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Placenta accreta is one of the most serious complications in obstetrics and gynecology. Villous trophoblasts (VT) and extravillous trophoblasts (EVT) play a central role in normal placentation. Placenta accreta is characterized by abnormal invasion of EVT cells through the uterine layers, due to changes in several parameters, including adhesion proteins. Although αvβ3 integrin is a central adhesion molecule, participating in multiple invasive pathological conditions including cancer, data on placenta accreta are lacking. To study the expression pattern of αvβ3 integrin in placenta accreta in comparison with normal placentas. We collected tissue samples from placentas defined as percreta, the most severe presentation of placenta accreta and from normal control placentas (n = 10 each). The samples underwent protein extractions for analyses of αvβ3 expression by Western blots (WB) and a parallel tissue assessment by immunohistochemistry (IHC). WB results indicated significantly elevated αvβ3 integrin expression in the percreta samples compared to normal placentas. These elevated levels were mainly contributed by EVT cells, as demonstrated by IHC. αvβ3 integrin demonstrated a classical membranal expression in the VT cells, whereas a uniformly distributed expression was documented in the EVT cells. These patterns of the αvβ3 integrin localization were similar in both accreta and normal placental samples. Enhanced αvβ3 integrin expression, mainly in extra villous trophoblasts of placenta percreta, implies for a role of this adhesion molecule in pathological placentation.

To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound. The study cohort was based on cases of chromosomal microarray analyses performed nationwide for the indication of short long bones. CMA was performed in 66 cases of short long bones. There were 4 cases with a pathogenic/likely pathogenic result (6%). The rate of chromosomal abnormalities was significantly higher compared to the background risk for copy number variations (CNVs) in pregnancies with no sonographic anomalies (P

Placenta accreta is one of the most serious complications in obstetrics and gynecology. Villous trophoblasts (VT) and extravillous trophoblasts (EVT) play a central role in normal placentation. Placenta accreta is characterized by abnormal invasion of EVT cells through the uterine layers, due to changes in several parameters, including adhesion proteins. Although αvβ3 integrin is a central adhesion molecule, participating in multiple invasive pathological conditions including cancer, data on placenta accreta are lacking.To study the expression pattern of αvβ3 integrin in placenta accreta in comparison with normal placentas.We collected tissue samples from placentas defined as percreta, the most severe presentation of placenta accreta and from normal control placentas (n = 10 each). The samples underwent protein extractions for analyses of αvβ3 expression by Western blots (WB) and a parallel tissue assessment by immunohistochemistry (IHC).WB results indicated significantly elevated αvβ3 integrin expression in the percreta samples compared to normal placentas. These elevated levels were mainly contributed by EVT cells, as demonstrated by IHC. αvβ3 integrin demonstrated a classical membranal expression in the VT cells, whereas a uniformly distributed expression was documented in the EVT cells. These patterns of the αvβ3 integrin localization were similar in both accreta and normal placental samples.Enhanced αvβ3 integrin expression, mainly in extra villous trophoblasts of placenta percreta, implies for a role of this adhesion molecule in pathological placentation.

This study measured cervical length (CL) at 14-16 and 21-24 weeks of gestation and assessed whether the difference between measurements is predictive of preterm birth (PTB) among asymptomatic women with twin gestations.This retrospective, cohort study included patients with two consecutive CL measurements with transvaginal sonography at 14-16 weeks of gestation (CL1) and 21-24 weeks (CL2). PTB was defined as delivery prior to 37 + 0 weeks of gestation. Electronic medical records were reviewed for demographic, medical and delivery data. CL1, CL2 and the change between scans were evaluated and correlated with the prediction of PTB.Among 103 women with twin gestations, 76 (73.7%) delivered at term and 27 (26.3%) had PTB. CL1 and CL2 were not good predictors of PTB (The delta between routine cervical length measurements at 14-16 and 21-24 weeks of twin gestations cannot be used as a reliable predictor of PTB.

Introduction: We evaluated the yield of chromosomal microarray analysis in pregnancies complicated with fetal growth restriction (FGR) according to specific clinical parameters. Methods: The study was based on national records from the Israeli Ministry of Health. Chromosomal microarray analyses of amniocenteses performed nationwide for the indication of FGR, from January 2016 to March 2018, were included. The CMA yield was compared to 2 cohorts that reported the background risk. Results: Of 174 tests performed for the indication of FGR, there were 11 cases with a pathogenic/likely pathogenic result (6.3%). The yield of CMA was significantly higher in cases with major structural findings (29.4 vs. 3.4%, p = 0.001), compared to isolated FGR but not for minor structural findings (6.1 vs. 3.4%, p = 0.5). The rate of chromosomal aberrations was significantly higher for all cases with FGR, when compared to the background risk of a cohort of normal pregnancies (odds ratio [OR] 4.7, 95% CI 2.5–9 and OR 6.09, 95% CI 3.2–11.4) but not for isolated cases or cases diagnosed after 24 weeks of pregnancy. Conclusions: Chromosomal microarray analysis should be performed for all pregnancies complicated with FGR diagnosed before 24 weeks and for cases with major structural anomalies.

To investigate the prevalence of pathogenic and likely-pathogenic variants detected by chromosomal microarray analysis (CMA), among pregnancies with fetal short long bones diagnosed by ultrasound.The study cohort was based on cases of chromosomal microarray analyses performed nationwide for the indication of short long bones.CMA was performed in 66 cases of short long bones. There were 4 cases with a pathogenic/likely pathogenic result (6%). The rate of chromosomal abnormalities was significantly higher compared to the background risk for copy number variations (CNVs) in pregnancies with no sonographic anomalies (P 0.001). The yield of CMA in our cohort was significantly higher for both isolated and non-isolated cases, for cases in which the lowest estimated bone length percentile was above the 3rd percentile (below 5th percentile), and for cases diagnosed with short long bones after 22 weeks but not for cases diagnosed after 24 weeks.The yield of CMA in cases with short long bones (both isolated and non-isolated) is significantly higher than the background risk for chromosomal anomalies in pregnancies with no sonographic anomalies. This suggests that CMA should be offered in pregnancies with a diagnosis of fetal short long bones.

Placenta percreta (PP) is an abnormal condition of trophoblast maturation and terminal differentiation through the uterine wall. We opted to study telomere homeostasis and senescence expression in trophoblasts from PP, the most severe subgroup of placenta accreta.Paraffin-embedded placental biopsies from pregnancies with percreta and normal placentation, matched by gestational age at delivery, were assessed for telomere length, aggregates, and senescence-associated heterochromatin foci using quantitative fluorescence in situ hybridization. Cyclin-dependent kinase inhibitors p21, p15, p16, and the tumor suppressor protein p53, known senescence-related markers, were assessed using immunohistochemical staining.Short telomeres were found more often in trophoblasts from the samples of PP (n = 9) compared to controls (n = 8; 54% ± 20% vs 2.3% ± 1.16%, respectively; P.05). More cells with telomere aggregates (18.3% ± 6.9%) were observed in the PP than in the control group (4.8% ± 5.4%; P = .0005). The percentage of nucleic senescence-associated heterochromatin foci in the PP and control samples was similar (10.9% ± 10.4% vs 10.7% ± 15%, respectively; P = .97). Immunohistochemistry of senescence markers was expressed differently in PP compared to the controls: higher p15 expression (46.42% ± 15.2% vs 36.63% ± 12.2%, P = .004), higher p21 expression (59.8% ± 22.1% vs 47.5% ± 21.9%, P = .011), lower p16 expression (54.8% ± 26.3% vs 73.4% ± 18.9%, P = .000), and lower p53 expression (24.4% ± 33.8% vs 34% ± 14.4%, P = .000).Placenta percreta exhibits telomere alterations and changes in expression of several senescence markers. These might be related to altered trophoblast invasion maturation and placental detachment postpartum.

The placenta is an autonomous organ that maintains fetal growth and development. Its multinucleated syncytiotrophoblast layer, providing fetal nourishment during gestation, exhibits characteristics of cellular senescence. We show that in human placentas from pregnancies with intrauterine growth restriction, these characteristics are decreased. To elucidate the functions of pathways regulating senescence in syncytiotrophoblast, we used dynamic contrast-enhanced MRI in mice with attenuated senescence programs. This approach revealed an altered dynamics in placentas of p53(-/-), Cdkn2a(-/-), and Cdkn2a(-/-);p53(-/-) mice, accompanied by histopathological changes in placental labyrinths. Human primary syncytiotrophoblast upregulated senescence markers and molecular pathways associated with cell-cycle inhibition and senescence-associated secretory phenotype. The pathways and components of the secretory phenotype were compromised in mouse placentas with attenuated senescence and in human placentas from pregnancies with intrauterine growth restriction. We propose that molecular mediators of senescence regulate placental structure and function, through both cell-autonomous and non-autonomous mechanisms.

To evaluate (a) the properties of high-density lipoproteins (HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1 (PON1), both are negative predictors of cardiovascular risk and (b) HDL function, among women with preeclampsia (PE). PE is a multi-system disorder, characterized by onset of hypertension and proteinuria or other end-organ dysfunction in the second half of pregnancy. Preeclampsia is associated with increased risk for later cardiovascular disease. The inverse association between HDL, cholesterol levels and the risk of developing atherosclerotic cardiovascular disease is well-established. Twenty-five pregnant women [19 with PE and 6 with normal pregnancy (NP)] were recruited during admission for delivery. HDL was isolated from blood samples. PON1 activity and HDL were analyzed. An in vitro model of endothelial cells was used to evaluate the effect of HDL on the transcription response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) mRNA expression. PON1 activity (units/ml serum) was lower in the PE group compared to normal pregnancy (NP) (6.51 ± 0.73 vs. 9.98 ± 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared to NP-HDL (3.54 ± 0.72 vs. 0.89 ± 0.35; P = 0.01). PE-HDL exhibited increased VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-α stimulated endothelial cells as compared to NP-HDL. HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.

To improve choice of vacuum-assisted delivery (VAD) system, we compared outcomes of Kiwi handheld system and Mityvac M-style conventional system (both use disposable plastic cups).Retrospective observational study with data collection from electronic medical records. The study was conducted at a tertiary medical center, with approximately 7000 deliveries annually. Categorical and continuous variables were analyzed using chi-square test and t-test, respectively. p value 0.05 considered significant. The main outcomes assessed were the overall failure rate of each system, failure rates for occipito-anterior (OA) vs. occipito-transverse/occipito-anterior (OT/OP) positions, +1 vs. +2 fetal stations, and early maternal/neonatal outcomes.During a 10-month period, there were 507 (8.4%) attempted VADs, 36 failed (7.1%) and 8 (1.5%) converted to cesarean section. Of these, 364 were Kiwi-assisted and 143 Mityvac-assisted. Background characteristics were similar. The handheld system had more failures overall (9.6 vs. 0.7%), at OA (7.6 vs. 0.9%) and non-OA positions (17.3% vs. none), at + 1 (13.25 vs. 0.96%) and at + 2/3 stations (6.1% vs. none), than the conventional system did, respectively. There was a higher rate of early post-partum hemorrhage (15.3 vs. 7.4%) in the conventional group. Both systems had similar rates of third/fourth degree perineal tears, shoulder dystocia and adverse neonatal outcomes.Our results suggest more failures with Kiwi compared to Mityvac, overall and at any fetal position/station, without a significant difference in adverse outcome profile.

To improve the choice of vacuum-assisted delivery (VAD) system, we compared the outcomes of Kiwi handheld system and Mityvac M-style conventional system (both use disposable plastic cups).Retrospective observational study with data collection from electronic medical records. The study was conducted at a tertiary medical center, with approximately 7000 deliveries annually. Categorical and continuous variables were analyzed using chi-square test and t-test, respectively. p value .05 was considered significant. The main outcomes assessed were the overall failure rate of each system, failure rates for occipito-anterior (OA) versus occipito-transverse/occipito-anterior (OT/OP) positions, +1 versus +2 fetal stations, and early maternal/neonatal outcomes.During a 10-month period, there were 507 (8.4%) attempted VADs, 36 failed (7.1%), and eight (1.5%) converted to cesarean section. Of these, 364 were Kiwi-assisted and 143 Mityvac-assisted. Background characteristics were similar. The handheld system had more failures overall (9.6 versus 0.7%), at OA (7.6 versus 0.9%), and non-OA positions (17.3% versus none), at +1 (13.25 versus 0.96%) and at +2/3 stations (6.1% versus none), than the conventional system did, respectively. There was a higher rate of early post-partum hemorrhage (15.3 versus 7.4%) in the conventional group. Both systems had similar rates of third/fourth degree perineal tears, shoulder dystocia and adverse neonatal outcomes.Our results suggest more failures with Kiwi compared to Mityvac, overall and at any fetal position/station, without a significant difference in adverse outcome profile.

Objective The aim of this research was to evaluate the ability of three-dimensional (3D) ultrasound for demonstrating the palate of fetuses at high risk for cleft palate. Method Fifty-seven fetuses at high risk for cleft palate were referred for specialist ultrasound at 12–40 weeks' gestation. A detailed assessment of palate was made using both two-dimensional and 3D ultrasounds on the axial plane. Antenatal diagnoses were compared with postnatal findings. Results Cleft palate was suspected in 13 (22.8%); a normal palate was demonstrated in 38 (67%), and in six (10.2%), the palate view could not be obtained. Mean gestational age at the first visit was 27 weeks 6 days (range of 12–40 weeks 3 days). Examination after delivery revealed that one of the 38 fetuses with presumed normal palate had a cleft hard palate, and one had a cleft soft palate (false negative 5%). Among the 13 fetuses with suspected cleft palate, three had an intact palate (false-positive 23%). Sensitivity, specificity, positive predictive value, and negative predictive value of detection of palatal clefts were 71.4%, 91.9%, 62.5%, and 94.4%, respectively. Conclusion Using 3D technology, we diagnosed a cleft palate in 83% of high-risk cases, with 5% false negative. 3D technology might produce some technical artifacts resulting in a 23% false-positive rate. © 2013 John Wiley & Sons, Ltd.

This study assessed the use and complications of late amniocentesis (AC) and analyzed factors that affect complication rate. A retrospective analysis of 167 genetic AC performed after 24 weeks during a 10-year period in two medical centers was conducted. Data regarding the indications for AC, genetic work-up, and pregnancy outcomes were retrieved from patient medical records and telephone-based questionnaires. Mean gestational age (GA) at the time of AC was 31.7 ± 2.7 weeks; 104 procedures were performed at ≤32 weeks, including 24 at ≤30 weeks. The overall pregnancy complication rate occurring at any time after the procedure was 6.6% (11). Of these, 4.8% (8) occurred within a month after AC, including 2.4% (4) that occurred within a week. An additional three occurred after 30 days. There were no differences in the total complication rate and in the rate of specific complications of procedures performed at ≤32 weeks or at ≤30 weeks. Maternal age did not affect outcomes. Genetic testing was abnormal in five cases (3%). Amniocyte culture failed in 3 cases (2.3%), with no technical failures in 52 chromosomal microarray tests. The complication rate of AC performed after 24 weeks was 4.8%, which is significantly higher than that of second trimester AC. GA and maternal age did not affect the complication rate.

Objective:To compare the predictive value of preterm birth (PTB) by transvaginal sonographic cervical length (CL) measurement to digital examination of the cervix (Bishop score – BS), in patients with premature contractions (PC) and intact membranes.Design:A retrospective case-control study.Setting:Meir Medical Center, Kfar Saba, Israel.Population:Women at 24–34 weeks of gestation who were hospitalized with PC and intact membranes.Methods:All patients underwent CL and BS measurements upon admission. Power analysis revealed that 375 patients were needed to show a significant difference between the two methods for predicting PTB. Each one served as her own control.Main outcome measures:PTBResults:Receiver-operator characteristic curve (ROC) and logistic regression analyses indicated a correlation between both shortened CL and increased BS to PTB (PConclusions:CL and BS have similar value in predicting PTB in patients with PC. For nulliparous women, CL is superior over the BS.

Introduction Our objective was to assess the cost implications of a vertical MRSA prevention program that led to a reduction in MRSA bacteremia. Methods We performed a matched historical cohort study and cost analysis in a single hospital in Israel for the years 2005-2011. The cost of MRSA bacteremia was calculated as total hospital cost for patients admitted with bacteremia and for patients with hospital-acquired bacteremia, the difference in cost compared to matched controls. The cost of prevention was calculated as the sum of the cost of microbiology tests, single-use equipment used for patients in isolation, and infection control personnel. Results An average of 20,000 patients were screened yearly. The cost of prevention was $208,100 per year, with the major contributor being laboratory cost. We calculated that our intervention averted 34 cases of bacteremia yearly: 17 presenting on admission and 17 acquired in the hospital. The average cost of a case admitted with bacteremia was $14,500, and the net cost attributable to nosocomial bacteremia was $9,400. Antibiotics contributed only 0.4% of the total disease management cost. When the annual cost of averted cases of bacteremia and that of prevention were compared, the intervention resulted in annual cost savings of $199,600. Conclusions A vertical MRSA prevention program targeted at high-risk patients, which was highly effective in preventing bacteremia, is cost saving. These results suggest that allocating resources to targeted prevention efforts might be beneficial even in a single institution in a high incidence country.

Background The optimal choice of skin closure at cesarean delivery has not yet been determined. Objective This study compared wound complications and scar healing following cesarean delivery between 2 methods of skin closure: glue (Dermabond; Ethicon, Somerville, NJ) and monofilament (Monocryl; Ethicon) epidermal sutures. Study Design We conducted a randomized controlled trial in which pregnant women undergoing a scheduled cesarean delivery were randomly assigned to skin (epidermis) closure with glue or with a monofilament synthetic suture. The subcutaneous tissue was sutured for all patients. Outcome assessors were blinded to group allocation. Scars were evaluated >8 weeks. Primary outcome measures were Patient and Observer Scar Assessment Scale scores. Secondary outcome measures were surgeon satisfaction, duration of surgery, duration of hospitalization after the cesarean delivery, and complications of surgical site infection or wound disruption (hematoma or seroma). A sample of 104 women was needed to achieve a clinically significant effect with a power of 80%. Results Demographic characteristics, patients' clinical background, prepregnancy body mass index, and subcutaneous thickness were similar in both groups. Length of surgery between the groups (37 ± 10 minutes for glue vs 39 ± 13 minutes for sutures, P = .515) was similar. Scores immediately after the wound closure were similar for both groups regarding surgeons' time estimate of closure ( P = .181) and closure appearance ( P = .082). Surgeons' satisfaction with the technique was significantly higher in the suture group ( P = .003). No significant differences were found between the groups in blood loss, surgical site infection, length of postpartum hospitalization, or wound disruption. Glue and suture skin closure scores using Patient and Observer Scar Assessment Scale were similar 8 weeks after surgery, at P = .710 for patients and P = .568 for a physician observer. Conclusion Skin closure using glue or a monofilament synthetic suture had similar results. Both methods were shown to be safe and successful for skin closure after a scheduled cesarean delivery and, therefore, can be used based on surgeon and patient preferences.

The aim of this research was to evaluate the ability of three-dimensional (3D) ultrasound for demonstrating the palate of fetuses at high risk for cleft palate.Fifty-seven fetuses at high risk for cleft palate were referred for specialist ultrasound at 12-40 weeks' gestation. A detailed assessment of palate was made using both two-dimensional and 3D ultrasounds on the axial plane. Antenatal diagnoses were compared with postnatal findings.Cleft palate was suspected in 13 (22.8%); a normal palate was demonstrated in 38 (67%), and in six (10.2%), the palate view could not be obtained. Mean gestational age at the first visit was 27 weeks 6 days (range of 12-40 weeks 3 days). Examination after delivery revealed that one of the 38 fetuses with presumed normal palate had a cleft hard palate, and one had a cleft soft palate (false negative 5%). Among the 13 fetuses with suspected cleft palate, three had an intact palate (false-positive 23%). Sensitivity, specificity, positive predictive value, and negative predictive value of detection of palatal clefts were 71.4%, 91.9%, 62.5%, and 94.4%, respectively.Using 3D technology, we diagnosed a cleft palate in 83% of high-risk cases, with 5% false negative. 3D technology might produce some technical artifacts resulting in a 23% false-positive rate.

Objectives—The purposes of this study were to identify the fetal hippocampus and fornix using 3-dimensional sonography, to measure their curved length during pregnancy, and to describe a systematic method for volume data set analysis of the fetal hippocampus and fornix. Methods—Three-dimensional volumes of the fetal brain were acquired prospectively in 34 patients between 14 and 37 weeks’ gestation. Volumes were acquired with transabdominal and transvaginal transducers. All volumes were analyzed offline by 2 examiners separately. The feasibility of identifying the fetal hippocampus and fornix was analyzed. The curved length of the hippocampus-fornix structure was measured on the right and left hemispheres. Results—The fetal hippocampus and fornix were identified bilaterally in 32 of 34 fetuses (94%) at gestational ages of 14 weeks 5 days to 37 weeks 1 day (mean, 23 weeks 3 days). In 1 fetus (3%), only one side was shown, and in another fetus (3%), both sides were obscured by acoustic shadows. A systematic approach for identification of the fetal hippocampus is described. Linear growth of the fetal hippocampus and fornix was shown during pregnancy and was correlated with both the gestational week and the head circumference (R = 0.71 and 0.74, respectively; P = .01). The length of the hippocampus and fornix did not differ between the left and the right hemispheres (P = .598). Conclusions—The fetal hippocampus and fornix can be identified by a systematic analysis of 3-dimensional data set volumes. The normal hippocampus and fornix show linear growth throughout pregnancy. Key Words—fetal brain; fetus; fornix; hippocampus; neurosonography; 3-dimensional sonography