Placental growth factor predicts time to delivery in women with signs or symptoms of early preterm preeclampsia: a prospective multicenter study.

BACKGROUND: There is a robust association between altered angiogenic factor concentrations, which includes placental growth factor and clinically recognized preeclampsia. Alterations in concentrations of angiogenic factors precede the clinical onset of preeclampsia by several weeks. The temporal relationship between the measured angiogenic factors and the time to delivery in women with suspected preeclampsia at <35 weeks gestation, however, remains to be clarified. OBJECTIVE: The purposes of this study were to examine the relationship between placental growth factor and time to delivery in women at <35 weeks gestation with signs or symptoms of preeclampsia and to compare the performance of placental growth factor to other clinical markers for prediction of time to delivery in preeclampsia. STUDY DESIGN: Women with signs or symptoms of preeclampsia between 20.0 and 35.0 weeks gestation were enrolled in a prospective, observational study at 24 centers. Blood was collected at presentation for placental growth factor, and subjects were evaluated and treated according to local protocols. Clinical outcomes were obtained, and all final diagnoses were adjudicated by an independent expert panel according to 2013 American College of Obstetricians and Gynecologists' Hypertension in Pregnancy criteria. Placental growth factor was measured retrospectively on the Alere, Inc, triage platform. A normal placental growth factor was defined as >100 pg/mL; the assay's limit of detection is 12 pg/mL. Two-by-2 tables were constructed for comparison of test outcomes that included negative predictive value; time-to-delivery was analyzed by survival curves and Cox regression. RESULTS: Seven hundred fifty-three subjects were enrolled; 538 (71%) had a final diagnosis of preeclampsia; 542 (72%) delivered at <37 weeks gestation, and 358 (47%) delivered at <34 weeks gestation. Among the 279 women (37%) with a normal placental growth factor at presentation, the negative predictive value for preeclampsia delivered within 14 days or within 7 days was 90% and 93%, respectively. Compared with women with normal placental growth factor, women with placental growth factor ≤100 pg/mL have a hazard ratio of 7.17 (confidence interval, 5.08-10.13) in Cox regression for time to delivery after adjustment for both gestational age at enrollment and the final diagnosis of preeclampsia. The placental growth factor levels of normal (>100 pg/mL), low (12-100 pg/mL), and very low (<12 pg/mL) have well-separated distributions of time to delivery, with median values of 45, 10, and 2 days, respectively. Subjects with placental growth factor ≤100 pg/mL have a perinatal death rate of 5.7% and a small-for-gestational-age rate of 51.7%; subjects with placental growth factor >100 pg/mL have a perinatal death rate of 0% (no observations in this cohort) and an a small-for-gestational-age rate of 16.8%. CONCLUSION: In women with suspected preeclampsia at <35.0 weeks gestation, a low placental growth factor was correlated strongly with preterm delivery independent of a diagnosis of preeclampsia or gestational age at presentation, whereas a normal placental growth factor was associated with pregnancy prolongation, even in patients who ultimately had a final diagnosis of preeclampsia. This suggests that placental growth factor levels are superior to clinical markers in the prediction of adverse pregnancy in women with suspected preeclampsia.

National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period.

Complications arising from hypertensive disorders of pregnancy are among the leading causes of preventable severe maternal morbidity and mortality. Timely and appropriate treatment has the potential to significantly reduce hypertension-related complications. To assist health care providers in achieving this goal, this patient safety bundle provides guidance to coordinate and standardize the care provided to women with severe hypertension during pregnancy and the postpartum period. This is one of several patient safety bundles developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. These safety bundles outline critical clinical practices that should be implemented in every maternity care setting. Similar to other bundles that have been developed and promoted by the Partnership, the hypertension safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. This commentary provides information to assist with bundle implementation.

Controversial clinical practices for patients with preeclampsia or HELLP syndrome: a survey.

BACKGROUND: Considerable controversy continues to surround the management of severe preeclampsia and HELLP syndrome. Experts, researchers, and those published in the field were surveyed about their specific practices. MATERIALS AND METHODS: An extensive literature search was undertaken to identify the cohort of authors with recent publications on the subjects of preeclampsia (2009-2012) and HELLP syndrome (2005-2012). Online surveys were sent to all authors using the email addresses found in their publications. RESULTS: Surveys were delivered by email to 363 authors of preeclampsia publications and 91 authors of HELLP syndrome publications. Completed surveys were received from 61 (13.4%) of the group. Except for consensus about the indication of corticosteroids for the enhancement of fetal lung maturation, there was considerable variation in corticosteroid practice and anesthesia techniques. CONCLUSIONS: A marked diversity in practice characterized the clinical care rendered by experts in the field of preeclampsia and HELLP syndrome. Thus, there is an urgent need for well-designed and executed prospective clinical trials to improve the evidence for best consensus practice in this area of obstetrical medicine.

Progesterone supplementation attenuates hypertension and the autoantibody to the angiotensin II type I receptor in response to elevated interleukin-6 during pregnancy.

OBJECTIVE: Preeclampsia is a multisystem disorder recognized as hypertension with proteinuria developing >20 weeks' gestation. Preeclampsia is associated with chronic immune activation characterized by increased T and B lymphocytes, cytokines, and antibodies activating the angiotensin II type I receptor (AT1-AA). Hypertension in response to elevated interleukin (IL)-6 during pregnancy occurs with increased renin activity and AT1-AA, and reduced kidney function. STUDY DESIGN: We aim to determine whether 17-alpha-hydroxyprogesterone caproate (17-OHPC), progesterone, improved inflammatory pathways during elevated IL-6 in pregnant rats. IL-6 (5 ng/d) was infused via miniosmotic pumps into normal pregnant (NP) rats beginning on day 14 of gestation and 17-OHPC (3.32 mg/kg) was diluted in normal saline and injected on day 18. Blood pressure (mean arterial pressure [MAP]) determination and serum collection were performed on day 19 of gestation. RESULTS: MAP in NP was 100 ± 3 mm Hg, which increased with IL-6 to 112 ± 4 mm Hg (P < .05). Pregnant rats given 17-OHPC alone had a MAP of 99 ± 3 mm Hg and MAP increased to 103 ± 2 mm Hg in IL-6+17-OHPC. AT1-AA was 1.2 ± 0.5 bpm in NP rats, increased to 17 ± 9 bpm with IL-6 infusion but administration of 17-OHPC significantly blunted AT1-AA to 4 ± 0.8 bpm in NP+IL-6+17-OHPC. Total circulating nitrate/nitrite was significantly decreased and placental Ser(1177)-phosporylated-eNOS/eNOS was lowered with IL-6 infusion. Supplementation of 17-OHPC significantly improved placental Ser(1177)-phosporylated-eNOS/eNOS however, circulating nitrate/nitrite was unchanged with 17-OHPC supplementation. CONCLUSION: This study illustrates that 17-OHPC attenuated hypertension, decreased AT1-AA activity, and improved placental nitric oxide in response to elevated IL-6 during pregnancy and could lend hope to a new potential therapeutic for preeclampsia.

Management of preeclampsia when diagnosed between 34-37 weeks gestation: deliver now or deliberate until 37 weeks?

OBJECTIVE: To evaluate maternal-newborn outcomes with immediate or expectantly managed preeclampsia first diagnosed at 34-37 weeks. METHODS: Late preterm patients with preeclampsia without severe features were randomly assigned to immediate delivery (n=94) or expectant management (n = 75) until 37 weeks gestation or earlier if severe features developed. Data were analyzed by appropriate tests for continuous or categorical outcomes with differences considered significant if p < 0.05. RESULTS: The two groups were similar at presentation. 41% of those expectantly managed developed severe features of preeclampsia within 72 hours versus 3% in the immediately delivered group (p < 0.001). Immediate delivery did not significantly increase cesarean delivery or neonatal morbidity. CONCLUSION: Immediate delivery of the late preterm patient with preeclampsia significantly lessens her development of severe features without significantly increasing newborn risks. For the expectantly managed late preterm patient with preeclampsia, close surveillance for the first 72 hours following diagnosis and twice weekly thereafter appears prudent.

Seeking the mechanism(s) of action for corticosteroids in HELLP syndrome: SMASH study.

INTRODUCTION: Administration of dexamethasone to the hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome patients (10 mg intravenously [IV] every 12 hours) shortens the disease course and reduces maternal morbidity in patients treated at the University of Mississippi Medical Center (UMMC), associated with this severe form of preeclampsia. However, the pathophysiological mechanisms involved with this intervention remain unclear. OBJECTIVE: We sought to investigate the potential role of IV dexamethasone to restore the imbalance among antiangiogenic and inflammatory factors known to be significantly elevated in women with HELLP syndrome. STUDY DESIGN: This was a single-center prospective study of women diagnosed with HELLP syndrome who were treated for IV dexamethasone at UMMC. Blood was drawn prior to dexamethasone administration and again 12 and 24 hours after the initial dexamethasone administration. Enzyme-linked immune assays were used to measure circulating inflammatory cytokines and antiangiogenic factors. A repeated-measures analysis of variance was used to analyze the data collected before, after, and during dexamethasone administration. RESULTS: Seventeen women with HELLP syndrome were enrolled in this study. Dexamethasone significantly decreased evidence of hemolysis (P = .002) and liver enzymes (P = .003), and significantly increased platelets (P = .0001) within 24 hours of administration. Circulating interleukin-6 levels after 24 hours were decreased (P < .001); soluble fms-like tyrosine kinase-1 and soluble endoglin were also significantly decreased by 24 hours after dexamethasone administration (P < .002 and P < .004, respectively). There were no significant differences in circulating levels of placental growth factor (P = .886) due to dexamethasone administration. Angiotensin II receptor autoantibody levels were unchanged by dexamethasone administration. CONCLUSION: We conclude that 1 important mechanism of dexamethasone administration is to blunt the release of both antiangiogenic and inflammatory factors suggested to play role in the pathophysiology of HELLP syndrome.

Posterior reversible encephalopathy syndrome in 46 of 47 patients with eclampsia.

OBJECTIVE: We sought to investigate the concurrence of posterior reversible encephalopathy syndrome (PRES) with eclampsia and to describe the obstetric, radiological, and critical care correlates. STUDY DESIGN: This was a single-center, 2001-2010 retrospective cohort study of all patients with eclampsia who underwent neuroimaging via magnetic resonance imaging (MRI) or computerized tomography (CT) with or without contrast. RESULTS: Forty-six of 47 of eclamptic patients (97.9%) revealed PRES on neuroimaging using 1 or more modalities: MRI without contrast, 41 (87.2%); MRI with contrast, 27 (57.4%); CT without contrast, 16 (34%); CT with contrast, 7 (14.8%); and/or magnetic resonance angiography/magnetic resonance venography, 2 (4.3%). PRES was identified within the parietal, occipital, frontal, temporal, and basal ganglia/brainstem/cerebellum areas of the brain. Eclampsia occurred antepartum in 23 patients and postpartum in 24 patients. Headache was the most common presenting symptom (87.2%) followed by altered mental status (51.1%), visual disturbances (34%), and nausea/vomiting (19.1%). Severe systolic hypertension was present in 22 patients (47%). CONCLUSION: The common finding of PRES in patients with eclampsia suggests that PRES is a core component of the pathogenesis of eclampsia. Therapy targeted at prevention or reversal of PRES pathogenesis may prevent or facilitate recovery from eclampsia.

Putting the "M" back in maternal-fetal medicine.

Although maternal death remains rare in the United States, the rate has not decreased for 3 decades. The rate of severe maternal morbidity, a more prevalent problem, is also rising. Rise in maternal age, in rates of obesity, and in cesarean deliveries as well as more pregnant women with chronic medical conditions all contribute to maternal mortality and morbidity in the United States. We believe it is the responsibility of maternal-fetal medicine (MFM) subspecialists to lead a national effort to decrease maternal mortality and morbidity. In doing so, we hope to reestablish the vital role of MFM subspecialists to take the lead in the performance and coordination of care in complicated obstetrical cases. This article will summarize our initial recommendations to enhance MFM education and training, to establish national standards to improve maternal care and management, and to address critical research gaps in maternal medicine.

Postpartum thrombotic microangiopathic syndrome.

OBJECTIVE: Characterization of syndromes for patients with life-threatening, progressively worsening hemolysis-elevated-liver-enzymes-and-platelet (HELLP) syndrome-like diseases and with thrombotic microangiopathies. RETROSPECTIVE STUDY DESIGN: Patients who underwent postpartum plasma-exchange (PPEX) for preeclampsia-related, and microangiopathy/coagulopathy illnesses unresponsive to medical therapy between 1994 and 2008 in our center and elsewhere. RESULTS: Nine patients were treated with PPEX in our center with 78% maternal survival. Treatment with PPEX increased platelet levels (p=0.048), decreased serum lactic dehydrogenase (p=0.0012) and aspartate aminotransferase (p=0.0001). CONCLUSION: Nineteen patients from publications combined with our patients suggest five categories of postpartum thrombotic microangiopathy syndrome that exhibit HELLP syndrome criteria and respond to PPEX.

Hypertension in response to CD4(+) T cells from reduced uterine perfusion pregnant rats is associated with activation of the endothelin-1 system.

We have shown that adoptive transfer of CD4(+) T cells from placental ischemia (reduction in uteroplacental perfusion, RUPP) rats causes hypertension and elevated inflammatory cytokines during pregnancy. In this study we tested the hypothesis that adoptive transfer of RUPP CD4(+) T cells was associated with endothelin-1 activation as a mechanism to increase blood pressure during pregnancy. CD4(+) T cells from RUPP or normal pregnant (NP) rats were adoptively transferred into NP rats on gestational day 13. Mean arterial pressure (MAP) was analyzed on gestational day 19, and tissues were collected for endothelin-1 analysis. MAP increased in placental ischemic RUPP rats versus NP rats (124.1 ± 3 vs. 96.2 ± 3 mmHg; P = 0.0001) and increased in NP recipients of RUPP CD4(+) T cells (117.8 ± 2 mmHg; P = 0.001 compared with NP). Adoptive transfer of RUPP CD4(+) T cells increased placental preproendothelin-1 mRNA 2.1-fold compared with NP CD4(+) T cell rats and 1.7-fold compared with NP. Endothelin-1 secretion from endothelial cells exposed to NP rat serum was 52.2 ± 1.9 pg·mg(-1)·ml(-1), 77.5 ± 4.3 pg·mg(-1)·ml(-1) with RUPP rat serum (P = 0.0003); 47.2 ± .16 pg·mg(-1)·ml(-1) with NP+NP CD4(+) T cell serum, and 62.2 ± 2.1 pg·mg(-1)·ml(-1) with NP+RUPP CD4(+) T cell serum (P = 0.002). To test the role of endothelin-1 in RUPP CD4(+) T cell-induced hypertension, pregnant rats were treated with an endothelin A (ET(A)) receptor antagonist (ABT-627, 5 mg/kg) via drinking water. MAP was 92 ± 2 mmHg in NP+ET(A) blockade and 108 ± 3 mmHg in RUPP+ET(A) blockade; 95 ± 5 mmHg in NP+NP CD4(+) T cells+ET(A) blockade and 102 ± 2 mmHg in NP+RUPP CD4(+) T cells+ET(A) blockade. These data indicate the importance of endothelin-1 activation to cause hypertension via chronic exposure to activated CD4(+) T cells in response to placental ischemia.

IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy.

Preeclampsia is associated with autoimmune cells T(H)17, secreting interleukin-17, autoantibodies activating the angiotensin II type I receptor (AT1-AA), and placental oxidative stress (ROS). The objective of our study was to determine whether chronic IL-17 increases blood pressure by stimulating ROS and AT1-AAs during pregnancy. To answer this question four groups of rats were examined: normal pregnant (NP, n = 20), NP+IL-17 (n = 12), NP+tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) (n = 7) (a superoxide dismutase mimetic that scavenges ROS), and NP+IL-17+tempol (n = 11). IL-17 (150 pg/day) was infused into NP rats while tempol was administered via the drinking water ad libitum. On day 19 blood pressure (MAP) was recorded, and plasma, urine, and tissue were collected for isolation of ROS detected by chemilluminescent technique. Urinary isoprostane was measured by ELISA. AT1-AAs were determined via cardiomyocyte assay and expressed as beats per minute. MAP increased from 98 ± 3 mmHg in NP to 123 ± 3 mmHg in IL-17-infused NP rats. Urinary isoprostane increased from 1,029 ± 1 in NP to 3,526 ± 2 pg·mg(-1)·day(-1) in IL-17-infused rats (P < 0.05). Placental ROS was 436 ± 4 RLU·ml(-1)·min(-1) (n = 4) in NP and 702 ± 5 (n = 5) RLU·ml(-1)·min(-1) in IL-17-treated rats. Importantly, AT1-AA increased from 0.41 ± 0.05 beats/min in NP rats (n = 8) to 18.4 ± 1 beats/min in IL-17 rats (n = 12). Administration of tempol attenuated the hypertension (101 ± 3 mmHg) ROS (459 ± 5 RLU·ml(-1)·min(-1)) and blunted AT1-AAs (7.3 ± 0.6 beats/min) in NP+IL-17+tempol-treated rats. Additionally, AT1 receptor blockade inhibited IL-17-induced hypertension and placental oxidative stress. MAP was 105 ± 5 mmHg and ROS was 418 ± 5 RLU·ml(-1)·min(-1) in NP+IL 17-treated with losartan. These data indicate that IL-17 causes placental oxidative stress, which serves as stimulus modulating AT1-AAs that may play an important role in mediating IL-17-induced hypertension during pregnancy.

Activating autoantibodies to the angiotensin II type I receptor play an important role in mediating hypertension in response to adoptive transfer of CD4+ T lymphocytes from placental ischemic rats.

Hypertension in rats with chronic placental ischemia (reduced uterine perfusion pressure, RUPP) is associated with elevated inflammatory cytokines, agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and CD4(+) T cells; all of which are elevated in preclamptic women. Additionally, we have shown that adoptive transfer of RUPP CD4(+) T cells increases blood pressure, inflammatory cytokines, and sFlt-1. The objective of this study was to determine the long-term effects of RUPP CD4(+) T cells on AT1-AA, renal and systemic hemodynamics in pregnant rats. To answer this question CD4(+) T splenocytes were magnetically isolated on day 19 of gestation from control RUPP and normal pregnant (NP) rats and injected into a new group of NP rats at day 13 of gestation. On day 19 of gestation mean arterial pressure (MAP) and renal function (glomerular filtration rates, GFR) were analyzed and serum collected for AT1-AA analysis. To determine a role for AT1-AA to mediate RUPP CD4(+) T cell-induced blood pressure increases, MAP was analyzed in a second group of rats treated with AT1 receptor blockade losartan (10 mg·kg(-1)·day(-1)) and in a third group of rats treated with rituximab, a B cell-depleting agent (250 mg/kg) we have shown previously to decrease AT1-AA production in RUPP rats. MAP increased from 101 ± 2 mmHg NP to 126 ± 2 mmHg in RUPP rats (P < 0.001) and to 123 ± 1 mmHg in NP rats injected with RUPP CD4(+) T cells (NP+RUPP CD4(+)T cells) (P < 0.001). Furthermore, GFR decreased from 2.2 ml/min (n = 7) in NP rats to 1.0 ml/min (n = 5) NP+RUPP CD4(+)T cell. Circulating AT1-AA increased from 0.22 ± 0.1 units in NP rats to 13 ± 0.7 (P < 0.001) units in NP+RUPP CD4(+)T cell-treated rats but decreased to 8.34 ± 1 beats/min in NP+RUPP CD4(+) T cells chronically treated with rituximab. Hypertension in NP+RUPP CD4(+)T cell group was attenuated by losartan (102 ± 4 mmHg) and with B cell depletion (101 ± 5 mmHg). Therefore, we conclude that one mechanism of hypertension in response to CD4(+) T lymphocytes activated during placental ischemia is via AT1 receptor activation, potentially via AT1-AA during pregnancy.

Immediate postpartum management of patients with severe hypertensive disorders of pregnancy: pathophysiology guiding practice.

Developing clinically-focused evidence and experience-based approaches to improve maternity care is a national priority. Safety and quality collaborative initiatives related to management of hypertensive disorders of pregnancy are vital in the implementation of improved care. We reviewed the obstetric literature to construct a concise summary of the core pathophysiologic issues, practice principles and clinical interventions which are foundational for physicians providing immediate postpartum care for patients with severe pregnancy-related hypertension (including those with eclampsia, HELLP syndrome, and superimposed preeclampsia inclusive of those with gestational hypertension that develop severe range blood pressures). While based largely upon the American College of Obstetrics and Gynecology (ACOG) Hypertension Task Force Guidelines released in 2013 as well as updated 2018 guidelines set forth by ACOG for hypertensive disorders of pregnancy, this summary goes beyond the basic safety bundles for hypertension management and lays a pathophysiologic foundation for the immediate postpartum care of patients with severe hypertensive disorders of pregnancy.

Endothelin type A receptor antagonist attenuates placental ischemia-induced hypertension and uterine vascular resistance.

OBJECTIVE: We sought to determine the effect of an endothelin type A receptor antagonist (ETA) on uterine artery resistive index (UARI) and mean arterial pressure (MAP) in a placental ischemia rat model of preeclampsia produced by reduction in uterine perfusion pressure (RUPP). STUDY DESIGN: UARI was assessed by Doppler velocimetry in RUPP and normal pregnant controls (NP) on gestational days (GD) 12, 15, and 18. UARI was also determined on GD 18 in NP and RUPP pregnant dams after pretreatment with ETA. MAP was recorded on GD 19. RESULTS: The RUPP group had a higher MAP and UARI on GD 15 and 18 than the NP group. Pretreatment with ETA attenuated both the MAP and GD-18 UARI in the RUPP group without affecting these parameters in the NP group. CONCLUSION: The improvement in UARI could be one potential mechanism for the reduction in MAP in response to ETA in pregnant dams with ischemic placentas.

HELLP syndrome with and without eclampsia.

We assessed pregnancy outcomes for patients with HELLP syndrome (hemolysis; elevated liver enzymes; low platelet count) with and without concurrent eclampsia. We performed a retrospective investigation of data spanning three decades of patients with class 1 or 2 HELLP syndrome with concurrent eclampsia (HELLP + E) and patients with HELLP syndrome without eclampsia. Data were analyzed by appropriate tests for continuous or categorical outcomes with differences considered significant if P < 0.05. During 1981 to 1996 and 2000 to 2006, there were 693 patients with class 1 or 2 HELLP syndrome; altogether, 70 patients had HELLP + E. The only demographic difference was greater nulliparity in HELLP + E patients. Otherwise, inconsistent and clinically insignificant differences were observed between groups. Despite the relatively large size of the study groups, we were unable to detect a significant worsening of maternal or perinatal outcome in HELLP + E patients compared with HELLP patients. In our experience, eclampsia does not appear to contribute a significant adverse impact upon the course or outcome of HELLP syndrome pregnancies.

Preterm parturition and pre-eclampsia: The confluence of two great gestational syndromes.

BACKGROUND: Preterm birth (PTB) and pre-eclampsia independently, and frequently concurrently, adversely affect the pregnancy outcomes of millions of mothers and infants worldwide each year. OBJECTIVES: To fill the gap between PTB and pre-eclampsia, which continue to constitute the two most important current global challenges to maternal and perinatal health. METHODS: Pubmed, Embase, and Cochrane databases were searched from inception until December 2019 using the terms spontaneous PTB (SPTB), indicated preterm delivery (IPTD), early-onset pre-eclampsia, and pre-eclampsia. RESULTS: History of PTB and pre-eclampsia were the strongest risk factors contributing to the occurrence of SPTB or IPTB. The risk of PTB and pre-eclampsia among non-Hispanic African American women was higher than the rate among all other racial/ethnic groups in the United States. Low-dose aspirin (LDA) has been reported to reduce the risk of pre-eclampsia by at least 10% and PTB by at least 14%. Lastly, women and their fetuses who develop early-onset pre-eclampsia are at higher risk for developing hypertension and cardiovascular disease later in life. CONCLUSIONS: While better clarity is needed, efforts to coordinate prevention of both PTB and pre-eclampsia, even though imperfect, are critically important as part of any program to make motherhood as safe as possible.

Acute kidney injury associated with preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

OBJECTIVE: To determine the prevalence of acute kidney injury (AKI), placental abruption and postpartum hemorrhage in patients with preeclampsia or HELLP syndrome. STUDY DESIGN: A retrospective study of patients with preeclampsia or HELLP syndrome treated at the University of Mississippi Medical Center from January 2000 through December 2010. MAIN OUTCOME MEASURES: Relationships among the obstetric complications of placental abruption, postpartum hemorrhage, and AKI (serum creatinine >107 µmol/L) of women with preeclampsia or HELLP syndrome. Additional analysis was undertaken to explore if there was a correlation between postpartum hemorrhage/placental abruption and the severity of HELLP syndrome according to the Mississippi classification system. RESULTS: Data from 1276 women over 11 years were included in the analysis. 67 of 466 patients (14.4%) with HELLP syndrome and 38 of 810 preeclampsia patients (4.7%) met criteria for AKI. Women with either placental abruption or postpartum hemorrhage had statistically significant increased odds of also having AKI (p < 0.01). Women with HELLP and AKI were also more likely to experience either placental abruption or postpartum hemorrhage. Women with Class 1 HELLP with placental abruption or postpartum hemorrhage were also more likely to have AKI than women with preeclampsia. CONCLUSION: HELLP syndrome, AKI and placental abruption or postpartum hemorrhage appear to be interrelated. AKI occurs more frequently in women with HELLP syndrome with or without associated postpartum hemorrhage and placental abruption.

17-Hydroxyprogesterone blunts the hypertensive response associated with reductions in uterine perfusion pressure in pregnant rats.

OBJECTIVE: Reduction in uteroplacental perfusion (RUPP) in pregnant rats is associated with hypertension, elevated cytokines, and activation of the endothelin (ET-1) system. Our objective was to determine whether the antiinflammatory properties of 17-alpha-hydroxyprogesterone caproate (17 OHP) reduce cytokine-stimulated vasoactive pathways that are associated with hypertension in response to placental ischemia. STUDY DESIGN: Mean arterial pressure (MAP), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and renal ET-1 were measured in the following: pregnant controls, pregnant controls plus 17 OHP (6.6 mg/kg), RUPP rats, and RUPP rats plus 17 OHP. RESULTS: MAP increased 29 mm Hg in RUPP rats compared with pregnant controls (P < .001), whereas in RUPP plus 17 OHP rats, MAP increased only 19 mm Hg (P < .05). TNF-alpha and IL-6 increased 2- to 3-fold, respectively, in response to placental ischemia but was normalized in RUPP rats treated with 17 OHP. ET-1 increased 3-fold in RUPP rats but was markedly less in RUPP plus 17 OHP rats. CONCLUSION: 17 OHP blunts hypertension associated with RUPP, possibly via suppression of cytokine-stimulated ET-1 activation.