Customizing EV-CATCHER to Purify Placental Extracellular Vesicles from Maternal Plasma to Detect Placental Pathologies.

Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, n = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, n = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP+ EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP+ EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.

Venous Thromboembolism Risk Assessment Models in Obstetrics: A Review of Current Practices and Future Directions.

Pregnancy is a major risk factor for venous thromboembolism (VTE) and its associated complications. The hypercoagulable state in both the antenatal and postnatal periods contributes to thromboembolism and continues to be a leading cause of maternal morbidity and mortality worldwide. The non-specific signs and symptoms of VTE in pregnancy and the lack of specific Risk Assessment Models (RAMs) propose a diagnostic challenge in the obstetric population. This review aims to discuss and compare existing RAMs and highlights the important challenges of using established RAMs in obstetric patients. It also emphasizes the importance of enhancing and individualizing RAMs in obstetrics to improve maternal healthcare. KEY POINTS: · VTE is a major complication of pregnancy, associated with increased maternal morbidity and mortality.. · VTE RAMs lack sensitivity and specificity in stratifying VTE risk in pregnancy.. · Validating VTE RAMs in the obstetric population aims to improve maternal outcomes..

Pulsatile vessel at the posterior bladder wall: A new sonographic marker for placenta percreta.

OBJECTIVE: We investigated using "pulsatile vessels at the posterior bladder wall" as a novel sonographic marker to demonstrate the severity of placenta accreta spectrum (PAS). METHODS: This observational case-control study of 30 pregnant women was performed at Hackensack Meridian Health's Center for Abnormal Placentation in 2020. The case group was made up of women with historically described sonographic signs of PAS and was compared against two control groups: (1) women with uncomplicated placenta previa and (2) women with no evidence of placenta previa sonographically. All patients were evaluated with Color Flow Doppler ultrasound to assess the presence of arterial vessels at the posterior bladder wall. The flow characteristics and resistance indices (RI) were noted in the presence of pulsatile vessels. All patients' placentation was clinically confirmed at delivery. Patients with clinical invasive placentation underwent histopathological diagnosis to confirm disease presence. RESULTS: Hundred percent of subjects in our series with suspected PAS exhibited pulsatile arterial vessels at the posterior bladder wall sonographically with a low RI of 0.38 ± 0.1 at an average of 24.6 ± 5.2 gestational weeks. Cases were histopathologically confirmed to have placenta percreta after delivery. Patients in either of the control groups did not display pulsatile vessels at the posterior bladder wall during antenatal sonographic evaluations and had no clinical evidence of PAS. CONCLUSION: The presence of posterior urinary bladder wall pulsatile arterial vessels with low RI, in addition to traditional sonographic markers increases the suspicion of severe PAS. Thus, these findings allow for the greater opportunity for coordination of patient care prior to delivery.

Clinical and laboratory evaluation of patients with SARS-CoV-2 pneumonia treated with high-titer convalescent plasma.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti-SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response.

Trophoblast invasion: Lessons from abnormally invasive placenta (placenta accreta).

The invasion of the uterine wall by extravillous trophoblast is acknowledged as a crucial component of the establishment of pregnancy however, the only part of this process that has been clearly identified is the differentiation of cytotrophoblast (CTB) into the invasive extravillous trophoblast (EVT). The control of invasion, both initiation and termination, have yet to be elucidated and even the mechanism of differentiation is unclear. This review describes our studies which are designed to characterize the intracellular mechanisms that drive differentiation. We have used the over-invasion observed in abnormally invasive placenta (AIP; placenta accreta) to further interrogate this mechanism. Our results show that first trimester CTB to EVT differentiation is accomplished via an epithelial-mesenchymal transition (EMT), with EVT displaying a metastable, mesenchymal phenotype. In the third trimester, while the invasiveness of the EVT is lost, these cells still demonstrate signs of the EMT, albeit diminished. EVT isolated from AIP pregnancies do not however, show the same degree of reduction in EMT shown by normal third trimester cells. They exhibit a more mesenchymal phenotype, consistent with a legacy of greater invasiveness. The master regulatory transcription factor controlling the EMT appears, from the observational data, to be ZEB2 (zinc finger E-box binding protein 2). We verified this by overexpressing ZEB2 in the BeWo and JEG3 trophoblast cell lines and showing that they became more stellate in shape, up-regulated the expression of EMT-associated genes and demonstrated a substantially increased degree of invasiveness. The identification of the differentiation mechanism will enable us to identify the factors controlling invasion and those aberrant processes which generate the abnormal invasion seen in pathologies such as AIP and preeclampsia.

IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery.

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, five of which are summarised in this report. These workshops discussed new perspectives and knowledge in the following areas of research: 1) preeclampsia; 2) abnormally invasive placenta; 3) placental infection; 4) gestational trophoblastic disease; 4) drug delivery to treat placental dysfunction.

Preoperative cystoscopy could determine the severity of placenta accreta spectrum disorders: An observational study.

AIM: In the surgical treatment of placenta accreta spectrum disorders, cystoscopy for prophylactic stent placement is performed to protect the ureters from potential injury. Despite its frequent use, the use of cystoscopy in assessing the severity of these disorders has not been explored. Our objective was to find out if the abnormal findings documented during cystoscopy are associated with disease severity. METHODS: In this retrospective, observational cohort study (n = 56), the bladder wall was evaluated at the time of ureteral stent placement via cystoscopy in prenatally diagnosed placenta accreta spectrum cases. Three abnormal findings were commonly present in these cases: bulging of the posterior bladder wall, neovascularization and arterial pulsatility in the area of neovascularization. These findings were stratified according to severity in histologically confirmed specimens. Continuous variables were compared via two-tailed t-tests and Wilcoxon rank sum tests. Categorical data were evaluated using logistic regression analysis. RESULTS: Neovascularization affected 84%, bulging 71% and pulsatility 54% of the cases. Bulging and neovascularization increased with disease severity. Pulsatility occurred exclusively in percretas. Bulging was associated with a 12-fold (OR = 11.6, 95% CI 2.94-46.33, P = 0.0005) increased likelihood of percreta and neovascularization with a 17-fold (OR = 17.06, 95% CI 2.98-97.79, P = 0.0014) increase. Neovascularization and/or the presence of bulging of the bladder have high positive predictive value for placenta increta and percreta (91.5% and 95.0%, respectively). Cystoscopy can be used to assess the severity of placenta accreta spectrum cases preoperatively, especially when placentation is over the previous uterine scar and is in proximity to the bladder wall.

Interpregnancy interval and abnormally invasive placentation.

INTRODUCTION: The presence of a previous uterine scar is a strong risk factor for developing abnormally invasive placentation (AIP). We sought to determine whether a short interpregnancy interval predisposes to AIP. We hypothesized that a short interpregnancy interval after a previous cesarean delivery increases the risk of AIP in comparison with a longer interpregnancy interval. MATERIAL AND METHODS: We performed a retrospective cohort study of women with a histological diagnosis of AIP and a history of a previous cesarean section. Women were included in the control group if they had a previous cesarean section with a placenta underlying the previous uterine scar or an anterior previa. The time interval between pregnancy and AIP data was analyzed using the chi-square test and two-tailed Fisher's exact test. RESULTS: There was no statistical difference in the interpregnancy interval between women who had AIP vs the control group. Gravidity and parity were found to be significantly higher in the women with AIP vs the controls. CONCLUSIONS: These results suggest that a short interpregnancy interval may not increase the risk of developing AIP.

ZEB2, a master regulator of the epithelial-mesenchymal transition, mediates trophoblast differentiation.

STUDY QUESTION: Does the upregulation of the zinc finger E-box binding homeobox 2 (ZEB2) transcription factor in human trophoblast cells lead to alterations in gene expression consistent with an epithelial-mesenchymal transition (EMT) and a consequent increase in invasiveness? SUMMARY ANSWER: Overexpression of ZEB2 results in an epithelial-mesenchymal shift in gene expression accompanied by a substantial increase in the invasive capacity of human trophoblast cells. WHAT IS KNOWN ALREADY: In-vivo results have shown that cytotrophoblast differentiation into extravillous trophoblast involves an epithelial-mesenchymal transition. The only EMT master regulatory factor which shows changes consistent with extravillous trophoblast EMT status and invasive capacity is the ZEB2 transcription factor. STUDY DESIGN, SIZE, DURATION: This study is a mechanistic investigation of the role of ZEB2 in trophoblast differentiation. We generated stable ZEB2 overexpression clones using the epithelial BeWo and JEG3 choriocarcinoma lines. Using these clones, we investigated the effects of ZEB2 overexpression on the expression of EMT-associated genes and proteins, cell morphology and invasive capability. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used lentiviral transduction to overexpress ZEB2 in BeWo and JEG3 cells. Stable clones were selected based on ZEB2 expression and morphology. A PCR array of EMT-associated genes was used to probe gene expression. Protein measurements were performed by western blotting. Gain-of-function was assessed by quantitatively measuring cell invasion rates using a Transwell assay, a 3D bioprinted placenta model and the xCelligenceTM platform. MAIN RESULTS AND THE ROLE OF CHANCE: The four selected clones (2 × BeWo, 2 × JEG3, based on ZEB2 expression and morphology) all showed gene expression changes indicative of an EMT. The two clones (1 × BeWo, 1 × JEG3) showing >40-fold increase in ZEB2 expression also displayed increased ZEB2 protein; the others, with increases in ZEB2 expression <14-fold did not. The two high ZEB2-expressing clones demonstrated robust increases in invasive capacity, as assessed by three types of invasion assay. These data identify ZEB2-mediated transcription as a key mechanism transforming the epithelial-like trophoblast into cells with a mesenchymal, invasive phenotype. LARGE SCALE DATA: PCR array data have been deposited in the GEO database under accession number GSE116532. LIMITATIONS, REASONS FOR CAUTION: These are in-vitro studies using choriocarcinoma cells and so the results should be interpreted in view of these limitations. Nevertheless, the data are consistent with in-vivo findings and are replicated in two different cell lines. WIDER IMPLICATIONS OF THE FINDINGS: The combination of these data with the in-vivo findings clearly identify ZEB2-mediated EMT as the mechanism for cytotrophoblast differentiation into extravillous trophoblast. Having characterized these cellular mechanisms, it will now be possible to identify the intracellular and extracellular regulatory components which control ZEB2 and trophoblast differentiation. It will also be possible to identify the aberrant factors which alter differentiation in invasive pathologies such as preeclampsia and abnormally invasive placenta (AKA accreta, increta, percreta). STUDY FUNDING AND COMPETING INTEREST(s): Funding was provided by the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Surgery at Hackensack Meridian Health, Hackensack, NJ. The 3D bioprinted placental model work done in Drs Kim and Fisher's labs was supported by the Children's National Medical Center. The xCELLigence work done in Dr Birge's lab was supported by NIH CA165077. The authors declare no competing interests.

Prophylactic Hypogastric Artery Ligation during Placenta Percreta Surgery: A Retrospective Cohort Study.

Objective To evaluate if prophylactic hypogastric artery ligation (HAL) decreases surgical blood loss and blood products transfused. Study Design This is a retrospective cohort study comparing patients with placenta percreta undergoing prophylactic HAL at the time of cesarean hysterectomy versus those who did not. Data were presented as means ± standard deviations, proportions, or medians with interquartile ranges. Demographic and clinical data were compared in the groups using Student's t -test for normally distributed data or the Mann-Whitney U test for nonnormally distributed data. Fisher's exact test was used for proportions and categorical variables. Data are reported as significant where p was <0.05. Results There were 26 patients included in the control group with no HAL and 11 patients included in the study group. Estimated blood loss for the study group was 1,000 mL versus 800 mL in the control. Units of PRCBs transfused were 4.5 units in the study group versus 2 units for the control group. None of these measures were found to be statistically significant. Conclusion Our data suggest there was no benefit in the use of prophylactic HAL in decreasing surgical blood loss or amount of blood products transfused in patients who had a cesarean hysterectomy performed for placenta percreta. Précis Prophylactic HAL does not decrease blood loss during surgery for placenta percreta.

Increased incidence of respiratory distress syndrome in neonates of mothers with abnormally invasive placentation.

BACKGROUND: The incidence of abnormally invasive placentation (AIP) is increasing. Most of these pregnancies are delivered preterm. We sought to characterize neonatal outcomes in AIP pregnancies. METHODS: In this retrospective case-control study (2006-2015), AIP neonates (n = 108) were matched to two controls each for gestational age, antenatal glucocorticoid exposure, sex, plurity, and delivery mode. Medical records were reviewed for neonatal and maternal characteristics/outcomes. Univariate and multivariate Poisson regressions were performed to determine relative risk ratios (RR). RESULTS: There were no mortalities. All neonatal outcomes were similar except for respiratory distress syndrome (RDS), which affected 37% of AIP neonates (versus 21% of controls). AIP neonates required respiratory support (64.8% vs. 51.9%) and continuous positive airway pressure (53.7% vs. 42.1%) for a longer duration. Univariate regression yielded elevated RRs for RDS for AIP (RR 1.78, 95% CI 1.24-2.54), placenta previa (RR = 1.94, 95% CI 1.36-2.76), and placenta previa with bleeding (RR 2.29, 95% CI 1.36-3.86). One episode of bleeding had a RR of 2.43 (95% CI 1.57-3.76), 2 or more episodes had a RR of 2.95 (95% CI 1.96-4.44), and bleeding/abruption as the delivery indication had a RR of 2.57 (95% CI 1.82-3.64). A multivariate regression stratifying for AIP and evaluating the combined and individual associations of AIP, bleeding, placenta previa, and GA, resulted in elevated RRs for placenta previa alone (RR 2.16, 95% CI 1.15-4.06) and placenta previa and bleeding (RR 1.69, 95% CI 1.001-2.85). CONCLUSIONS: The increased incidence of RDS at later gestational ages in AIP is driven by placenta previa. AIP neonates required respiratory support for a longer duration than age-matched controls. Providers should be prepared to counsel expectant parents and care for affected neonates.

Serial Uterine Artery Embolization for the Treatment of Placenta Percreta in the First Trimester: A Case Report.

Two patients with placenta percreta underwent uterine artery embolization (UAE) for abnormally invasive placenta (AIP) in the first trimester. Patient 1 had a 9-week cervical ectopic, while Patient 2 had a 9-week cesarean scar pregnancy. Elective termination of pregnancy was performed in both patients. UAE was performed with tris-acryl gelatin microspheres as well as gelfoam until stasis and was repeated in cases of revascularization. Both patients were followed with US/MRI/MRA scans and ß-hCG levels. Revascularization occurred in both patients following UAE, requiring multiple embolizations to achieve complete placental involution. Serial bland UAE may be an effective technique in the treatment of first-trimester AIP, with the distinct advantage of maintaining a patient's fertility. LEVEL OF EVIDENCE: Level IV.

Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta.

Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchorage-dependent epithelial phenotype into the mesenchymal-like invasive extravillous trophoblast (EVT) is crucial in the development of the maternal-fetal interface. We showed previously that differentiation of first trimester CTB to EVT involves an epithelial-mesenchymal transition (EMT). Here we compare the epithelial-mesenchymal characteristics of CTB and EVT derived from normal third trimester placenta or placenta previa versus abnormally invasive placenta (AIP). CTB and EVT were isolated from normal term placenta or placenta previa following Caesarean section and EVT from AIP following Caesarean hysterectomy. Cell identity was validated by measurement of cytokeratin-7 and HLA-G. Comparing normal term CTB with EVT from normal term placenta or placenta previa for differential expression analysis of genes associated with the EMT showed changes in >70% of the genes probed. While demonstrating a mesenchymal phenotype relative to CTB, many of the gene expression changes in third trimester EVT were reduced relative to the first trimester EVT. We suggest that third trimester EVT are in a more constrained, metastable state compared to first trimester equivalents. By contrast, EVT from AIP demonstrate characteristics that are more mesenchymal than normal third trimester EVT, placing them closer to first trimester EVT on the EMT spectrum, consistent with a more invasive phenotype.

Clinical Experience with the Implementation of Accurate Measurement of Blood Loss during Cesarean Delivery: Influences on Hemorrhage Recognition and Allogeneic Transfusion.

OBJECTIVE: This article compares hemorrhage recognition and transfusion using accurate, contemporaneous blood loss measurement versus visual estimation during cesarean deliveries. STUDY DESIGN: A retrospective cohort study using visually estimated blood loss (traditional, n = 2,025) versus estimates using a mobile application that photographs sponges and canisters and calculates their hemoglobin content (device, n = 756). RESULTS: Blood loss > 1,000 mL was recognized in 1.9% of traditional visual estimation patients, while measured blood loss of > 1,000 mL occurred in 8.2% of device patients (p < 0.0001). In both groups, this was accompanied by a greater decrease in transfusion-adjusted hemoglobin levels than occurred in patients without hemorrhage (p < 0.0001). Despite similar transfusion rates (1.6% in both groups), fewer red cell units were given to transfused patients in the device group (1.83 ± 0.58 versus 2.56 ± 1.68 units; p = 0.038). None of the patients in the device group received plasma or cryoprecipitate. Seven patients in the traditional group received these products (p = 0.088). Device use was associated with shorter hospital stays (4.0 ± 2.3 versus 4.4 ± 2.9 days; p = 0.0006). CONCLUSION: The device identified hemorrhages more frequently than visual estimation. Device-detected hemorrhages appeared clinically relevant. Blood product transfusion was reduced possibly due to earlier recognition and treatment, although further studies are needed to verify the conclusion.

Differentiation of first trimester cytotrophoblast to extravillous trophoblast involves an epithelial-mesenchymal transition.

The transformation of cytotrophoblast (CTB) to extravillous trophoblast (EVT) is an essential process for placental implantation. EVT generated at the tips of the anchoring villi migrate away from the placenta and invade the endometrium and maternal spiral arteries, where they modulate maternal immune responses and remodel the arteries into high-volume conduits to facilitate uteroplacental blood flow. The process of EVT differentiation has several factors in common with the epithelial-to-mesenchymal transition (EMT) observed in embryonic development, wound healing and cancer metastasis. We hypothesized that the generation of invasive EVT from CTB was a form of EMT. We isolated paired CTB and EVT from first trimester placentae, and compared their gene expression using a PCR array comprising probes for genes involved in EMT. Out of 84 genes, 24 were down-regulated in EVT compared to CTB, including epithelial markers such as E-cadherin (-11-fold) and occludin (-75-fold). Another 30 genes were up-regulated in EVT compared to CTB including mesenchymal markers such as vimentin (235-fold) and fibronectin (107-fold) as well as the matrix metalloproteinases, MMP2 and MMP9 (357-fold, 129-fold). These alterations also included major increases in the ZEB2 (zinc finger E-box binding homeobox 2, 198-fold) and TCF4 (transcription factor 4, 18-fold) transcription factors, suggesting possible stimulatory mechanisms. There was substantial up-regulation of the genes encoding TGFß1 and TGFß2 (48-fold, 115-fold), which may contribute to the maintenance of the mesenchymal-like phenotype. We conclude that transformation of CTB to EVT is consistent with an EMT, although the differences with other types of EMT suggest this may be a unique form.

Three-Dimensional Power Doppler Ultrasonography for Diagnosing Abnormally Invasive Placenta and Quantifying the Risk.

OBJECTIVE: To test an objective ultrasound marker for diagnosing the presence and severity of abnormally invasive placenta. METHODS: Women at risk of abnormally invasive placenta underwent a three-dimensional power Doppler ultrasound scan. The volumes were examined offline by a blinded observer. The largest area of confluent three-dimensional power Doppler signal (Area of Confluence [Acon], cm) at the uteroplacental interface was measured and compared in women subsequently diagnosed with abnormally invasive placenta and women in a control group who did not have abnormally invasive placenta. Receiver operating characteristic curves were plotted for prediction of abnormally invasive placenta and abnormally invasive placenta requiring cesarean hysterectomy. RESULTS: Ninety-three women were recruited. Results were available for 89. Abnormally invasive placenta was clinically diagnosed in 42 women; 36 required hysterectomy and had abnormally invasive placenta confirmed histopathologically. Median and interquartile range for Acon was greater for abnormally invasive placenta (44.2 [31.4-61.7] cm) compared with women in the control group (4.5 cm [2.9-6.6], P<.001) and even greater in the 36 requiring hysterectomy (46.6 cm [37.2-72.6], P<.001). Acon rose with histopathologic diagnosis: focal accreta (32.2 cm [17.2-57.3]), accreta (59.6 cm [40.1-89.9]), and percreta (46.6 cm [37.5-71.5]; P<.001 analysis of variance for linear trend). Receiver operating characteristic analysis for prediction of abnormally invasive placenta revealed that with an Acon of 12.4 cm or greater, 100% sensitivity (95% confidence interval [CI] 91.6-100) could be obtained with 92% specificity (95% CI 79.6-97.6); area under the curve is 0.99 (95% CI 0.94-1.0). For prediction of abnormally invasive placenta requiring hysterectomy, 100% sensitivity (95% CI 90.3-100) can be obtained with an Acon of 17.4 cm or greater with 87% specificity (95% CI 74.7-94.5; area under the curve 0.98 [0.93-1.0]). CONCLUSION: The marker Acon provides a quantitative means for diagnosing abnormally invasive placenta and assessing severity. If further validated, subjectivity could be eliminated from the diagnosis of abnormally invasive placenta. LEVEL OF EVIDENCE: II.

Maternal and fetal outcomes in placenta accreta after institution of team-managed care.

INTRODUCTION: Placenta accreta significantly contributes to maternal morbidity and mortality. We evaluated whether planned delivery and experienced, team-managed surgical intervention results in improved outcomes. We also examined whether risk factors differed for accreta, increta, and percreta and evaluated whether excess lower segment uterine vascularity correlates with disease severity. METHODS: We retrospectively analyzed patients before versus after institution of a management protocol. Of the 58 044 deliveries over 10 years, there were 67 women whose pregnancies were histopathologically confirmed as placenta accreta, increta, or percreta (1/866). Clinical outcome measures were estimated blood loss (EBL), packed red blood cells (pRBCs) transfused, maternal and fetal complications, intensive care unit admission, and length of stay. RESULTS: There were no maternal or infant deaths. In the managed cohort, EBL was reduced by 48% (P < .001), intraoperative pRBCs transfused by 40% (P < .01), total transfused pRBCs per case by 50% (P < .01), and surgical intensive care unit admissions by >50% (P < .01). Assessment of maternal risk factors by diagnosis revealed marked differences between accreta versus increta and percreta. Clinically assessed excess vascularity of the lower uterine segment correlated with disease severity. The incidence of neonatal complications was similar in both cohorts. CONCLUSIONS: Targeted delivery at 34 weeks and team-managed diagnosis, treatment, and care of patients with placenta accreta were associated with improved maternal, but not neonatal outcomes.

Brain natriuretic peptide in term pregnancy.

OBJECTIVE: To determine the normal range of serum brain natriuretic peptide (BNP) in uncomplicated, singleton term pregnant patients. STUDY DESIGN: Serum for analysis of BNP was drawn at admission to labor and delivery (= 104), prior to administration of intravenous fluid. RESULTS: Median BNP was 20 pg/mL, with an interquartile range of 20 pg/mL (range 5-70 pg/mL; or a mean ± standard deviation [SD] of 23 ± 16 pg/mL). Brain natriuretic peptide negatively correlated with prepregnant (r = -.24, P < .05) and pregnant weight (r = -26, P < .01) and with heart rate (r = -.35, P < 0.001); heart rate was also positively correlated with BMI (r = .32). Brain natriuretic peptide levels were higher in Hispanic than African American women, independent of body mass index (BMI) and heart rate. CONCLUSIONS: Brain natriuretic peptide values found in term pregnant patients are similar to those of prepregnant women of reproductive age. Brain natriuretic peptide levels appear to be set by conditions present in the prepregnant condition and maintained, despite changes in plasma volume, systemic vascular resistance, and cardiac output.

Measurement of intraabdominal pressure in pregnant women at term.

OBJECTIVE: To determine the baseline intraabdominal pressure (IAP) in pregnant women at term. STUDY DESIGN: Pregnant women at term undergoing scheduled cesarean delivery in the absence of labor had IAP measured via an intravesical catheter. Abdominal pressures were obtained in the dorsal supine position with a leftward tilt after the placement of spinal anesthesia. Measurements were taken immediately before and after cesarean delivery. RESULTS: One hundred subjects were included in this Institutional Research Board-approved study. The median preoperative IAP measurement was 22 mm Hg, and the median postoperative IAP measurement was 16 mm Hg. The decrease in the IAP from the preoperative to the postoperative measurement was statistically significant (p < 0.0001). CONCLUSION: The median IAP measurement for pregnant patients at term is 22 mm Hg and is followed by a statistically significant decline after delivery.

The influence of race on the incidence of respiratory distress syndrome after antenatal betamethasone or dexamethasone.

OBJECTIVE: To compare the incidence of respiratory distress syndrome (RDS) in African American and Caucasian neonates after antenatal betamethasone or dexamethasone. STUDY DESIGN: This was a retrospective review of all deliveries occurring at < or = 32 weeks' gestation at Hackensack University Medical Center from 2001 to 2004. Only patients who received a complete course of antenatal steroids were included. The type (betamethasone or dexamethasone) was based on pharmacy supply. Statistical analysis was performed using Pearson's chi2 and Fisher's exact test. RESULTS: The African American (n = 32) and Caucasian (n = 86) groups were similar in terms of maternal age, gestational age and infant birth weight. African Americans receiving dexamethasone had a 1.65-fold increased risk of delivering infants with RDS as compared to those who received betamethasone (91.3% vs. 55.6%, respectively; p = 0.038). No difference was noted among Caucasians. CONCLUSION: Among African American neonates, the incidence of RDS was higher in those who received dexamethasone vs. betamethasone.