Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in the Multidisciplinary Management of Morbidly Adherent Placenta.

BACKGROUND: Morbidly adherent placentation (MAP) increases the risk for obstetric hemorrhage. Cesarean hysterectomy is the prevalent perioperative approach. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive and relatively simple endovascular procedure to temporarily occlude the aorta and control below diaphragm bleeding in trauma. It has been effectively used to reduce obstetric hemorrhage. OBJECTIVES: To evaluate whether REBOA during cesarean delivery (CD) in women with morbidly adherent placentation is a safe and effective treatment modality. METHODS: We introduced REBOA for CD with antepartum diagnosis of MAP in 2019 and compared these patients (RG) to a standard approach group (SAG) treated in our center over the preceding year, as a control. All relevant data were collected from patient electronic files. RESULTS: Estimated blood loss and transfusion rates were significantly higher in SAG; 54.5% of SAG patients received four RBC units or more vs. one administered in RG. No fresh frozen plasma, cryoprecipitate, or platelets were administered in RG vs. mean 3.63, 6, and 3.62 units, respectively in SAG. Ten SAG patients (90.9%) underwent hysterectomy vs. 3 RG patients (30%). Five SAG patients (45%) required post-surgical intensive care unit (ICU) admission vs. no RG patients. Bladder injury occurred in five SAG cases (45%) vs. 2 RG (20%). One RG patient had a thromboembolic event. Perioperative lactate levels were significantly higher in SAG patients. CONCLUSIONS: Use of REBOA during CD in women with MAP is safe and effective in preventing massive bleeding, reducing the rate of hysterectomy, and improving patient outcome.

A decade's experience in primipara, term, singleton, vertex parturients with a sustained low rate of CD.

Background Cesarean delivery (CD) in primiparas with a term singleton vertex fetus (PTSV) is a sentinel event for the future mode of delivery and determinant of repeat CD risk. We aimed to evaluate the risk factors for primary CD in a population with a decade of sustained low rate of intrapartum CD. Methods This was a retrospective single-center cohort study between 2005 and 2014. The primary outcome of the study was the mode of delivery. PTSV who attempted vaginal delivery were identified and categorized according to the mode of delivery: vaginal delivery vs. CD. Risk factors for intrapartum CD adjusted odds ratio (aOR) [95% confidence interval (CI)] in multivariate analysis were reported. Results During the study, 121,483 deliveries were registered; 26,301 (21.6%) PTSV were admitted in labor, of which 1944 (7.4%) had an intrapartum CD. Significantly in multivariate analysis, this group had a unique risk profile as compared to those who delivered vaginally; non modifiable risks included advanced maternal age: 3.06 (2.16-4.33), P < 0.001; prior multiple (≥3) miscarriages: 1.94 (1.04-3.62), P = 0.04; low (<6) modified admission cervical score: 2.41 (2.07-2.82), P < 0.001; low birth weight (BW): 1.42 (1.00-2.01), P = 0.05 or macrosomia: 2.38 (1.77-3.21), P < 0.001; modifiable risks included induction of labor: 1.79 (1.51-2.13), P < 0.001 and oxytocin labor augmentation: 8.36 (6.84-10.22), P < 0.001. Conclusion In a population of PTSV with a sustained low risk for intrapartum cesarean maintained by a strict labor management, induction of labor remains a significant and sole potentially modifiable risk factor for CD.

Maternal-fetal vitamin D receptor polymorphisms significantly associated with preterm birth.

PURPOSE: Preterm birth (PTB) is a complex trait with strong genetic background, whose etiology is not fully understood. It was recently suggested that pregnancy duration is affected by fetal genetic variation even more than by the maternal genome. Vitamin D receptor (VDR) is involved in embryonic implantation and fertility. We studied the association between both maternal and neonatal vitamin D receptor (VDR) genetic variation and PTB. METHODS: Maternal and fetal (umbilical cord) DNA was isolated from Jewish Israeli idiopathic preterm newborns (24-36 weeks, n = 146) and control term newborns (>37 weeks, n = 229). Maternal and fetal VDR polymorphisms (FokI, ApaI, BsmI, TaqI) were analyzed by restriction fragment length polymorphism analysis. Using SPSS analysis to correlate VDR genotypes with phenotypic variation: pregnancy duration, preterm birth and spontaneous miscarriages, adjusted for gravidity, parity and gender of newborn. RESULTS: Women homozygous to VDR ApaI (AA) genotype had significant twofold increase risk for PTB [OR 1.973, (CI) 1.183-3.289, p = 0.009] compared to heterozygous women. Male newborns had significant (p < 0.05) 1.73-fold increase of PTB. Women with history of previous (≥1) spontaneous miscarriage had a significant increased risk for PTB if their newborn carried either of the VDR BsmI homozygous (BB or bb) genotypes compared to the heterozygous (Bb) genotype [OR 6.857, (CI) 1.273-36.934, p = 0.018 and OR 9.231, (CI) 1.753-48.618, p = 0.008, respectively], or VDR ApaI homozygous (AA or aa) genotype compared to heterozygous (Aa) genotype [OR 4.33, (CI) 1.029-18.257, p = 0.046 and OR 7.2, (CI) 1.34-38.917, p = 0.021, respectively]. CONCLUSIONS: We show association between maternal and fetal VDR genotype variants with PTB.

Repair of uterine rupture following vaginal delivery: A comparison between minimally invasive and open repair.

OBJECTIVE: To compare operative data and patient satisfaction between open and laparoscopic surgery for postpartum-diagnosed uterine rupture. METHODS: In this questionnaire-based cohort study, the authors collected all cases of postpartum-diagnosed uterine rupture after vaginal delivery between 2016 and 2020 in a single academic tertiary center. The cohort was divided according to surgical method of repair, and demographic, clinical, operative and postoperative data were collected and compared between groups. A phone questionnaire on various satisfaction domains was conducted and satisfaction rates were compared between groups. RESULTS: Eight cases of uterine rupture following vaginal delivery were treated by laparoscopy and eight were treated by laparotomy. The median operative time was 103 min (interquartile range [IQR], 86.3-129.0 min) for the laparoscopy group and 61 min (IQR, 59.0-75.0 min) for the laparotomy group (P = 0.04). Blood transfusion was required in 25% of women who underwent laparoscopy, as compared with 88% of women who underwent laparotomy (P = 0.01 < 0.05). Median hospitalization time was 3 days (IQR, 3-4 days) in the laparoscopy group and 4 days (IQR, 4-4 days) in the laparotomy group (P = 0.2). Overall satisfaction, satisfaction from recovery, satisfaction from scars, satisfaction from ability to care for the neonate, and postoperative pain and mood were all improved in the laparoscopy group, as compared with the laparotomy group. CONCLUSION: Minimally invasive surgery is a viable surgical option for patients with uterine rupture diagnosed after vaginal delivery and may result in better patient recovery and satisfaction.

Outcome predictors and patient progress following delivery in pregnant and postpartum patients with severe COVID-19 pneumonitis in intensive care units in Israel (OB-COVICU): a nationwide cohort study.

BACKGROUND: A key unresolved controversy in severe COVID-19 pneumonitis in pregnancy is the optimum timing of delivery and whether delivery improves or worsens maternal outcomes. We aimed to assess clinical data on every intensive care unit (ICU) day for pregnant and postpartum women admitted to the ICU with COVID-19, with a particular focus on the days preceding and following delivery. METHODS: In this multicentre, nationwide, prospective and retrospective cohort study, we evaluated all pregnant women who were admitted to an ICU in Israel with severe COVID-19 pneumonitis from the 13th week of gestation to the 1st week postpartum. We excluded pregnant patients in which the ICU admission was unrelated to severe COVID-19 pneumonitis. We assessed maternal and neonatal outcomes and longitudinal clinical and laboratory ICU data. The primary overall outcome was maternal outcome (worst of the following: no invasive positive pressure ventilation [IPPV], use of IPPV, use of extracorporeal membrane oxygenation [ECMO], or death). The primary longitudinal outcome was Sequential Organ Failure Assessment (SOFA) score, and the secondary longitudinal outcome was the novel PORCH (positive end-expiratory pressure [PEEP], oxygenation, respiratory support, chest x-ray, haemodynamic support) score. Patients were classified into four groups: no-delivery (pregnant at admission and no delivery during the ICU stay), postpartum (ICU admission ≥1 day after delivery), delivery-critical (pregnant at admission and receiving or at high risk of requiring IPPV at the time of delivery), or delivery-non-critical (pregnant at admission and not critically ill at the time of delivery). FINDINGS: From Feb 1, 2020, to Jan 31, 2022, 84 patients were analysed: 34 patients in the no-delivery group, four in postpartum, 32 in delivery-critical, and 14 in delivery-non-critical. The delivery-critical and postpartum groups had worse outcomes than the other groups: 26 (81%) of 32 patients in the delivery-critical group and four (100%) of four patients in the postpartum group required IPPV; 12 (38%) and three (75%) patients required ECMO, and one (3%) and two (50%) patients died, respectively. The delivery-non-critical and no-delivery groups had far better outcomes than other groups: six (18%) of 34 patients and two (14%) of 14 patients required IPPV, respectively; no patients required ECMO or died. Oxygen saturation (SpO2), SpO2 to fraction of inspired oxygen (FiO2) ratio (S/F ratio), partial pressure of arterial oxygen to FiO2 ratio (P/F ratio), ROX index (S/F ratio divided by respiratory rate), and SOFA and PORCH scores were all highly predictive for adverse maternal outcome (p<0·0001). The delivery-critical group deteriorated on the day of delivery, continued to deteriorate throughout the ICU stay, and took longer to recover (ICU duration, Mantel-Cox p<0·0001), whereas the delivery-non-critical group improved rapidly following delivery. The day of delivery was a significant covariate for PORCH (p<0·0001) but not SOFA (p=0·09) scores. INTERPRETATION: In patients who underwent delivery during their ICU stay, maternal outcome deteriorated following delivery among those defined as critical compared with non-critical patients, who improved following delivery. Interventional delivery should be considered for maternal indications before patients deteriorate and require mechanical ventilation. FUNDING: None.

Peripartum use of cell salvage: a university practice audit and literature review.

INTRODUCTION: Obstetrical hemorrhage is the second leading cause of direct maternal mortality (18% of maternal deaths) in developed countries and is the leading cause of severe maternal morbidity. The rising rate of obstetrical hemorrhage attributed to the repeated cesarean sections and invasive placental disorders, requiring blood transfusion has emphasized the need for alternatives to allogeneic blood donation. METHODS AND RESULTS: The Shaare Zedek Medical Center is a teaching hospital with the largest obstetric service in the region-13,500 live births per year. The medical records of all parturients requiring use of intraoperative cell salvage system (IOCS) (2007-2011) were reviewed to evaluate our experience with this unique system and possible complications in the obstetrical milieu of a large obstetric unit. CONCLUSION: Using our combined medical records, we found that IOCS is a rapid method of blood replacement that allows blood bank service recruitment and presents no adverse reaction to the parturient. However, this sophisticated system is appropriate for tertiary surgical centers and its routine use should be assessed by national medical boards.

Trial of labor of vertex-nonvertex twins following a previous cesarean delivery.

BACKGROUND: Maternal and neonatal outcomes of trial of labor after cesarean delivery of twins are similar to those of singleton trials of labor after cesarean delivery. However, previous studies did not stratify outcomes by second-twin presentation on admission to labor. OBJECTIVE: To examine maternal and neonatal outcomes following trial of labor after cesarean delivery in twins with vertex-nonvertex presentation. STUDY DESIGN: A retrospective multicenter study was conducted including data on deliveries occurring between the years 2005 and 2020. We included trials of labor after a previous cesarean delivery (at ≥320/7 weeks' gestation) of twin gestations with a vertex-presenting first twin on admission to labor. The exposed group was defined as deliveries with a nonvertex second twin at admission to labor, whereas the comparison group included deliveries with a vertex second twin at admission. Only parturients who attempted vaginal delivery were included. Cases of prelabor fetal death of either twin or major fetal anomalies were excluded. The primary outcome was uterine rupture. RESULTS: A total of 236 twin trials of labor after cesarean delivery were included, of which 128 involved nonvertex second twins and 108 a second vertex twin. Uterine rupture rates were comparable between the groups (1/128 [0.9%] vs 1/108 [0.8%]; P=1.000). Successful trial of labor after cesarean delivery of both twins occurred in 76.6% of the exposed group vs 81.5% of the comparison group, whereas cesarean delivery of both twins was performed in 21.9% of the exposed group vs 17.6% of the comparison group (P=.418; odds ratio, 1.32; confidence interval, 0.7-2.5). Two cases of cesarean delivery of the second twin occurred in the exposed group and 1 in the comparison group (1.6% vs 0.9%, respectively, P=1.000). There was no difference between the groups in maternal outcomes, including rates of postpartum hemorrhage, blood transfusion, placental abruption, thromboembolic events, and maternal fever. Neonatal outcomes were also comparable between the groups, including rates of intensive care admission and low (≤7) 5-minute Apgar scores. CONCLUSION: Our data show that trial of labor after cesarean delivery of noncephalic second twins holds favorable maternal and neonatal outcomes, comparable with those of vertex-vertex trials of labor after cesarean delivery. Second-twin noncephalic presentation should not discourage parturients and caregivers from considering trial of labor after cesarean delivery if desired.

General Versus Regional Anesthesia for Emergency Cesarean Delivery in a High-volume High-resource Referral Center: A Retrospective Cohort Study.

OBJECTIVE: The choice of anesthesia for emergency cesarean delivery (CD) is one of the most important choices to make in obstetric anesthesia. In this study, we examine which type of anesthesia was used for emergency CD in our hospital, and how the choice affected the time from entry to the operation room until incision (TTI), time until delivery (TTD), and maternal/neonatal outcomes. METHODS: Retrospectively, we examined all emergency CD's performed in Shaare Zedek Medical Center between January-December 2018. Results: 1059 patients met the inclusion criteria, of which 7.7% underwent general anesthesia (GA), 36.2% - conversion from labor epidural analgesia to surgical anesthesia, 52% - spinal anesthesia and 4.1% - combined spinal epidural. We did not find a significant difference between the GA and conversion epidural groups in terms of TTI or TTD. Nevertheless, GA was found to be correlated to a high rate of blood-products requirement and ICU admission. The rate of newborns with an APGAR score of less than 7, in both first and fifth second after birth, was significantly higher in the GA group, as well as the need for NICU admission. CONCLUSION: This study clearly emphasizes that the TTI are shortest when using GA or conversion of labor epidural analgesia to surgical anesthesia. Meanwhile, GA is also linked to higher rates of admissions to ICU as well as poorer neonatal outcomes compared to the other groups. Additionally, our study uncovered a low rate of GA, and relatively low rate of regional anesthesia failure, which meets the accepted standards.

Fertility status among women treated for aggressive non-Hodgkin's lymphoma.

In young women treated for intermediate-high-grade non-Hodgkin's lymphoma with CHOP (cyclophosphamide, adriamycin, oncovine and prednisone), there is insufficient data concerning gonadotoxicity or the need for fertility-preserving measures. The aim of the present study was to evaluate the fertility status in the first complete remission of women who were treated for aggressive non-Hodgkin's lymphoma. A cohort of 36 women with aggressive non-Hodgkin's lymphoma in first remission, who were treated in five university-affiliated hospitals in Israel, was evaluated. All women were aged younger than 40 years at diagnosis and received frontline protocols, including cyclophosphamide and adriamycin, mostly CHOP. Menstrual cycle characteristics, as well as pregnancies before the diagnosis, during treatment and in first complete remission, were evaluated. The patients' mean age at the diagnosis was 28 +/- 7 years (range 17 - 40 years). All patients were treated with chemotherapy, although 10 patients received additional radiotherapy. Follow-up time at first complete remission was 84 +/- 48 months. Before diagnosis, all patients had menstrual cycles, which were regular in 31 (86%). Three patients received gonadtropin-releasing hormone analogs, whereas nine received contraceptive pills together with cytotoxic treatment. During treatment, 18 patients (50%) had amenorrhea, six (17%) had irregular menstrual cycles, and 12 (33%) continued their regular cycles. All but two women resumed menses in the first complete remission, and these were regular in 22 (61%) patients. In 63% of patients, the menstrual cycle recovered within 3 months of the discontinuation of chemotherapy. Eighteen patients (50%) became pregnant during the first complete remission. There was no significant difference between those patients who received fertility-preserving measures versus the remainder concerning regular menstrual cycles recovery or pregnancies. The two patients who developed amenorrhea were 40 years old at the time of diagnosis. In conclusion, the rate of gonadal dysfunction is very low among young, CHOP treated, non-Hodgkin's lymphoma female patients. Fertility-preserving techniques are not needed for women aged younger than 40 years and should probably be reserved for those who are at high risk for gonadal toxicity.

Maternal serum ferritin concentration in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the relationship between maternal serum ferritin concentrations in the second trimester and the risk of preterm delivery (PTD). METHODS: A prospective observational study was conducted. Fifty consecutive women with singleton pregnancies, who were admitted to the Maternal Fetal Medicine Unit due to preterm labor in the second trimester, were included. Maternal serum samples for determination of ferritin concentrations were obtained. Multiple logistic regression analysis was performed to control for confounders. RESULTS: Out of fifty patients enrolled in the study, 38% (19/50) delivered prematurely. Eight women (16%) had maternal serum ferritin concentrations above 30 ng/ml in the second trimester. Among them, 75% (n = 6) subsequently presented with preterm delivery (odds ratio (OR) = 6.7 with 95% confidence interval (CI) 1.1-56.2, p = 0.04). Only two patients with increased maternal ferritin concentrations delivered at term. However, 13 patients with second trimester ferritin concentrations below 30 ng/ml had preterm delivery. No significant differences in mean maternal ferritin concentrations were found between patients who delivered preterm and those that delivered at term, 31.9 +/- 50.6 vs. 13.6 +/- 15.2, respectively (p = 0.064). Using a multivariable analysis, controlling for anemia, leucocytosis and maternal age, increased serum ferritin concentrations were found to be an independent risk factor for PTD (OR = 8.6; 95% CI 1.4-52.5; p < 0.019). No significant correlation was found between serum ferritin concentrations and gestational age at birth (Pearson correlation coefficient r = -0.093; p = 0.522). CONCLUSIONS: Maternal ferritin concentrations above 30 ng/ml in the second trimester can serve as a marker for preterm delivery. However, since no correlation was found between serum ferritin concentrations and gestational age at birth, the routine use of serum ferritin as a marker for preterm delivery warrants further investigation.

Protease-activated-receptor 1 polymorphisms correlate with risk for unexplained recurrent pregnancy loss: a pilot study querying an association beyond coagulation.

BACKGROUND: Recurrent pregnancy loss (RPL) has been associated with impaired maternal-fetal communication. Protease-activated-receptor 1 (PAR1) is critical for trophoblast invasion and establishment unrelated to its role in vascular biology. OBJECTIVES: To analyze whether polymorphisms of PAR1 [-1426C/T], [-506I/D], and/or IVS[-14A/T] are associated with unexplained RPL. PATIENTS/METHODS: A case-control pilot study conducted in 39 healthy women with history of unexplained RPL and 98 women with a full-term, uncomplicated deliveries and no history of RPL. RESULTS: Women with RPL were significantly more likely to be heterozygous for [-1426C/T] (12.8% versus 3.2%; p=0.049); the heterozygous state for IVS[-14A/T] was also more common (15.4% versus 4.4%; p=0.064). There was no difference between groups for [-506I/D] genotypes. The functional consequence for [-1426C/T] and IVS[-14A/T] polymorphisms is underscored by the markedly low PAR1 mRNA levels in those women. Bioinformatics indicate generation of a new consensus motif for repressor Kruppel-like factor 3 (KLF3) in [-1426T]. Moreover, chromatin immunoprecipitation (ChIP) analysis confirmed a physical association between KLF3 protein and the hPar1 DNA obtained from women with the [-1426C/T] polymorphism. CONCLUSIONS: We hypothesize that the significantly low PAR1 levels impact placenta establishment and consequently pregnancy outcome, thereby profiling a novel risk factor for unexplained RPL.

Vitamin D receptor polymorphism FokI is associated with spontaneous idiopathic preterm birth in an Israeli population.

OBJECTIVE: The active form of vitamin D (1,25[OH]2D3) has been established to have potent anti-proliferative, immuno-modulatory, and anti-microbial action in addition to its effects on bone. The nuclear vitamin D receptor (VDR) is expressed in the placenta-decidua, regulating genes associated with implantation and implantation immuno-tolerance. If VDR polymorphisms regulate VDR functionality at the placenta-decidua interface, VDR genotypes may be involved in idiopathic preterm birth (PTB). STUDY DESIGN: Maternal and fetal (umbilical cord) blood samples from 33 Jewish and Arab mothers with PTB of a singleton neonate were compared to 98 samples from Jewish and Arab maternal and fetal blood samples from full-term, uncomplicated singleton births. Maternal age and ethnicity were comparable between groups. PCR amplification/digestion identified the VDR SNPs: FokI, ApaI, TaqI, and BsmI. RESULTS: Allele frequency for the FokI VDR in maternal blood samples from preterm births (but not umbilical cord samples) was significantly different (p=0.01) from that in maternal and umbilical cord blood samples from full-term singleton births, with an odds ratio for FokI carriers of 3.317 (95% CI, 1.143, 9.627) for preterm birth. The FokI VDR variant may therefore be a maternal risk trait for PTB among these women. CONCLUSION: This study may support a future platform for the study of vitamin D during pregnancy and treatment of selective target populations with vitamin D and/or VDR "tissue-specific therapeutic intervention" for prevention of PTB.

Association study of protease activated receptor 1 gene polymorphisms and adverse pregnancy outcomes: results of a pilot study in Israel.

Protease activated receptor 1 (PAR1), the thrombin receptor, is implicated in hemostasis, tissue remodeling, and is critical in early placentation. PAR1 polymorphisms that influence coagulation and adhesion molecule expression may compromise formation of a normal placenta, thereby resulting in adverse outcomes. This study is a prospective, case-control comparison of Israeli mother-neonate (singletons) pairs of complicated pregnancies: 33 preterm deliveries (PTDs), 20 preeclampsia (PE), and 28 idiopathic small for gestational age neonates (SGA) versus 98 pairs of uncomplicated singleton deliveries. PCR amplification identified polymorphisms in the 5' regulatory region of the PAR1 gene at [-1426(C/T)], insertion at [-506 (I/D)], and IVS at [-14 (A/T)]. We found that 15.2% mothers with PTD were heterozygous for [-1426] versus 3% in uncomplicated deliveries; however, maternal allele frequency was not significantly different between pregnancies complicated by PE or SGA versus uncomplicated pregnancies. Maternal allele frequencies for [-506] and [-14] polymorphisms were not significantly different between any of the study groups compared to the uncomplicated group. Haplotype analysis recapitulated the genotype pattern. Maternal homozygous allele frequency for each of the polymorphic variants was low (<2%) in all pregnancies, and equally distributed. Neonatal genotypes did not differ between groups and were not associated with adverse outcomes. Maternal heterozygous allele state for PAR1 polymorphism [-1426] and the haplotype with [-506 wild-type]/[-1426T]/[IVS-14A] is associated with PTD.