Abdulla Al-Khan

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.

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], cm2) 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] cm2) compared with women in the control group (4.5 cm2 [2.9–6.6], P<.001) and even greater in the 36 requiring hysterectomy (46.6 cm2 [37.2–72.6], P<.001). Acon rose with histopathologic diagnosis: focal accreta (32.2 cm2 [17.2–57.3]), accreta (59.6 cm2 [40.1–89.9]), and percreta (46.6 cm2 [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 cm2 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 cm2 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

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 TGFβ1 and TGFβ2 (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.

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.

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.

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.

Preoperative cystoscopy could determine the severity of placenta accreta spectrum disorders: An observational study: Cystoscopy to assess PAS severity

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.

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 β-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 EvidenceLevel IV

Human trophoblast epithelial-mesenchymal transition in abnormally invasive placenta

Abstract Differentiation of first trimester human placental cytotrophoblast (CTB) from an anchoragedependent 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. Summary Sentence Extravillous trophoblast cells from abnormally invasive placenta demonstrate more mesenchymal characteristics than normal third trimester cells, consistent with an overinvasive phenotype.

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 Students t -test for normally distributed data or the Mann–Whitney U test for nonnormally distributed data. Fishers 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.