Publications by authors named "Rinat Gabbay-Benziv"

74 Publications

The expression of heparanase in term and preterm human placentas.

J Matern Fetal Neonatal Med 2021 Mar 10:1-6. Epub 2021 Mar 10.

Laboratory for Reproductive Immunology, Department of Obstetrics and Gynecology, The Hillel Yaffe Medical Center, Hadera, Israel, The Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

Purpose: Heparanase is an endo--glucuronidase that cleaves side chains of heparan-sulfate proteoglycans, an integral constituent of the extra cellular matrix. The abundance of heparanase in placental trophoblast cells implies its role in the processes of placentation and trophoblast invasion. This study aims to explore the involvement of heparanase in parturition and preterm deliveries (PTD).

Methods: Sixteen human placentas were collected following singleton spontaneous onset term vaginal deliveries ( = 6), spontaneous onset preterm vaginal deliveries ( = 7) and term elective cesarean sections ( = 3). Placentas were excluded in case of any maternal chronic illness, pregnancy or delivery complications apart from PTD. Placental tissue samples were dissected, homogenized and proteins were extracted. Additionally, cryosections were prepared from the placental tissues. Heparanase expression was evaluated utilizing western blot analysis and immunofluorescence staining using heparanase specific antibodies. Heparanase expression was compared between the study groups qualitatively and quantitatively.

Results: Western blot analysis results demonstrated higher expression of both pro-heparanase and heparanase in PTD placentas compared to term vaginal placentas. Accordingly, immunofluorescence staining shows elevated heparanase expression in PTD placentas compared to term vaginal placentas (5.1 ± 0.92 vs. 1.2 ± 0.18,  < .005). Expression level of heparanase was higher in term cesarean section placentas as compared to term vaginal deliveries placentas, but did not reach statistical significance (1.8 ± 0.39 vs. 1.2 ± 0.18,  = .06).

Conclusion: This study demonstrates for the first time that preterm vaginal deliveries are associated with higher expression of heparanase in placental tissue. This may imply a direct effect of heparanase on preterm labor. Further studies should evaluate the functional role by which heparanase influence preterm delivery.
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http://dx.doi.org/10.1080/14767058.2021.1895743DOI Listing
March 2021

The Accuracy of Sonographic Fetal Head Circumference in Twin Pregnancies.

J Obstet Gynaecol Can 2021 Feb 20. Epub 2021 Feb 20.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel; The Rappaport Faculty of Medicine, Technion, Haifa, Israel.

Objective: To assess the accuracy of sonographic estimation of fetal head circumference in twin gestations.

Methods: A retrospective analysis of sonographic evaluations of twin gestations >34 weeks, performed within 7 days of delivery, in a single university-affiliated medical centre. Sonographic head circumference was compared with neonatal head circumference. Measures of accuracy included systematic error, random error, proportion of estimates within 5% of neonatal head circumference, and reliability analysis. Accuracy of sonographic head circumference was compared between the first and second twin.

Results: Overall, 103 twin gestations were evaluated at a median of 4 days before delivery. The majority of twins were dichorionic-diamniotic (83%). Median gestational age at delivery was 37 weeks, with a median birthweight of 2645 grams for the first twin and 2625 grams for the second twin. For all fetuses, median sonographic head circumference was lower than the neonatal head circumference (first twin: 317.5 vs. 330 mm; second twin: 318.4 vs. 330 mm, P > 0.05 for both). Measures of accuracy showed no significant difference between first and second twin. There was no difference in the number of sonographic head circumference evaluations that were within 5% of the neonatal head circumference between fetuses (64% for both twins). Cronbach α value was higher for the second twin (0.746 vs. 0.613), suggesting higher accuracy for head circumference measurement for the second twin.

Conclusion: In our cohort, sonographic head circumference underestimated postnatal head circumference. Accuracy measurements were not significantly different between the first and second twin.
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http://dx.doi.org/10.1016/j.jogc.2021.02.114DOI Listing
February 2021

Parity and Interval from Previous Delivery-Influence on Perinatal Outcome in Advanced Maternal Age Parturients.

J Clin Med 2021 Jan 26;10(3). Epub 2021 Jan 26.

Obstetrics and Gynecology Department, Hillel Yaffe Medical Center, Hadera 38100, Israel.

Objective: To investigate the effect of parity and interpregnancy interval (IPI) on perinatal outcomes in advanced maternal age (AMA) parturients.

Methods: A population-based retrospective cohort study of all women older than 40 years, who had a singleton live birth after 24 weeks in the United States in 2017 Women were categorized to three groups by parity and interval from last delivery: primiparas, multiparas with IPI ≤ 5 years, and multiparas with IPI > 5 years. Primary outcome was composite adverse neonatal outcome (preterm delivery <34 weeks, birthweight <2000 g, neonatal seizure, neonatal intensive care unit admission, Apgar score <7 at 5 min, or assisted ventilation >6 h). Secondary outcome was composite adverse maternal outcome and other adverse perinatal outcomes. Univariate and multivariate analysis were used to compare between groups.

Results: During 2017, 3,864,754 deliveries were recorded into the database. Following exclusion, 109,564 AMA gravidas entered analysis. Of them, 24,769 (22.6%) were nulliparas, 39,933 (36.4%) were multiparas with IPI ≤ 5 years, and 44,862 (40.9%) were multiparas with IPI > 5 years. Composite neonatal outcome was higher in nulliparas and in multiparas with IPI > 5 years, in comparison to multiparas with IPI ≤ 5 years (16% vs. 13% vs. 10%, respectively, < 0.05). Maternal composite outcome was similar between groups. In the multivariable analysis, relative to nulliparas, only multiparity with IPI ≤ 5 years had a protective effect against the composite neonatal outcome (aOR 0.97, 95% CI 0.95-0.99, < 0.001).

Conclusion: Among AMA gravidas, multiparity with IPI ≤ 5 years has a significant protective effect against adverse neonatal outcomes when compared to nulliparas. Multiparity with IPI > 5 years is no longer protective.
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http://dx.doi.org/10.3390/jcm10030460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865726PMC
January 2021

Continuous Maternal Hemodynamics Monitoring at Delivery Using a Novel, Noninvasive, Wireless,PPG-Based Sensor.

J Clin Med 2020 Dec 22;10(1). Epub 2020 Dec 22.

Obstetrics and Gynecology department, Hillel Yaffe Medical Center, Hadera 38100, Israel.

Objective: To evaluate continuous monitoring of maternal hemodynamics during labor and delivery utilizing an innovative, noninvasive, reflective photoplethysmography-based device.

Study Design: The Biobeat Monitoring Platform includes a wearable wristwatch monitor that automatically samples cardiac output (CO), blood pressure (BP), stroke volume (SV), systemic vascular resistance (SVR), heart rate (HR) every 5 s and uploads all data to a smartphone-based app and to a data cloud, enabling remote patient monitoring and analysis of data. Low-risk parturients at term, carrying singletons pregnancies, were recruited at early delivery prior to the active phase. Big data analysis of the collected data was performed using the Power BI analysis tool (Microsoft). Next, data were normalized to visual presentation using Excel Data Analysis and the regression tool. Average measurements were compared before and after rupture of membranes, epidural anesthesia, fetal delivery, and placental expulsion.

Results: Eighty-one parturients entered analysis. Epidural anesthesia was associated with a slight elevation in CO (5.5 vs. 5.6, L/min, 10 min before and after EA, 0.05) attributed to a non-significant increase in both HR and SV. BP remained stable as of counter decrease in SVR (1361 vs. 1319 mmHg⋅min⋅mL, 10 min before and after EA, 0.05). Fetal delivery was associated with a peak in CO after which it rapidly declined (6.0 vs. 7.2 vs. 6.1 L/min, 30 min before vs. point of delivery vs. after delivery, 0.05). The mean BP remained stable throughout delivery with a slight increase at fetal delivery (92 vs. 95 vs. 92.1 mmHg, 0.05), reflecting the increase in CO and decrease in SVR (1284 vs. 1112 vs. 1280 mmHg⋅min⋅mL,0.05)with delivery. Placental expulsion was associated with a second peak in CO and decrease in SVR.

Conclusions: We presented a novel application of noninvasive hemodynamic maternal monitoring throughout labor and delivery for both research and clinical use.
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http://dx.doi.org/10.3390/jcm10010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793094PMC
December 2020

Abdominal circumference discordance for prediction of small for gestational age at birth in twin pregnancies.

J Matern Fetal Neonatal Med 2020 Oct 12:1-6. Epub 2020 Oct 12.

Department of Obstetrics and Gynecology, The Rappaport Faculty of Medicine, Hillel Yaffe Medical Center, Hadera, Israel.

Objective: To evaluate whether single sonographic abdominal circumference (AC) discordancy estimation can predict small for gestational age (SGA) at birth in twin gestations.

Methods: A retrospective analysis of prospectively collected data. Cohort included all twin gestations delivered at one university-affiliated medical center between 2010 and 2018, with available sonographic evaluation from 22 gestational weeks to term. Pregnancies complicated by fetal chromosomal abnormalities, major anomalies or twin to twin transfusion syndrome were excluded. One sonographic evaluation per pregnancy was selected randomly. AC discordance was calculated as (large twin AC - small twin AC)/large twin AC*100. Prediction of SGA at birth for at least one newborn (<10% percentile for gestational age by gender-specific local curves for multiples) was evaluated using ROC statistics with calculation of Youden index to establish best AC discordance cutoff. AC discordance prediction performance was compared to estimated fetal weight discordance performance. Results were adjusted for confounders using logistic regression analysis.

Results: After exclusion, 236 twin gestations entered analysis. Of them, 200/236 (84.7%) were dichorionic-diamniotic twins. Mean gestational age at ultrasound evaluation and at delivery were 30.9 ± 4.4 and 35.9 ± 2.4 weeks, respectively. In 28/236 (11.8%) pregnancies, at least one neonate was born SGA. AC discordance predicted SGA at birth as good as sonographic estimated fetal weight (sEFW) discordance: ROC-AUC 0.76, 95% CI 0.67-0.85 vs. 0.77 95% CI 0.66-0.87,  < .001 for all. Best AC discordance cutoff for prediction of SGA at birth was 7.1% (57% sensitivity, 87% specificity), ROC-AUC 0.72 (95% CI 0.61-0.84,  < .001). Results remained significant after adjustment for maternal age, nulliparity, chorionicity and ultrasound to delivery interval (aOR 1.21 95% CI 1.1-1.32,  < .001).

Conclusion: According to our results, AC discordance at single sonographic evaluation can predict SGA at birth in twin gestations as good as sEFW discordance. Best cutoff for SGA prediction was 7.1%.
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http://dx.doi.org/10.1080/14767058.2020.1832071DOI Listing
October 2020

Extremely high levels of alkaline phosphatase and pregnancy outcome: case series and review of the literature.

J Perinat Med 2021 Feb 14;49(2):191-194. Epub 2020 Sep 14.

The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.

Objectives: To evaluate the association between extremely elevated alkaline phosphatase (ALKP) levels (above 1000 U/L) and adverse perinatal outcome.

Methods: A retrospective case series of all parturients with extremely elevated ALKP levels taken throughout pregnancy at a single university-affiliated medical center (2010-2018). Demographics and medical data were retrieved. Following literature review, previously reported similar cases were added to the cohort. We report perinatal outcome of our cohort as well as literature review.

Results: During study period 11 parturients with high ALKP were identified. Ten more cases were retrieved from PubMed search. Overall, median ALKP levels were 1880 (range 1052-4488 U/L). Reasons for evaluation were mostly nonspecific symptoms (pruritus, headache, abdominal pain) or routine obstetrical evaluation. In 10/12 (83%) cases, elevated ALKP levels were of placental origin; the rest had osteal origin. Median gestational age at delivery was 38 (range 35-41); four (19%) women had preterm delivery. Six patients (29%) had gestational diabetes mellitus and six (29%) had hypertensive disorders. Histopathology of the placenta was available in eight cases: three normal histology (38%) and five with different non-specific pathologies.

Conclusions: We report the largest case series of extremely elevated levels of ALKP in pregnancy thus far. Our data suggest association with adverse perinatal outcome.
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http://dx.doi.org/10.1515/jpm-2020-0205DOI Listing
February 2021

Novel extra cellular-like matrices to improve human ovarian grafting.

J Assist Reprod Genet 2020 Sep 24;37(9):2105-2117. Epub 2020 Jul 24.

IVF and Infertility Unit, Beilinson Women Hospital, Rabin Medical Center, 49100, Petach Tikva, Israel.

Purpose: To investigate if human ovarian grafting with pure virgin human recombinant collagen type-1 from bioengineered plant lines (CollPlant™) or small intestine submucosa (SIS) yields better implantation results for human ovarian tissue and which method benefits more when combined with the host melatonin treatment and graft incubation with biological glue + vitamin E + vascular endothelial growth factor-A.

Methods: Human ovarian tissue wrapped in CollPlant or SIS was transplanted into immunodeficient mice with/without host/graft treatment. The tissue was assessed by follicle counts (including atretic), for apoptosis evaluation by terminal deoxynucleotidyl transferase assay and for immunohistochemical evaluation of neovascularization by platelet endothelial cell adhesion molecule (PECAM) expression, and for identification of proliferating granulosa cells by Ki67 expression.

Results: Human ovarian tissue transplanted with CollPlant or SIS fused with the surrounding tissue and promoted neovascularization. In general, implantation with CollPlant even without additives promoted better results than with SIS: significantly higher number of recovered follicles, significantly fewer atretic follicles, and significantly more granulosa cell proliferation. Moreover, results with CollPlant alone seemed to be at least as good as those after host and graft treatments.

Conclusions: CollPlant is a biomaterial without any potential risks, and grafting ovarian tissue with CollPlant is easy and the procedure may be easily modified, with limited or no foreseeable risks, for auto-transplantation in cancer survivors. Further studies are needed using other novel methods capable of enhancing neovascularization and reducing apoptosis and follicle atresia.
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http://dx.doi.org/10.1007/s10815-020-01832-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492340PMC
September 2020

Interpregnancy interval and the risk for recurrence of placental mediated pregnancy complications.

J Perinat Med 2020 Apr;48(4):322-328

Lis Maternity Hospital, Sourasky Medical Center, Tel Aviv, Israel.

Objective The aim of this study was to investigate the effect of short or long interpregnancy interval (IPI) with placental mediated pregnancy complications after already complicated first delivery. Methods We performed a retrospective cohort analysis of all women with singleton pregnancies who delivered their first three consecutive deliveries in one university-affiliated medical center (1994-2013). Placental mediated complications included placental abruption, small for gestational age, preeclampsia, gestational hypertension, or preterm delivery. Following first complicated delivery, IPI was compared stratified by second delivery outcome. Following two complicated deliveries, IPI was compared stratified by third delivery outcome. IPI was evaluated as continuous or categorical variable (>18, 18-60, >60 months). Related samples Cochrans' Q test and Mann-Whitney analysis were used as appropriate. Results Overall, 4310 women entered analysis. Of them, 18.3%, 10.5%, and 9.3% had complicated first, second, and third delivery, consecutively. Evaluated continuously, longer IPI, but not short IPI, was associated with higher rates of complicated second delivery. Stratified to categories, IPI had no effect on recurrent complications evaluated separately or as composite. Conclusion Our results suggest that long IPI may increase risk for placental mediated pregnancy complications. Further studies are needed to evaluate this effect.
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http://dx.doi.org/10.1515/jpm-2019-0471DOI Listing
April 2020

False diagnosis of small for gestational age and macrosomia - clinical and sonographic predictors.

J Matern Fetal Neonatal Med 2020 May 19:1-7. Epub 2020 May 19.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

To investigate clinical and sonographic features associated with sonographic accuracy for the prediction of small for gestational age (SGA) and macrosomia at birth. The database of a tertiary medical center was retrospectively searched for women who gave birth at term to a singleton healthy neonate in 2007-2014 and underwent sonographic estimated fetal weight (sEFW) evaluation within 3 d before delivery. Fetal growth restriction (FGR) and SGA were defined as sEFW or birth weight <10th percentile for gestational age; macrosomia was defined as birth weight >4000 grams. Data on maternal age, parity, gestational age, fetal gender, presentation, placental location, diabetes, hypertension, and oligo/polyhydramnios were compared between pregnancies with a false-negative and false-positive diagnosis of SGA or macrosomia. Of the 5425 fetal weight evaluations, 254 (4.7%) deviated by >15% from the actual birth weight. Nulliparity, absence of diabetes, neonatal female gender, anterior placenta, lower birth weight, and oligohydramnios were associated with a high deviation. We identified 482 SGA neonates (8.9%) and 633 macrosomic neonates (11.7%). A false-positive diagnosis of FGR was associated with oligohydramnios, absence of diabetes, and posterior placenta, and a false-negative diagnosis, with older maternal age, nulliparity, and male gender. A false-positive diagnosis of macrosomia was associated with older maternal age, multiparity, polyhydramnios, anterior placenta, and lack of hypertensive complications, and a false-negative diagnosis, with diabetes, hypertension, oligohydramnios, and vertex presentation. The accuracy of sEFW is affected by clinical and sonographic pregnancy characteristics. Further analyses should focus on improving accuracy especially at the fetal weight extremes.
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http://dx.doi.org/10.1080/14767058.2020.1762559DOI Listing
May 2020

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

Birth 2020 06 12;47(2):237-245. Epub 2020 Feb 12.

Bob Shapell School of Social Work, Tel Aviv University, Tel Aviv, Israel.

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.
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http://dx.doi.org/10.1111/birt.12484DOI Listing
June 2020

Determination of reference values for third trimester amniotic fluid index: a retrospective analysis of a large cohort of pregnancies with comparison to previous nomograms.

J Matern Fetal Neonatal Med 2020 Jan 12:1-7. Epub 2020 Jan 12.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

To establish a new set of reference values for third-trimester amniotic fluid index (AFI) and compare them to other previously published normograms. A retrospective cross-sectional cohort analysis of all singleton sonographic evaluations >22 gestational weeks in one university affiliated medical center between 2013 and 2017. Pregnancies complicated by rupture of membranes, major anomalies/chromosomal abnormalities were excluded. One evaluation per patient per pregnancy was randomly selected. Reference values were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age after normalization of variables and compared with previously published norms. A total of 7037 ultrasound evaluations entered the analysis. Correlation between AFI and gestational age was best represented by a first-degree polynomial equation. AFI decreased gradually from 16.4 at 22 weeks to 13.3 at 40 weeks (cm, median). The standard deviation increased with gestational age with AFI ranging from 12.9-20.2 at 22 weeks and 4.7-26.2 at 40 weeks (cm, 2.5-97.5 percentile). Compared to other curves, our reference values demonstrated a higher median AFI throughout all gestation. Reference values for the third trimester AFI were established. Curves should be correlated with perinatal outcome prior to wide clinical implementation.
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http://dx.doi.org/10.1080/14767058.2020.1712711DOI Listing
January 2020

Accuracy of Sonographic Estimated Fetal Weight: Is there Still Room for Improvement?

Isr Med Assoc J 2019 Dec;21(12):831-832

Department of Obstetrics and Gynecology and Reproductive Science, Hillel Yaffe Medical Center, Hadera, Israel.

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December 2019

Endometriosis-related Hemoperitoneum in Late Pregnancy.

Isr Med Assoc J 2019 Aug;21(8):557-559

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

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August 2019

New reference values for biometrical measurements and sonographic estimated fetal weight in twin gestations and comparison to previous normograms.

J Perinat Med 2019 Sep;47(7):757-764

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera 38100, Israel.

Objective To construct new reference values for biometrical measurements and sonographic estimated fetal weight (sEFW) in twin gestations and compare them to previously published normograms. Methods A retrospective analysis of sEFW evaluations of twin gestations was performed between 2011 and 2016 in a single university-affiliated medical center. sEFW was calculated using the Hadlock 1985 formula. To avoid selection bias, one evaluation per pregnancy was randomly selected. Following mathematical transformation to obtain normality of values, normograms were constructed using a best-fit regression model for estimation of mean and standard deviation at each gestational age (GA). Normograms were validated by applying all observations to ensure equal distribution at parallel percentiles. Our normograms were then compared to previously published sEFW normograms for twin gestations. Results A total of 864 sEFW evaluations were performed on 195 twin pregnancies at 22-39 gestational weeks. Of them, 390 entered the primary analysis. The rest were left for validation. Seventy percent of the cohort were dichorionic-diamniotic twins (136/195), 16% (32/195) were monochorionic-diamniotic twins and three (1.5%) were monochorionic-monoamniotic twins. Twenty-four fetuses lacked data on chorionicity. The rest were monochorionic twins or were of unknown chorionicity. Values corresponding to the 2.5th, 10th, 50th, 90th and 97.5th percentiles for sEFW are presented for every GA. Validation by applying all 864 evaluations on constructed normograms was achieved. Comparison to previously published twins' sEFW normograms demonstrated wide variation between curves. Conclusion New reference values for biometrical measurements and sEFW in twin gestations are presented for clinical and research use. Comparison to other curves demonstrates the wide variability and need for further investigation on twin's normal growth.
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http://dx.doi.org/10.1515/jpm-2019-0207DOI Listing
September 2019

Prolonged early antenatal indomethacin exposure is safe for fetus and neonate.

J Matern Fetal Neonatal Med 2021 Jan 4;34(2):167-176. Epub 2019 Apr 4.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

To evaluate fetal and neonatal safety of early-onset long-term antenatal indomethacin treatment (LIT) for short cervix. In this cohort study, women started LIT for short cervix (<25 mm) before completing 25 weeks. They followed a standardized regiment of oral indomethacin: 100 mg loading, 50 mg qid for 48 h, 25 mg qid until delivery or at 32 weeks gestational age (GA), whichever comes first. Weekly monitoring for oligohydramnios and ductus arteriosus (DA) constriction included confirmation of compliance with treatment/dose. This approach is established in our clinical practice. To identify LIT complications separate from prematurity, each neonate exposed to LIT were matched to two unexposed neonatal controls within ±3 days of GA of delivery and birth weight of ±10%. Odds ratios for neonatal variables included pulmonary hemorrhage, patent DA (PDA) requiring medical or surgical correction, necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), intraventricular hemorrhage (IVH) grade III-IV, other intracranial hemorrhage (ICH), neonatal mortality, calculated individually, and for total composite morbidity. Statistical determinants of neonatal morbidity were assessed using binary logistic regression. Exposure to LIT, maternal age, parity, BMI, GA at delivery, birth-weight (BW), neonatal gender, cord artery pH, and 5-min Apgar score were independent variables. 166 LIT cases were matched with 332 controls. LIT median duration was 49 (3-108) days. Mean delivery GA was 34 weeks. LIT was stopped for 5 patients (2.9%) with oligohydramnios and 1 (0.6%) with DA constriction, without consequent morbidity. 71 cases (43%) completed LIT, stopping at 32 weeks. 95 stopped early for preterm premature ruptures of membranes (PPROM) (20%), active labor (11%) or patient choice (22%). Odds of any individual complication did not differ between treated cases and controls. LIT was not a statistical determinant of composite morbidity or any individual neonatal problem. Continuous early-onset indomethacin exposure, up to 15 weeks antenatally, did not increase fetal or neonatal complications. This level of safety is permissive to a randomized trial of indomethacin for the treatment of short cervix.
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http://dx.doi.org/10.1080/14767058.2019.1599351DOI Listing
January 2021

Predictors for cesarean delivery in preterm premature rupture of membranes.

J Matern Fetal Neonatal Med 2020 Nov 4;33(22):3761-3766. Epub 2019 Mar 4.

Hillel Yaffe Medical Center, The Rappaport faculty of Medicine, Technion, Hadera, Haifa, Israel.

To determine predictors for cesarean delivery (CD) in pregnancies complicated by preterm premature rupture of membranes (PPROM) with an intention for vaginal delivery. A retrospective cohort analysis of all singleton, preterm deliveries (24 + 0 to 36 + 6 weeks) following PPROM (2007-2014). Exclusion criteria included: cases intended for CD prior to delivery; short interval from PPROM to delivery (<24 hours); cervical dilatation upon admission ≥4 cm; and major fetal anatomical/chromosomal abnormalities. Potential CD predictors were evaluated by univariate followed by multivariate regression analysis. Overall, 465 deliveries met inclusion criteria. Of them, 53 (11.4%) ended with CD. Women in the CD group delivered at an earlier gestational age (34 versus 35 weeks) with lower birth weights (2115 versus 2386 grams),  < .05 for both. On univariate analysis, smaller cervical dilatation upon admission and prior to delivery, longer PPROM to delivery interval and delivery indication were the only significant determinants associated CD ( < .001 for all). On multivariable regression analysis, only la rger cervical dilatation prior to delivery remained an independent factor for lower rates of CD (aOR 0.15, 95% CI 0.08-0.28,  < .001). Small cervical dilatation prior to delivery is an independent risk factor for CD in pregnancies complicated by PPROM.
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http://dx.doi.org/10.1080/14767058.2019.1585422DOI Listing
November 2020

[VENOUS THROMBOEMBOLISM DURING PREGNANCY AND THE PUERPERIUM - WHO? WHEN? AND HOW TO TREAT?]

Harefuah 2019 Jan;158(1):53-59

Maternal Fetal Medicine Unit, the Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

Introduction: Venous thromboembolism (VTE) is a potentially life-threatening medical condition during pregnancy and the puerperium. During pregnancy, the risk of VTE is increased four to tenfold compared to non-pregnant women of comparable age. The risk is even higher in the puerperium. Physician awareness followed by adequate treatment may reduce the number of events. The most important risk factors are previous VTE or thrombophilia, although other acquired risk factors may result in similar impacts. Treatment is based on personalized risk assessment at the first patient visit during pregnancy, followed by repeated assessment of complications or at admission and final assessment at delivery. Hydration and mobilization are advised for all women. Pharmacological prevention by low-molecular-weight heparin (LMWH) is advised based on risk stratification. International guidelines differ by indications and range of management options. The purpose of this review is to summarize our knowledge on risk factors for VTE during pregnancy and puerperium and guide management options.
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January 2019

Sonographic prediction of macrosomia in pregnancies complicated by maternal diabetes: finding the best formula.

Arch Gynecol Obstet 2019 01 16;299(1):97-103. Epub 2018 Oct 16.

Hillel Yaffe Medical Center, Hadera, Israel.

Purpose: To evaluate the best performing formula for macrosomia prediction in pregnancies complicated by diabetes.

Methods: A retrospective analysis was performed of 1060 sonographic fetal biometrical measurements performed within 7 days of delivery in term pregnancies (37-42 gestational weeks) complicated by diabetes. Sonographic prediction of macrosomia (≥ 4000, ≥ 4250, and ≥ 4500 g) was evaluated utilizing ten previously published formulas by: (1) calculating for each macrosomia threshold the sensitivity, specificity, positive and negative predictive value, and ± likelihood ratio for macrosomia prediction; (2) comparing the systematic and random error and the proportion of estimates < 10% of birth weights between macrosomic and non-macrosomic neonates. Best performing formula was determined based on Euclidean distance.

Results: 97 (9.2%) macrosomic neonates (> 4000 g) were included. Median birth weight was 3380 (1866-3998) g for non-macrosomic and 4198 (4000-5180) g for macrosomic neonates. Higher macrosomia cutoff was associated with higher specificity and lower sensitivity. We found a considerable variation between formulas in different accuracy parameters. Hadlock's formula (1985), based on abdominal circumference, femur length, head circumference and biparietal diameter, had the shortest Euclidean distance, reflecting the highest accuracy.

Conclusion: Prediction of macrosomia among women with diabetes differs significantly between formulas. In our cohort, the best performing formula for macrosomia prediction was Hadlock's formula (1985).
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http://dx.doi.org/10.1007/s00404-018-4934-yDOI Listing
January 2019

Reply.

J Ultrasound Med 2019 02 19;38(2):555. Epub 2018 Jul 19.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

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http://dx.doi.org/10.1002/jum.14705DOI Listing
February 2019

Complicated primary cesarean delivery increases the risk for uterine rupture at subsequent trial of labor after cesarean.

Arch Gynecol Obstet 2018 08 24;298(2):273-277. Epub 2018 May 24.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, 38100, Hadera, Israel.

Purpose: To evaluate whether cesarean delivery (CD) indication, labor status, and other primary CD characteristics affect the risk for uterine rupture in subsequent deliveries.

Methods: A case-control study of women attempting trial of labor after cesarean (TOLAC) in a single, tertiary, university-affiliated medical center (2007-2016). Deliveries complicated by uterine rupture were matched to successful vaginal birth after cesarean (VBAC) deliveries in a 1:3 ratio. Indication, labor status and post-partum complications (postpartum hemorrhage and postpartum infection) at primary CD were compared between study and control group.

Results: During study period, there were 75,682 deliveries, of them, 3937 (5.2%) were TOLAC. Study group included 53 cases of uterine rupture at TOLAC and 159 women with successful VBAC. Women in study group had significantly lower rates of previous VBAC (15.1 vs. 28.9%, p = 0.047). Rate of postpartum complications at primary CD was significantly higher in women with TOLAC complicated by uterine rupture (7.5 vs. 1.9%, respectively, p = 0.042). Utilizing the multivariate logistic regression analysis, postpartum complications remained an independent risk factor for uterine rupture in the following TOLAC (aOR 4.07, 95% CI 1.14-14.58, p = 0.031).

Conclusion: Postpartum hemorrhage and infection, in primary CD, seem to be associated with increased risk for uterine rupture during subsequent TOLAC.
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http://dx.doi.org/10.1007/s00404-018-4801-xDOI Listing
August 2018

The association between neonatal head circumference and second stage duration.

J Matern Fetal Neonatal Med 2019 Dec 13;32(24):4086-4092. Epub 2018 Jun 13.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

To determine if head circumference (HC) is an independent factor influencing second stage duration stratified by parity and epidural use. A retrospective cohort analysis of all live, singleton, term (37-42 weeks) vaginal deliveries in one university affiliated medical center (2012-2014). Exclusion criteria included operative deliveries due to fetal distress, major fetal anomalies/chromosomal abnormalities or cases with missing anthropometric data. Maternal demographics, labor characteristics and neonatal anthropometrics including birth weight and HC were retrieved. Multivariate linear regression was utilized to evaluate the association between HC and second stage duration. Analysis was stratified into four groups by parity and epidural use. Of the 16 240 singleton vaginal deliveries during study period, 12 428 deliveries met inclusion criteria. Stratification by parity and epidural analgesia yielded four groups: 3337 (26.9%), 735 (5.9%), 5099 (41.0%) and 3257 (26.2%) deliveries - nullipara with/without epidural and multipara with/without epidural, respectively. In all groups, a large neonatal HC was significantly and independently associated with longer second stage duration: nullipara with epidural (beta 10.06, 95% CI 7.75-12.37), nullipara without epidural (beta 7.58, 95% CI 4.73-10.43), multipara with epidural (beta 4.64, 95%CI 3.47-5.8) and multipara without epidural (beta 1.35, 95% CI 0.76-1.94),  < .001 for all. Birth weight was not associated with second stage duration in any of the groups ( > .05). Large neonatal HC is significantly associated with longer second stage duration.
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http://dx.doi.org/10.1080/14767058.2018.1481386DOI Listing
December 2019

The impact of epidural analgesia on the duration of the second stage of labor.

Birth 2018 12 22;45(4):377-384. Epub 2018 May 22.

Hillel Yaffe Medical Center, Hadera, Israel.

Background: We aimed to describe the length of second stage of labor in a contemporary cohort. We calculated the 5th, 50th, and 95th percentiles for second-stage length stratified by parity and epidural analgesia use and evaluated the effect of labor induction and oxytocin augmentation in our cohort.

Methods: We did a retrospective analysis of all live, singleton, term vaginal deliveries in one tertiary hospital. Multivariate linear regression was used to evaluate second-stage duration confounders. First, we calculated the second-stage length and presented it as 5th, 50th, and 95th percentiles stratified by epidural analgesia and parity. Second, we evaluated the effect of labor induction and oxytocin augmentation on second-stage length, and third, we determined the demographic and obstetrical confounders that affected second-stage length.

Results: Overall, 15 500 deliveries were included. Nulliparity, oxytocin augmentation, epidural use, birthweight, labor induction, lower body mass index, and higher maternal age were found to be significantly associated with prolongation of the second stage. Epidural use was associated with an additional 82 minutes for the 95th percentile for both nulliparas and multiparas and tripled the rate of prolonged second stage for the entire cohort. Labor induction was associated with clinically significant prolongation of the second stage in nulliparas with epidural analgesia only. Oxytocin was associated with longer duration of the second stage for nulliparas, regardless of epidural use.

Discussion: Our findings suggest a significant prolongation of the second stage in women receiving epidural analgesia. Recommendations for management of second stage should be reconsidered by contemporary data.
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http://dx.doi.org/10.1111/birt.12355DOI Listing
December 2018

Antiphospholipid syndrome characteristics and adverse pregnancy outcomes after 20 weeks of pregnancy.

Int J Gynaecol Obstet 2018 Aug 10;142(2):214-220. Epub 2018 May 10.

Helen Schneider Hospital for Women, Rabin Medical Center, Petah Tikva, Israel.

Objective: To assess outcomes after 20 weeks of pregnancy according to autoantibody profile and clinical presentation of maternal antiphospholipid syndrome (APS).

Methods: The present retrospective cohort analysis included women diagnosed with APS at a tertiary medical center in Israel between January 1, 2012, and December 31, 2016. Anticardiolipin antibodies, anti-β2-glycoprotein antibodies, and lupus anticoagulant were assessed. Participants were stratified by type of APS (obstetric vs thrombotic), antibody profile, and antibody titer (low vs high). Primary composite outcomes were rated as severe (stillbirth, fetal growth restriction at <34 weeks, severe pre-eclampsia, or delivery at <32 weeks) and mild (stillbirth, any fetal growth restriction, any pre-eclampsia, or delivery at <34 weeks).

Results: A total of 99 women were included in the analysis. The primary composite outcomes were similar regardless of stratification. Lupus anticoagulant positivity was associated with delivery before 37 weeks. When compared with low antibody titer, high antibody titer was associated delivery at or before 32 weeks (P=0.045) and 34 weeks (P=0.029).

Conclusion: High antibody titer might be associated with an increased risk of severe prematurity among pregnant women with APS.
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http://dx.doi.org/10.1002/ijgo.12511DOI Listing
August 2018

Exposure of the developing heart to diabetic environment and early cardiac assessment: A review.

Echocardiography 2018 Feb 21;35(2):244-257. Epub 2018 Jan 21.

ObstetricsGynecology & Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.

Hyperglycemia during organogenesis is associated with an increased risk of congenital cardiac defects (CHDs). The pathophysiology leading to CHDs is not completely uncovered. However, elevated oxidative stress is considered to be the primary trigger that causes CHDs in fetuses of diabetic mothers. Maternal diabetes has been found to increase the risk for all types of CHDs. Diabetes may also impact the fetal cardiac performance at all gestational ages. Early detection of CHDs has certain advantages, such as making early decision about termination of pregnancy, enabling early genetic testing, and early reassurance if scan is normal. Combined transabdominal and transvaginal approach at 13-14 weeks of gestation is a reasonable strategy to assess fetal heart in diabetic women. Diagnostic accuracy of early fetal echocardiography has reached to above a reasonable cutoff when it is done in the late first trimester or early second trimester in the hands of expert sonographers. However, the literature is less certain to provide a firm conclusion about functional heart assessment in fetuses of diabetic mothers.
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http://dx.doi.org/10.1111/echo.13811DOI Listing
February 2018

Yield rate of chromosomal microarray analysis in fetuses with congenital heart defects.

Eur J Obstet Gynecol Reprod Biol 2018 02 12;221:172-176. Epub 2017 Dec 12.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, United States.

Objective: The purpose of this study was to calculate the yield rates of CMA in fetuses diagnosed with various CHDs in a tertiary center.

Study Design: This cohort study collected prenatal genetic test results of 145 fetuses diagnosed with CHD. All 145 cases underwent Conventional karyotype (CK), followed by CMA in cases of negative CK result. "Detection rate" of genetic abnormalities was calculated as the percentage of cases with genetic abnormalities identified. The rate of genetic abnormalities detected by CK was first calculated, and then the cumulative detection rate was calculated in the study population. "Yield rate of CMA" was determined by subtracting the cumulative detection rate from the detection rate of CK. The cumulative detection rate was assumed to represent the detection rate of CMA since it is due to the fact that if CMA had been done for all patients before CK, it would have diagnosed all the genetic abnormalities in the study population, and thus it was named as anticipated CMA.

Results: Of the 145 CHD cases, 92 (63.4%) had isolated CHD and 53 (36.6%) had concomitant CHD and extracardiac anomaly (ECA). The detection rate of genetic abnormalities was 14% and 33.8% for CK and anticipated-CMA respectively (p < .001). The yield rate of CMA was 19.8% and 16.1% before and after the exclusion of cases with 22q.11.2 deletion/duplication, respectively. The detection rates of genetic abnormalities for isolated CHD, and concomitant CHD-ECA groups were 6.5% and 26.4% by CK, and 23.9% and 50.9% by anticipated-CMA, respectively (p < .01). The yield rate of CMA was 17.4% and 24.5% for isolated CHD and concomitant CHD-ECA cases, respectively.

Conclusion: CMA increases the diagnostic yield in fetuses with CHD, regardless of whether it is isolated or not. CMA should be the modality of choice when investigating the genetic origin of CHDs until whole exome or genome sequencing is implemented into routine clinical practice.
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http://dx.doi.org/10.1016/j.ejogrb.2017.12.019DOI Listing
February 2018

Cytogenetic analysis in fetuses with late onset abnormal sonographic findings.

J Perinat Med 2018 Nov;46(9):975-982

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

Objective: To determine the rate of chromosomal cytogenetic abnormalities in fetuses with late onset abnormal sonographic findings.

Design: Retrospective cohort of women who underwent amniocentesis at or beyond 23 weeks of gestation, for fetal karyotype and chromosomal microarray analysis, indicated due to late onset abnormal sonographic findings.

Results: All 103 fetuses had a normal karyotype. Ninety-five women also had chromosomal microarray analysis (CMA) performed. The detection rate of abnormal CMA (5/95, 5.3%) was similar to that of women who underwent amniocentesis due to abnormal early onset ultrasound findings detected at routine prenatal screening tests during the first or early second trimester (7.3%, P=0.46) and significantly higher than that for women who underwent amniocentesis and CMA upon request, without a medical indication for CMA (0.99%, P<0.0001).

Conclusions: Late onset sonographic findings are an indication for amniocentesis, and if performed, CMA should be applied to evaluate fetuses with late onset abnormal sonographic findings.
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http://dx.doi.org/10.1515/jpm-2017-0071DOI Listing
November 2018

Cup detachment during vacuum-assisted vaginal delivery and birth outcome.

Arch Gynecol Obstet 2017 Nov 4;296(5):877-883. Epub 2017 Sep 4.

Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Hadera, Israel.

Objective: To determine the perinatal outcome associated with cup detachment during vacuum-assisted vaginal delivery (VAVD).

Methods: A retrospective cohort study of all women attempting VAVD in a tertiary hospital (2012-2014). Singleton-term pregnancies were included. Antepartum fetal death and major fetal structural or chromosomal abnormalities were excluded. Primary outcome was neonatal birth trauma (subgaleal hematoma, subarachnoid hematoma, subdural hematoma, skull fracture, and/or erb's palsy). Secondary outcomes were maternal complications or other neonatal morbidities. Outcomes were compared between women after ≥1 cup detachment (study group) and the rest (control group). Logistic regression analysis was utilized to adjust results to potential confounders.

Results: Overall, 1779 women attempted VAVD during study period. Of them, in 146 (8.2%), the cup detached prior to delivery; 130/146 (89%) had a single detachment. After detachment, 4 (2.7%) delivered by cesarean section, 77 (52.7%) delivered after cup reapplication, and 65 (44.6%) delivered spontaneously. Women in the study group were more likely to undergo VAVD due to prolonged second stage, and were characterized by lower rates of metal cup use. Neonates in the detachment group had higher rates of subarachnoid hematoma and composite neonatal birth trauma (2.7 vs. 0.1% and 4.8 vs. 1.8%, respectively, p < 0.05). This remained significant after adjustment to potential confounders (subarachnoid hematoma aOR = 45.44, 95% CI 6.42-321.62 and neonatal birth trauma aOR = 2.62, 95% CI 1.1-6.22, p < 0.05 for all). Other neonatal and maternal morbidities were similar between groups.

Conclusion: Cup detachment is associated with a higher rate of adverse neonatal outcome. Cup reapplication should be considered carefully.
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http://dx.doi.org/10.1007/s00404-017-4507-5DOI Listing
November 2017

Erratum to: Obstetric antiphospholipid syndrome and long term arterial thrombosis risk.

J Thromb Thrombolysis 2017 Oct;44(3):376

The Department of Emergency Medicine, Rabin Medical Center, Petach-Tikva, 49100, Israel.

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http://dx.doi.org/10.1007/s11239-017-1538-5DOI Listing
October 2017

Obstetric antiphospholipid syndrome and long term arterial thrombosis risk.

J Thromb Thrombolysis 2017 Oct;44(3):371-375

The Department of Emergency Medicine, Rabin Medical Center, Petach-Tikva, 49100, Israel.

Antiphospholipid syndrome (APS) is classified as the association of a thrombotic event and/or obstetric morbidity in patients persistently positive for antiphospholipid antibodies and/or lupus anticoagulant. To evaluate the incidence of subsequent thrombosis among women diagnosed with purely obstetric APS. We retrospectively reviewed and collected demographic and clinical data from the computerized charts of all patients with obstetric APS, from 1992 to 2017. Eligibility criteria included all women diagnosed with APS, according to the 2006 revised criteria, for whom the clinical manifestations were purely obstetric. The primary endpoint was the occurrence of subsequent thromboembolic events, following diagnosis of obstetric APS. The study included 115 women diagnosed with obstetric APS. During the study's follow up period, 12 (10.4%) women developed thrombosis. Of the 12 women who developed thrombosis, 9 (75%) of the thrombotic events were arterial. The site of arterial thrombosis was cerebral in all cases. Venous thrombosis occurred in 3 (25%) women, including one in each of the following sites-pulmonary embolism, ovarian vein thrombosis and proximal leg deep vein thrombosis. Our data suggests that women with obstetric APS are at risk for subsequent long-term thrombosis, especially arterial cerebral events. We did not identify any clinical or laboratory unique features among women with obstetric APS who will eventually develop thrombosis.
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http://dx.doi.org/10.1007/s11239-017-1526-9DOI Listing
October 2017

Sonographic prediction of small and large for gestational age in breech-presenting fetuses.

J Perinat Med 2018 Sep;46(7):744-749

Helen Schneider Hospital for Women, Rabin Medical Center, Petach-Tikva, Israel.

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http://dx.doi.org/10.1515/jpm-2016-0323DOI Listing
September 2018