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Objective: To assess the association between aspartate aminotransferase (AST) to platelet count ratio index (APRI score), during the first and third trimesters of pregnancy and the development of intrahepatic cholestasis in pregnancy (ICP)., Methods: Case-control study was conducted. The study included patients diagnosed with ICP by elevated bile acids (n = 118) and a control group of women with symptoms such as elevated liver enzymes or pruritus with normal level of bile acids (n = 127) who attended a large tertiary teaching medical center between the years 2014 and 2021. The groups were compared in terms of obstetrical characteristics, perinatal outcomes, first- and third-trimester laboratory tests, and APRI scores during the first and third trimester. A receiver operating characteristic (ROC) analysis was performed to determine the APRI score cutoff value that could predict ICP., Results: The third-trimester APRI scores of patients with ICP were significantly higher than those of the control group (P < 0.001). The ROC analysis revealed that the cutoff value for the APRI score was 0.42 with 65.3% sensitivity and 73.2% specificity., Conclusion: Our results suggest that the third-trimester APRI score is positively associated with ICP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: To evaluate whether epidural analgesia is an independent risk factor for OASIS., Methods: A population-based cohort study including all women who delivered by spontaneous vaginal delivery or by instrumental delivery beyond 24 weeks gestation was conducted. Deliveries occurred between 1988 and 2016 at a large university tertiary medical center. Women with multiple gestations and those lacking prenatal care were excluded from the analysis., Results: During the study period, 252,542 women delivered at the Soroka University Medical Center and met the inclusion criteria. Of these, 583 (0.23%) were diagnosed with OASIS. Women with OASIS were more likely to be younger, nulliparous, with suspected fetal macrosomia, had higher rates of labor induction and vacuum extraction delivery, higher rates of conceiving after infertility treatments, more advanced gestational age at delivery, higher mean birth weight, higher rates of post-partum hemorrhage and need for blood transfusions. Use of epidural analgesia during pregnancy was significantly high among the OASIS group. Rates of episiotomy were not significantly different between the groups. Using a multimodal logistic regression model, after controlling for vacuum delivery, large for gestational age, nulliparity, gestational age, ethnicity, maternal age, induction of labor, fertility treatments, non-reassuring fetal heart rate and non-progressive second stage of labor, epidural analgesia was found to be significantly associated with OASIS., Conclusion: Epidural analgesia was found to be an independent risk factor for OASIS in our population., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To examine demographic and obstetrical factors that are associated with adhesion formation following cesarean delivery., Methods: We conducted a population-based study that included all women over 18 years og age who underwent two cesarean deliveries between the years 1988 and 2016 in a large tertiary medical center. We excluded women with adhesions already diagnosed during the first cesarean delivery, history of other abdominal or pelvic surgery, history of pelvic infection or pelvic inflammatory disease, history of endometriosis and history of uterine Müllerian anomalies. In addition, women with a classical or T-shaped uterine incision, non-singleton pregnancies, and fetal chromosomal or structural abnormalities were excluded., Results: During the study period, 32.6% (n = 2283) of women were diagnosed with peritoneal adhesions during the second cesarean delivery. Factors found to be significantly associated with peritoneal adhesions were maternal age 35 years or older at the first cesarean delivery, Bedouin Arab ethnicity, composite of intrapartum and postpartum infectious morbidity, and cesarean deliveries that were performed after the onset of labor. In contrast, having a previous vaginal birth was found to be protective., Conclusions: Our results suggest that a woman's characteristics at her first cesarean delivery and her obstetrical history may be predictive of the likelihood of adhesion formation., (© 2023 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: To investigate adverse pregnancy outcomes in patients complicated with GDMA1 who delivered at term before or after 40 weeks of gestation., Study Design: A population-based cohort study including all women with GDMA1 during pregnancy was conducted. Deliveries occurred between 1988 and 2016 at a large university tertiary medical center., Results: During the study period, 11,765 women with GDMA1 met the inclusion criteria. Of these, 1303 (11 %) delivered after 40 weeks (post-date, study group), while 10,462 (89 %) delivered at term before 40 weeks of gestation (before date, control group). Those who delivered after 40 weeks of gestation (the study group) had a significantly lower percent of cesarean deliveries (CD), higher rates of spontaneous vaginal deliveries and induction of labor in comparison to those who delivered before 40 weeks of gestation (the control group). The control group had significantly higher rates of preeclampsia and intrauterine growth restriction than the study group. Using a multivariable logistic regression model, delivery after 40 weeks was noted as an independent protective factor for CD (adjusted OR = 0.78, 95 %CI 0.66-0.92, p value = 0.001). Delivery after 41 + 0 weeks had a significantly higher rate of CD and LGA., Conclusion: No significant increase in adverse pregnancy outcomes at term post-date pregnancies complicated with GDMA1 was demonstrated. Furthermore, there was no increase in the rate of CD with the increase in gestational age until 41 weeks of gestation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction and Hypothesis: Pregnancy and mode of delivery have a major effect on pelvic floor disorders (PFD). Assessing knowledge regarding PFD is essential not only for making more informed decisions regarding mode of delivery, but also for seeking help when PFD appear. The Prolapse and Incontinence Knowledge Questionnaire (PIKQ) is a validated tool that assesses women's knowledge regarding urinary incontinence (UI) and pelvic organ prolapse (POP). Validation of the Arabic version of the PIKQ had never been carried out. The purpose of this study was to conduct a condition specific validation among parturients of the PIKQ in the Arabic language., Methods: Translation of the PIKQ to the Arabic language was carried out according to international recommended guidelines. A cross-sectional study of pregnant women was conducted from June to September 2020 at the Soroka University Medical Center, Israel. The recommended 10:1 ratio between the number of subjects and the number of items in the questionnaire (n=24) was maintained. A total of 244 third trimester pregnant women have completed the Arabic version of the PIKQ. In addition to the validation of the psychometric characteristics, construct validity, criterion validity, and reliability were tested as well., Results: Initially, exploratory factor analysis (EFA) was conducted, resulting in two 12-item scales representing UI and POP. Then, to validate the scale construct we conducted confirmatory factor analysis (CFA). Results of the CFA demonstrated that the PIKQ displayed construct validity, with standardized factor loadings ranging from 0.30 to 0.62. Finally, Cronbach's alpha indicated a good internal reliability for the two factors UI and POP. Criterion validity further supported the validity of the scale., Conclusions: The Arabic version of the PIKQ is a new, reliable, consistent, and valid instrument to examine the level of knowledge regarding UI and POP in Arabic speaking pregnant women. This instrument may be used to assess women's knowledge about PFD and to direct the need for educational interventions that may empower women to make informed decisions regarding perinatal care., (© 2022. The International Urogynecological Association.)

Objective: Since women with GDM have an increased risk to develop type 2 DM, a 75 g OGTT is recommended 6-12 weeks postpartum for all women with GDM. However, screening rates remain low. The aim of this study was to find factors affect the rate of postpartum DM screening., Materials and Methods: A retrospective cohort study between 2016 and 2017 at the Soroka Medical Center, comparing women with GDM who underwent postpartum DM screening test to those who did not., Results: 257 women who had a diagnosis of GDM and met the inclusion criteria were included. 53 (20.6%) had a postpartum DM screening test and 204 (79.4%) did not complete the postpartum DM screening. Women who underwent a DM screening postpartum were more likely to be older, with significantly higher rates of vacuum-assisted delivery, more likely to be diagnosed with GDMA2 as compared to GDMA1 during pregnancy and, with high probability of receiving recommendations for screening at a postpartum visit., Conclusions: The rates of postpartum DM screening for women with GDM are low and need to increase. Age greater than 25, vacuum delivery, GDMA2, and having received a recommendation for postpartum screening increased the likelihood of undergoing a postpartum DM screening., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction and Hypothesis: Striae gravidarum are linear atrophic scars appearing on the abdomen of pregnant women reported to be related to pregnancy-induced changes in the connective tissue. Pelvic floor distress symptoms are also known to be linked to connective tissue weakness. Given that common pathophysiological pathways may play a role in both striae gravidarum and pelvic floor dysfunction symptoms, we sought to examine whether there is a correlation between them during pregnancy., Methods: A prospective observational study among third-trimester pregnant women who visited a tertiary medical center for routine pregnancy follow-up was conducted by using the Pelvic Floor Distress Inventory (PFDI-20) questionnaire to evaluate pelvic floor distress symptoms and the Davey method for evaluating striae gravidarum severity. Obstetrical characteristics as well as pelvic floor distress symptoms were compared between two groups according to the severity of striae gravidarum. Univariate analysis was carried out using appropriate tests; PFDI scores were compared between the groups using the Mann-Whitney test., Results: Women with striae gravidarum were significantly older (31.06 vs. 28.83 years, p < 0.01), had a lower body mass index (27.5 vs. 30.98, p < 0.01), and gave birth to smaller neonates (3155 vs. 3389 g, p < 0.01). In addition, the overall and median PFDI-20 scores differed between the groups (with severe SG having the highest median score of 20 and those with milder SG having a score of 16 compared to 14 in those without SG). A distinct association between the PFDI-20 score and SG severity was not demonstrated (p = 0.63)., Conclusions: In our population, an association was demonstrated between pelvic floor distress symptoms and the presence of striae gravidarum. However, following a linear regression model, no statistically significant association between SG severity and total PFD-20 score was seen. Our findings strengthen the hypothesis of common connective tissue involvement in the pathophysiology of both conditions., (© 2022. The International Urogynecological Association.)

Introduction and Hypothesis: The objective was to examine knowledge regarding pelvic floor disorders (PFDs) among women during the third trimester of pregnancy., Methods: A cross-sectional study was conducted at a large teaching medical center in Israel between June and September 2020. Women in their third trimester (N = 649) were asked to complete the validated Hebrew and Arabic versions of the Prolapse and Incontinence Knowledge Questionnaire (PIKQ). The PIKQ instrument examines the knowledge of two major PFDs: urinary incontinence (UI) and pelvic organ prolapse (POP). The study population included women over 18 years of age, in the third trimester, who speak and read Hebrew or Arabic fluently. Two separate scores were calculated, one for each section of the PIKQ. The association of questionnaire scores with the different independent variables was examined using Student's t test or one-way ANOVA. Correlations were examined using Pearson's or Spearman's correlation coefficient., Results: The Hebrew version was filled out by 405 women, and 244 women completed the Arabic version. The average questionnaire scores were 7.65 ± 2.8 and 5.32 ± 2 for the UI and POP sections respectively. Significantly higher average scores in both the UI and the POP sections were noted among health care workers (UI: 10.19 ± 2.3 vs 7.34 ± 2.6, p < 0.001; POP: 8.27 ± 2.7 vs 4.97 ± 2.6, p < 0.001), women with higher education (p < 0.001 in both parts) and those with higher incomes (p < 0.001 for both parts)., Conclusions: Knowledge of PFD among women in the third trimester of pregnancy in Israel was found to be low. Founding educational programs for targeted groups may improve both the knowledge of PFD and the quality of life for these women., (© 2022. The International Urogynecological Association.)

Introduction and Hypothesis: Pregnancy and delivery have a major effect on pelvic floor disorders. Assessing knowledge regarding pelvic floor disorders in childbearing age women and appropriate interventions will enable women to seek appropriate medical advice once pelvic floor disorders have developed. The purpose of this study was to validate the prolapse and incontinence knowledge questionnaire in the Hebrew language., Methods: Translation of the prolapse and incontinence knowledge questionnaire to the Hebrew language according to international recommended guidelines. A study was conducted to validate the questionnaire. The study took place between June to September 2020 in a tertiary medical center in Israel. A total of 240 third trimester pregnant women completed the Hebrew version of the prolapse and incontinence knowledge questionnaire. Construct validity, criterion validity and reliability tests were performed., Results: Factor analysis of the Hebrew version of the prolapse and incontinence knowledge questionnaire demonstrated 12 strong positive factor loadings to one principal factor in the prolapse and incontinence knowledge questionnaire-pelvic organ prolapse domain (FL > 0.3) and 10/12 in the prolapse and incontinence knowledge questionnaire-urinary incontinence domain. The Hebrew prolapse and incontinence knowledge questionnaire was found to have internal consistency, with Cronbach alpha coefficient of 0.745 for the urinary incontinence domain and 0.796 for the pelvic organ prolapse domain., Conclusions: The Hebrew version of the prolapse and incontinence knowledge questionnaire is a new, reliable, consistent, and valid instrument to examine the level of knowledge regarding pelvic floor disorders in Hebrew-speaking pregnant women., (© 2021. The International Urogynecological Association.)

Purpose: Prolactin (PRL)-secreting tumors are the most common functional pituitary adenomas. They usually respond to dopamine agonist (DA) treatment, with PRL normalization and adenoma shrinkage. Our aim was to characterize patients with prolactinoma resistant to DA treatment., Methods: This retrospective case series included patients diagnosed with DA-resistant prolactinomas between 1993-2017 in three medical centers. Resistance was defined as PRL levels above three times the upper limit of normal (ULN) despite a weekly dose of ≥2 mg cabergoline (CAB). Clinical and biochemical information, and response to treatment, were retrieved from medical records., Results: Twenty-six patients were identified; 20 males. Of 25 macroadenomas, three were giant tumors (>40 mm) and 15 (57.7%) were invasive. The mean age at diagnosis was 31.8 ± 14.9 years (range: 13-62). The median maximal CAB dose was 3.5 mg/week (IQR, 2.5-5). Half the patients received only CAB in escalating doses, nine received CAB and underwent transsphenoidal surgery, and four underwent surgery and radiotherapy in addition to CAB treatment. PRL levels at baseline between patients treated only with CAB and those operated were (91.6 [51.1-296.7] vs. 73.1 [22.6-170.9] XULN p = 0.355), and under maximal CAB dose PRL levels between patients treated only with CAB and those operated were similar (5.77 [1.27-11.27] vs 5.27 (2.9-26) XULN p = 0.317). At the last visit patients who received combined therapy achieved lower PRL levels than those treated with DA only (5.22 [1.7-21.6] vs 1.1 [0.44-3.99] XULN p = 0.017) PRL normalization was attained in seven patients and levels below 3 × ULN in fourteen patients; the overall response was 56%., Conclusions: Resistant prolactinomas usually require a multi-modal treatment strategy. We were able to control 14/25 (56%) of resistant tumors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Diabetic ketoacidosis (DKA) during pregnancy is a life-threatening emergency for both the mother and the fetus. The pathophysiology of DKA in pregnancy has its own characteristics due to multiple factors, such as insulin resistance, accelerated starvation and respiratory alkalosis, thus creating ketosis-prone state, with DKA occurring at milder degrees of hyperglycemia, even in normoglycemic levels, which can result in delayed diagnosis and treatment with potential for adverse metabolic consequences., Study Design: In this article, we presented 8 clinical cases of DKA during pregnancy. We discuss the spectrum of the clinical picture, the entity of euglycemic DKA vs hyperglycemic DKA, the period of pregnancy in appearance of episode of DKA and triggers of DKA., Conclusion: The treatment of DKA in pregnant women must be started immediately and must be accentuated on intravenous fluids, insulin and electrolyte replacement. DKA in pregnancy may be euglycemic. Prevention, early recognition, immediate hospitalization, and aggressive management remain the cornerstones in DKA management in pregnancy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Treatment of paediatric trauma requires specialized infrastructure, medical equipment, medical staff and ancillary support personnel that have been specifically trained for such tasks., Aims and Objectives: To examine the perceptions and attitudes of physicians and nurses in general and paediatric emergency departments (PEDs) on training, confidence, and management of paediatric trauma in order to facilitate the establishment of an optimal model for admitting and treating paediatric trauma patients., Design: Drawing on published literature and a previously conducted qualitative study that explored the provision of medical care to paediatric trauma patients, we conducted an attitude survey., Methods: A 26-item paper-based questionnaire was distributed by nurse managers to all staff working within general EDs and PEDs of 22 medical centres across Israel., Results: Of 843 physicians and nurses who completed the survey, 61.1% considered PEDs the most appropriate facility for treating both minor and severe paediatric trauma, 88.5% believed that minor paediatric trauma should be treated in designated paediatric trauma centres, and 53.6% deemed that paediatric emergency medicine specialists are the most suitable primary decision makers in paediatric trauma. PED teams expressed greater professional confidence for treating paediatric trauma and multiple casualty incident patients. Greater professional confidence was positively correlated with paediatric trauma training, greater exposure to paediatric trauma cases, and working in larger medical centres., Conclusions: The results of the current study suggest that PEDs are perceived to be more appropriate for dealing with paediatric trauma. Also, treatment of severe trauma may be more appropriate in centres that admit large numbers of paediatric trauma cases., Relevance to Clinical Practice: Emergency medicine teams should undergo training for dealing with paediatric trauma. Such training would develop their skills, increase their confidence, and enhance their emotional abilities to cope with paediatric trauma., (© 2021 British Association of Critical Care Nurses.)

Objective: Previous studies suggested maternal hypothyroidism during pregnancy to be associated with cognitive impairment of the offspring. Scarce data exist regarding long-term endocrine health of the offspring. This study was aimed to assess whether children born to mothers with hypothyroidism during pregnancy are at an increased risk for long-term endocrine morbidity., Study Design: A retrospective population-based cohort study compared long-term endocrine morbidity of children born between the years 1991 and 2014 to mothers with and without hypothyroidism. Multiple gestations, fetuses with congenital malformations, and women lacking prenatal care were excluded. Hospitalizations of the offspring up to the age of 18 years involving endocrine morbidity were evaluated according to a predefined set of ICD-9 codes. Kaplan-Meier's survival curves were used to compare the cumulative risk and a Cox multivariable model was used to adjust for confounders., Results: During the study period, 217,910 deliveries met the inclusion criteria; 1.1% of which were with maternal hypothyroidism ( n  = 2,403). During the follow-up period, the cumulative incidence of endocrine morbidity among children born to mothers with hypothyroidism was 27 per 1,000 person-years and 0.47 per 1,000 person-years in the comparison group (relative risk: 2.14; 95% confidence interval [CI]: 1.21-3.79). The Kaplan-Meier's survival curve demonstrated a significantly higher cumulative endocrine morbidity in children born to mothers with hypothyroidism (log-rank test, p  = 0.007). In the Cox regression model controlled for maternal age, birth weight, preterm birth, maternal diabetes, hypertensive disorders of pregnancy, induction of labor, and mode of delivery, maternal hypothyroidism was found to be independently associated with pediatric endocrine morbidity in the offspring (adjusted hazard ratio = 1.92, 95% CI: 1.08-3.4, p  = 0.025)., Conclusion: Maternal hypothyroidism appears to be independently associated with long-term pediatric endocrine morbidity of the offspring., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Euglycemic DKA (eu-DKA) is a life-threatening emergency. It may occur in patients with both type 1 and type 2 DM, and characterized by milder degrees of hyperglycemia with blood glucose level < 200 mg/dl, which can result in delayed diagnosis and treatment with potential for adverse metabolic consequences. Following the wide introduction of the sodium glucose transporter 2 inhibitors (SGLT2i) in therapeutic practice for DM type 2 treatment the amount of eu-DKA increased and therefore, interest to this entity rose. Other causes associated with eu-DKA include pregnancy, decreased caloric intake, heavy alcohol use, insulin use prior to hospital admission, cocaine abuse, pancreatitis, sepsis, chronic liver disease and liver cirrhosis. Patients with eu-DKA as well as with DKA need immediate referral for emergency evaluation and treatment. The treatment includes rapid correction of dehydration, correction electrolyte abnormalities, and use of insulin drip until the anion gap, and bicarbonate levels normalize. Increased glucose administration using higher percentages of dextrose (10 or 20%) are required to facilitate the concomitant administration of the relatively large amounts of insulin that are needed to correct the severe acidosis in these patients., (Copyright © 2019. Published by Elsevier B.V.)

Introduction: An over-active bladder is a common disorder which influences women's health and quality of life. There is difficulty defining the exact prevalence of the disorder since there are various definitions in the literature. The ICS definition from 2002 on the over-active bladder (OAB) syndrome enables more uniformity, by declaring that OAB syndrome is a symptomatic syndrome defined as presence of urgency with or without urinary incontinence, mostly accompanied by frequency and nocturia. In this article we reviewed the current medical literature on the prevalence of the OAB syndrome by focusing on relevant crosssectional and longitudinal studies, the trend changes during life, co-morbidities, the influence of quality of life and the economic burden following the disorder and its treatment. The authors' hope is that elevating awareness of the OAB syndrome will help improve its diagnosis and treatment.

Objective: To determine whether women with a previous uterine rupture have a higher risk of adverse perinatal outcome in subsequent births., Methods: A retrospective study comparing all subsequent singleton cesarean deliveries (CD) of women with a previous uterine rupture, with CD of women with no such history, during the years 1988-2011 was conducted., Results: Out of 34,601 singleton CD that occurred during the study period, 0.1 % (n = 46) were of women with a previous uterine rupture. Previous uterine rupture was significantly associated with preterm delivery (<37 weeks), low birth weight (<2500 g), cervical tears, and dehiscence of the uterine scar. Pregnancies following a previous uterine rupture were associated with lower Apgar scores at 5 min. However, the perinatal mortality rate did not differ between the two groups. A recurrent uterine rupture occurred in 15.2 % of patients with a previous uterine rupture., Conclusion: Previous uterine rupture is a risk factor for adverse maternal and perinatal outcome and specifically recurrent uterine rupture. Appropriate consultation regarding these risks is needed for patients with a previous uterine rupture.

Implantation, trophoblast development and placentation are crucial processes in the establishment and development of normal pregnancy. Abnormalities of these processes can lead to pregnancy complications known as the great obstetrical syndromes: preeclampsia, intrauterine growth restriction, fetal demise, premature prelabor rupture of membranes, preterm labor, and recurrent pregnancy loss. There is mounting evidence regarding the physiological and therapeutic role of heparins in the establishment of normal gestation and as a modality for treatment and prevention of pregnancy complications. In this review, we will summarize the properties and the physiological contributions of heparins to the success of implantation, placentation and normal pregnancy.

Objective: To determine whether women with a previous uterine scar dehiscence are at increased risk of adverse perinatal outcomes in the following delivery., Methods: A retrospective cohort study was conducted of all subsequent singleton cesarean deliveries performed at the Soroka University Medical Center, Beer-Sheva, Israel, between January 1, 1988, and December 31, 2011. Clinical and demographic characteristics, maternal obstetric complications, and fetal complications were evaluated among women with or without a previous documented uterine scar dehiscence., Results: Of the 5635 pregnancies associated with at least two previous cesarean deliveries, 180 (3.2%) occurred among women with a previous uterine scar dehiscence. Women with this condition in a prior pregnancy were more likely than those without previous uterine scar dehiscence to experience subsequent preterm delivery (86 [47.8%] vs 1350 [24.7%]; P<0.001), low birth weight (47 [26.1%] vs 861 [15.8%]; P<0.001), and peripartum hysterectomy (5 [2.8%] vs 20 [0.4%]; P<0.001). Nevertheless, previous uterine scar dehiscence did not increase the risk of uterine rupture, placenta accreta, or adverse perinatal outcomes, such as low Apgar scores at 5 minutes and perinatal mortality., Conclusion: Uterine scar dehiscence in a previous pregnancy is a potential risk factor for preterm delivery, low birth weight, and peripartum hysterectomy in the following pregnancy., (Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Drugs of abuse affect pregnancy outcomes, however, the mechanisms in which cannabis exerts its effects are not well understood. The aim of this study was to examine the influence of short-term (1-2 hours) exposure to cannabidiol, a major phytocannabinoid, on human placental breast cancer resistance protein function., Study Design: The in vitro effect of short-term exposure to cannabidoil on breast cancer resistance protein in BeWo and Jar cells (MCF7/P-gp cells were used for comparison) was tested with mitoxantrone uptake, and nicardipine was used as positive control. The ex vivo perfused cotyledon system was used for testing the effect of cannabidoil on glyburide transport across the placenta. Glyburide (200 ng/mL) was introduced to maternal and fetal compartments through a recirculating 2 hour perfusion, and its transplacental transport was tested with (n = 8) or without (n = 8) cannabidoil., Results: (1) Cannabidoil inhibition of breast cancer resistance protein-dependent mitoxantrone efflux was concentration dependent and of a noncell type specific nature (P < .0001); (2) In the cotyledon perfusion assay, the administration of cannabidoil to the maternal perfusion media increased the female/male ratio of glyburide concentrations (1.3 ± 0.1 vs 0.8 ± 0.1 at 120 minutes of perfusion, P < .001)., Conclusion: (1) Placental breast cancer resistance protein function is inhibited following even a short-term exposure to cannabidoil; (2) the ex vivo perfusion assay emphasize this effect by increased placental penetration of glyburide to the fetal compartment; and (3) these findings suggest that marijuana consumption enhances placental barrier permeability to xenobiotics and could endanger the developing fetus. Thus, the safety of drugs that are breast cancer resistance protein substrates is questionable during cannabis consumption by pregnant women., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24-72 h) exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(rh123)). Cyclosporine A (CsA) served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and rh123) was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

Objective: To determine whether perineal massage during the second stage of labor using oil enriched with vitamins, increases the chances of delivering with an intact perineum as compared to perineal massage using pure liquid wax., Method: A prospective, randomized, double-blind study was conducted. Women were assigned to liquid wax (jojoba oil) versus purified formula of almond and olive oil, enriched with vitamin B1, B2, B6, E and fatty acids. The caregivers used the oils during the second stage of labor., Results: A total of 164 women undergoing vaginal delivery were recruited. No significant differences regarding perineal lacerations, number of sutures and length of suturing were noted between the two groups. Likewise, while analyzing separately nulliparous and multiparous women, no significant differences were noted. Controlling for birth weight >4000 g, using the Mantel-Haenszel technique, no association was noted between perineal lacerations and the type of oil used (weighted OR = 0.9, 95% CI 0.3-2.4; p = 0.818)., Conclusion: The type of the oil used during the second stage of labor for prevention of perineal tears has no effect on the integrity of the perineum. Accordingly, it seems that there is no perfect oil.

Objective: To evaluate the effect of magnesium sulfate (MgSO(4)) on placental expression levels of vascular endothelial growth factor (VEGF)., Materials and Methods: Cotyledons of term normotensive and preeclamptic placentas were dually perfused for 6 h, with MgSO(4) (6-7 mg%) in the maternal reservoir [normotensive (n = 3); preeclamptic (n = 4)] and with the control medium (without MgSO(4)) [normotensive (n = 3); preeclamptic (n = 6)]. After perfusion, placental tissue samples were collected from four different placental compartments (amnion, chorion, placental villous and decidua). The collected placental tissues were homogenized and examined for VEGF by ELISA. Statistical significance was determined using a two-way analysis of variance., Results: After perfusion with control medium, significantly lower levels of VEGF were detected in the chorion and placental villous compartments of preeclamptic placentas (70 ± 24 pg/g protein and 29 ± 11 pg/g protein; respectively), as compared with normotensive placentas (172 ± 80 pg/g protein and 51 ± 17 pg/g protein; respectively; p < 0.05). Exposure of preeclamptic placentas to MgSO(4) resulted in decreased VEGF levels by the amnion (57 ± 26 pg/g protein), as compared with the control group (153 ± 62 pg/g protein) (p < 0.05). On the other hand, MgSO(4) significantly increased VEGF levels by the placental villous and the decidua (58 ± 15 pg/g protein, 70 ± 29 pg/g protein; respectively), as compared with the control group (29 ± 11 pg/g protein, 33 ± 14 pg/g protein; respectively) (p < 0.01, p < 0.05; respectively). Exposure to MgSO(4) did not affect VEGF levels in normotensive placentas., Conclusion: Reduced levels of VEGF are expressed by some placental compartments in preeclampsia compared with normotensive pregnancy. Perfusion with MgSO(4) affects VEGF expression differently by preeclamptic and normotensive placentas. Increased production of placental VEGF in preeclampsia may play a role in the therapeutic action of MgSO(4).

Objective: We sought to evaluate risk factors and perinatal outcomes of pregnancies complicated with placenta accreta and to study perinatal outcomes in subsequent pregnancies., Study Design: A retrospective study comparing all singleton cesarean deliveries (CD) of women with and without placenta accreta was conducted. In addition, a retrospective comparison of all subsequent singleton CD of women with a previous placenta accreta, with CD of women with no such history, was performed during the years 1988 through 2011. Stratified analysis using multiple logistic regression models was performed to control for confounders., Results: During the study period, there were 34,869 CD, of which 0.4% (n = 139) were complicated with placenta accreta. Using a multivariable analysis with backward elimination, year of birth (adjusted odds ratio [aOR], 1.06; 95% confidence interval [CI], 1.03-1.09; P < .001), previous CD (aOR, 5.11; 95% CI, 3.42-7.65; P < .001), and placenta previa (aOR, 50.75; 95% CI, 35.57-72.45; P < .001) were found to be independently associated with placenta accreta. There were 30 subsequent pregnancies of women with placenta accreta. Recurrent accreta occurred in 4 patients (13.3%). Previous placenta accreta was significantly associated with uterine rupture (3.3% vs 0.3%, P < .01) peripartum hysterectomy (3.3% vs 0.2%, P < .001), and the need for blood transfusions (16.7% vs 4%, P < .001). Nevertheless, increased risk for adverse perinatal outcomes such as low Apgar scores at 1 and 5 minutes and perinatal mortality was not found in these patients., Conclusion: Prior CD and placenta previa are independent risk factors for placenta accreta. A pregnancy following a previous placenta accreta is at increased risk for adverse maternal outcomes such as recurrent accreta, uterine rupture, and peripartum hysterectomy. However, adverse perinatal outcomes were not demonstrated., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objective: To examine the effect of magnesium sulfate (MgSO(4)) on sFlt (soluble fms-like tyrosine kinase)-1 in the fetal and maternal compartments of normotensive and preeclamptic placentas., Methods: Cotyledons of term normotensive and preeclamptic placentas were dually perfused for six hours, with control medium and MgSO(4) (6-7 mg %) in the maternal reservoir. Perfusate sFlt-1 concentrations were measured., Results: Median sFlt-1 concentration was higher in the maternal than in the fetal side in both groups and perfusion media (p < 0.0001). When perfused with control medium, the maternal side median sFlt-1 concentration was higher in the preeclampsia than in the control group (p < 0.0001). After perfusion with MgSO(4), the median maternal and fetal sides perfusate sFlt-1 concentration were higher in the preeclampsia than in the control group (p < 0.0001). In comparison to perfusion with control medium, the median sFlt-1 concentration of normal pregnant women decreased in the fetal and increased in the maternal side. In the preeclampsia group, only median fetal side sFlt-1 concentration increased., Conclusion: In contrast to normal pregnant women, perfusion with MgSO(4) of preeclamptic placentas did not increase their sFlt-1 concentration. This may indicate that MgSO(4) role may be limited to its anti-eclamptic and does not affect the anti-angiogenic state associated with preeclampsia.

It has become clear that almost any drug or chemical substance administered to the mother is able to cross the placenta to some extent, unless it is metabolized or altered during passage, or else its molecular size and low lipid solubility do not allow transplacental transfer. A number of transport systems have been identified in the placenta, which recognizes a wide variety of pharmacological active drugs as substrates. In recent years, research on human placental transporters has been developing due to the increase of knowledge technology in pharmacology. In this review we will focus on the main placental transporters which are known today. The P-glycoprotein (P-gp), Breast cancer resistance protein (BCRP/ABCG2) and Multidrug resistance associated protein 2 (MDR2) transporters are expressed at the apical surface of the syncytiotrophoblast, and have a protective effect. Transporters for 5-HT (SERT) and NE (NET) are also expressed at the apical surface and regulate extracellular concentrations of monoamines. The physiologic function of Multidrug resistance associated protein (MRP) transporters (which is expressed at the basal surface of the syncytiotrophoblast) may be the removal of metabolic end products from the fetus. Some of the members of the organic anion transporters are also expressed at the basolateral surface of the syncytiotrophoblast.