Association between Group B Streptococcus and Clinical Chorioamnionitis by Gestational Week at Delivery-A Multicenter Cohort Study.

OBJECTIVE: In the era of group B Streptococcus (GBS) screening and intrapartum antibiotic prophylaxis (IAP), GBS colonization has been associated with a lower risk of chorioamnionitis, possibly due to a protective effect of IAP. We sought to confirm this finding and assess whether this association varies by gestational week at delivery. STUDY DESIGN: We performed a retrospective cohort study of term (37.0-42.6 weeks), singleton parturients with known GBS status who delivered from 2005 to 2021 at two academic medical centers in Israel. We excluded patients who underwent planned cesarean, out of hospital birth, or had a fetal demise. Patients received GBS screening and IAP for GBS positivity as routine clinical care. The primary outcome was a diagnosis of clinical chorioamnionitis as determined by the International Classification of Diseases 10th Revision code, compared between GBS-positive and -negative groups, and assessed by gestational week at delivery. RESULTS: Of 292,126 deliveries, 155,255 met inclusion criteria. In total, 30.1% were GBS positive and 69.9% were negative. GBS-positive patients were 21% less likely to be diagnosed with clinical chorioamnionitis than GBS-negative patients, even after controlling for confounders (1.5 vs. 2.2%, adjusted odds ratio: 0.79, 95% confidence interval: 0.68-0.92). When assessed by gestational week at delivery, there was a significantly greater difference in rates of clinical chorioamnionitis between GBS-positive versus GBS-negative groups with advancing gestational age: 1.5-fold difference at 38 to 40 weeks, but a twofold difference at 42 weeks. The risk of clinical chorioamnionitis remained stable in the GBS-positive group, but increased significantly in the GBS-negative group at 41- and 42-week gestation (2.0 vs. 2.9%, p < 0.01 at 41 weeks; up to 3.9% at 42 weeks, p < 0.01). CONCLUSION: In a large multicenter cohort with universal GBS screening and IAP, GBS positivity was associated with a lower risk of chorioamnionitis, driven by an increasing rate of chorioamnionitis among GBS-negative patients after 40 weeks. KEY POINTS: · GBS positivity and IAP may be associated with lower risk of chorioamnionitis.. · GBS-positive patients were less likely to be diagnosed with chorioamnionitis.. · This difference increased with advancing gestational age after 40 weeks..

Impact of gestational diabetes mellitus on neonatal outcomes in small for gestational age infants: a multicenter retrospective study.

OBJECTIVE: To evaluate obstetric and perinatal outcomes among small for gestational age (SGA) infants born to patients diagnosed with Gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A multicenter retrospective cohort study between 2005 and 2021. The perinatal outcomes of SGA infants born to patients with singleton pregnancy and GDM were compared to SGA infants born to patients without GDM. The primary outcome was a composite adverse neonatal outcome. Infants with known structural/genetic abnormalities or infections were excluded. A univariate analysis was conducted followed by a multivariate analysis (adjusted odds ratio [95% confidence interval]). RESULTS: During the study period, 11,662 patients with SGA infants met the inclusion and exclusion criteria. Of these, 417 (3.6%) SGA infants were born to patients with GDM, while 11,245 (96.4%) were born to patients without GDM. Overall, the composite adverse neonatal outcome was worse in the GDM group (53.7% vs 17.4%, p < 0.01). Specifically, adverse neonatal outcomes such as a 5 min Apgar score < 7, meconium aspiration, seizures, and hypoglycemia were independently associated with GDM among SGA infants. In addition, patients with GDM and SGA infants had higher rates of overall and spontaneous preterm birth, unplanned cesarean, and postpartum hemorrhage. In a multivariate logistic regression assessing the association between GDM and neonatal outcomes, GDM was found to be independently associated with the composite adverse neonatal outcome (aOR 4.26 [3.43-5.3]), 5 min Apgar score < 7 (aOR 2 [1.16-3.47]), meconium aspiration (aOR 4.62 [1.76-12.13]), seizures (aOR 2.85 [1.51-5.37]) and hypoglycemia (aOR 16.16 [12.79-20.41]). CONCLUSIONS: Our study demonstrates that GDM is an independent risk factor for adverse neonatal outcomes among SGA infants. This finding underscores the imperative for tailored monitoring and management strategies in those pregnancies.

PGT pregnancies have a similar risk for post-partum complications as naturally conceived pregnancies.

RESEARCH QUESTION: Do preimplantation genetic testing (PGT) pregnancies have higher post-partum complications compared with naturally conceived pregnancies? DESIGN: Retrospective cohort study conducted in 2008-2020 at the Shaare Zedek Medical Center (SZMC), including all patients aged 18-45 years old who conceived following PGT with a singleton live birth >24 weeks. Data were collected from computerized hospital databases and patient files. There were two control groups: (i) pregnancies following IVF-ICSI (intracytoplasmic sperm injection); (ii) four neighbourhood controls for each case delivery (two women delivered before and two after) of women with naturally conceived pregnancies. RESULTS: Overall, 120 PGT, 779 IVF-ICSI and 3507 naturally conceived deliveries were included. Demographic variables were similar apart from slightly higher age in the PGT (P = 0.003) and ICSI (P = 0.002) groups (31.07 ± 4.38 PGT, 31.66 ± 5.03 ICSI, 28.77 ± 5.72 naturally conceived). Composite post-partum placental-related complications (manual lysis of placenta, revision of uterine cavity, haemoglobin drop ≥3 g/dl, post-partum haemorrhage, need for blood transfusion) were more prevalent in both the PGT and IVF-ICSI groups as opposed to naturally conceived (20.0% versus 18.9% versus 10.3%, respectively, P < 0.001, P = 0.007). In a multivariate regression model PGT was not found to be independently associated with composite post-partum placental-related complications (adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.83-2.15), while IVF-ICSI pregnancies had increased risk (aOR 1.52, 95% CI 1.20-1.97) compared with natural conception. No difference was found between fresh and frozen cycles or between day 3 and day 5 embryo transfer. CONCLUSIONS: PGT pregnancies have a comparable risk of post-partum placental-related complications to naturally conceived pregnancies, unlike IVF-ICSI pregnancies. It is possible that infertility itself is the main mediator for post-partum complications in IVF-ICSI pregnancies.

A Scoring System Developed by a Machine Learning Algorithm to Better Predict Adnexal Torsion.

STUDY OBJECTIVE: To establish a clinically relevant prediction score for the diagnosis of adnexal torsion (AT) in women who were operated on for suspected AT. DESIGN: A retrospective cohort study conducted between 2014 and 2021. SETTING: A large tertiary teaching medical center. PATIENTS: Women who underwent urgent laparoscopy for suspected AT. INTERVENTIONS: Analyses included univariate and multivariate models combined with the machine learning (ML) Random Forest model, which included all information available about the women and reported the accuracy of the model and the importance of each variable. Based on this model, we created a predictive score and evaluated its accuracy by receiver operating characteristic (ROC) curve. MEASUREMENTS AND MAIN RESULTS: A total of 503 women were included in our study, 244 (49%) of whom were diagnosed with AT during the surgery, and 44 (8.8%) cases of necrotic ovary were found. Based on the Random Forrest and multivariate models, the most important preoperative clinical predictive variables for AT were vomiting, left-side complaints, and concurrent pregnancy; cervical tenderness and urinary symptoms decreased the likelihood of surgically confirmed AT. The most important sonographic findings that predicted increased risk of surgically confirmed AT were ovarian edema and decreased vascular flow; in contrast, hemorrhagic corpus luteum decreased the likelihood of surgically confirmed AT. The accuracy of the Random Forest model was 71% for the training set and 68% for the testing set, and the area under the curve for the multivariate model was 0.75 (95% confidence interval [CI] 0.69-0.80). Based on these models, we created a predictive score with a total score that ranges from 4 to 12. The area under the curve for this score was 0.72 (95% CI 0.67-0.76), and the best cutoff for the final score was >5, with a sensitivity, specificity, positive predictive value, and negative predictive value of 64%, 73%, 70%, and 67%, respectively. CONCLUSION: Clinical characteristics and ultrasound findings may be incorporated into the emergency room workup of women with suspected AT. ML in this setting has no diagnostic/predictive advantage over the performance of logistic regression methods. Additional prospective studies are needed to confirm the accuracy of this model.

Covid-19 third vaccination during pregnancy: maternal and neonatal outcomes-a retrospective study.

PURPOSE: To evaluate the impact of Covid-19 (Pfizer-BioNTech BNT162b2) third booster dose vaccination during pregnancy on maternal and neonatal outcomes. METHODS: This is a multicenter, retrospective computerized database study. Parturients who delivered in Israel between August and December 2021 with full records of Covid-19 disease and vaccination status were included. Those who received third booster during pregnancy were compared to those who received two doses of vaccine during pregnancy and to unvaccinated parturients. Various adverse maternal and neonatal outcomes were evaluated. Parturients who were previously positive with Covid-19 PCR swabs during pregnancy or before pregnancy were excluded. Univariate analysis was followed by multivariate analysis. RESULTS: A total of 2583 women were included in the analysis; 626 received the third booster dose of the BNT162b2 Covid-19 vaccine, 1094 received two doses of the vaccine, and 863 unvaccinated women. Maternal and neonatal outcomes were comparable between the study groups. An adjusted multivariable logistic regression analysis demonstrated that receiving the third booster was not associated with an increase in neither composite adverse maternal or neonatal outcome (aOR 0.9; 95% CI [0.65-1.22], p = 0.47; aOR 0.7; 95% CI [0.53-1.035], p= 0.09, respectively) when compared to those who received two doses of the vaccine. However, administration of the third booster dose during pregnancy was associated with a reduced composite adverse neonatal outcome when compared to unvaccinated women (aOR 0.6; 95% CI [0.42-0.86], p = 0.01). CONCLUSION: Receiving the third booster dose of the BNT162b2 Covid-19 vaccine during pregnancy is not associated with an increased risk of any adverse maternal outcomes and may be beneficial for the neonates.

Prolonged operative time of cesarean is a risk marker for subsequent cesarean maternal complications.

PURPOSE: Prolonged cesarean operative time (OT) is a well-established proxy for post-operative maternal complications. We aimed to study whether prolonged OT may serve as a proxy for maternal complications in the subsequent cesarean delivery. METHODS: A retrospective cohort study of women who underwent cesarean delivery between 2005 and 2019. Parturients who had two subsequent cesarean deliveries were included and those with Placenta Accreta Syndrome (PAS) were excluded. Prolonged operative time was defined as the duration of cesarean delivery above 60 min. Univariate analyses were followed by multivariate analysis (adjusted Odds Ratio (aORs); [95% Confidence Interval]). RESULTS: A total of 5163 women met the inclusion and exclusion criteria of which 360 (7%) had prolonged operative time. Prolonged operative time of a cesarean section in the index pregnancy was significantly associated in the subsequent cesarean delivery with the following: Prolonged operative time, intra-operative blood loss > 1000 ml, postpartum hemorrhage, blood products transfusion, injuries to the urinary system in the subsequent delivery, and hysterectomy. Multivariate analysis revealed that prolonged OT in the index delivery was associated with composite adverse maternal outcome (aOR 1.46 [1.09-1.95]; P = 0.01) and blood products transfusion (aOR 2.93 [1.90-4.52]; P < 0.01) in the subsequent delivery. CONCLUSION: Prolonged operative may serve as a proxy for adverse maternal outcomes, mostly blood products transfusion, in the subsequent cesarean delivery among women undergoing repeat cesarean delivery.

Trial of labor following cesarean in patients with bicornuate uterus: a multicenter retrospective study.

OBJECTIVE: This study aimed to evaluate whether a trial of labor after cesarean delivery (TOLAC) in women with a bicornuate uterus is associated with increased maternal and neonatal morbidity compared to women with a non-malformed uterus. METHODS: A multicenter retrospective cohort study was conducted at two university-affiliated centers between 2005 and 2021. Parturients with a bicornuate uterus who attempted TOLAC following a single low-segment transverse cesarean delivery (CD) were included and compared to those with a non-malformed uterus. Failed TOLAC rates and the rate of adverse maternal and neonatal outcomes were compared using both univariate and multivariate analyses. RESULTS: Among 20,844 eligible births following CD, 125 (0.6%) were identified as having a bicornuate uterus. The overall successful vaginal delivery rate following CD in the bicornuate uterus group was 77.4%. Failed TOLAC rates were significantly higher in the bicornuate group (22.4% vs. 10.5%, p < 0.01). Uterine rupture rates did not differ between the groups, but rates of placental abruption and retained placenta were significantly higher among parturients with a bicornuate uterus (9.8% vs. 4.4%, p < 0.01, and 9.8% vs. 4.4%, p < 0.01, respectively). Neonatal outcomes following TOLAC were less favorable in the bicornuate group, particularly in terms of neonatal intensive care unit admission and neonatal sepsis. Multivariate analysis revealed an independent association between the bicornuate uterus and failed TOLAC. CONCLUSIONS: This study found that parturients with a bicornuate uterus who attempted TOLAC have a relatively high overall rate of vaginal birth after cesarean (VBAC). However, their chances of achieving VBAC are significantly lower compared to those with a non-malformed uterus. Obstetricians should be aware of these findings when providing consultation to patients.

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.

Is Oxytocin Administration During Childbirth Associated With Increased Risk for Postpartum Posttraumatic Stress Symptoms?: A Preliminary Investigation.

INTRODUCTION: Synthetic oxytocin is one of the most regularly administered medications to facilitate labor induction and augmentation. The present study examined the associations between oxytocin administration during childbirth and postpartum posttraumatic stress symptoms (PTSS). MATERIALS AND METHODS: In a multicenter longitudinal study, women completed questionnaires during pregnancy and at 2 months postpartum (N = 386). PTSS were assessed with the Impact of Event Scale. Logistic regression was used to examine the difference in PTSS at Time 2 between women who received oxytocin and women who did not. RESULTS: In comparison with women who did not receive oxytocin, women who received oxytocin induction were 3.20 times as likely to report substantial PTSS (P = .036, 95% confidence interval: 1.08-9.52), and women who received oxytocin augmentation were 3.29 times as likely to report substantial PTSS (P = .036, 95% confidence interval: 1.08-10.03), after controlling for being primiparous, preeclampsia, prior mental health diagnosis, mode of birth, postpartum hemorrhage, and satisfaction with staff. DISCUSSION: Oxytocin administration was associated with a 3-fold increased risk of PTSS. The findings may reflect biological and psychological mechanisms related to postpartum mental health and call for future research to establish the causation of this relationship.

Laparoscopic negative appendectomy during pregnancy is associated with adverse neonatal outcome.

BACKGROUND: The impact on pregnancy of laparoscopy for acute appendicitis is well documented. However, with an accurate pre-operative diagnosis being more challenging in pregnant patients, the incidence of a negative appendectomy (NA) is higher in this cohort. The aim of this study was to evaluate the maternal and neonatal implications of a NA during pregnancy. METHODS: A single center retrospective study between 2004 and 2019 was performed. Pregnant women who underwent laparoscopic appendectomy for suspected appendicitis were identified from which those who had a pathologically normal appendix were selected. The maternal and neonatal outcome of this group were compared with a matched control group of pregnant women who underwent diagnostic laparoscopy for a presumed ovarian torsion in whom no further surgical intervention was performed. Multivariate regression analysis was performed to explore factors that gestational size. RESULTS: Of the 225 pregnant women who underwent laparoscopy appendectomy, a NA was performed in 33 (14.7%). These were compared with 50 pregnant women in the diagnostic laparoscopy group. The former was characterized by higher rate of nulliparity and later gestational age at the time of the surgery (17.8 ± 7.5 vs 11.3 ± 6.3, p < 0.001). Whilst the rate of maternal complications during pregnancy were similar between the groups, NA was associated with significantly lower neonatal birthweights (2733.9 ± 731.1 vs 3200.7 ± 458.5 g, p = 0.002) and a significantly higher risk of small for gestational age (SGA) infants (OR 5.6, 95% CI 1.02-30.9). CONCLUSIONS: Performing a NA during pregnancy is an indicator for perioperative counseling and antenatal follow up.

Obstetric outcomes of young women following in-vitro fertilization: a case-control study.

BACKGROUND: Women undergoing in-vitro fertilization (IVF) treatments are at increased risk for maternal and neonatal complications compared to women who conceive spontaneously. Though spontaneous pregnancies of young women and adolescents have an increased risk for adverse maternal and neonatal outcomes, pregnancy outcomes of this age group, following IVF treatment have been scarcely reported. The aim of this study was to report maternal and neonatal outcomes of young women who conceived following IVF compared to women in the same age group with spontaneous conception. METHODS: We performed a multicenter case-control study. The study group included women aged 17-25 years who conceived by IVF with an ongoing singleton pregnancy. For the purpose of the study, a control group matched (1:2 ratio) for maternal age at delivery and parity was constructed. Demographic, medical history, pregnancy related characteristics and maternal and neonatal outcomes were compared between groups. Finally, factors associated with spontaneous vaginal delivery were assessed for the entire cohort using a univariate and multivariate logistic regression model. RESULTS: Between 2005 and 2021, we identified 80 women aged 19-25 years who conceived by IVF. A control group of 160 women was matched to the study group by age and parity. The unmatched maternal characteristics and pregnancy associated complications were similar among the groups. However, the IVF group had a significantly higher rate of induction of labor (48.1% vs. 26.6%, p = 0.001), meconium-stained amniotic fluid (27.6% vs. 14.1%, p = 0.025), prolonged second stage of labor (26.0% vs. 7.3%, p = 0.001) and operative vaginal delivery (22.5% vs.12.5%, p = 0.048). Neonatal outcomes were for the most part comparable; nevertheless, we found a higher rate of neonates with an umbilical artery pH < 7.1 in the IVF group (9.8% vs. 0.0%, respectively; p = 0.022). A logistic regression analysis for spontaneous vaginal delivery (vs. cesarean or operative vaginal deliveries) found that spontaneous onset of labor (vs. induction of labor) (OR = 2.08; 95% CI = 1.07-4.05, p = 0.03) was positively associated with spontaneous vaginal delivery while prolonged second stage of labor (OR = 0.35; 95% CI = 0.13-0.95, p = 0.04) was negatively associated with this parameter. CONCLUSION: Young women who conceive by in-vitro fertilization are expected to reach favorable pregnancy outcomes, comparable to women who conceived spontaneously.

Secundiparas following a failed vacuum delivery-factors associated with a successful vaginal delivery: a historical prospective cohort.

BACKGROUND: Few studies have focused on the delivery subsequent to a failed vacuum delivery (failed-VD) in secundiparas. The objective of the current study was to examine the factors associated with a vaginal delivery following a failed-VD. METHODS: An historical prospective cohort. Obstetric characteristics of secundiparas who underwent a planned caesarean delivery (CD) were compared to those who elected a trial of labour (TOLAC) at single medical-centre, throughout 2006-2019. The latter were further analysed to study for factures associated with successful vaginal birth (VBAC). RESULTS: Among the 115 secundiparas included, 89 (77%) underwent TOLAC. Compared to women who underwent an elective CD, those who underwent TOLAC were younger by a mean of 4 years, were more likely to have conceived spontaneously, and had a more advanced gestation by a mean of 10 days. VBAC was achieved in 62 women (70%). New-borns of women with VBAC had in average a lower birth weight compared to those with failed TOLAC, (-)195 g ± 396 g versus ( +)197 g ± 454 g respectively, P < 0.01. Having a higher neonatal birthweight at P2 by increments of 500 g, 400 g or 300 g was associated with a failed TOLAC; OR of 9.7 (95%CI; 2.3, 40.0), 11.5 (95%CI; 2.8, 46.7) and 4.5 (95%CI; 1.4, 13.9), respectively. CONCLUSIONS: Among secundiparas with a previous CD due to a failed-VD, the absolute difference of neonatal BW was found to be significantly associated with achieving VBAC.

Outcomes of attempted vaginal births after previous recurrent operative vaginal deliveries: An individual cumulative risk analysis.

BACKGROUND: Data about the risk of recurrence of vacuum extraction (VE) in multiple consecutive deliveries are scarce. We aimed to evaluate the pattern and individual cumulative risk of recurrence of VE in consecutive term deliveries. STUDY DESIGN: A retrospective cohort study based on a validated electronic database at a single center between 2005 and 2019. For the purpose of the study, we focused on consecutive term deliveries of all primiparas (P1) that had a record of at least one additional delivery during the study period. We identified P1 VE deliveries (reference group) and calculated the individual cumulative risk of repeated VE for three consecutive deliveries. Multivariate analysis was conducted adjusting for potential confounders. RESULTS: We identified 35 113 primiparas that met inclusion criteria. The overall VE rate for P1 was 17.9% (6969 parturient). The cumulative rates of repeated VEs at the 2nd, 3rd, and 4th deliveries were 8.6%, 26.8%, and 25.0%, respectively. The risk of recurrent VE for each of the consecutive deliveries was confirmed after adjustment for confounders (aOR [95% CI]: 5.8 [4.76-7.04], 34.2 [18.59-62.81], and 113.9 [9.77-1328.69] for the 2nd, 3rd, and 4th consecutive deliveries, respectively). CONCLUSION: Women with VE at the first and second deliveries have a substantially increased risk of VE in their following deliveries; this finding may influence woman's preference when choosing future mode of delivery.

Factors Associated With Operatively Confirmed Adnexal Torsion Among Pregnant Women - A Multicenter Cohort Study.

PURPOSE: The aim of this study was to investigate the association of clinical, laboratory, and ultrasound findings with the surgical diagnosis of adnexal torsion in a retrospective cohort of women operated for suspected torsion during pregnancy. MATERIALS AND METHODS: A multicenter retrospective study of pregnant women who underwent urgent laparoscopy for suspected adnexal torsion during 2004-2019 in three tertiary medical centers. RESULTS: Adnexal torsion was found in 143/208 (68.8 %) cases. Women with adnexal torsion had lower parity and lower rates of previous cesarean section, but higher rates of fertility treatments and multiple gestations, and were more likely to report right lower abdominal pain, with shorter duration of symptoms (< 24 hrs) and vomiting but not nausea. Women with adnexal torsion were found to have higher rates of sonographic findings suggestive of ovarian edema, while normal-appearing ovaries on ultrasound were more common in women without torsion. A multivariate logistic regression analysis showed that complaints of right abdominal pain were positively associated with adnexal torsion (aOR [95 % CI] 5.03 (1.45-17.49), while previous cesarean delivery and ultrasound findings of normal-appearing ovaries were negatively associated with adnexal torsion (aOR of 0.17 (0.05-0.52) and 0.10 (0.02-0.43), respectively). CONCLUSION: Clinical characteristics and ultrasound findings may be incorporated into the emergency room workup of pregnant women with suspected adnexal torsion.

PAR1&2 driven placenta EVT invasion act via LRP5/6 as coreceptors.

While the involvement of protease-activated receptors (PARs) in the physiological regulation of human placenta development, as in tumor biology, is recognized, the molecular pathway is unknown. We evaluated the impact of PAR1 and PAR2 function in cytotrophoblast (CTB) proliferation and invasion in a system of extravillous trophoblast (EVT) organ culture and in human cell-lines. Activation of PAR1 - and PAR2 -induced EVT invasion and proliferation, while the shRNA silencing of low-density lipoprotein receptor-related protein 5/6 (LRP5/6) inhibited these processes. PAR1 and PAR2 effectively induce ß-catenin stabilization in a manner similar to that shown for the canonical ß-catenin stabilization pathway yet independent of Wnts. Immunoprecipitation analyses and protein-protein docking demonstrated the co-association between either PAR1 or PAR2 with LRP5/6 forming an axis of PAR-LRP5/6-Axin. Noticeably, in PAR1 -PAR2 heterodimers a dominant role is assigned to PAR2 over PAR1 as shown by inhibition of PAR1 -induced ß-catenin levels, and Dvl nuclear localization. This inhibition takes place either by shRNA silenced hPar2 or in the presence of a TrPAR2 devoid its cytoplasmic tail. Indeed, TrPAR2 cannot form the PAR1 -PAR2 complex, obstructing thereby the flow of signals downstream. Elucidation of the mechanism of PAR-induced invasion contributes to therapeutic options highlighting key partners in the process.

Risk of postpartum hemorrhage in multiparous women with Gaucher disease: A call for reconsidering enzyme replacement therapy in all pregnant patients.

For the last three decades, enzyme replacement therapy (ERT) for Gaucher disease (GD) has been available. We aimed to evaluate the effect of ERT on the pregnancy and obstetric outcome in a unique group of multiparous women with type 1 GD (GD1) who had pregnancies with and without ERT. The Gaucher Unit database (1987-2019) was searched for multiparous women who had pregnancies before and after the institution of ERT. Data were collected from the clinic files and study-specific questionnaires. Descriptive, correlation analysis and generalized estimating equations (GEE) were used to study the effect of ERT and confounding variables on study outcomes. We identified 19 women with 105 pregnancies, among which 26 (24.7%) terminated in first-trimester miscarriage. The risk for miscarriage was associated with the severity of GD1 genotype and phenotype, but not with ERT usage. Early postpartum hemorrhage (PPH) was reported in 16 (84%) women after 25 deliveries (31.6%, 95% CI 21.6%-43.1%). The risks of early PPH and red blood cell (RBC) transfusions were significantly lower when ERT was used during pregnancy, OR (95% CI) 0.13 (0.03-0.54) and 0.27 (0.08-0.94), respectively, compared to pregnancies without the use of ERT. Enzyme replacement therapy during pregnancy is risk reducing for early PPH and RBC transfusions in women with GD1. We suggest considering ERT for the benefit of all pregnant women with GD1, including mild GD1.

Induction of labor at second delivery subsequent to a primary cesarean: is stage of labor at previous cesarean a factor?

PURPOSE: Parturients with a history of a cesarean delivery (CD) in the first delivery (P1), undergoing induction of labor (IOL) in the subsequent delivery (P2) are at increased risk for obstetric complications. The primary aim was to study if "the stage of labor" at previous cesarean (elective/latent/first/second) is associated with a successful IOL. The secondary aim was to search for other obstetric characteristics associated with a successful IOL. METHODS: A retrospective longitudinal follow-up study in a large tertiary medical center. All parturients at term who underwent IOL at P2 with a singleton fetus in cephalic presentation, with a prior CD, between the years 2006 and 2014 were included. A univariate analysis was performed including the stage of labor at previous cesarean, birth weight of newborn at P1 and P2, gestational week of delivery at P2, time of interpregnancy interval, indication and mode of IOL, epidural analgesia and augmentation of labor at P2. Significant factors were incorporated in a multivariate logistic regression model. RESULTS: During the study period, 150 parturients underwent IOL (P2) subsequent to a previous CD (P1). VBAC was achieved in 78 (52%). We found no association between the stages of labor in which the previous CD was performed to a successful IOL. Applying the multivariate logistic regression revealed that augmentation of labor with oxytocin, OR 4.17, [1.73-10.05], epidural analgesia OR 3.30 [1.12-9.73] and birth weight (P2) < 4000 g, OR 5.88, [1.11-33.33] were associated with a successful IOL. CONCLUSION: The stage of labor at previous CD should not be incorporated among the variables found to be associated with a successful IOL. As a result of our findings, clinician's will be able to adjust a personalized consult prior to initiating IOL.

Intrapartum fetal monitoring and perinatal risk factors of neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) in term infants, is a major cause of neonatal mortality and severe neurologic disability. OBJECTIVES: To identify in labor fetal monitoring characteristic patterns and perinatal factors associated with neonatal HIE. STUDY DESIGN: Single-center retrospective case-control study between 2010 and 2017. Cases clinically diagnosed with neonatal HIE treated by therapeutic hypothermia according to strict criteria (HIE-TH) were compared to a group of neonates born in the same period, gestational age-matched diagnosed with fetal distress according to fetal monitoring interpretation that was followed by prompt delivery, without subsequent HIE or therapeutic hypothermia (No-HIE). The primary outcome of the study was the electronic fetal monitoring (EFM) pattern during 60 min prior to delivery; the secondary outcome was the identification of perinatal associated factors. RESULTS: 54 neonates with HIE were treated by therapeutic hypothermia. EFM parameters most predictive of HIE-TH were indeterminate baseline heart rate OR = 47.297, 95% (8.17-273.76) p < 0.001, bradycardia OR = 15.997 95% (4.18-61.18) p < 0.001, low variability OR = 10.224, 95% (2.71-38.45) p < 0.001, higher baseline of the fetal heart rate calculated for each increment of 1 BPM OR = 1.0547, 95% (1.001-1.116) p = 0.047. Rupture of a previous uterine cesarean scar and placental abruption were characteristic of the HIE-TH group 14.8% vs. 1% p < 0.05; and 16.7% vs. 6% p < 0.05, respectively. Adverse neonatal outcomes also differed significantly: HIE-TH had a higher rate of neonatal seizures 46.2% vs. 0% p < 0.001 and mortality 7.7% vs. 0% p < 0.001. CONCLUSIONS: Characteristic fetal monitoring pattern prior to delivery together with acute obstetric emergency events are associated with neonatal HIE, neurological morbidity, and mortality.

Fertility intentions and the way they change following birth- a prospective longitudinal study.

BACKGROUND: Women's fertility intentions, their desired number of children and desired inter-pregnancy interval (IPI) are related to micro (personal) and macro (socio-cultural) level factors. We investigated factors that contribute to changes in women's fertility intentions in Israel, a developed country with high birth rates. METHODS: Pregnant women (N = 1163), recruited from prenatal clinics and hospitals in two major metropolitan areas, completed self-report questionnaires prenatally (≥24 weeks gestation) and postpartum (2 months after childbirth). Women reported their socio-demographic background and obstetric history prenatally, their desired number of children and IPI at both time-points, and their objective and subjective birth experiences postpartum. RESULTS: The findings indicated that background characteristics were related to prenatal fertility intentions. The strongest contributor to prenatal fertility intentions was women's degree of religiosity- the more religious they were, the more children they desired and the shorter their intended IPI. Women's postpartum fertility intentions were mostly consistent with their prenatal reports. In regression models, women who were very-religious, more educated and had previously given birth were less likely to report a lower number of desired of children at postpartum, compared to their prenatal report. Women who reported greater birth satisfaction and gave birth for the first time were less likely to change desired IPI. CONCLUSION: Having a negative birth experience could adversely affect women's fertility intentions. Yet, in a pronatalist and medicalized birth culture, social pressures may decrease the effects of birth experiences on fertility intentions.

Women's preferences for mode of second birth-A prospective study of two Israeli birth cohorts.

INTRODUCTION: Various biopsychosocial factors affect women's preferences with respect to mode of birth, but they are usually not examined simultaneously and prospectively. In the current study, we assessed the contribution of personal characteristics of first-time mothers, their prior prenatal perceptions, events during birth, and subjective birth experiences, on their preference about mode of second birth. METHODS: This was a secondary analysis of two prospective birth cohort studies. Participants included 832 primiparous women recruited mostly from women's health centers in Israel, and through natural birth communities and cesarean birth websites. Women completed questionnaires prenatally and were followed up at 6-8 weeks postpartum to understand their preferences for a second birth. RESULTS: Regression models indicated that after vaginal first birth, being less religious, believing that birth is a medical process, and having a negative experience increased the odds of preferring primary cesarean for the second birth. After cesarean birth, being more religious, having higher education, conceiving spontaneously, having a more negative birth experience, and perceiving better treatment from the staff during birth contributed to preferring vaginal birth for the second birth. CONCLUSIONS: Religiosity is central to women's preferences, probably because of its association with the desire to have many children. Modifiable factors, such as women's beliefs about the nature of birth, their overall birth experience, and their perceived treatment from the staff, could influence the uptake of having vaginal births. Intrapartum care that is empathic and encouraging, along with education about modes of birth, could help decrease cesarean birth rates.