Publications by authors named "Simcha Yagel"

144 Publications

Homeostasis of mucosal glial cells in human gut is independent of microbiota.

Sci Rep 2021 Jun 17;11(1):12796. Epub 2021 Jun 17.

The Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

In mammals, neural crest cells populate the gut and form the enteric nervous system (ENS) early in embryogenesis. Although the basic ENS structure is highly conserved across species, we show important differences between mice and humans relating to the prenatal and postnatal development of mucosal enteric glial cells (mEGC), which are essential ENS components. We confirm previous work showing that in the mouse mEGCs are absent at birth, and that their appearance and homeostasis depends on postnatal colonization by microbiota. In humans, by contrast, a network of glial cells is already present in the fetal gut. Moreover, in xenografts of human fetal gut maintained for months in immuno-compromised mice, mEGCs persist following treatment with antibiotics that lead to the disappearance of mEGCs from the gut of the murine host. Single cell RNAseq indicates that human and mouse mEGCs differ not only in their developmental dynamics, but also in their patterns of gene expression.
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http://dx.doi.org/10.1038/s41598-021-92384-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211706PMC
June 2021

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine.

J Clin Invest 2021 May 20. Epub 2021 May 20.

Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel.

Background: The significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.

Methods: A multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to three study groups: vaccinated (n=86); PCR confirmed SARS-CoV-2 infected during pregnancy (n=65), and unvaccinated non-infected controls (n=62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD and N).

Results: BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (Anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer rate was significantly lower for third-trimester as compared to second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.

Conclusions: Antenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.

Funding: Israel Science Foundation KillCorona grant 3777/19 (to MN, MK, SY, AM). Research grant from the Weizmann Institute Fondazione Henry Krenter (to MN).
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http://dx.doi.org/10.1172/JCI150319DOI Listing
May 2021

The impact of peak and duration of maternal intrapartum fever on perinatal outcomes.

Am J Obstet Gynecol MFM 2021 May 10;3(4):100390. Epub 2021 May 10.

Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Mount Scopus, Jerusalem, Israel (Dr Hochler, Mss Lipschuetz and Cohen, and Drs Yagel and Walfisch).

Background: Intrapartum fever is a common perinatal complication, associated with short- and long-term adverse outcomes. Limited data exist regarding the association between the peak and duration of maternal fever and the extent and severity of maternal and neonatal complications.

Objective: This study aimed to examine the association between maternal intrapartum fever peak and duration and perinatal outcomes.

Study Design: A retrospective cohort analysis of term singleton live births in 2 medical centers between the years 2003 and 2015 was conducted. The study group included parturients who experienced intrapartum fever, defined as a temperature of ≥38.0°C (100.4°F). Fever duration was defined as the time elapsed between the first documented fever and subsequent first documented normal body temperature (<38°C or <100.4°F) or if the temperature did not return to normal until delivery. Adjusted risks for adverse perinatal outcomes were calculated using multiple logistic regression models to control for confounders.

Results: A cohort study of 85,713 deliveries was analyzed, of which 1517 (1.8%) parturients experienced fever during delivery. Adverse composite neonatal outcome gradually worsens, in a dose-response manner, with higher maximal maternal temperature. Similar dose-response deterioration was found when maximal parturient temperature was combined with fever duration (P=.015). Higher or longer maternal fever was not independently associated with cesarean or instrumental deliveries (P=.648). Duration alone was not significantly associated with worsening neonatal outcomes (P=.711).

Conclusion: Maximal intrapartum maternal fever, solely and when combined with fever duration, is correlated with neonatal complications in a dose-dependent manner. Further prospective studies are needed to examine the potential benefit of rigorous maternal body temperature control on perinatal outcomes.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100390DOI Listing
May 2021

NF-kappa-B activation unveils the presence of inflammatory hotspots in human gut xenografts.

PLoS One 2021 3;16(5):e0243010. Epub 2021 May 3.

Department of Basic Sciences, Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel.

The single-epithelial cell layer of the gut mucosa serves as an essential barrier between the host and luminal microflora and plays a major role in innate immunity against invading pathogens. Nuclear factor kB (NF-κB), a central component of the cellular signaling machinery, regulates immune response and inflammation. NF-κB proteins are activated by signaling pathways downstream to microbial recognition receptors and cytokines receptors. Highly regulated NF-κB activity in intestinal epithelial cells (IEC) is essential for normal gut homeostasis; dysregulated activity has been linked to a number of disease states, including inflammatory bowel diseases (IBD) such as Crohn's Disease (CD). Our aim was to visualize and quantify spatial and temporal dynamics of NF-κB activity in steady state and inflamed human gut. Lentivirus technology was used to transduce the IEC of human gut xenografts in SCID mice with a NF-κB luminescence reporter system. NF-κB signaling was visualized and quantified using low resolution, intravital imaging of the whole body and high resolution, immunofluorescence microscopic imaging of the tissues. We show that NF-κB is activated in select subset of IEC with low "leaky" NF-κB activity. These unique inflammatory epithelial cells are clustered in the gut into discrete hotspots of NF-κB activity that are visible in steady state and selectively activated by systemic LPS and human TNFα or luminal bacteria. The presence of inflammatory hotspots in the normal and inflamed gut might explain the patchy mucosal lesions characterizing CD and thus could have important implications for diagnosis and therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092666PMC
May 2021

Neonatal outcome of second-stage cesarean delivery versus vacuum extraction among neonates <34 weeks.

J Matern Fetal Neonatal Med 2020 Dec 1:1-8. Epub 2020 Dec 1.

Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Ramat-Gan, Israel.

Objective: Among deliveries <34 weeks, there is inconclusive evidence regarding the preferred route of delivery when there is a need to expedite delivery during the second stage of labor. As it is unreasonable that future randomized controlled trials will be conducted to settle this query, every clinical data concerning this topic, may be helpful. We aim to compare neonatal outcomes among women undergoing emergent cesarean delivery (ECD) versus vacuum-assisted delivery (VAD) during the second stage of labor among singleton gestations <34 weeks.

Methods: A retrospective cohort study including all women who underwent either ECD or VAD at the second stage of labor between 30° and 33weeks, during 2011-2019. The primary outcome was the rate of adverse neonatal outcomes, defined as intrapartum death, mechanical ventilation, asphyxia, respiratory distress syndrome, subgaleal hemorrhage, intraventricular hemorrhage, necrotizing enterocolitis, and phototherapy.

Results: Of the 153,672 live singleton deliveries during the study period, 2871 (1.9%) delivered before 34°. Of those 1674 (58.3%) delivered vaginally unassisted and 1137 (39.6%) delivered by a CD during the first stage of labor. A total of 60 deliveries were analyzed, with a median gestational age of 32 weeks, interquartile range (IQR) 31-33. Median birth weight at delivery was 1845 g, IQR 1574-2095. Overall 25 (42%) of women were delivered by VAD and 35 by CD (58%). Indications for expeditious delivery did not differ between the study groups. Neonates delivered by VAD had a higher median birth weight (1940 vs. 1620 g,  = .02). Second stage of labor was longer in the ECD group as compared to the VAD group (median 200 vs. 52 min,  = .01). The rate of Apgar score at 1 min <7 was higher among the CD group (10 (40%) vs. 5 (14%), OR [95% CI]: 4.0 (1.1-13.8),  = .03). Longer length of stay was evident in the CD group as compared to the VAD group (median 30 vs. 21 days,  = .001). The rate of composite neonatal adverse outcome was comparable between the study groups. Adverse outcomes were associated with lower body mass index (median 27.7 vs. 34.9,  = .04), higher rate of premature preterm rupture of membranes (40 (91%) vs. 5 (31%), OR [95% CI]: 22.0 (5.0-91.1),  < .001) and labor dystocia as the indication for expedited delivery (38 (86%) vs. 7 (44%), OR [95% CI]: 8.1 (2.1-30.1),  = .001).

Conclusions: Cesarean delivery during the second stage of labor of gestations <34 weeks was associated with a higher rate of lower Apgar scores and longer length of stay.

Synopsis: Delivery by second stage CD of premature neonates <34 weeks is associated with a higher rate of lower Apgar score.
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http://dx.doi.org/10.1080/14767058.2020.1852208DOI Listing
December 2020

Second stage expedite delivery of low birth weight neonates: Emergent cesarean delivery versus vacuum assisted delivery.

J Gynecol Obstet Hum Reprod 2021 Apr 2;50(8):102136. Epub 2021 Apr 2.

The Department of Obstetrics and Gynecology, The Chaim Sheba Medical Center, Israel and the Faculty of Medicine, Tel-Aviv University, Ramat-Gan, Tel-Aviv, Israel. Electronic address:

Objective: To determine maternal and neonatal outcomes among women undergoing second stage emergent cesarean delivery (ECD) versus vacuum-assisted delivery (VAD) of low birthweight neonates.

Materials And Methods: A retrospective cohort study from two tertiary medical centers. We included women who underwent either ECD or VAD during the second stage of labor, and delivered neonates with a birthweight of <2500 g during 2011-2019. Characteristics and outcomes were compared between the groups. The primary outcome was the rate of a composite adverse neonatal outcome, defined as the presence of ≥1 of the following: Apgar 5 min < 7, respiratory distress syndrome, neonatal intensive care unit admission, mechanical ventilation and intrapartum fetal death.

Results: The study cohort included 611 patients, of whom 46 had ECD and 565 had VAD. Baseline characteristics did not differ between the groups. The rate of Apgar score < 7 at 1 min was higher among the ECD group]10 (22%) vs. 29 (5%), OR (95% CI) 5.1 (2.3-11.3), p < 0.001[. Other neonatal and maternal outcomes were similar in both groups.

Conclusions: Neonatal and maternal outcomes do not differ substantially between ECD and VAD of neonates weighing <2500 g. This information may be useful when contemplating the preferred mode of delivery in this setting.
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http://dx.doi.org/10.1016/j.jogoh.2021.102136DOI Listing
April 2021

An integrated model of preeclampsia: a multifaceted syndrome of the maternal cardiovascular-placental-fetal array.

Am J Obstet Gynecol 2021 Mar 9. Epub 2021 Mar 9.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Maternal tolerance of the semiallogenic fetus necessitates conciliation of competing interests. Viviparity evolved with a placenta to mediate the needs of the fetus and maternal adaptation to the demands of pregnancy and to ensure optimal survival for both entities. The maternal-fetal interface is imagined as a 2-dimensional porous barrier between the mother and fetus, when in fact it is an intricate multidimensional array of tissues and resident and circulating factors at play, encompassing the developing fetus, the growing placenta, the changing decidua, and the dynamic maternal cardiovascular system. Pregnancy triggers dramatic changes to maternal hemodynamics to meet the growing demands of the developing fetus. Nearly a century of extensive research into the development and function of the placenta has revealed the role of placental dysfunction in the great obstetrical syndromes, among them preeclampsia. Recently, a debate has arisen questioning the primacy of the placenta in the etiology of preeclampsia, asserting that the maternal cardiovascular system is the instigator of the disorder. It was the clinical observation of the high rate of preeclampsia in hydatidiform mole that initiated the focus on the placenta in the etiology of the disease. Over many years of research, shallow trophoblast invasion with deficient remodeling of the maternal spiral arteries into vessels of higher capacitance and lower resistance has been recognized as hallmarks of the preeclamptic milieu. The lack of the normal decrease in uterine artery resistance is likewise predictive of preeclampsia. In abdominal pregnancies, however, an extrauterine pregnancy develops without remodeling of the spiral arteries, yet there is reduced resistance in the uterine arteries and distant vessels, such as the maternal ophthalmic arteries. Proponents of the maternal cardiovascular model of preeclampsia point to the observed maternal hemodynamic adaptations to pregnancy and maladaptation in gestational hypertension and preeclampsia and how the latter resembles the changes associated with cardiac disease states. Recognition of the importance of the angiogenic-antiangiogenic balance between placental-derived growth factor and its receptor soluble fms-like tyrosine kinase-1 and disturbance in this balance by an excess of a circulating isoform, soluble fms-like tyrosine kinase-1, which competes for and disrupts the proangiogenic receptor binding of the vascular endothelial growth factor and placental-derived growth factor, opened new avenues of research into the pathways to normal adaptation of the maternal cardiovascular and other systems to pregnancy and maladaptation in preeclampsia. The significance of the "placenta vs heart" debate goes beyond the academic: understanding the mutuality of placental and maternal cardiac etiologies of preeclampsia has far-reaching clinical implications for designing prevention strategies, such as aspirin therapy, prediction and surveillance through maternal hemodynamic studies or serum placental-derived growth factor and soluble fms-like tyrosine kinase-1 testing, and possible treatments to attenuate the effects of insipient preeclampsia on women and their fetuses, such as RNAi therapy to counteract excess soluble fms-like tyrosine kinase-1 produced by the placenta. In this review, we will present an integrated model of the maternal-placental-fetal array that delineates the commensality among the constituent parts, showing how a disruption in any component or nexus may lead to the multifaceted syndrome of preeclampsia.
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http://dx.doi.org/10.1016/j.ajog.2020.10.023DOI Listing
March 2021

Length of the Second Stage of Labor in Women Delivering Twins.

Obstet Gynecol 2021 04;137(4):664-669

Departments of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Chaim Sheba Medical Center, Ramat-Gan, and Tel-Aviv University and Lis Maternity Hospital, Tel-Aviv, Israel, and Washington University in St. Louis School of Medicine, St. Louis, Missouri.

Objective: To evaluate the length of the second stage of labor in twin deliveries and to compare the length of the second stage in twin and singleton gestations.

Methods: This is a retrospective cohort study from three large hospitals in Israel. Clinical data were collected from the electronic medical record. The primary outcome was the length of the second stage (the time from documented 10-cm dilation until spontaneous vaginal delivery of the first twin). Multivariable linear regression was used to examine the association of clinical factors with the length of the second stage. The length of the second stage in twin and singleton pregnancies was compared.

Results: From 2011 to June, 2020, there were 2,009 twin deliveries and 135,217 singleton deliveries. Of the twin deliveries, 655 (32.6%) of the patients were nulliparous (95th percentile length of the second stage 3 hours and 51 minutes), 1,235 (61.5%) were parous (95th percentile 1 hour 56 minutes), and 119 (5.9%) were grand multiparous (five or more prior deliveries) (95th percentile 1 hour 24 minutes). In women delivering twins, epidural use was associated with a statistically significant increase in the length of the second stage of 40 minutes in nulliparous patients and 15 minutes in parous patients. In all groups, the length of the second stage was longer in patients delivering twins compared with singletons. Second-stage length longer than the 95th percentile in twins was associated with admission to the neonatal intensive care unit and need for phototherapy.

Conclusion: Second-stage labor is longer in twins than singletons and is associated with obstetric history. Normal ranges for the second stage may be useful in guiding clinical practice.
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http://dx.doi.org/10.1097/AOG.0000000000004308DOI Listing
April 2021

The role of sonographic head circumference in the occurrence of subgaleal hemorrhage following vacuum delivery.

J Matern Fetal Neonatal Med 2021 Feb 3:1-6. Epub 2021 Feb 3.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Objective: Subgaleal hemorrhage (SGH) is a severe neonatal morbidity that is associated with vacuum-assisted delivery (VAD). Large sonographic head circumference (sHC) was previously associated with complicated VAD. Nevertheless, the association of large sHC with SGH formation following VAD is underreported. We aim to evaluate the role of sonographic head circumference (sHC) with SGH formation following attempted VAD.

Methods: A retrospective case-control study. Cases comprised singleton pregnancies for whom attempted VAD resulted in SGH with an sHC measured within 2 weeks from delivery. Controls were VAD deliveries which not resulted in SGH, with an sHC measured within 2 weeks from delivery. We matched controls in a 1:1 ratio by gestational age, parity and year of delivery.

Results: Overall, 118 women were included in the SGH study group and were matched to 118 controls. Baseline maternal and fetal characteristics were similar between the groups except for higher neonatal birth weight in the SGH group (median 3422 vs. 3195 grams,  = .001). sHC did not vary between groups (median 336 mm in SGH groups vs. 333,  = .08). Rate of sHC >90th and >95th percentile did not significantly differ between the groups (13.6% vs. 8.5%, 6.8% vs. 3.4%,  = .21,  = .37, for SGH vs. controls, respectively). In multivariate regression analysis, sHC was not found to be independently associated with SGH - aOR (95% CI) 1.004 (0.97-1.03). Receiver operating characteristic curves of sHC for SGH formation underlined an area under the curve of 0.58 (95% CI) (0.51-0.65).

Conclusions: sHC is not associated with SGH formation following VAD.
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http://dx.doi.org/10.1080/14767058.2021.1882983DOI Listing
February 2021

Induction of labor in women with a scarred uterus: does grand multiparity affect the risk of uterine rupture?

Am J Obstet Gynecol MFM 2020 02 20;2(1):100081. Epub 2019 Dec 20.

Departments of Obstetrics and Gynecology, Hadassah University Medical Center, Mount Scopus, Jerusalem, Israel.

Background: Previous cesarean delivery is the most important risk factor for subsequent uterine rupture. Data are inconsistent regarding grand multiparity (≥6th delivery) and a risk for uterine rupture. Specifically, no data exist regarding the risk that is associated with labor induction or augmentation in grand multiparous women after cesarean delivery.

Objective: This study aimed to examine whether grand multiparity elevates the risk for uterine rupture in trials of labor after 1 previous cesarean that involved induction or augmentation of labor.

Study Design: A retrospective multicenter study was conducted that included all trials of labor after cesarean delivery at 24-42 gestational weeks with vertex presentation between the years 2003-2015. The study groups were defined in the following manner: (1) grand multiparous parturients (current delivery ≥6) who underwent labor induction or augmentation; (2) multiparous parturients (delivery 2-5) who underwent induction or augmentation; (3) grand multiparous parturients with no induction or augmentation of labor. The primary outcome was uterine rupture rate, which was defined as complete separation of all uterine layers. Secondary outcomes were obstetric and neonatal complications.

Results: A total of 12,679 labors were included in the study. The study group included 1304 labors of grand multiparous parturients after 1 previous cesarean delivery, of which 800 parturients underwent induction of labor and 504 parturients received labor augmentation. The multiparous group included 3681 parturients with either labor induction or augmentation. The third group included 7694 grand multiparous parturients without induction or augmentation. Incidence of uterine rupture was similar among the 3 study groups (0.3%, 0.3%, and 0.2%, respectively; P=.847). In the multivariable model that was adjusted for maternal age, ethnicity, diabetes mellitus, birthweight, and prolonged second stage of labor, no association was found between grand multiparity and uterine rupture in women with a scarred uterus who underwent labor induction or augmentation.

Conclusion: Labor induction/augmentation during trial of labor after cesarean delivery in grand multiparous parturients appears to be a reasonable option that has a similar uterine rupture risk as in multiparous parturients. Avoiding a mandatory cesarean delivery enables reduction of the risk for future multiple cesarean deliveries.
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http://dx.doi.org/10.1016/j.ajogmf.2019.100081DOI Listing
February 2020

Wireless, remote solution for home fetal and maternal heart rate monitoring.

Am J Obstet Gynecol MFM 2020 05 17;2(2):100101. Epub 2020 Mar 17.

Obstetrics & Gynecology Division, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Background: Access to prenatal care can be challenging due to physician shortages and rural geography. The multiple prenatal visits performed to collect basic fetal measurements lead to significant patient burden as well. The standard of care tools for fetal monitoring, external fetal heart rate monitoring with cardiotocography, as used today, must be applied by a medical professional in a healthcare setting. Novel tools to enable a remote and self-administered fetal monitoring solution would significantly alleviate some of the current barriers to care.

Objective: To compare maternal and fetal heart rate monitoring data obtained by 'Invu system' (a wireless, wearable, self-administered, fixed-location device containing passive electrical and acoustic sensors) to cardiotocography, toward a true remote fetal monitoring solution.

Materials And Methods: A prospective, open-label, multicenter study evaluated concurrent use of Invu and cardiotocography in pregnant women, aged 18 to 50 years, with singleton pregnancies ≥32+0 weeks' gestation (NCT03504189). Simultaneous recording sessions from Invu and cardiotocography lasted for ≥30 minutes. Data from the 8 electrical sensors and 4 acoustic sensors in the Invu belt were acquired, digitized, and sent wirelessly for analysis by an algorithm on cloud-based servers. The algorithm validates the data, preprocesses the data to remove noise, detects heartbeats independently from the two data sources (electrical and acoustic), and fuses the detected heartbeat arrays to calculate fetal heart rate (FHR) and maternal heart rate (MHR). The primary performance endpoint was Invu FHR limit of agreement within ± 10 beats per minute (bpm) of FHR measured with cardiotocography.

Results: A total of 147 women were included in the study analysis. The mean (SD) maternal age was 31.8 ±6.9 years, and the mean gestational age was 37.7 ±2.3 weeks. There was a highly significant correlation between FHR measurements from Invu and cardiotocography (r = 0.92; P<0.0001). The 95% limits of agreement for the difference, the range within which most differences between the two measurements will lie, were -8.84 bpm to 8.24 bpm. Invu measurements of MHR were also very similar to cardiotocography and were highly significantly correlated (r = 0.97; P<0.0001). No adverse events were reported during the study.

Conclusion: Although captured by very different methods, the FHR and MHR outputs wirelessly obtained by the Invu system through passive methods were very similar to those obtained by the current standard of care. The limits of agreement for FHR measured by Invu were within a clinically acceptable ± 8 bpm of cardiotocography FHR. The Invu device uses passive technology to allow for safe, non-invasive and convenient monitoring of patients in the clinic and remotely. Further work should investigate how remote perinatal monitoring could best address some of the recent challenges seen with prenatal care and maternal and fetal outcomes.

Clinical Trial Information: Registration date: April 20, 2018; First participant enrollment: February 28, 2018; ClinicalTrials.gov registration NCT03504189; https://clinicaltrials.gov/ct2/show/NCT03504189.
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http://dx.doi.org/10.1016/j.ajogmf.2020.100101DOI Listing
May 2020

Is real-time dynamic cervical shortening predictive of preterm birth?- A case control study.

J Matern Fetal Neonatal Med 2020 Dec 15:1-8. Epub 2020 Dec 15.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Objectives: We aimed to assess the risk of preterm birth in those with real-time dynamic cervical shortening.

Methods: A retrospective matched case-control study. The study group comprised all women with dynamic cervical shortening (≥4 mm) noted from 24 to 34 weeks of gestation during 2010-2017 at a university hospital. Two control groups of women were established by matching the minimal and maximal cervical length measured, as well as age, parity, gestational age, history of spontaneous preterm birth, symptoms of preterm labor, and delivery year.

Results: Data from 339 women were analyzed, 113 with dynamic cervical shortening comprised the study group, and two groups with 113 women each, matched for the minimal and maximal cervical lengths measured comprised the control groups. Rates of spontaneous preterm birth rate at <37 weeks (32.7% vs. 15.9%; OR [95% CI]: 2.60 (1.36, 4.87),  = .004) and <35 weeks (15.9% vs. 5.3%; OR [95% CI]: 3.38 (1.29, 8.86),  = .013) were significantly higher among those with dynamic cervix than among the control group matched for the maximal cervical length, and comparable to the control group matched for the minimal cervical length. The negative predictive values of cervical length for preterm birth occurrence at various cutoff values were lower in those with dynamic cervix.

Conclusions: The minimal cervical length measured should be used to guide patient management when dynamic cervix is noted. In the setting of dynamic cervical change, the value of cervical length as a negative predictor of preterm birth is limited.
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http://dx.doi.org/10.1080/14767058.2020.1860936DOI Listing
December 2020

Fetal Head Station at Second-Stage Dystocia and Subsequent Trial of Labor After Cesarean Delivery Success Rate.

Obstet Gynecol 2021 Jan;137(1):147-155

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, and the Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Ramat-Gan, Israel.

Objective: To investigate whether fetal head station at the index cesarean delivery is associated with a subsequent trial of labor success rate among primiparous women.

Methods: A retrospective cohort study conducted at two tertiary medical centers included all primiparous women with subsequent delivery after cesarean delivery for second-stage dystocia during 2009-2019, identified from the electronic medical record databases. Univariate and multivariate analyses were performed to assess the factors associated with successful trial of labor after cesarean (TOLAC) (primary outcome). Additionally, all women with failed TOLAC were matched one-to-one to women with successful TOLAC, according to factors identified in the univariate analysis.

Results: Of 481 primiparous women with prior cesarean delivery for second-stage dystocia, 64.4% (n=310) attempted TOLAC, and 222 (71.6%) successfully delivered vaginally. The rate of successful TOLAC was significantly higher in those with fetal head station below the ischial spines at the index cesarean delivery, as compared with those with higher head station (79.0% vs 60.5%, odds ratio [OR] 2.46, 95% CI 1.49-4.08). The proportion of neonates weighing more than 3,500 g in the subsequent delivery was lower in those with successful TOLAC compared with failed TOLAC (29.7% vs 43.2%, OR 0.56, 95% CI 0.33-0.93). In a multivariable analysis, lower fetal head station at the index cesarean delivery was the only independent factor associated with TOLAC success (adjusted OR 2.38, 95% CI 1.43-3.96). Matching all women with failed TOLAC one-to-one to women with successful TOLAC, according to birth weight and second-stage duration at the subsequent delivery, lower fetal head station at the index cesarean delivery remained the only factor associated with successful TOLAC.

Conclusion: Lower fetal head station at the index cesarean delivery for second-stage dystocia was independently associated with a higher vaginal birth after cesarean rate, with an overall acceptable success rate. These findings should improve patient counseling and reassure those who wish to deliver vaginally after prior second-stage arrest.
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http://dx.doi.org/10.1097/AOG.0000000000004202DOI Listing
January 2021

Successful vaginal birth after cesarean in the second delivery is not associated with the stage of labor of the primary unplanned cesarean delivery.

Eur J Obstet Gynecol Reprod Biol 2021 Jan 4;256:109-113. Epub 2020 Nov 4.

Division of Obstetrics & Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Background: Candidates for trial of labor after cesarean must be carefully screened to maximize success and minimize morbidity. Demographic and obstetric characteristics affecting success rates must be delineated.

Objective: We examined whether the labor stage of the primary delivery in which a woman underwent an unplanned cesarean delivery would affect the likelihood that she could achieve a subsequent vaginal birth.

Study Design: Electronic medical records-based study of 676 parturients. Trial of labor rates and outcomes were compared between women whose primary cesarean delivery was performed in the first vs. the second stage of labor.

Setting: Hadassah Medical Center, Israel POPULATION: Women in their second pregnancies, with singleton fetuses, who underwent unplanned cesarean delivery in their first pregnancy and elected trial of labor in the second delivery. The main outcome measures were maternal and neonatal complications and vaginal birth rates in first vs. second stage of labor groups.

Results: In our population, 76 % of women attempt trial of labor after cesarean. Rates of successful vaginal delivery did not differ significantly between those who underwent primary cesarean in the first vs. second stage of labor: 67.4 % vs. 70.2 %, p = 0.483, respectively. Among women whose primary UCD was in the second stage, only 18.2 % (35/192) required a UCD in the second stage in the subsequent delivery, while 58.9 % (113/192) underwent UCD in the first stage in both deliveries.

Conclusion: Labor stage of the primary unplanned cesarean delivery, should not dissuade women from a trial of labor after cesarean in their second delivery.
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http://dx.doi.org/10.1016/j.ejogrb.2020.10.045DOI Listing
January 2021

Placental vascular tree characterization based on ex-vivo MRI with a potential application for placental insufficiency assessment.

Placenta 2020 11 31;101:252-260. Epub 2020 Aug 31.

Sagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Introduction: Understanding regarding the whole placental vascular network structure is limited. Our aim was to quantitatively characterize the human placental vascular tree ex-vivo using high-resolution MRI.

Methods: 34 normal placentas were rinsed and injected with a solution of gelatin and contrast agent through the umbilical vessels. A sample of six placentas taken from pregnancies with intrauterine-growth-restriction (IUGR) was used to demonstrate the potential application to cases with placental insufficiency. Structural ex-vivo MR scans of the placenta were performed using high resolution T weighted images. A semi-automatic method was developed to segment and characterize the placental vascular architecture: placental volume and cord insertion location; number of bifurcations, generations and vessels diameters.

Results: Different vascular patterns were found in placentas with central versus marginal cord-insertion. Based on the placental volume and number of bifurcations we were able to predict birth weight. Furthermore, preliminary results on IUGR sample demonstrated the potential of this method to differentiate between small newborns with suspected IUGR from small normal newborns who reached their full growth potential. Results obtained using the automatic method were validated against manual values demonstrating no significant differences or bias. Histopathology supported the imaging findings.

Discussion: This is the first study to quantitatively characterize the human placental vascular architecture using high resolution ex-vivo MRI. Different patterns of vascular architecture may be related to different functioning of the placenta and affect fetal development. This method is simple, relatively fast, provides detailed information of the placental vascular architecture, and may have important clinical applications.
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http://dx.doi.org/10.1016/j.placenta.2020.08.001DOI Listing
November 2020

The length of the second stage of labor in nulliparous, multiparous, grand-multiparous, and grand-grand multiparous women in a large modern cohort.

Eur J Obstet Gynecol Reprod Biol 2020 Oct 23;253:273-277. Epub 2020 Aug 23.

The Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Objective: The objectives of this study were to characterize the length of the second stage of labor in a large contemporary cohort of women with varying obstetrical histories and to investigate the factors associated with the length of the second stage.

Study Design: This was a retrospective cohort study conducted at a tertiary medical center. Women with singleton spontaneous vaginal deliveries between the years 2005-2017 were included. The length of the second stage was compared between groups based on obstetrical history and maternal and obstetrical characteristics were evaluated to identify factors associated with the length of the second stage.

Results: There were 100,759 deliveries included in the study. The second stage of labor was longest in nulliparous women with an epidural (median 96 min, interquartile range 53-142 min), which was 57 min longer than in nulliparous women without an epidural. In parous, grand-multiparous, grand-grand multiparous, and women with a prior cesarean delivery, all without an epidural, there was no clinically significant difference in the length of the second stage (median 6-7 min). The length of the second stage was significantly shorter in women delivering preterm compared to women delivering at term. Birthweight, previous cesarean delivery, gestational age, use of epidural analgesia, and induction of labor were all independently positively associated with the length of the second stage, while parity was negatively associated with the length of the second stage.

Conclusion: The median length of the second stage of labor was considerably longer than historically described in nulliparous women and relatively shorter in parous women.
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http://dx.doi.org/10.1016/j.ejogrb.2020.08.029DOI Listing
October 2020

Trophoblast lineage specific expression of the alternative splicing factor RBFOX2 suggests a role in placental development.

Placenta 2020 10 7;100:142-149. Epub 2020 Jul 7.

The Magda and Richard Hoffman Center for Human Placenta Research, Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

Introduction: RBFOX2, an RNA-binding protein, controls tissue-specific alternative splicing of exons in diverse processes of development. The progenitor cytotrophoblast of the human placenta differentiates into either the syncytiotrophoblast, formed via cell fusion, or the invasive extravillous trophoblast lineage. The placenta affords a singular system where a role for RBFOX2 in both cell invasion and cell fusion may be studied. We investigated a role for RBFOX2 in trophoblast cell differentiation, as a foundation for investigations of RBFOX2 in embryo implantation and placental development.

Methods: Immunohistochemistry of RBFOX2 was performed on placental tissue sections from three trimesters of pregnancy and from pathological pregnancies. Primary trophoblast cell culture and immunofluorescence were employed to determine RBFOX2 expression upon cell fusion. Knockdown of RBFOX2 expression was performed with βhCG and syncytin-1 as molecular indicators of fusion.

Results: In both normal and pathological placentas, RBFOX2 expression was confined to the cytotrophoblast and the extravillous trophoblast, but absent from the syncytiotrophoblast. Additionally, we showed that primary trophoblasts that spontaneously fused in cell culture downregulated RBFOX2 expression. In functional experiments, knockdown expression of RBFOX2 significantly upregulated βhCG, while the upregulation of syncytin-1 did not reach statistical significance.

Discussion: RBFOX2, by conferring mRNA diversity, may act as a regulator switch in trophoblast differentiation to either the fusion or invasive pathways. By studying alternative splicing we further our understanding of placental development, yielding possible insights into preeclampsia, where expression of antiangiogenic isoforms produced through alternative splicing play a critical role in disease development and severity.
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http://dx.doi.org/10.1016/j.placenta.2020.07.004DOI Listing
October 2020

Placental vascular tree characterization based on ex-vivo MRI with a potential application for placental insufficiency assessment.

Placenta 2020 07 19;96:34-43. Epub 2020 May 19.

Sagol Brain Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Introduction: Understanding regarding the whole placental vascular network structure is limited. Our aim was to quantitatively characterize the human placental vascular tree ex-vivo using high-resolution MRI.

Methods: 34 normal placentas were rinsed and injected with a solution of gelatin and contrast agent through the umbilical vessels. A sample of six placentas taken from pregnancies with intrauterine-growth-restriction (IUGR) was used to demonstrate the potential application to cases with placental insufficiency. Structural ex-vivo MR scans of the placenta were performed using high resolution T weighted images. A semi-automatic method was developed to segment and characterize the placental vascular architecture: placental volume and cord insertion location, number of bifurcations, generations and vessels diameters.

Results: Different vascular patterns were found in placentas with central versus marginal cord-insertion. Based on the placental volume and number of bifurcations we were able to predict birth weight. Furthermore, preliminary results on IUGR sample demonstrated the potential of this method to differentiate between small newborns with suspected IUGR from small normal newborns who reached their full growth potential. Results obtained using the automatic method were validated against manual values demonstrating no significant differences or bias. Histopathology supported the imaging findings.

Discussion: This is the first study to quantitatively characterize the human placental vascular architecture using high resolution ex-vivo MRI. Different patterns of vascular architecture may be related to different functioning of the placenta and affect fetal development. This method is simple, relatively fast, provides detailed information of the placental vascular architecture, and may have important clinical applications.
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http://dx.doi.org/10.1016/j.placenta.2020.05.001DOI Listing
July 2020

Perinatal Outcome of Twin Pregnancies Complicated by Rupture of Membranes at 13-20 Weeks: Is Selective Termination an Appropriate Management Option?

Ultraschall Med 2020 Aug 15;41(4):e17-e22. Epub 2020 Jun 15.

ObGyn, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Objective:  To evaluate the outcome of twin pregnancies that were complicated by rupture of membranes at 13-20 weeks of gestation and were managed by expectant management or by selective termination.

Methods:  A retrospective cohort study of all bichorionic twin pregnancies that were referred to three fetal medicine units between 2001 and 2016, due to rupture of membranes of one sac at 13-20 weeks of gestation. Women without clinical signs of infection who opted for expectant management or selective termination were included.

Results:  20 patients met the inclusion criteria. 7 of them were managed expectantly and 13 underwent selective termination. In the expectant management group there was one case of fetal demise and two cases of neonatal death, resulting in a survival rate of 79 %. The median gestational age at delivery was 30 weeks. 3 neonates suffered from prematurity-related complications and 2 suffered from oligohydramnios-related orthopedic complications. Following selective termination the survival rate was 50 % (all fetuses that were not reduced), the median gestational age at delivery was 39 weeks, and the neonatal outcome was favorable. The maternal outcome was favorable in both groups.

Conclusion:  Selective termination in twin pregnancies complicated by rupture of membranes at 13-20 weeks has a favorable outcome and should be offered.
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http://dx.doi.org/10.1055/a-1176-0919DOI Listing
August 2020

Real-time data analysis using a machine learning model significantly improves prediction of successful vaginal deliveries.

Am J Obstet Gynecol 2020 09 17;223(3):437.e1-437.e15. Epub 2020 May 17.

Division of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Background: The process of childbirth is one of the most crucial events in the future health and development of the offspring. The vulnerability of parturients and fetuses during the delivery process led to the development of intrapartum monitoring methods and to the emergence of alternative methods of delivery. However, current monitoring methods fail to accurately discriminate between cases in which intervention is unnecessary, partly contributing to the high rates of cesarean deliveries worldwide. Machine learning methods are applied in various medical fields to create personalized prediction models. These methods are used to analyze abundant, complex data with intricate associations to aid in decision making. Initial attempts to predict vaginal delivery vs cesarean deliveries using machine learning tools did not utilize the vast amount of data recorded during labor. The data recorded during labor represent the dynamic process of labor and therefore may be invaluable for dynamic prediction of vaginal delivery.

Objective: We aimed to create a personalized machine learning-based prediction model to predict successful vaginal deliveries using real-time data acquired during the first stage of labor.

Study Design: Electronic medical records of labor occurring during a 12-year period in a tertiary referral center were explored and labeled. Four different models were created using input from multiple maternal and fetal parameters. Initial risk assessments for vaginal delivery were calculated using data available at the time of admission to the delivery unit, followed by models incorporating cervical examination data and fetal heart rate data, and finally, a model that integrates additional data available during the first stage of labor was created.

Results: A total of 94,480 cases in which a trial of labor was attempted were identified. Based on approximately 180 million data points from the first stage of labor, machine learning models were developed to predict successful vaginal deliveries. A model using data available at the time of admission to the delivery unit yielded an area under the curve of 0.817 (95% confidence interval, 0.811-0.823). Models that used real-time data increased prediction accuracy. A model that includes real-time cervical examination data had an initial area under the curve of 0.819 (95% confidence interval, 0.813-0.825) at first examination, which increased to an area under the curve of 0.917 (95% confidence interval, 0.913-0.921) by the end of the first stage. Adding the real-time fetal heart monitor data provided an area under the curve of 0.824 (95% confidence interval, 0.818-0.830) at first examination, which increased to an area under the curve of 0.928 (95% confidence interval, 0.924-0.932) by the end of the first stage. Finally, adding additional real-time data increased the area under the curve initially to 0.833 (95% confidence interval, 0.827-0.838) at the first cervical examination and up to 0.932 (95% confidence interval, 0.928-0.935) by the end of the first stage.

Conclusion: Real-time data acquired throughout the process of labor significantly increased the prediction accuracy for vaginal delivery using machine learning models. These models enable translation and quantification of the data gathered in the delivery unit into a clinical tool that yields a reliable personalized risk score and helps avoid unnecessary interventions.
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http://dx.doi.org/10.1016/j.ajog.2020.05.025DOI Listing
September 2020

Low volume forceps practice and anal sphincter injury rate.

Arch Gynecol Obstet 2020 05 6;301(5):1133-1138. Epub 2020 Apr 6.

The Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.

Purpose: While the increased rates of high degree perineal tears were previously associated with the use of forceps, in the current era of low volume of forceps practice, factors associated with the occurrence of this potential complication remain understudied. We aim to evaluate factors associated with obstetric anal sphincter injury (OASIS) in obstetric units with a low volume forceps practice.

Methods: A retrospective cohort study was conducted at two tertiary medical centers. All singleton pregnancies delivered by forceps extraction between 2011 and 2019 were analyzed. Women who experienced anal sphincter injury were compared to those who did not.

Results: The study cohort included 764 forceps deliveries. There were 19 (2.5%) cases of OASIS. Women with anal sphincter injury had higher rates of gestational diabetes mellitus (21% vs. 5.6%, OR [95% CI] 4.46 (1.41-14.04), p = 0.02). Birth weights and the rate of macrosomia did not differ between groups. Induction of labor was more common among the OASIS group (68% vs. 41.7%, OR [95% CI] 3.0 (1.1-8.0), p = 0.02). Sequential use of forceps (after failed vacuum attempt) was associated with OASIS (8 (42%) vs. 76 (10.2%), OR [95% CI] 6.4 (2.5-16.4), p < 0.001). In a multivariate logistic regression, sequential forceps was the only factor independently associated with OASIS (OR [95% CI] 4.7 (1.3-18.2), p = 0.02).

Conclusions: Rate of OASIS was relatively low in the current cohort. Sequential use of forceps was found to be the most important determinant in OASIS occurrence.
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http://dx.doi.org/10.1007/s00404-020-05519-0DOI Listing
May 2020

[UTERINE PRESERVING METHODS FOR TREATING PLACENTA ACCRETA SPECTRUM: A PROPOSAL FOR A SURGICAL PROTOCOL].

Harefuah 2020 Mar;159(3):186-190

Obstetrics and Gynecology Department, Hadassah Mt. Scopus Medical Center, Jerusalem, Israel.

Introduction: Placenta accrete spectrum (PAS) is a complicated obstetrical condition arising from abnormal implantation of the placenta into the myometrium. The placenta might partially or completely adhere to the myometrium and in rare cases invade adjacent organs (placenta percreta). The abnormal placentation might cause life-threatening hemorrhages during pregnancy and birth, increasing maternal and neonatal mortality and morbidity. Detachment of the placenta after delivery in PAS might be difficult and requires manual removal of the placenta as well as advanced surgical procedures in more serious cases. In the past decades, several studies have demonstrated that removing the uterus while the placenta is still in situ avoided massive hemorrhage. However, in some cases, preserving the uterus and the fertility of the patient is desired and therefore advanced surgical procedures have been developed. Several techniques for uterine preserving procedures have been described: conservative management - closing the uterus while the placenta is still in situ and complementary procedures to remove the placenta, using interventional radiology to reduce the blood supply to the uterus and other surgical approaches to reduce the blood supply to the uterus. In this article we will review the different methods for uterine preserving techniques in treating advanced cases of PAS and propose a surgical protocol for such a method we use in our medical center.
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March 2020

Which way is better to deliver the very heavy baby: mode of delivery, maternal and neonatal outcome.

Arch Gynecol Obstet 2020 04 3;301(4):941-948. Epub 2020 Mar 3.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.

Purpose: Currently there are no existing data regarding the maternal and neonatal outcomes for nulliparous women delivering neonates with birthweight above 4500 g. We aim to evaluate birth outcome among these subset of parturients.

Methods: A retrospective study of nulliparous delivering a singleton fetus weighing  ≥ 4500 g in two tertiary medical centers between 2007 and 2018. Women who chose to undergo a trial of labor (TOL) were compared to those who underwent elective cesarean delivery (CD).

Results: Overall, 121 women were included. Seventy eight (65.4%) women elected a TOL while 43 (34.6%) had elective CD. Of women who chose TOL, 46 (59%) delivered with unassisted vaginal delivery, 28 (36%) by intrapartum CD, and 4 (5%) by assisted vaginal delivery, reaching TOL success rate of 64% (50/78). The rates of shoulder dystocia and anal sphincter injury in vaginal deliveries were 5/50 (10%) and 2/50 (4%) respectively. Successful TOL was negatively associated with the presence of gestational diabetes [5 (18%) vs. 0 (0%), OR 0.8 (95% CI 0.7-0.9), p = 0.005], and was positively associated with maternal height (median 170 cm vs. 165 cm, p = 0.002), epidural analgesia [42 (84%) vs. 16 (57%), OR 3.5 (95% CI 1.2-9.8), p = 0.009] and spontaneous onset of labor (38 (76%) vs. 10 (36%), OR 5.7 (95% CI 2.1-15.6), p = 0.001. Neonates born after TOL were more commonly complicated by meconium aspiration syndrome as compared to no TOL (9 (11%) vs. 0 (0%), OR 1.1 (95% CI 1.04-1.22, p = 0.02). Only maternal height was independently associated with successful TOL (aOR 6.9 (95% CI 1.03-46.3, p = 0.04). Maternal and neonatal adverse composite outcomes were associated with gestational hypertensive disorders (10 (50%) vs. 5 (5%). OR 19.2 (5.5-67.4), p < 0.001) and with delivery before 40 weeks (9 (57%) vs, 86 (82%), OR 3.5 (95% CI 1.2-10.6, p = 0.02), respectively.

Conclusions: Trial of vaginal delivery in nulliparous with fetuses ≥ 4500 g was associated with a high failure rate, with only two thirds of parturients achieving successful vaginal delivery. Nevertheless, neonatal outcomes mostly did not differ according to the mode of delivery. Maternal height was the only factor associated with successful vaginal delivery.
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http://dx.doi.org/10.1007/s00404-020-05474-wDOI Listing
April 2020

Trial of Labor After Cesarean in Adolescents - A Multicenter Study.

J Pediatr Adolesc Gynecol 2020 Aug 19;33(4):398-402. Epub 2020 Feb 19.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Study Objective: Data regarding trial of labor after cesarean delivery (TOLAC) among young women are limited. The aim of this study was to assess the TOLAC success rate and its related factors among adolescent women who had never delivered vaginally.

Design: A multicenter retrospective cohort study of all adolescent women aged ≤21 years with a history of 1 previous cesarean delivery, who delivered in 2 tertiary medical centers during 2007-2019. Women were allocated to 2 groups: 1) women who underwent TOLAC, and 2) women who had a repeat cesarean delivery with no trial of labor. Maternal and neonatal outcomes were compared between the two groups. In addition, perinatal outcomes were compared between women with successful and unsuccessful TOLAC.

Results: The study cohort included 167 women who had a previous caesarean delivery; 117 underwent TOLAC and 50 underwent a repeat cesarean delivery with no trial of labor. Neonatal birthweight (median 2937 vs 3170 g, P = .03) and gestational age at delivery (median 38 weeks vs 39, P = .009) were lower in the repeat cesarean group as compared to those undergoing TOLAC. Overall, 97 of 117 participants (83%) had a successful TOLAC. Failed TOLAC was associated low birthweight as compared to successful TOLAC (5 [25%] vs 7 [7%], odds ratio [OR] 4.3, 95% confidence interval [CI] 1.2-15.3, P = .02), and birthweight difference between current and previous deliveries was higher in the failed TOLAC group (median 315 vs 197 g, P = .04). Rates of neonatal Apgar score at 1 minute < 7 and of neonatal intensive care unit admission were higher in the TOLAC failure group (4 [20%] vs 5 [5%], OR 4.6, 95% CI 1.1-19.0, P = .03, and 4 [20%] vs 4 [4%], OR 5.8, 95% CI 1.3-25.6, P = .02), respectively). In a multivariable logistic regression analysis, only low birthweight was independently associated with TOLAC failure (adjusted OR 9.9, 95% CI 2.1-45.4, P = .003). Two cases of uterine rupture occurred in the no trial of labor group, whereas none were encountered in participants undergoing TOLAC.

Conclusions: TOLAC in adolescent women who had never delivered vaginally is associated with a relatively high success rate.
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http://dx.doi.org/10.1016/j.jpag.2020.02.006DOI Listing
August 2020

Factors associated with postcesarean blood transfusion: a case control study.

J Matern Fetal Neonatal Med 2020 Feb 11:1-8. Epub 2020 Feb 11.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Cesarean delivery (CD) is a known risk factor for postpartum hemorrhage. However, the characteristics associated with post-CD transfusion are not well-established. We aimed to assess blood transfusion rates and associated factors following CD. A retrospective case-control study of women who underwent CD at a university hospital. The study group comprised all women who received blood transfusion following surgery. A control group of women who did not receive postoperative blood transfusion was assigned in a two-to-one ratio. During study period, the overall post-CD blood transfusion rate was 4.7%. The study group comprised 170 women, and the control group 340. Maternal age (aOR [95% CI]: 1.07 (1.03, 1.11),  = .001), parity (aOR [95% CI]: 1.26 (1.09, 1.47),  = .002), gestational hypertensive disorders (aOR [95% CI]: 4.07 (1.52, 10.91),  = .005), maternal comorbidities (aOR [95% CI]: 4.16 (1.88, 9.1),  < .001), lower predelivery hemoglobin level (aOR [95% CI]: 0.43 (0.34, 0.54),  < .001), and major placental abnormalities (aOR [95% CI]: 2.74 (1.04, 7.18),  = .04) were independently associated with blood transfusion requirement. Intrapartum characteristics associated with blood transfusion requirement included nonelective procedure (aOR [95% CI]: 3.21 (1.72, 5.99),  < .001), prolonged second stage of labor (aOR [95% CI]: 5.50 (2.57, 11.78),  < .001), longer duration of surgery (aOR [95% CI]: 1.03 (1.02, 1.04),  < .001), general anesthesia (aOR [95% CI]: 2.11 (1.14, 3.91),  = .02), and greater estimated operative blood loss (aOR [95% CI]: 5.72 (3.15, 10.36),  < .001). Among women who underwent CD, we identified 11 factors associated with blood transfusion following surgery. Prospective studies are warranted to assess the implementations of prophylactic interventions to reduce transfusion rates among those deemed at high risk for CD-related bleeding.
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http://dx.doi.org/10.1080/14767058.2020.1724945DOI Listing
February 2020

Cervical dilation at the time of epidural catheter insertion is not associated with the degree of prolongation of the first or second stages of labor, or the rate of instrumental vaginal delivery.

Acta Obstet Gynecol Scand 2020 08 21;99(8):1039-1049. Epub 2020 Feb 21.

Division of Obstetrics & Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Introduction: Epidural analgesia (EA) is an established option for efficient intrapartum analgesia. Meta-analyses have shown that EA differentially affects the first stage of labor but prolongs the second. The question of EA timing remains open. We aimed to investigate whether EA prolongs delivery in total and whether the EA administration timing vis-à-vis cervical dilation at catheter insertion is associated with a modulation of its effects on the duration of the first and second stages, as well as the rate of instrumental vaginal delivery in primiparas and multiparas.

Material And Methods: A retrospective electronic medical records-based study of 18 870 singleton term deliveries occurring in our institution from 2003 to 2015. Cervical dilation was determined within a half-hour of EA administration. We examined whether cervical dilation at EA administration correlated with the duration of the first and/or second stage, with the rate of prolonged second stage, and with the rate of interventional delivery. The study group was stratified to 10 subgroups defined by 1-cm intervals of cervical dilation at EA administration. Logistic regression modeling was applied to analyze the association between EA timing and rate of instrumental delivery while controlling for possible confounders.

Results: In primiparas, receiving EA correlated with longer medians of active first stage (+51 minutes; P < .001) and second stage (+55 minutes; P < .001). In multiparas, median increases in active first stage (+43 minutes; P < .001) and second stage (+8 minutes; P < .001) were noted. The timing of EA, vis-à-vis cervical dilation (1-10 cm) was not associated with a substantial modulation of these effects. Logistic regression showed that cervical dilation at EA was not associated with a higher instrumental vaginal delivery rate.

Conclusions: Epidural analgesia prolonged the first and second stages of labor vs no epidural. Having EA was associated with a higher instrumental delivery rate but not with higher rates of maternal or neonatal complications, in primi- and multiparas. Importantly, the timing of EA, vis-à-vis cervical dilation, was not associated with substantial changes in the duration of labor stages or the instrumental delivery rate. Thus, EA may be offered early in the first stage of labor.
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http://dx.doi.org/10.1111/aogs.13822DOI Listing
August 2020

Recurrence risk of preterm birth in a subsequent singleton pregnancy after a spontaneous preterm triplet delivery.

Eur J Obstet Gynecol Reprod Biol 2020 Mar 22;246:123-128. Epub 2020 Jan 22.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Objective: History of prior preterm birth (PTB) represents one of the strongest risk factors for recurrent PTB. Nevertheless, whether the occurrence of PTB in multifetal gestation is associated with increased risk of PTB in subsequent pregnancies remains unclear. We aimed to determine the recurrence risk of PTB in a subsequent singleton pregnancy after a previous spontaneous preterm triplet delivery.

Study Design: A retrospective matched case-control study. The study group comprised all women with spontaneous preterm trichorionic triplet delivery who had a subsequent singleton pregnancy during 2006-2017 at two university hospitals. A control group of women with spontaneous preterm dichorionic twin delivery and a subsequent singleton pregnancy, was established by matching, four-to-one, according to maternal age, parity, gestational age at delivery, and delivery year.

Results: Data from 170 women were analyzed, 34 with preterm triplet delivery and 136 matched control women with preterm twin delivery. Gestational age at the subsequent singleton delivery was higher in those with preterm triplet delivery than in those with preterm twin delivery (median 39 vs 38 weeks, P = 0.02). Women with prior triplet PTB had a significantly lower rate of recurrent PTB as compared with women with prior twin PTB (5.9 % vs. 25.0 %; OR [95 % CI]: 0.19 (0.04, 0.82), P = 0.02) with lower proportions of low-birth weight infants (<2500 g) (0 % vs. 11.8 %, P = 0.04).

Conclusions: The risk of recurrent PTB following spontaneous PTB in triplet pregnancy was low compared to preterm twin delivery. These data provide reassurance for those who experienced preterm triplet delivery and suggest the need for further studies to understand the mechanisms contributing to PTB in multifetal pregnancies.
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http://dx.doi.org/10.1016/j.ejogrb.2020.01.026DOI Listing
March 2020

Prediction of vaginal birth after cesarean deliveries using machine learning.

Am J Obstet Gynecol 2020 06 30;222(6):613.e1-613.e12. Epub 2020 Jan 30.

Obstetrics & Gynecology Division, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Background: Efforts to reduce cesarean delivery rates to 12-15% have been undertaken worldwide. Special focus has been directed towards parturients who undergo a trial of labor after cesarean delivery to reduce the burden of repeated cesarean deliveries. Complication rates are lowest when a vaginal birth is achieved and highest when an unplanned cesarean delivery is performed, which emphasizes the need to assess, in advance, the likelihood of a successful vaginal birth after cesarean delivery. Vaginal birth after cesarean delivery calculators have been developed in different populations; however, some limitations to their implementation into clinical practice have been described. Machine-learning methods enable investigation of large-scale datasets with input combinations that traditional statistical analysis tools have difficulty processing.

Objective: The aim of this study was to evaluate the feasibility of using machine-learning methods to predict a successful vaginal birth after cesarean delivery.

Study Design: The electronic medical records of singleton, term labors during a 12-year period in a tertiary referral center were analyzed. With the use of gradient boosting, models that incorporated multiple maternal and fetal features were created to predict successful vaginal birth in parturients who undergo a trial of labor after cesarean delivery. One model was created to provide a personalized risk score for vaginal birth after cesarean delivery with the use of features that are available as early as the first antenatal visit; a second model was created that reassesses this score after features are added that are available only in proximity to delivery.

Results: A cohort of 9888 parturients with 1 previous cesarean delivery was identified, of which 75.6% of parturients (n=7473) attempted a trial of labor, with a success rate of 88%. A machine-learning-based model to predict when vaginal delivery would be successful was developed. When features that are available at the first antenatal visit are used, the model showed a receiver operating characteristic curve with area under the curve of 0.745 (95% confidence interval, 0.728-0.762) that increased to 0.793 (95% confidence interval, 0.778-0.808) when features that are available in proximity to the delivery process were added. Additionally, for the later model, a risk stratification tool was built to allocate parturients into low-, medium-, and high-risk groups for failed trial of labor after cesarean delivery. The low- and medium-risk groups (42.4% and 25.6% of parturients, respectively) showed a success rate of 97.3% and 90.9%, respectively. The high-risk group (32.1%) had a vaginal delivery success rate of 73.3%. Application of the model to a cohort of parturients who elected a repeat cesarean delivery (n=2145) demonstrated that 31% of these parturients would have been allocated to the low- and medium-risk groups had a trial of labor been attempted.

Conclusion: Trial of labor after cesarean delivery is safe for most parturients. Success rates are high, even in a population with high rates of trial of labor after cesarean delivery. Application of a machine-learning algorithm to assign a personalized risk score for a successful vaginal birth after cesarean delivery may help in decision-making and contribute to a reduction in cesarean delivery rates. Parturient allocation to risk groups may help delivery process management.
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http://dx.doi.org/10.1016/j.ajog.2019.12.267DOI Listing
June 2020

Unplanned Cesarean Delivery in the Second Stage of Labor Holds Higher Odds of Complications than in the First Stage, while Similar in Primiparas and Multiparas.

Fetal Diagn Ther 2020 24;47(7):565-571. Epub 2020 Jan 24.

The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

Background: While endeavors to reduce cesarean delivery (CD) rates are given priority worldwide, it is important to evaluate if these efforts place parturients and neonates at risk. CD performed in the second stage of labor carries higher risks of maternal and fetal complications and is a more challenging surgical procedure than that performed in the first stage or before labor. In a population with a low CD rate, we sought to evaluate the rate of maternal and fetal complications associated with unplanned CD (UCD) performed in the second vs. the first stage of labor, in primiparas and multiparas, as well as the risk factors leading to and the complications associated with UCD in the second stage of labor in this low-CD rate setting.

Methods: This was a retrospective, electronic medical record-based study of 7,635 term and preterm singletons born via UCD in the period 2003-2015. Maternal and neonatal background and outcome parameters were compared between groups. Logistic regression modeling was applied to adjust for clinically and statistically significant risk factors.

Results: UCD was more likely to be performed in the second stage of labor in mothers delivering larger fetuses (head circumference and body weight ≥90 centile) and those with persistent occiput posterior (POP) presentation. UCD in the second stage was strongly associated with serious maternal complications (excessive hemorrhage and fever) compared to UCD performed in the first stage, in both primiparas and multiparas.

Conclusions: UCD performed in the second stage of labor, while less frequent than first-stage UCD, is more likely with larger neonates and POP presentation, and is associated with a higher rate of maternal complications in primiparas and multiparas. Complication rates in our low-CD-rate population did not exceed those reported in the literature from high-CD-rate areas.
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http://dx.doi.org/10.1159/000504573DOI Listing
May 2021

Factors associated with the severity of neonatal subgaleal haemorrhage following vacuum assisted delivery.

Eur J Obstet Gynecol Reprod Biol 2020 Feb 28;245:205-209. Epub 2019 Dec 28.

Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Objective: To evaluate factors associated with subgaleal hemorrhage (SGH) severity following attempted vacuum-assisted delivery (VAD).

Study Design: This retrospective cohort study was conducted in a tertiary medical center. The population comprised parturients who delivered at our medical center during 2009-2018, and who underwent attempted VAD with singleton pregnancies that resulted in neonatal SGH formation. SGH severity was classified as mild and non-mild (moderate or severe). The main outcome measures were determinants associated with SGH severity.

Results: Among 350 neonates with SGH, the degree of severity was non-mild for 48 (13.7%). Compared to the mild group, in the non-mild group, small for gestational age was more common (8.2% vs. 2.6%, p = 0.04). Compared to the mothers in the mild group, in the non-mild group, the proportion with two or more deliveries was lower (0% vs. 7.3%, p = 0.05), gestational diabetes was more common (12.5% vs. 4.6%, p = 0.02), the rate of cervical ripening was higher (27.1% vs. 12.9%, p = 0.02), the duration of the second stage of delivery was longer (mean 177 vs. 152 min, p = 0.04), and the rate of two dislodgments was higher (31.2% vs. 15.2%, p = 0.006). On multivariate analysis, only cervical ripening (adjusted odds ratio [OR]: 2.50; 95% confidence interval [CI]: 1.20-5.26; P = 0.01 and second stage duration (adjusted OR: 1.13; 95% [CI]: 1.00-1.29; P = 0.05) were independently associated with more severe SGH.

Conclusions: The duration of second stage and ripening of the cervix during induction of labor are independently associated with SGH severity following attempted VAD.
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http://dx.doi.org/10.1016/j.ejogrb.2019.12.012DOI Listing
February 2020