First-trimester fasting plasma glucose levels and progression to type 2 diabetes: A 5-year cohort study.

OBJECTIVE: Impaired fasting glucose is a prediabetic condition defined as glucose levels of 100-125 mg/dL and is considered a risk factor for type 2 diabetes. However, this definition does not confer to pregnancy. The significance of first-trimester fasting glucose and future progression to diabetes is not well defined. Therefore, we aimed to evaluate the progression to type 2 diabetes according to first- trimester fasting plasma glucose levels, as compared with gestational diabetes, a well-established risk factor for diabetes, in up to 5-year follow-up postpartum. METHODS: A retrospective analysis of 69 001 parturients, evaluating fasting plasma glucose levels measured during the first trimester. The primary outcome was the incidence of type 2 diabetes within 5 years post-delivery. Fasting plasma glucose levels were categorized in 10 mg/dL increments. Receiver operating characteristic-area under the curve (ROC-AUC) statistics and the Youden index were employed to identify the optimal fasting plasma glucose cutoff for progression to type 2 diabetes. Survival analysis was applied to calculate the adjusted hazard ratios (aHRs) for type 2 diabetes progression with further stratification to maternal obesity status. RESULTS: The identified fasting plasma glucose cutoff for progression to type 2 diabetes was 86.5 mg/dL. This cut-off demonstrated superior performance compared with gestational diabetes diagnosis. Stratification by maternal obesity revealed enhanced predictive capabilities for type 2 diabetes, particularly among patients without obesity. CONCLUSIONS: Increased first-trimester fasting plasma glucose levels are associated with progression to type 2 diabetes, at least as gestational diabetes. For patients without obesity, first-trimester fasting plasma glucose has a more pronounced impact on progression to diabetes.

Pregnancy Outcomes in Women with Poorly Controlled Pregestational Diabetes Mellitus.

BACKGROUND: The prevalence of pregestational diabetes mellitus (PGDM) in women of reproductive age has surged globally, contributing to increased rates of adverse pregnancy outcomes. Hemoglobin A1c (HbA1c) is a crucial marker for diagnosing and monitoring PGDM, with periconceptional levels influencing the risk of congenital anomalies and complications. OBJECTIVES: To evaluate the association between periconceptional HbA1c levels and perinatal complications in pregnant women with poorly controlled PGDM. METHODS: We conducted a retrospective analysis of prospectively collected data of pregnancies between 2010 and 2019, HbA1c > 6% at 3 months prior to conception or during the first trimester. Outcomes of periconceptional HbA1c levels were compared. RESULTS: The cohort included 89 women: 49 with HbA1c 6-8%, 29 with HbA1c 8-10%, and 11 with HbA1c > 10%. Higher HbA1c levels were more prevalent in type 1 diabetics and were associated with increased end-organ damage risk. Women with elevated HbA1c levels tended toward unbalanced glucose levels during pregnancy. The cohort exhibited high rates of preterm delivery, hypertensive disorders, cesarean delivery, and neonatal intensive care unit admission. Overall live birth rate was 83%. While a significant correlation was found between HbA1c levels and preterm delivery, no consistent association was observed with other adverse outcomes. CONCLUSIONS: Periconceptional glycemic control in PGDM pregnancies is important. Elevated HbA1c levels are associated with increased risks of adverse outcomes. Beyond a certain HbA1c level, risks of complications may not proportionally escalate.

The MISOPRED score: Development and validation of a clinical scoring system to predict the effectiveness of Misoprostol treatment for early pregnancy loss.

BACKGROUND: Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. OBJECTIVE: To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. STUDY DESIGN: Retrospective cohort and validation study. METHODS: Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. RESULTS: The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. CONCLUSIONS: MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.

One abnormal value in oral glucose tolerance test during pregnancy and type 2 diabetes risk: Insights from a 5-Year Follow-Up study.

OBJECTIVES: To evaluate the risk of type 2 diabetes(T2D) following one abnormal value(OAbV) in an oral glucose tolerance test(oGTT) performed during pregnancy. STUDY DESIGN: A retrospective analysis of parturients between 01.01.2017 and 31.12.2020 with 5 years of follow-up after delivery. Glucose levels during pregnancy were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes. Women with multiple gestations or pregestational diabetes were excluded. Maternal characteristics and risk of T2D were stratified and compared between 3 groups: normal glucose status, OAbV in oGTT, and gestational diabetes. Statistical analysis included univariate analysis followed by survival analysis. Further analysis was stratified to women with and without obesity. RESULTS: 58,693 women entered the analysis. Following an adjustment to maternal age, obesity, hypertension, and hyperlipidemia, OAbV in oGTT was associated with a 1.8-fold increased risk of T2D in a 5-year follow-up compared to normal glucose status. When stratified by obesity, OAbV was associated with a 3.7-fold increase in T2D in women without obesity, however, was no longer a statistically significant predictor of T2D among women with obesity. CONCLUSIONS: Women with OAbV oGTT during pregnancy are at increased risk for developing T2D over 5 years of follow-up.

Factors Associated with Progression to Preeclampsia with Severe Features in Pregnancies Complicated by Mild Hypertensive Disorders.

In this retrospective cohort study, we aimed to investigate the variables associated with progression to preeclampsia with severe features in parturients already diagnosed with mild hypertensive disorders of pregnancy. The study was conducted in a single university-affiliated medical center between 2018 and 2020. All women admitted due to hypertensive disorders were included. Data collected was compared between parturients who progressed and did not progress to preeclampsia with severe features. Among 359 women presenting without severe features, 18 (5%) developed severe features, delivered smaller babies at lower gestational age, and with higher rates of cesarean delivery (p < 0.001 for all). Chronic hypertension, maternal diabetes, any previous gestational hypertensive disorder, gestational diabetes, number of hospitalizations, earlier gestational age at initial presentation, and superimposed preeclampsia as the preliminary diagnosis were all associated with preeclampsia progression to severe features. Previous delivery within 2-5 years was a protective variable from preeclampsia progression. Following regression analysis and adjustment to confounders, only gestational age at initial presentation and superimposed preeclampsia remained significant variables associated with progression to severe features (aOR 0.74 (0.55-0.96) and 34.44 (1.07-1111.85), aOR (95% CI), respectively, p < 0.05 for both) with combined ROC-AUC prediction performance of 0.89, 95% CI 0.83-0.95, p < 0.001. In conclusion, according to our study results, early gestational age at presentation and superimposed preeclampsia as the preliminary diagnosis are the only independent factors that are associated with progression to severe features in women already diagnosed with mild hypertensive disorders during pregnancy.

Oral Glucose Tolerance Test Performed after 28 Gestational Weeks and Risk for Future Diabetes-A 5-Year Cohort Study.

Gestational diabetes mellitus (GDM) is diagnosed by an oral glucose tolerance test (oGTT), preferably performed at 24 + 0-28 + 6 gestational weeks, and is considered a risk factor for type 2 diabetes (T2DM). In this study, we aimed to evaluate the risk of T2DM associated with abnormal oGTT performed after 28 weeks. We conducted a retrospective cohort study that included parturients with available glucose levels during pregnancy and up to 5 years of follow-up after pregnancy. Data were extracted from the computerized laboratory system of Meuhedet HMO and cross-tabulated with the Israeli National Registry of Diabetes (INRD). The women were stratified into two groups: late oGTT (performed after 28 + 6 weeks) and on-time oGTT (performed at 24 + 0-28 + 6 weeks). The incidence of T2DM was evaluated and compared using univariate analysis followed by survival analysis adjusted to confounders. Overall, 78,326 parturients entered the analysis. Of them, 6195 (7.9%) performed on-time oGTT and 5288 (6.8%) performed late oGTT. The rest-66,846 (85.3%)-had normal glucose tolerance. Women who performed late oGTT had lower rates of GDM and T2DM. However, once GDM was diagnosed, regardless of oGTT timing, the risk of T2DM was increased (2.93 (1.69-5.1) vs. 3.64 (2.44-5.44), aHR (95% CI), late vs. on-time oGTT, p < 0.001 for both). Unlike in oGTT performed on time, one single abnormal value in late oGTT was not associated with an increased risk for T2DM.

Unintended uterine extension at the time of cesarean delivery - risk factors and associated adverse maternal and neonatal outcomes.

OBJECTIVE: To identify risk factors, maternal and neonatal adverse outcomes related to unintended lower segment uterine extension during cesarean delivery (CD). METHODS: A retrospective cohort analysis in a single, university-affiliated medical center between 1 January 2018 and 31 December 2019. All singleton pregnancies delivered by CD were included. Univariate and multivariate analyses were performed to identify maternal and obstetrical predictors for uterine extension during CD. For secondary outcomes, we assessed the correlation between uterine extension and any adverse maternal or neonatal outcome. Risk factors were analyzed using ROC statistics to measure their prediction performance for a uterine extension. RESULTS: Overall, 1746 (19.3%) CDs were performed during the study period. Of them, 121 (6.9%) CDs were complicated by unintended uterine extension. There was no difference in maternal demographics and clinical data stratified by uterine extension at CD. Uterine extensions were significantly more common following induction of labor, intrapartum fever, premature rupture of membranes, a trial of labor after cesarean, advanced gestational age, emergent CD, and in particular CD during the second stage of labor (37.2% vs. 6.5%) and after failed vacuum extraction (6.6% vs. 1.1%), p < .05 for all. The incidence of postpartum hemorrhage and re-laparotomy did not differ between the groups. Most of the extensions were caudal-directed (40.4%), and were closed by a two-layer closure (92%). Mean extension size was 4.5 ± 1.7 cm. Using multivariable analysis, the only factor that remained significant was CD at the second stage of labor (adjusted odds ratio (aOR) 54.2, 95% CI 4.5-648.9, p = .002), with an area under the ROC curve 0.653 (95% CI 0.595-0.712, p < .001). Emergent CD, body mass index, birth weight, failed vacuum attempt, and trial of labor after cesarean were not significant. For secondary outcomes, an unintended uterine extension was associated with longer operation time, higher estimated blood loss, greater pre- to post-CD hemoglobin difference, increased blood products transfusion, puerperal fever, and longer hospital stay. No clinically significant neonatal adverse outcomes were observed. CONCLUSIONS: In our cohort, second-stage CD was the strongest predictor for an unintended uterine extension. Following uterine extension, women had increased infectious and blood-loss morbidity.

Single Sporadic Deceleration during Reactive Nonstress Test-Clinical Significance and Risk for Cesarean Delivery.

OBJECTIVE: Evidence regarding the clinical significance of a single sporadic variable deceleration (SSD) in reactive non-stress test (NST) is scarce, and optimal management has yet to be established. We aim to evaluate whether SSD during a reactive NST at term is associated with a higher risk for fetal heart rate decelerations during labor and the need for intervention. METHODS: This was a retrospective, case-control study of singleton term pregnancies at one university-affiliated medical center in 2018. The study group consisted of all pregnancies with an SSD in an otherwise reactive NST. For each case, two consecutive pregnancies without SSD were matched in a 1:2 ratio. The primary outcome was the rate of cesarean delivery (CD) due to non-reassuring fetal heart rate monitoring (NRFHRM). RESULTS: 84 women with an SSD were compared to 168 controls. SSD during antenatal fetal surveillance did not increase the rate of CD overall or for NRFHRM (17.9% vs. 13.7% and 10.7% vs. 7.7%, respectively, p > 0.05). Rates of assisted deliveries and maternal and neonatal complications were similar between the groups. CONCLUSIONS: SSD during a reactive NST in term pregnancies is not associated with an increased risk for adverse perinatal outcomes. SSD should not necessarily require induction of labor, and expectant management is a reasonable alternative.

The Accuracy of Sonographically Estimated Fetal Weight and Prediction of Small for Gestational Age in Twin Pregnancy-Comparison of the First and Second Twins.

Accurate sonographic estimation of fetal weight is essential for every pregnancy, especially in twin gestation. We conducted a retrospective analysis of the sonographically estimated fetal weight (sEFW) of all twin gestations performed within 14 days of delivery in a single center that aimed to evaluate the accuracy of sEFW in predicting neonatal weight and small for gestational age (SGA) by comparing the first fetus to the second. A total of 190 twin gestations were evaluated for the study. There was no statistically significant difference in the sEFW between the first and the second twins, but the second twin had a statistically significant lower birth weight (2434 vs. 2351 g, p = 0.028). No difference was found in median absolute systematic error (p = 0.450), random error, or sEFW evaluations that were within 10% of the birth weight between the fetuses (65.3% vs. 67.9%, p = 0.587). Reliability analysis demonstrated an excellent correlation between the sEFW and the birth weight for both twins; however, the Euclidean distance was slightly higher for the first twin (12.21%). For SGA prediction, overall, there was a low sensitivity and a high specificity for all fetuses, with almost no difference between the first and second twins. We found that sEFW overestimated the birth weight for the second twin, with almost no other difference in accuracy measures or SGA prediction.

When the lights go down in the delivery room: Lessons from a ransomware attack.

OBJECTIVE: To describe the challenges facing the obstetric division following a cyberattack and discuss ways of preparing for and overcoming another one. METHODS: A retrospective descriptive study conducted in a mid-sized medical center. Division activities, including the number of deliveries, cesarean sections, emergency room visits, admissions, maternal-fetal medicine department occupancy, and ambulatory encounters, from 2 weeks before the attack to 8 weeks following it (a total of 11 weeks), were compared with the retrospective period in 2019 (pre-COVID-19). In addition, we present the challenges and adaptation measures taken at the division and hospital levels leading up to the resumption of full division activity. RESULTS: On the day of the cyberattack, critical decisions were made. The media announced the event, calling on patients not to come to our hospital. Also, all elective activities other than cesarean deliveries were stopped. The number of deliveries, admissions, and both emergency room and ambulatory clinic visits decreased by 5%-10% overall for 11 weeks, reflecting the decrease in division activity. Nevertheless, in all stations, there were sufficient activities and adaptation measures to ensure patient safety, decision-making, and workflow of patients were accounted for. CONCLUSIONS: The risk of ransomware cyberattacks is growing. Healthcare systems at all levels should recognize this threat and have protocols for dealing with them once they occur.

External validation of vaginal birth after cesarean delivery calculator in Israeli cohort of parturients and construction of an improved model.

OBJECTIVE: To validate the Maternal Fetal Medicine Unit's (MFMU) vaginal birth after cesarean delivery (VBAC) calculator in an Israeli cohort, and to detect other variables associated with VBAC and construct an improved VBAC calculator. METHODS: A retrospective cohort study was performed at a single university-affiliated medical center. Women carrying a singleton, term, cephalic-presenting fetus, with previous one low transverse cesarean delivery who opted for trial of VBAC were included. Demographic and obstetric characteristics were incorporated into the MFMU's calculator, to predict probabilities of VBAC and compare prediction performance with the original publication utilizing receiver operating characteristic (ROC) statistics. Logistic regression analysis was used to investigate other variables and construct an improved model for success of VBAC. RESULTS: Of 490 parturients, 396 (80.8%) had a successful vaginal delivery. Compared to the original publication, the MFMU's calculator underperformed: area under the ROC curve (AUC) was 0.709 (95% confidence interval [CI] 0.652-0.766, P < 0.001). Sensitivity, specificity, positive and negative predictive values, and overall accuracy were 67.42%, 65.96%, 89.30%, 32.46%, and 32.46%, respectively. An improved model that included previous VBAC, prior vaginal delivery, spontaneous onset of delivery, and maternal diabetes resulted in improved prediction performance with an AUC of 0.771 (95% CI 0.723-0.82, P < 0.001). CONCLUSION: MFMU's VBAC calculator needs to be validated in different populations before implementation.

Greater risk of type 2 diabetes progression in multifetal gestations with gestational diabetes: the impact of obesity.

BACKGROUND: The relationship between gestational diabetes mellitus and adverse outcomes in multifetal pregnancies is complex and controversial. Moreover, limited research has focused on the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus specifically in multifetal pregnancies, resulting in conflicting results from existing studies. OBJECTIVE: This study aimed to assess the risk of gestational diabetes mellitus progression to type 2 diabetes mellitus between singleton and multifetal pregnancies in a large cohort of parturients with a 5-year follow-up. STUDY DESIGN: A retrospective study was conducted on a prospective cohort of pregnant individuals with pregnancies between January 1, 2017, and December 31, 2020, followed up to 5 years after delivery. Glucose levels during pregnancy were obtained from the Meuhedet Health Maintenance Organization laboratory system and cross-linked with the Israeli National Diabetes Registry. The cohort was divided into 4 groups: singleton pregnancy without gestational diabetes mellitus, singleton pregnancy with gestational diabetes mellitus, multifetal pregnancy without gestational diabetes mellitus, and multifetal pregnancy with gestational diabetes mellitus. Gestational diabetes mellitus was defined according to the American Diabetes Association criteria using the 2-step strategy. Univariate analyses, followed by survival analysis that included Kaplan-Meier hazard curves and Cox proportional-hazards models, were used to assess differences between groups and calculate the adjusted hazard ratios with 95% confidence intervals for progression to type 2 diabetes mellitus. RESULTS: Among 88,611 parturients, 61,891 cases met the inclusion criteria. The prevalence of type 2 diabetes mellitus was 6.5% in the singleton pregnancy with gestational diabetes mellitus group and 9.4% in the multifetal pregnancy with gestational diabetes mellitus group. Parturients with gestational diabetes mellitus, regardless of plurality, were older and had higher fasting plasma glucose levels in the first trimester of pregnancy. The rates of increased body mass index, hypertension, and earlier gestational age at delivery were significantly higher in the gestational diabetes mellitus group among patients with singleton pregnancies but not among patients with multifetal pregnancies. Survival analysis demonstrated that gestational diabetes mellitus was associated with adjusted hazard ratios of type 2 diabetes mellitus of 4.62 (95% confidence interval, 3.69-5.78) in singleton pregnancies and 9.26 (95% confidence interval, 2.67-32.01) in multifetal pregnancies (P<.001 for both). Stratified analysis based on obesity status revealed that, in parturients without obesity, gestational diabetes mellitus in singleton pregnancies increased the risk of type 2 diabetes mellitus by 10.24 (95% confidence interval, 6.79-15.44; P<.001) compared with a nonsignificant risk in multifetal pregnancies (adjusted hazard ratio, 9.15; 95% confidence interval, 0.92-90.22; P=.059). Among parturients with obesity, gestational diabetes mellitus was associated with an increased risk of type 2 diabetes mellitus for both singleton and multifetal pregnancies (adjusted hazard ratio, 3.66; [95% confidence interval, 2.81-4.67; P<.001] and 9.31 [95% confidence interval, 2.12-40.76; P=.003], respectively). CONCLUSION: Compared with gestational diabetes mellitus in singleton pregnancies, gestational diabetes mellitus in multifetal pregnancies doubles the risk of progression to type 2 diabetes mellitus. This effect is primarily observed in patients with obesity. Our findings underscore the importance of providing special attention and postpartum follow-up for patients with multifetal pregnancies and gestational diabetes mellitus, especially those with obesity, to enable early diagnosis and intervention for type 2 diabetes mellitus.

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

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, p < .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, p < .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, p < .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%.

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

PURPOSE: To establish a new set of reference values for third-trimester amniotic fluid index (AFI) and compare them to other previously published normograms. METHODS: 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. RESULTS: 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. CONCLUSIONS: Reference values for the third trimester AFI were established. Curves should be correlated with perinatal outcome prior to wide clinical implementation.

The expression of heparanase in term and preterm human placentas.

PURPOSE: Heparanase is an endo-ß-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 (n = 6), spontaneous onset preterm vaginal deliveries (n = 7) and term elective cesarean sections (n = 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, p < .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, p = .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.

The association between congenital uterine anomalies and perinatal outcomes - does type of defect matters?

OBJECTIVE: To evaluate the association between congenital uterine anomalies (CUA) and adverse perinatal outcomes stratified by type of anomaly. METHODS: A retrospective cohort study of all women delivered in one university-affiliated medical center between 2010 and 2017 with CUA. Multiple pregnancies and pregnancies complicated by fetal anomalies were excluded. Maternal and short-term neonatal outcomes were evaluated and compared between women with unification defects (unicornuate, bicornuate, or uterus didelphys), and canalization defects represented by septate uterus. Univariate analysis was utilized followed by multivariate analysis to adjust for confounders. p < .05 was considered significant. RESULTS: Among 167 pregnancies with CUA, 92 (55.1%) had bicornuate uterus, 32 (19.1%) septate uterus, 26 (15.6%) didelphys uterus, and 17 (10.1%) unicornuate uterus. Maternal demographics and obstetric characteristics were similar between women with unification and canalization defects. The entire cohort had high rates of preterm delivery (PTD), malpresentation, and cesarean delivery (CD) (25.7%, 42.5%, and 63.5%, respectively). In comparison to unification defects, pregnancies in women with canalization defects (septate uterus), had increased risk for PTD <32 weeks (12.5% vs. 2.9%, p = .02), and placental abruption (12.5% vs. 3%, p = .02), however, a lower overall rate of CD (46.9% vs. 67.4%, p = .03). Following adjustment to confounders (age, BMI, nulliparity, chronic hypertension, and smoking) none of the results remained statistically significant. There were no differences in neonatal outcomes between the groups. CONCLUSIONS: Overall, women with CUA have a high prevalence of adverse pregnancy outcomes. However, outcome does not differ by type of anomaly.

Hypoglycemia during the oral glucose tolerance test in pregnancy-maternal characteristics and neonatal outcomes.

OBJECTIVE: To evaluate maternal and neonatal outcomes in pregnancies complicated by hypoglycemia on 100-g oral glucose tolerance test (OGTT). METHODS: A retrospective cohort analysis of all live-born deliveries in a single medical center during 2018 and 2019 with available OGTT results and birth outcomes. Preterm deliveries (<34 weeks), multiple pregnancies and major anomalies were excluded. Hypoglycemia during OGTT was defined as at least one glucose value below 60 mg/dl. Maternal characteristics and perinatal outcomes were compared between three groups: Hypoglycemia on OGTT, Normal OGTT and Abnormal OGTT. Univariate followed by multivariate analyses were used to control for confounders. RESULTS: Overall, 2079 women were entered into the analysis. Of these, 216 (10.4%) had at least one hypoglycemic value, 1072 (51.6%) had normal OGTTs and 791 (38%) abnormal OGTTs. Hypoglycemia in OGTT was more prevalent in multiparous women and was associated with fetal male gender. Absolute birth weight, low birth weight and small for gestational age differed between groups; however, there was no difference between groups in overall birth weight centiles (60.1 ± 26.8 versus 63 ± 26 versus 60.9 ± 27; P > 0.05). Following adjustment of confounders, hypoglycemia was not associated with rates of low birth weight or small for gestational age (P < 0.05). There were no other differences in perinatal outcomes between groups. CONCLUSION: Hypoglycemia in OGTT is not associated with maternal or neonatal adverse outcomes.

High incidence of gynecologic sarcomas in Israel-A comparison to European and American reports: Gynecologic Sarcoma in Israel.

OBJECTIVE: Gynecologic Sarcomas are rare, aggressive tumors. The aim of this study was to explore the incidence and outcomes of gynecologic sarcomas in a large national data registry and to compare them with reports from other countries. STUDY DESIGN: Records of gynecologic sarcomas diagnosed in Israel (1980-2014) were extracted from the National Cancer Registry and classified according to International Classification of Diseases for Oncology-3 and characterized according to anatomical site, morphology and demographics. Age-standardized incidence rates and 1, 3, 5 and 10-year relative survival rates were calculated for 3 time periods (1980-1994, 1995-2001 and 2005-2014) according to patient age, stage and years of diagnosis. RESULTS: During 1980-2014, 1271 new gynecologic sarcomas were diagnosed in Israel, with incidence slightly increasing in 1980-2004, to an age-standardized incidence rate of 13 per million women. The most common histologic diagnosis was leiomyosarcoma (48%) and the most common anatomical site was the uterus (89%). The age-standardized incidence rate for uterine sarcoma is higher in Israel (10.55 per million) than in England (7.4 per million) and Germany (5.8 per million) respectively. The 5-year overall survival was significantly poorer in patients >70-years, as compared to younger patients (p<0.001) and in those with leiomyosarcoma compared to endometrial stromal sarcoma (p<0.001). The survival rate of patients with leiomyosarcoma in Israel are comparable to survival rates reported by other studies, although substantially lower regarding endometrial stromal sarcoma. CONCLUSIONS: Uterine leiomyosarcoma was the most common gynecologic sarcoma found in the Israeli, European and American registries. Older patients and those with leiomyosarcoma have the worst prognoses. Histological and anatomical variations in Israel are comparable with global statistics, but the incidence in Israel seems higher than in Europe.

Increased incidence with improved survival of gynecologic carcinosarcoma: A population-based study.

OBJECTIVE: To evaluate trends in the incidence and survival of gynecologic carcinosarcoma over the last 35 years and to explore ethnic disparities. STUDY DESIGN: Using the Israeli National Cancer Registry database, all cases of gynecologic carcinosarcoma were included (1980-2014). Age at diagnosis, patient's ethnicity and anatomical site were extracted. Age-standardized incidence rates (ASRs) were calculated for 3 time periods (1980-1994, 1995-2004 and 2005-2014). Relative survival was calculated using the Pohar-Perme method. RESULTS: Overall, 935 cases of gynecologic carcinosarcomas were diagnosed during 1980-2014. The most common gynecologic anatomical site was the uterus (83.4%). Most cases (66%) were diagnosed at ages 60-80, with median age of 69 years. There was a steady increase in ASRs from 5.6 to 8.2 per million women. Throughout 1980-1994 and 2005-2014, ASRs were significantly higher in the Jewish compared to the Arab population (5.8 vs. 3.1, p = 0.02 and 8.5 vs. 5.2, p = 0.002, respectively). Relative survival rates increased throughout the study period. No significant differences were noted in relative survival between the Jewish and Arab populations (p = 0.18). CONCLUSION: The incidence of gynecologic carcinosarcoma increased significantly from 1980 through 2014. Nevertheless, survival rates increased during this time, with no difference in survival between the Jewish and Arab populations.