Vered Klaitman

Placenta accreta is an independent risk factor for late pre-term birth and perinatal mortality

Abstract Objective: This study is aimed to identify the risk factors for the development of placenta accreta (PA) and characterize its effect on maternal and perinatal outcomes. Study design: This population-based retrospective cohort study included all deliveries at our medical center during the study period. Those with placenta accreta (n = 551) comprised the study group, while the rest of the deliveries (n = 239 089) served as a comparison group. Results: The prevalence of placenta accerta is 0.2%. Women with this complication had higher rates of ≥2 previous CS (p < 0.001), recurrent abortions (p = 0.03), and previous placenta accreta [p < 0.001]. The rates of placenta previa and peripartum hemorrhage necessitating blood transfusion were higher in women with placenta accreta than in the comparison group. PTB before 34 and 37 weeks of gestation was more common among women with placenta accreta (p < 0.01), as was the rate of perinatal mortality (p < 0.001). Placenta accreta was an independent risk factor for perinatal mortality (adj. OR 8.2; 95% CI 6.4–10.4, p < 0.001) and late PTB (adj. OR 1.4; 95% CI 1.1–1.7, p = 0.002). Conclusion: Placenta accreta is an independent risk factor for late PTB and perinatal mortality.

A prior placenta accreta is an independent risk factor for post-partum hemorrhage in subsequent gestations

OBJECTIVE The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of placenta accreta on subsequent pregnancies. STUDY DESIGN A population based retrospective cohort study was designed, including all women who delivered at our medical center during the study period. The study population was divided into two groups including pregnancies with: (1) a history of placenta accreta (n=514); and (2) control group without placenta accreta (n=239,126). RESULTS (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage (adjusted OR 4.1, 95% CI 1.5-11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0-36.0) and placenta previa (adjusted OR 7.6, 95% CI 4.4-13.2) in the current pregnancy, and a prior cesarean section (adjusted OR 1.7, 95% CI 1.3-2.2); (2) in addition, placenta accreta in a previous pregnancy is associated with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26-0.98); (3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5-1.9) after adjusting for confounders. CONCLUSION A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This should be taken into account in order to ensure a safety pregnancy and delivery of these patients.

LMWH in the prevention of preeclampsia and fetal growth restriction in women without thrombophilia. A systematic review and meta-analysis.

Placental mediated pregnancy complications such as preeclampsia and fetal growth restriction (FGR) are common, serious, and associated with increased morbidity and mortality. We conducted a systematic review and meta-analysis to determine the effect of treatment with low-molecular-weight heparins (LMWHs) for secondary prevention of these complications in non thrombophilic women. We searched the electronic databases PubMed, Scopus, and Cochrane Library for randomised controlled trials addressing this question. Five studies including 403 patients met the inclusion criteria, 68 developed preeclampsia and 118 FGR. The studies were very heterogeneous in terms of inclusion criteria, LMWH preparation, and dosage. Meta-analyses were performed using random-effect models. The overall use of LMWHs was associated with a risk reduction for preeclampsia (Relative risk (RR) 0.366; 95 % confidence interval (CI), 0.219-0.614) and FGR (RR 0.409; 95 % CI, 0.195-0.932) vs. no treatment. From the data available for analysis it appears that the use of Dalteparin is associated with a risk reduction for preeclampsia (p=0.002) and FGR (p<0.001); while Enoxaparin is associated with risk reduction for preeclampsia (p=0.013) but not for FGR (p=0.3). In spite of the small number of studies addressing the research question, and the high variability among them, our meta-analysis found a modest beneficial effect of LMWH for secondary prevention of preeclampsia and FGR. Further studies are needed to address these questions before a definite conclusion can be reached.

Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromes

Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal–fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.

Early preterm delivery due to placenta previa is an independent risk factor for a subsequent spontaneous preterm birth

BackgroundTo determine whether patients with placenta previa who delivered preterm have an increased risk for recurrent spontaneous preterm birth.MethodsThis retrospective population based cohort study included patients who delivered after a primary cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were determined.ResultsPatients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence [crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS pregnancy was 55.9%; and these patients had a higher rate of recurrent preterm delivery than the rest of the study population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent preterm birth [OR of 3.6 (95% CI 1.5-8.5)].ConclusionsWomen with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended.

Maternal total cell-free DNA in preeclampsia and fetal growth restriction: Evidence of differences in maternal response to abnormal implantation

Objectives Preeclampsia and fetal growth restriction are obstetrical syndromes associated with abnormal placental implantation and changes in the activation status of maternal leukocytes. This study is aimed to determine by a simple, rapid fluorescent assay the changes in maternal serum total cell-free DNA (t-cfDNA) concentrations in women with preeclampsia and those with fetal growth restriction (FGR). Study design A cross-sectional study was conducted measuring maternal serum t-cfDNA concentrations. Women were classified into the following groups: 1) patients with preeclampsia (n = 21); 2) FGR-estimated fetal weight below the 10thpercentile (n = 28); and 3) normal pregnancy (n = 39). Serum samples were directly assayed for t-cfDNA using a rapid fluorescent SYBR Gold assay. Elevated maternal serum t-cfDNA concentrations were defined as a cutoff>850ng/ml. Nonparametric statistics were used for analysis. Results Women with preeclampsia had a higher median maternal serum concentration (802 ng/ml, 400–2272 ng/ml) than women with a normal pregnancy (499 ng/ml, 0–1892 ng/ml, p = 0.004) and those with FGR (484 ng/ml, 72–2187 ng/ml, p = 0.012). Moreover, even patients with FGR <5th percentile and abnormal Doppler had a lower median maternal serum t-cfDNA than those with preeclampsia (median 487 ng/ml, 144–1971 ng/ml, p = 0.022). The median concentration of t-cfDNA did not differ between women with a normal pregnancy and those with FGR (p = 0.54), as well as those with fetuses <5th percentile and abnormal Doppler (p = 0.7). Women with preeclampsia had a higher proportion of elevated t-cfDNA than those with a normal pregnancy (p = 0.015) and patients with FGR (p = 0.025). Conclusions Preeclampsia is associated with higher maternal serum t-cfDNA concentration than normal pregnancy or FGR. This observation may reflect an increased systemic activation of the maternal inflammation, rather than placental; this assumption is supported by the fact that we did not observe a significant change in the maternal serum t-cfDNA in patients with placental-mediated FGR.

The Role of the Coagulation System in Preterm Parturition

Term and preterm parturition have a common pathway that includes irregular uterine contractions, cervical effacement and dilatation, along with decidual activation and rupturing of the chorioamniotic membrane. This pathway is observed in the physiologic labor at term as well as in the pathological processes leading to premature delivery. Indeed, the clinical presentation of preterm parturition involves all components of this common pathway: 1. Preterm contractions in women with spontaneous preterm labor with intact membranes; 2.cervical effacement and dilatation in women with cervical insufficiency; and/or 3.decidual activation and rupture of membranes in those with preterm PROM.