Tamar Eshkoli

Placenta accreta: risk factors, perinatal outcomes, and consequences for subsequent births.

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.

Drug transport across the placenta.

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.

The physiologic and therapeutic role of heparin in implantation and placentation.

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.

Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

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.

The consequences of previous uterine scar dehiscence and cesarean delivery on subsequent births

To determine whether women with a previous uterine scar dehiscence are at increased risk of adverse perinatal outcomes in the following delivery.

Can we find the perfect oil to protect the perineum? A randomized-controlled double-blind trial.

Abstract 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.

Perfusion with magnesium sulfate increases sFlt-1 secretion only in the fetal side of placenta of women with preeclampsia

Objective: To examine the effect of magnesium sulfate (MgSO4) 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 MgSO4 (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 pefusion with MgSO4, 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 MgSO4 of preeclamptic placentas did not increase their sFlt-1 concentration. This may indicate that MgSO4 role may be limited to its anti-eclamptic and does not affect the anti-angiogenic state associated with preeclampsia.

The effects of magnesium sulfate on placental vascular endothelial growth factor expression in preeclampsia

Objective: To evaluate the effect of magnesium sulfate (MgSO4) 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 MgSO4 (6–7 mg%) in the maternal reservoir [normotensive (n = 3); preeclamptic (n = 4)] and with the control medium (without MgSO4) [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 MgSO4 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, MgSO4 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 MgSO4 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 MgSO4 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 MgSO4.

Magnesium Role in Cytokine Regulation of Hypoxic Placentas Related to Certain Placental Pathology

This chapter deals with the issue of magnesium and placenta. Our group studied the area of proinflammatory cytokines in phathological conditions during pregnancy and the influence of MgSO4.