomes within a 2-week time period.This was a prospective observational cohort study performed in a single tertiary hospital. Patients with a singleton fetal growth restriction pregnancy between 24 and 37 weeks' gestation were evaluated using serial 2-week encounters from the time of enrollment to delivery. Pregnancies with proven genetic or infectious etiology of fetal growth restriction or congenital anomalies were excluded. Ultrasound growth and Doppler measurements were obtained at the start of every encounter with routine preeclampsia laboratory tests and blood pressure checks when clinically indicated. Maternal serum was collected for all serial encounters and measured for soluble fms-like tyrosine kinase-1 and placental growth factor after delivery in a double-blinded fashion. Maternal charts were reviewed for baseline demographic characteristics, pregnancy diagnoses and outcomes, and neonatal outcomes.A total of 45 patients were enrolled for a total of 77 encounters, with the median (quartile 1, quartile 3) gestational age of the study enrolled at 31.43 (28.14-33.57) weeks. Patients were divided into low-risk (ratio of38) and high-risk (ratio of ≥38) groups. Baseline characteristics of patients did not show any marked differences, including preeclampsia labs or ultrasound parameters, between the 2 groups. Systolic and diastolic blood pressures upon enrollment were statistically elevated when soluble fms-like tyrosine kinase-1 to placental growth factor ratio was ≥38 (P=.02 and P=.01, respectively). Compared to patients with a low ratio, patients with a high ratio had a greater proportion of preeclampsia diagnosis, higher rates of preterm delivery under 34 and 37 weeks gestation, smaller neonatal birthweight, and a shorter time to delivery from testing to delivery.Among patients with fetal growth restriction, the soluble fms-like tyrosine kinase-1 to placental growth factor ratio may serve as a potential biomarker for identifying at risk patients for developing preeclampsia and subsequently preterm delivery.

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.

Cardiogenic shock (CS) may occur during pregnancy and dramatically worsen peripartum outcomes.We analyzed the National Inpatient Sample from 2002 to 2013 to describe the incidence of, risk factors for and outcomes of CS during pregnancy.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.CS during pregnancy occurs more commonly in the postpartum period and is associated with a high mortality.

Preeclampsia-related morbidity and mortality is rising predominantly because of delayed identification of patients at risk for preeclampsia with severe features and associated complications. This study explored the association between angiogenic markers (sFlt1 [soluble fms-like tyrosine kinase-1]) and PlGF [placental growth factor]) and preeclampsia-related peripartum complications. Normotensive women or those with hypertensive disorders of pregnancy were enrolled. Blood samples were collected within 96 hours before delivery, and angiogenic markers were measured on an automated platform. Our study included 681 women, 375 of which had hypertensive disorders. Of these, 127 (33.9%) had severe preeclampsia, and 71.4% were black. Compared with normotensive women, women with severe preeclampsia had higher levels of sFlt1 (9372.5 versus 2857.0 pg/mL; P P P P P valuesP =0.004). This study demonstrates a significant association between an abnormal angiogenic profile before delivery and severe preeclampsia and peripartum complications.

Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hypertension (group C). Blood was drawn and sFlt1 and sEng levels measured using enzyme-linked immunosorbent assay. Comprehensive echocardiograms, including measurement of GLS, were performed on all patients. Overall, GLS was worse in women in group A (preeclampsia) than those in group B or C. Increasing sFlt1 and sEng levels correlated with worsening GLS ( r =0.44 for sFlt1 and r =0.46 for sEng, both P r =0.18 and r =0.22, both P ≤0.01). Increasing levels also correlated with increasing left ventricular mass index, which also remained significant after multivariable analysis ( r =0.20 for sFlt1 and 0.19 for sEng, both P =0.01). Elevated circulating levels of antiangiogenic proteins in HDP correlate with and may contribute to myocardial dysfunction as measured by GLS.

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN71416914.

Angiogenic factors have been implicated in the pathogenesis of preeclampsia. This pilot study explored the association between antenatal blood pressure levels and angiogenic biomarkers (sFlt1 and PlGF) among women with chronic hypertension (cHTN).Blood samples were collected from women with cHTN (with/without superimposed preeclampsia) within 96 h prior to delivery. Subjects were stratified by mean outpatient BP as controlled (cBP 140/90) or uncontrolled (uBP ≥ 140/90). Descriptive statistics were generated and assessed as appropriate. Logistic regression was employed to assess for adverse pregnancy outcomes between groups.Data from seventy-eight women were analyzed, of which 58 (74.4%) were African American. Fifty-six (71.8%) had cBP and 22 (28.2%) had uBP. Use of antepartum outpatient antihypertensive medications was more frequent in patients with uBP (46.4% vs. 13.6%, p = 0.01). Compared to women with cBP, women with uBP had higher levels of pre-delivery sFlt1 and sFlt1/PlGF ratio (sFlt: 4218.5 vs. 3056.0 pg/ml, p = 0.046; sFlt/PlGF: 62.5 vs. 25.0, p = 0.04). Additionally, more uBP patients had superimposed preeclampsia with severe features (54.6% vs. 25.0%; p = 0.01) and preterm delivery (defined as a gestational age35 weeks (40.9% vs. 10.7%; p = 0.002)) than cBP patients. In the multivariable model, women with uBP had greater odds of preterm delivery (OR 6.78; p = 0.01), superimposed preeclampsia (OR 3.20; p = 0.03) and preeclampsia with severe features (OR 3.27; p = 0.04) than women with cBP.In women with cHTN, elevated antepartum BP is associated with worsened outcomes and may be associated with abnormal angiogenic profile at delivery. Larger studies are needed to confirm these findings.

Background Household air pollution (HAP) is associated with adverse pregnancy outcomes. Objectives Investigate impact of in-utero HAP exposure on placental development and chronic hypoxia. Methods Markers of chronic placental hypoxia [Hofbauer cells (HBC), syncytial knots (SK), chorionic vascular density (cVD) and hypoxia-inducible factor (HIF)] were stained by hematoxylin-eosin and/or immunohistochemically in placenta samples collected from firewood −/kerosene-users (A, n = 16), and ethanol-users (B, n = 20) that participated in a randomized controlled intervention trial in Ibadan, Nigeria. A third group of non-smoking and presumed natural gas-using Chicago women (C, n = 12) were included in this exploratory pilot to assess for possible differences in placenta histology between similar racial groups. All patients had uncomplicated pregnancies and delivered at term. Results HBC, SK and cVD were significantly increased among firewood-/kerosene-users compared to ethanol-users and natural gas-using Chicago women (HBC medians 5.5, 3.5, and 2.0, respectively; SK means 55.6, 41.8 and 30.1; cVD means 8.8, 6.2, and 5.2; all p p Conclusions In-utero exposure to HAP is associated with pathologic changes and HIF expression consistent with chronic hypoxia in placenta of firewood/kerosene-users compared to ethanol-users with less HAP exposure and Chicago women with no presumed HAP exposure. Presence of chronic hypoxic signature in placenta of women exposed to HAP has implications for adverse pregnancy complications and future growth and development of the young children. Future larger studies need to focus on HAP exposure and placental disorders like preeclampsia and long-term health impact of in-utero exposure to HAP.

Background The prevalence of hypertensive disorders during pregnancy is high in developing countries such as Haiti, however little is known about postpartum hypertension (PPHTN). Methods This is a prospective study done at Hospital Albert Schweitzer in rural Haiti among pregnant women age 18 or older who were admitted for labor. Blood pressures were collected before and after delivery and medical charts were reviewed to gather delivery characteristics and fetal/neonatal outcomes. Differences between groups are presented based on postpartum blood pressures (BP) as mild PPHTN (systolic BP ≥ 140 or diastolic BP ≥ 90) and severe PPHTN (systolic BP ≥ 160 or diastolic BP ≥ 110). Results Of 175 women, the prevalence of PPHTN during the two-month study period was 57.1% (97/172) and included 56 parturients with mild and 41 with severe PPHTN. Severe PPHTN was associated with a higher proportion of complications including abruption (14.6%), fetal (14.6%) and neonatal death (7.3%). Thirty-nine (69.6%) patients with mild PPHTN and 9 (21.9%) patients with severe PPHTN did not receive any antihypertensive medications postpartum. Patients with severe PPHTN had prolonged hospitalization compared to the normal group (3.5 vs. 2.0 days, p = 0.0003). There was a strong correlation between antepartum and postpartum systolic and diastolic BP’s (r = 0.62 and 0.54, p Conclusion In this study, we identified a high prevalence of PPHTN in rural Haiti. Severe PPHTN was associated with adverse outcomes and treatment is not universal. This data is a starting point to develop region-specific protocols to treat and control PPHTN.

Background Peripartum cardiomyopathy (PPCM) affects young females and mortality occurs after the peripartum period. Hospital readmissions for patients discharged with PPCM are poorly understood. The aim of this study was to evaluate differences in readmission rates, risk factors, and mortality in women with PPCM. Methods We conducted a retrospective cohort analysis using the Healthcare Cost and Utilization Project 2013 National Readmissions Database. From the database, we selected patients with PPCM to include patients discharged between January and November 2013. Readmission rate, mortality rate and risk factors were analyzed. In our cohort of 3800 patients, we found a readmission rate of 15.1% and a mortality rate of 1.6%. Comorbidities associated with readmission were pulmonary hypertension, obesity, renal failure, and drug abuse. Mortality on initial admission was associated with coagulation disorders and respiratory failure. Women who delivered on initial admission had a statistically lower rate of readmission than women who did not deliver on initial admission. Conclusions In a large retrospective nationwide analysis of PPCM patients, we found associated conditions that may help predict which patients will have a higher risk for readmission and mortality.

Background Maternal exposure to ambient air pollution affects placental growth markers. Objectives Investigate impact of household air pollution (HAP) on placental growth markers. Methods Two groups of pregnant women were identified: firewood/kerosene stove-users (A, n = 33) and bioethanol stove-users (B, n = 44) that participated in a randomized control trial in Ibadan, Nigeria. A third group of non-smoking and presumed liquefied petroleum gas-using Chicago women (C, n = 19) were included in this exploratory pilot to assess for possible differences between similar racial groups. Levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) were measured in maternal and cord plasma using ELISA. Results Maternal and cord blood sFlt-1 and PlGF did not differ significantly between women of groups A and B. Nevertheless, both groups differed significantly from the Chicago group in that group A women had lower maternal sFlt-1 (1372.50 vs. 3194.19) but higher PlGF (1607.87 vs. 442.80), and higher cord blood sFlt-1 (2925.02 vs. 107.53) and PlGF (223.68 vs. 6.92), all p ≤ 0.001. Group B showed similar trends (all p ≤ 0.002). Maternal PlGF levels were positively correlated to minutes of HAP exposure when PM 2.5 concentration was above 100 μg/m 3 in Nigerian women. Conclusions Maternal levels of PlGF and cord blood levels of sFlt-1 and PlGF in Nigerian women with varying HAP exposures were significantly higher than Chicago-based women who had no presumed HAP exposure. It suggests that in-utero exposure to HAP influenced levels of angiogenic factors involved in normal placentation and growth and could represent compensation for pollutants exposure to preserve fetal viability.

See related article, pp 469–474 Preeclampsia is a leading cause of morbidity and mortality in mothers particularly in the developing world.1 Sub-Saharan Africa and South Asia collectively account for 86% of global maternal deaths, and a substantial percentage of these deaths is attributed to preeclampsia and related disorders. Historically, preeclampsia had been primarily viewed as medically important because it could presage eclamptic seizures. The word eclampsia derived from the Greek word for lightening refers to the sudden and unpredictable convulsive phase of a form of hypertension specific to preeclampsia. However, in the past century, it became apparent that preeclampsia is a dangerous condition in its own right; not only preconvulsive but also presevere hypertension, pre–HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), prerenal failure, pre-abruption, prefetal death, and prenumerous complications related to the specific disorder, which also affects cardiac and renal health later in life. In developed countries, most women have adequate access to prenatal care and therefore are seen regularly for blood pressure and spot urine protein check. In this setting, if there is a concern for preeclampsia, the patient is usually admitted for frequent monitoring of blood pressures, laboratory work, management of hypertension, administration of betamethasone for fetal lung maturity, and close observation for development of warning signs that may indicate the need for delivery.2 Despite the absence of specific tests to predict complications, this management and treatment plan has resulted in a dramatic reduction of maternal deaths related to preeclampsia, though at the cost of increased rates of …

BACKGROUND Asian American/Pacific Islanders (AAPIs) are the fastest-growing racial group in the United States. Despite a higher socioeconomic status, AAPI women experience higher rates of maternal morbidity and mortality. METHODS Using the National Inpatient Sample, we performed a retrospective cohort analysis of women who were hospitalized for delivery from 2002 to 2013. The primary outcome variable was inpatient mortality rate, and the presence of severe maternal morbidities was estimated using the Bateman Comorbidity Index, a validated tool for predicting obstetric morbidity. RESULTS AAPI women presenting for delivery between 2003 and 2012 were older, more likely to reside in a zip code in the top quartile of annual income, be privately insured than Caucasian women, and less likely to have a higher Bateman Comorbidity Index. However, AAPI women had a higher likelihood of postpartum hemorrhage (3.4% vs 2.7%, P < .001), uterine atony, severe perineal lacerations, and severe maternal morbidities. Procedures such as transfusion, hysterectomy, and mechanical ventilation were also more common in AAPI women. Furthermore, AAPI women had a higher mortality rate that persisted despite adjustment for an apparently higher income and comorbidities (odds ratio 1.72, 95% confidence interval: 1.14-2.59, P = .01). CONCLUSIONS Despite having a higher socioeconomic status, AAPI women had higher rates of maternal mortality during hospitalization for delivery. This increase persisted even after adjustment for factors known to affect peripartum outcomes. Further investigation is needed to better clarify the causes of racial differences in maternal morbidity and mortality.

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 Conclusion: Mean arterial pressure correlates with worsening cardiac function as measured by MPI and serum levels of angiogenic factors. Further studies are needed to evaluate whether a reduction in blood pressure will reverse changes in MPI or reduce levels of angiogenic proteins seen among women with HDP.

This study aimed to investigate the relationship between maternal hypertensive disease and other risk factors and the neonatal development of necrotizing enterocolitis (NEC).This was a retrospective case-control study of infants with NEC from 2008 to 2012. The primary exposure of interest was maternal hypertensive disease, which has been hypothesized to put infants at risk for NEC. Other variables collected included demographics, pregnancy complications, medications and neonatal hospital course. Data were abstracted from medical records.Twenty-eight cases of singleton neonates with NEC and 81 matched controls were identified and analyzed. There was no significant difference in the primary outcome. Fetuses with an antenatal diagnosis of growth restriction were more likely to develop NEC (p = 0.008). Infants with NEC had lower median birth weight than infants without NEC (p = 0.009). Infants with NEC had more late-onset sepsis (p = 0.01) and mortality before discharge (p = 0.001).The factors identified by this case-control study that increased the risk of neonatal NEC included intrauterine growth restriction and lower neonatal birth weight. The primary exposure, hypertensive disease, did not show a significantly increased risk of neonatal NEC; however, there was a nearly two-fold difference observed. Our study was underpowered to detect the observed difference.

To evaluate if placental histopathological changes of vascular insufficiency correlate with circulating angiogenic factors in patients with preeclampsia.Subjects were selected from a previous prospective cohort study of preeclampsia based on the availability of plasma anti-angiogenic factor (sFlt1) and pro-angiogenic factor (PlGF) measurements and placental histology specimens. Preeclamptic patients were divided into two groups based on plasma levels of these factors described as a ratio: anti-angiogenic preeclampsia with sFlt1/PlGF ratio ≥85 and normal angiogenic preeclampsia with sFlt1/PlGF 85. The placental lesions of vascular insufficiency that were studied specifically included atherosis, infarcts, syncytial knots, acute and chronic abruption, hematoma, and fetal thrombosis. The data are shown as median (quartile 1 and quartile 3) or n (%) when appropriate.The anti-angiogenic preeclampsia group (N = 48) presented at an earlier gestational age (weeks) than the normal angiogenic group (N = 28); {32 (28, 34) versus 35 (32, 36), p = 0.002}, had higher systolic blood pressure (mmHg) {154 (147, 168) versus 147 (132, 158), p = 0.02}, delivered early (weeks) {(32 (29, 34) versus 36 (34, 37), p 0.001} and had lower birth weight (grams) {(1550 (1055, 2060) versus 2655 (2285, 3343), p 0.001}. Several pathologic lesions were found significantly more often in the anti-angiogenic preeclampsia group; atherosis {27.7% versus 3.6%, p 0.05}, infarcts {58.3% versus 3.6%, p = 0.002}, and syncytial knots {81.3% versus 39.3%, p 0.001}.Preeclamptic patients with imbalance in circulating angiogenic factors have disproportionally higher rates of placental vascular lesions historically associated with severe disease.

A 23 year-old woman who was 14 weeks pregnant presented with progressive dyspnea. Physical exam was notable for peripheral edema and an intermittent low pitched diastolic murmur. Transthoracic echocardiogram (TTE) revealed a left atrial mass creating moderate functional mitral stenosis (mean