Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation.

Hemochorial placentation involves the differentiation of invasive trophoblast cells, specialized cells that possess the capacity to exit the placenta and invade into the uterus where they restructure the vasculature. Invasive trophoblast cells arise from a well-defined compartment within the placenta, referred to as the junctional zone in rat and the extravillous trophoblast cell column in human. In this study, we investigated roles for AKT1, a serine/threonine kinase, in placental development using a genome-edited/loss-of-function rat model. Disruption of AKT1 resulted in placental, fetal and postnatal growth restriction. Forkhead box O4 (Foxo4), which encodes a transcription factor and known AKT substrate, was abundantly expressed in the junctional zone and in invasive trophoblast cells of the rat placentation site. Foxo4 gene disruption using genome editing resulted in placentomegaly, including an enlarged junctional zone. AKT1 and FOXO4 regulate the expression of many of the same transcripts expressed by trophoblast cells, but in opposite directions. In summary, we have identified AKT1 and FOXO4 as part of a regulatory network that reciprocally controls critical indices of hemochorial placenta development.

The cerebroplacental ratio and prediction of fetal growth restriction in twin pregnancies.

OBJECTIVES: The cerebroplacental ratio (CPR) represents the relationship between blood flow in the placenta and blood flow in the fetal brain. A low CPR in the third trimester has been associated with poor perinatal outcomes in both singleton and twin gestations. This study aimed to evaluate whether low CPR defined or high CPR discordance at 20-24 weeks in twin pregnancies is associated with an increased risk of fetal growth restriction (FGR) in the third trimester. METHODS: A total of 247 twin pregnancies were included in this retrospective cohort study. Monoamniotic monochorionic twins were excluded. An abnormal CPR was defined as one or both CPR <5%-ile or CPR discordance between fetuses >20%. FGR was evaluated using the last growth measurement performed between 28 and 36 weeks. RESULTS: Of the candidates for study, 177 twin pregnancies had normal CPRs and 70 twin pregnancies had abnormal CPRs. Maternal demographics were similar between groups. There was no difference in the risk of selective FGR, FGR of both twins, or growth discordance >20% in the third trimester between twin pregnancies with normal vs. abnormal CPRs at 20-24 weeks. The adjusted odds ratio for any growth disturbance was 1.00 (95% CI 0.56-1.79). CONCLUSIONS: This study suggests that FGR in twins may be the consequence of numerous maternal, fetal, and placental factors, and not fully explained by redistribution of blood flow or adaptive hypoxia in the mid-trimester.

Racial and Ethnic Differences in Urine Drug Screening on Labor and Delivery.

INTRODUCTION: This study evaluates racial and ethnic differences in urine drug screening and patient consent to urine drug screening at a single tertiary care center. METHODS: We conducted a retrospective cohort study of all deliveries at a single tertiary care center from January 1, 2015 to December 31, 2019. Medical records were queried for demographic data, performance of urine drug screening, commonly used diagnoses that prompted screening, documentation of patient consent, and result of screen. Associations between these outcomes were then assessed using Chi-square analysis and logistic regression. RESULTS: During the study period, 685 of 9953 (6.9%) of patients had a urine drug screen performed. Non-Hispanic Black patients comprised 33.6% of patients receiving screening, but only 16.6% of the total population. Of examined indications for urine drug screening, only insufficient prenatal care and trauma differed significantly between groups. After adjusting for commonly used diagnoses prompting screening, non-Hispanic black patients were significantly more likely to have urine drug screening performed (OR 2.0, 95% CI 1.6-2.4). Non-Hispanic Black and Hispanic patients were not significantly more likely to have a positive screen result when compared to Non-Hispanic White patients. Consent to urine drug screening was poorly documented (only 11.7% of patients had documented consent). This did not differ significantly between the major racial or ethnic groups. CONCLUSION: Non-Hispanic Black and Hispanic patients experience differences in urine drug screening during admission for delivery that cannot be solely explained by differences in incidence of diagnoses that typically trigger screening. Documentation of patient consent to urine drug screening is poor.

Do patients with a short cervix, with or without an ultrasound-indicated cerclage, have an increased risk for a small for gestational age newborn?

INTRODUCTION: Mothers with a short cervix have been shown to have increased risk of spontaneous preterm delivery (PTD) and newborn morbidity. Those who require an ultrasound-indicated cerclage experience the highest rates of morbidity. Inflammation has been linked to a short cervix, and it has been linked to pregnancies affected by small for gestational age (SGA) newborns. To date, there are no studies that have investigated an association between a short cervix, with or without an ultrasound-indicated cerclage, and a SGA newborn. METHODS: This was a case-control study examining all pregnancies with a transvaginal cervical length <25 mm found at their second trimester anatomy scan. Cases were subdivided into those who received an ultrasound-indicated cerclage (Group 1, n = 52) and those who did not (Group 2, n = 139). Controls were defined as pregnancies with a transvaginal cervical length >25 mm with no cerclage (Group 3, n = 186) whose due date was within 2 months of the case pregnancy. Each short cervix case was matched with a control from group 3 in a 1:1 ratio. The primary outcome was birthweight <10% (SGA). Unadjusted data was analyzed with simple odds ratios. A logistic regression was used to control for confounding variables and provide an adjusted odds ratios (aOR). RESULTS: The incidence of SGA among cases overall (group 1 + group 2) was 13.6% (26/191). In group 3, the SGA incidence was 4.3% (8/186). The adjusted odds ratio (aOR) for a SGA infant was significant, 2.8 (95% CI 1.2, 6.6). Subgroup analysis showed that Group 1 had an increased risk for an SGA infant [aOR 4.9 (95% CI 1.8, 13.7)], but Group 2 did not show a significant finding [aOR 2.3 (95% CI 0.9, 5.7)]. CONCLUSION: Pregnancies complicated by a short cervical length <25mm, with or without a cerclage, were associated with an increased risk for a SGA newborn. Most of this significance was due to the pregnancies which received an ultrasound-indicated cerclage for a mid-trimester short cervix.

Second trimester cerebroplacental ratio versus umbilicocerebral ratio for the prediction of adverse perinatal outcomes.

INTRODUCTION: An abnormal third trimester cerebroplacental ratio has been previously associated with adverse perinatal outcome. The less studied inverse of the cerebroplacental ratio, the umbilicocerebral ratio, has been proposed as a better predictor of adverse perinatal outcome. However, little is known about the implication of either an abnormal cerebroplacental ratio or umbilicocerebral ratio in the second trimester. The objective of this study was to evaluate the relationship between an abnormal second trimester cerebroplacental ratio and adverse perinatal outcome and provide comparison to an abnormal second trimester umbilicocerebral ratio. MATERIALS AND METHODS: This retrospective cohort study in a single tertiary referral center utilized data from all non-anomalous singleton pregnancies that underwent Doppler assessment of the cerebroplacental ratio between 20 and 28 weeks gestation. The study period was 1 January 2015 to 31 July 2018. Abnormal cerebroplacental ratio was defined as less than the 5th percentile for gestational age. If patients had more than one ultrasound during the study period (i.e. for serial assessment of fetal growth), the lowest value of the cerebroplacental ratio was recorded. The primary outcome was a composite of clinically relevant adverse perinatal outcomes including preterm delivery, small for gestational age, and neonatal intensive care unit admission. Secondary outcomes included urgent delivery for fetal distress (operative vaginal delivery or cesarean section) and hypertensive disorders of pregnancy. An abnormal umbilicocerebral ratio was defined as greater than 95th percentile for gestational age. Areas under the curve were calculated and compared for cerebroplacental ratio and umbilicocerebral ratio. RESULTS: 2326 pregnancies met inclusion criteria. Of these, 91 (3.9%) had an abnormal second trimester cerebroplacental ratio. Fetuses with an abnormal second trimester cerebroplacental ratio had a 2.3-fold (95% CI 1.5-3.6, p < .05) increased risk of adverse perinatal outcome after adjusting for potential confounders such as chronic hypertension, pregestational diabetes, and smoking during pregnancy. Significantly increased risks of preterm delivery (OR 2.0, 95% CI 1.1-38, p < .05) and neonatal intensive care unit admission (OR 2.1, 95% CI 1.2-3.6, p < .05) were also seen in a subgroup analysis of abnormal cerebroplacental ratio in appropriate for gestational age infants. 132 (5.7%) fetuses had an abnormal second trimester umbilicocerebral ratio, and these fetuses had a 2.0-fold (95% CI 1.4-3.0, p < .05) increased risk of adverse perinatal outcome. The area under the curve for CPR and UCR for prediction of the primary outcome was 0.6 for both (95% CI 0.57-0.61 and 0.57-0.62, respectively, both p < .05). CONCLUSION: An abnormal second trimester cerebroplacental ratio or umbilicocerebral ratio is associated with adverse perinatal outcome. However, the predictive ability of either ratio remains suboptimal.

Left ventricular assist device in pregnancy: Case report and review of the literature.

Left ventricular assist devices have emerged as a safe and effective therapy for end-stage heart failure patients. However, little is known about the safety of these devices during pregnancy. We describe a 23-year-old woman who received a left ventricular device for nonischemic cardiomyopathy of uncertain origin. She became pregnant approximately 1 year later. With close monitoring of her hemodynamic parameters, she was able to achieve a gestational age of 34 weeks, at which time she delivered a healthy male infant by cesarean delivery. Pregnancies in women with left ventricular assist devices may be successful, but remain medically challenging and complex pregnancies. Close multidisciplinary involvement and frequent assessment of device parameters during pregnancy is warranted.

Exposure to placental insufficiency alters postnatal growth trajectory in extremely low birth weight infants.

Growth in the immediate postnatal period for extremely low birth weight (ELBW, birth weight < 1000 g) infants is an important topic in neonatal medicine. The goal is to ensure adequate postnatal growth and to minimize complications resulting from suboptimal growth. Past efforts have focused on postnatal nutrition as well as on minimizing comorbidities. It has not been systematically assessed whether antenatal factors play a role in postnatal growth. In this report, we conducted a retrospective study on 91 maternal-neonatal pairs. We prospectively collected maternal and neonatal demographic data, neonatal nutrition in the first 7 days of life and after enteral nutrition is fully established, comorbidity data, as well as weight data from birth to 50 weeks corrected gestational age. We developed a linear mixed-effects model to examine the role of placental insufficiency, as defined by fetal Doppler studies, in postnatal weight z-score trajectory over time in the ELBW population. We relied on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for model selection. Interestingly, the selected model included a quadratic term of time and a placental insufficiency-by-time interaction term. In a covariate analysis, AIC and BIC both favored a model that included calories intake in the first 7 days of life and the total duration of antibiotics as fixed-effects, but not their interaction terms with time. Overall, we demonstrated for the first time that placental insufficiency, an antenatal factor, is a major determinant of postnatal weight trajectory in the ELBW population. Prospective studies are warranted to confirm our findings.

Eculizumab Maintenance and the Prevention of Atypical Hemolytic Uremic Syndrome Relapse During Pregnancy: A Case Report.

Atypical hemolytic uremic syndrome is a thrombotic microangiopathy that can cause life-threatening anemia, thrombocytopenia, and acute renal failure. When triggered during pregnancy or the acute postpartum period, the disease is referred to as pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS). Women who suffer P-aHUS may later want to consider future pregnancy. These patients are at high, though not well-estimated, risk of relapse. Eculizumab, a monoclonal antibody against complement 5 (C5), has been highly successful in treating acute attacks of P-aHUS, but little is known about the effectiveness of eculizumab maintenance therapy throughout pregnancy. In this case report, we present a woman whose first pregnancy was complicated by severe P-aHUS. In her next pregnancy, she was maintained on eculizumab. She delivered a healthy infant at term and had no recurrences of P-aHUS during the pregnancy or in the postpartum period.

Maternal/Perinatal Outcome in Women with Sickle Cell Disease: A Comparison of Two Time Periods.

OBJECTIVE: To compare pregnancy outcomes in women with sickle cell disease from recent deliveries with a similar group delivered earlier. METHODS: During a 12-year period (2005-2016), data from pregnant women with hemoglobin SS or SC were collected from three university medical centers and compared with earlier studies (1979-2003) involving similar patients. The primary endpoints were maternal complications during pregnancy and newborn outcomes. RESULTS: There were 278 patients in the control group (1979-2003) compared with 150 patients in the study group (2005-2016). Women in the study group were older (P < 0.0001) and of less parity (P =0.0001), and complications of preterm delivery, preeclampsia, and having a transfusion were similar between the two groups (P = 0.45, 0.95, and 0.49, respectively). Pain crises were more common in the study group (P = 0.02) as was cesarean section (P < 0.0001), but there was a reduction in pulmonary complications (P = 0.0002). Maternal mortality was uncommon (control group [N=4] vs study group [N=3], P = 0.40). Newborn statistics revealed a similar gestational age at delivery (37 weeks), and the incidence of intrauterine growth restriction, as well as 5-minute Apgar score <7 did not differ by group (P = 0. 91, 0.85, and 0.16, respectively). Infants in the study group were heavier on average by approximately 220 g (P = 0.02), whereas the neonatal death rate was low (control group [N=1], study group [N=2] P = 0.60). CONCLUSIONS: Recent pregnancy outcome statistics in women with sickle cell disease have not changed through the years. Innovative strategies to improve maternal and newborn outcomes among such patients are needed.

Previable Preeclampsia Diagnosed by Renal Biopsy in Setting of Novel Diagnosis of C4 Glomerulopathy.

BACKGROUND: Preeclampsia diagnosed before 20 weeks' gestational age is a rare entity, particularly without any predisposing factors. We report a case of preeclampsia occurring prior to 20 weeks' gestational age in the setting of a novel diagnosis of C4 glomerulopathy. CASE: A G3P0020 at 18 weeks presented with new onset hypertension and proteinuria, requiring multiple antihypertensive agents to maintain control. Renal biopsy demonstrated thrombotic microangiopathic lesions and glomerular endotheliosis. C4-dominant staining and numerous subendothelial and mesangial electron dense deposits were found within the glomerulus. With no other definable etiologies, preeclampsia was diagnosed. She developed posterior reversible encephalopathic syndrome and pregnancy termination was recommended. CONCLUSION: The lectin complement pathway may play a role in the pathophysiology of severe, early onset preeclampsia. Renal biopsy may play an integral role in diagnosis.

Pregnancy outcomes after cerclage placement in nulliparous women with a short cervix on transvaginal ultrasonography.

OBJECTIVE: Little is known about pregnancy outcomes associated with a short cervix and cerclage placement in nulliparous women. METHODS: An electronic query of our ultrasound database was used to identify patients whose cervical length measured < 25 mm between 16-24 weeks of gestation. Any nulliparous women, with no prior pregnancy lasting beyond 13 weeks 6 d gestational age, were included in the analysis. The primary outcome was the interval of time from the diagnosis of a short cervix (<25 mm) to the time of delivery. RESULTS: Our query identified 70 patients for analysis. The interval of time from diagnosis of a short cervix to delivery was observed to be 85 d (12.1 weeks) in the cerclage group and 116 d (16.6 weeks) in the expectantly managed group (p = 0.02). In those women receiving a cerclage, there was a statistically significant risk of spontaneous preterm birth <32 weeks gestational age (R.R. 6.7 [95% CI 1.45-30.6]). CONCLUSIONS: The impact of a short cervix is largely unknown in patients with an uncomplicated obstetrical history. Our investigation would suggest that in this subset of patients, cerclage would not be beneficial in preventing preterm delivery.

Cesarean Delivery with External Negative Pressure Dressing System: A Retrospective Cohort Study.

Objective To determine whether the use of external negative pressure dressing system (ENPDS) can reduce the incidence of wound complications after cesarean delivery (CD) compared with traditional dressings. Methods Retrospective review of all patients undergoing CD between November 2011 and March 2013. Information was collected on demographics, body mass index (BMI), duration of labor, pre- and postnatal infections, incision and dressing type, and postoperative course. Comparisons were made between traditional dressing and an external negative pressure dressing system. Results Of 970 patients included in the study, wound complications occurred in 50 patients (5.2%). Comparisons of ENPDS ( n = 103) and traditional dressing ( n = 867) groups revealed higher wound complications for ENPDS with odds ratio (OR) 3.37 and confidence interval (CI) 1.68 to 6.39. ENPDS was more commonly used in patients with BMI > 30 and preexisting diabetes. After controlling for BMI and pregestational diabetes in logistic regression analysis, ENPDS was equivalent to traditional dressing for risk of wound complications with an adjusted OR 2.76 (CI 0.97 to 7.84), with a trend toward more wound complications with ENPDS. Wound separation also tended to be more common in ENPDS group versus traditional dressing with an adjusted OR 2.66 (CI 0.87 to 8.12), although this result did not reach significance. Conclusion ENPDS is equivalent to traditional dressing for preventing wound complications after controlling for the higher-risk population selected for its use. In particular, wound separation appears to occur more frequently in women treated with ENPDS versus traditional dressing and should be regarded as a potential hazard of the system.

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.

Sickle cell crisis and pregnancy.

Pregnant women with sickle cell disease appear to be more likely to experience antepartum, intrapartum, and postpartum complications when compared with unaffected women. Access to high-risk obstetric care, patient education, and close follow-up is important to minimize maternal morbidity and mortality. A high index of suspicion and good diagnostic acumen is necessary to obtain optimal results in the pregnant patient affected by sickle cell crisis.

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.

Control of soluble fms-like tyrosine-1 (sFlt-1) production response to placental ischemia/hypoxia: role of tumor necrosis factor-α.

Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of preeclampsia (PE), the mechanisms that regulate the production of sFlt-1 during PE are unclear. While our laboratory has shown tumor necrosis factor-α (TNF-α) and sFlt-1 to be elevated in pregnant rats in response to placental ischemia, the importance of TNF-α in the regulation of sFlt-1 production is unknown. Therefore, the purpose of this study was to determine the role of TNF-α in mediating the increase in sFlt-1 in response to placental ischemia or hypoxia. Reductions in uterine perfusion pressure in pregnant rats significantly increased plasma levels of sFlt-1 and tended to increase TNF-α, an effect markedly attenuated by pretreatment with a TNF-α inhibitor etanercept (0.4 mg/kg). To further assess chronic interactions between TNF-α and sFlt-1, we examined a chronic effect of TNF-α infusion (50 ng/day) into normal pregnant rats to increase plasma sFlt-1 levels, as well as the effects of acute hypoxia on placental sFlt-1 production in the absence and presence of TNF-α blockade. Placental explants exposed to hypoxic conditions had enhanced TNF-α levels versus normoxic conditions, as well as increased sFlt-1 production. Pretreatment of placental explants with etanercept (15 µM) significantly reduced TNF-α levels in response to hypoxia but did not attenuate sFlt-1 production. These data suggest that while TNF-α may not play an important role in stimulating sFlt-1 production in response to acute hypoxia, a more chronic hypoxia, or placental ischemia may be an important stimulus for enhanced sFlt-l production.

Agonistic autoantibodies to the angiotensin II type I receptor cause pathophysiologic characteristics of preeclampsia.

BACKGROUND: Preeclampsia (PE), new-onset hypertension with proteinuria during pregnancy, is associated with increased reactive oxygen species, the vasoactive peptide endothelin-1 (ET-1), T and B lymphocytes, soluble antiangiogenic factors sFlt-1 and sEndoglin (sFlt-1 and sEng), and agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA). OBJECTIVES: One important area of investigation for our laboratory was to determine what role AT1-AA plays in the pathophysiology associated with PE. METHODS: To achieve this goal, we examined the effect of AT1-AA suppression on hypertension in response to placental ischemia as well as the effect of AT1-AA on increased blood pressure, ET-1, reactive oxygen species, and sFlt-1 in normal pregnant rats (NP). RESULTS: We demonstrated reductions in uterine perfusion pressure (RUPP) to be a stimulus for AT1-AA during pregnancy. We utilized the technique of B-cell depletion to suppress circulating AT1-AA in RUPP rats and found that AT1-AA suppression in RUPP rats was associated with lower blood pressure and ET-1 activation. To determine a role for AT1-AA to mediate hypertension during pregnancy, we infused purified rat AT1-AA (1:50) into NP rats, and analyzed blood pressure and soluble factors. We consistently found that AT1-AA infused rats had significantly increased AT1-AA and blood pressure above NP rats. This hypertension was associated with significantly increased ET-1 in renal cortices (11-fold) and placenta (4-fold), and there was an approximately 2- to 3-fold increase in placental oxidative stress. Furthermore, antiangiogenic factors sFlt-1 and sEng were significantly increased in the AT1-AA induced hypertensive group compared with the NP controls. CONCLUSIONS: Collectively, these data indicated an important role for AT1-AA stimulated in response to placental ischemia that caused hypertension during pregnancy.

Impedance cardiography facilitates differentiation of severe and superimposed preeclampsia from other hypertensive disorders.

OBJECTIVE: To determine if hemodynamic profiling using noninvasive impedance cardiography (ICG) reliably identifies the patient with severe (SPRE) or superimposed (SuPRE) preeclampsia. METHODS: Late gestation hypertensive pregnant patients underwent immediate ICG evaluation. Findings were compared between patients subsequently achieving or not achieving American College of Obstetricians and Gynecologists criteria for SPRE or SuPRE. RESULTS: Patients with severe disease were more likely to have depressed cardiac function and higher systolic blood pressure, mean arterial blood pressure, systemic vascular resistance, and thoracic fluid content compared to nonsevere hypertensive disease. CONCLUSION: ICG hemodynamic profiling of late gestation hypertensive patients can rapidly and reliably identify those with SPRE or SuPRE.