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Inherited and acquired thrombophilia: pregnancy outcome and treatment.

Maternal thrombophilias increases the risk of an adverse pregnancy outcome. An extensive literature review highlights the role of inherited and acquired thrombophilic disorders in spontaneous abortion, both early and late, recurrent or isolate, in intrauterine growth retardation, in placenta abruption, in pre-eclampsia and in venous thromboembolism. We have particularly focused attention on the following factors: antithrombin III (ATIII), proteins C (PC) and S (PS) deficiencies, genetic mutations particularly factor V Leiden (FVL), prothrombin gene G20210A (PTM) and the thermolabile variant of the methylene tetrahydrofolate reductase C677T (MTHFR) gene, lupus anticoagulant (LAC) and anticardiolipin antibodies, VIIIc factor, hyperhomocysteinemia and acquired activated protein C resistance. Appropriate treatment can improve pregnancy outcome without teratogenic effects.

Abortion, Spontaneous↗

[Pathomorphological changes in the uterine wall in gestosis].

With the purpose of studying a morphological substrate of the uterine contractile function disorder in gestosis, an investigation was conducted designed to study biopsy specimens of the uterine wall having been taken during the cesarean section in 80 parturient women. The womb of those parturient women having mild and severe gestosis complicated by uterine inertia (40 observations) or premature dethachement of the normally situated placenta (8 cases) was studied together with that of controls (32 cases). The indentified micro-circulatory disturbances and alterative changes in the myometrium structures in gestosis are regarded as one of the generalized blood circulation disorders, hemostasis (dissaminated intravascular blood coagulation) and systemic abnormalities of metabolism presenting as a multiorgan failure developing in the pathology under consideration. Microcirculatory disturbances and hypoxia-related dystrophic changes in the smooth myoblasts and connective tissue leading to its fibrosis--all these constitute a morphological substrate of changes in the contractile function of the womb.

Abruptio Placentae↗

Placental abruption and subchorionic hemorrhage in the first half of pregnancy: US appearance and clinical outcome.

In 30 pregnant patients who experienced vaginal bleeding between 10 and 20 weeks gestation, subchorionic hematomas were demonstrated on ultrasound examination. In 18 patients (60%), the margin of the placenta was separated from the uterine wall. In 15 patients the outcome was favorable (full-term delivery of normal infant) and in 15 patients the outcome was unfavorable (seven preterm births, four stillbirths, three spontaneous abortions, one therapeutic abortion). The major prognostic factor related to pregnancy outcome was the volume of the hematoma and, to a lesser extent, the relative volume of the hematoma (volume of hematoma divided by volume of gestational sac). For a volume less than 60 ml, the outcome tended to be favorable, and for a relative volume less than 0.4, the outcome tended to be favorable.

Abruptio Placentae↗

Deep venous thrombosis during pregnancy and after delivery: indications for and results of thrombectomy.

PURPOSE: Pregnancy and the puerperium are time periods of an increased risk for venous thromboembolism. An ideal treatment should lead to complete restoration of the venous lumen, elimination of the embolic source, and prevention of severe postphlebitic syndrome. Anticoagulation therapy with heparin or thrombectomy are treatment options. In the current literature, these options are discussed controversially. METHODS: From January 1982 to December 2001, 97 women underwent (93% transfemoral) thrombectomy and construction of an arteriovenous fistula (AVF) for deep venous thrombosis related to pregnancy. The clinical and coagulation parameters were evaluated. The AVF was ligated 3 to 6 months later. Follow-up with duplex ultrasound scan, photoplethysmography, and strain-gauge plethysmography was completed in 87 women. RESULTS: Surgery was performed without any maternal death or pulmonary embolization. A cesarean section was carried out during the same anesthesia in 11 cases. Thrombectomy was completed with construction of a temporary AVF in 90 patients (92.8%). One fetal death occurred in the recovery room for unknown reasons. In the early postoperative course, 16 patients (16.5%) underwent redo surgery for rethrombosis with or without the occlusion of the fistula. In 14 of these patients, the venous system remained patent thereafter. Fetal or neonatal death occurred in five cases 2 to 10 weeks after surgery, mainly because of abruption of the placenta probably from anticoagulation. Among 247 preoperatively occluded anatomic regions, 221 could be restored, and the secondary patency rate amounted to 89.5%. After a mean follow-up period of 6 years, 49 patients (56.3%) were seen without a postphlebitic syndrome, and only three patients (3.5%) had had a leg ulcer develop. CONCLUSION: In experienced hands, venous thrombectomy is a safe method to prevent pulmonary embolism and postphlebitic syndrome in women during pregnancy and the puerperium. The frequency of a severe postphlebitic syndrome after our surgical approach is lower than the rates published for anticoagulation treatment alone.

Abruptio Placentae↗

Causes of birth asphyxia and trauma.

Causes of birth asphyxia and trauma were determined in the 208 most severely affected infants of 10,995 consecutive live births; 159 infants had cerebral disturbances, 39 had fractures and palsies, and 10 had fractures or palsies in addition to cerebral disturbances. Most frequent causes of birth asphyxia and trauma were: prolonged labour, midforceps or breech delivery in full-term infants; abruption placentae, difficult breech delivery, and maternal sedation in premature infants; and unattended precipitate deliveries in immature infants. Asphyxia following normal labour and delivery usually occurred in infants with fetal malnutrition.Improved obstetrical management with more frequent use of Cesarean section delivery might have been of value in preventing much of this fetal injury.Asphyxia and trauma due to complications of delivery were twice as frequent on the ward as on the private service. This may have been due in part to a lower Cesarean section rate on the ward service. A monthly review of birth asphyxia and trauma is recommended to help maintain a high standard of obstetrical practice.

Abruptio Placentae↗

[Intimate mechanism of premature separation of the normally inserted placenta].

Retro-placental haemorrhage comes from rupture of patent utero-placental arteries which are neither sclerosed nor thrombosed. This applies whether the form of haemorrhage is minor (simple depression found when the placenta is examined) or grave with utero-placental apoplexy (with complete detachment of the placenta and syndrome of shock). The method by which the arteries rupture depend on the intensity and excessive duration of uterine contractions: --moderate; normal uterine contractions give rise to a prolonged blockage of the return circulation, whereas the arterial flow has not stopped. Rupture occurs because the distended utero-placental arterial wall bursts under the insult of raised pressure during the uterine contraction; --intense; these anomalies come from total blockage, both veinous and arterial, and the arterial rupture is due to anoxaemic necrosis of the utero-placental arterial wall. The rupture of the utero-placental arterial wall, which is normally very fragile because it has no elasticity in its musculature, gives the explanation for the histogenesis of retro-placental haemorrhages.

Abruptio Placentae↗

[Premature separation of the placenta--clinical findings and fetal monitoring].

In a study group of 41 pregnant women of postpartally confirmed placental abruption, the prognostic value of clinical and diagnostic findings was investigated. The incidence of placental abruption was 1.4% of all deliveries within a three-year interval. 51% of patients showed vaginal bleeding before delivery. Retroplacental haematoma was found in 49% of cases ultrasonographically. A total of 75% had a pathological CTG test. More than 95% of these findings occurred within 3 days before delivery. Abnormal Doppler flow findings in foetal vessels more than 3 days before delivery were seen in 62% of cases. In the last three days before delivery, 86% were abnormal. Preterm delivery before 37 weeks of gestation was registered in 82% of patients. Perinatal mortality amounted to 12%. The rate of severely dystrophic newborn was 30%. Even in cases with lack of the clinical and/or sonographical findings, the possibility of placental abruption should be considered, if an acute deterioration of cardiotocographic or Doppler-sonographic findings.

Abruptio Placentae↗

Clinical presentation and risk factors of placental abruption.

BACKGROUND: To study the risk factors of placental abruption during the index pregnancy. METHODS: One hundred and ninety-eight women with placental abruption and 396 control women were identified among 46,742 women who delivered at a tertiary referral university hospital between 1997 and 2001. Clinical variables were compared between the groups. Multivariate logistic regression analysis was applied to identify independent risk factors. The clinical manifestations of placental abruption were also studied. RESULTS: The overall incidence of placental abruption was 0.42%. The independent risk factors were maternal (adjusted OR 1.8; 95% CI 1.1, 2.9) and paternal smoking (2.2; 1.3, 3.6), use of alcohol (2.2; 1.1, 4.4), placenta previa (5.7; 1.4, 23.1), pre-eclampsia (2.7; 1.3, 5.6), and chorioamnionitis (3.3; 1.0, 10.0). Vaginal bleeding (70%), abdominal pain (51%), bloody amniotic fluid (50%), and fetal heart rate abnormalities (69%) were the most common manifestations. Neither bleeding nor pain was present in 19% of the cases. Overall, 59% had preterm labor (OR 12.9; 95% CI 8.3, 19.8), and 91% were delivered by cesarean section (34.7; 20.0, 60.1). Of the newborns, 25% were growth restricted. The perinatal mortality rate was 9.2% (OR 10.1; 95% CI 3.4, 30.1). Retroplacental blood clot was seen by ultrasound in 15% of the cases. CONCLUSIONS: Maternal alcohol consumption and smoking, and smoking by the partner turned out to be independent risk factors for placental abruption. Smoking by both partners multiplied the risk. The liberal use of ultrasound examination contributed little to the management of women with placental abruption.

Abruptio Placentae↗

[Syndrome of disseminated intravascular coagulation as the principal morphologic manifestation of shock].

Examinations of 43 section observations of shock established that the role of the syndrome of disseminated intravascular blood coagulation (DIBC) in the development of shock was variable: in some cases it caused the shock condition (embolism with amniotic waters, premature desquamation of the placenta), in others it is its consequence (hemorrhagic, cardiogenic shock). Morphogenesis of the DIBC syndrome is different depending on its role in the development of the shock condition. The DIBC syndrome as the cause of shock is characterized by completeness of thrombus formation processes and the presence of thrombi consisting of fibrin and/or formed blood elements. The time of formation of microthrombi in various organs is approximately the same and coincides with the period of shock development in the clinical picture. The characteristic morphological features of DIBC as the consequence of the shock include incomplete thrombus formation processes with the presence of pre-thrombi and/or strands and filaments of fibrin, involvement of the adrenals, the presence of the phenomenon of fibrin lining of vascular walls. The time of development of intravascular coagulation does not coincide with shock occurrence and may be different in various parts of the microcirculatory bed.

Abruptio Placentae↗

[Sucessful pregnancy outcome following three severe placental abruptions and intrauterine fetal death in the patient--heterozygous carrier of R506Q mutation of factor V (Leiden)].

A case of successful pregnancy outcome is reported in a patient with 3 preceding severe placental abruptions with intrauterine fetal death and caesarean deliveries. In the course of the current pregnancy heterozygosity for R506Q mutation of factor V (Leiden) was diagnosed in 26 weeks of gestation [w.g.] and low molecular weight heparin [LMWH] therapy initiated. Maternal condition was stable until delivery and all laboratory findings were within normal range. The fetus was followed up by ultrasound biometry and Doppler blood flow studies. From 28 w.g. on NST and biophysical profile were included. An emergency caesarean section was performed in 34 w.g. because of contractions not responding to tocolysis. The newborn was in good condition with weight and length corresponding to the 10th centile for gestational age [g.a]. Histologic study of the placenta showed anemic infarctions and recent haemorrhages in the basal and the chorionic plate. The initiation of LMWH therapy in the case reported was late (26 w.g.). By that moment there was already evidence of impaired fetal growth with fetal biometry corresponding to the 10th centile for g.a. After LMWH therapy was started no further slow down of fetal growth was registered. Successful pregnancy outcome may be related not only to LMWH therapy but also to other factors like active fetal monitoring after 28 w.g. and the emergency caesarian delivery immediately after the onset of uterine contractions. Patients with past obstetric history of severe preeclampsia, placental abruption or fetal growth restriction have to be screened for hereditary or acquired thrombophilia. If a thrombophillic state is present early LMWH therapy has to be considered. It is aimed to prevent anaemic placental infarctions and thrombotic complications.

Abruptio Placentae↗

Dysphoria among high-risk pregnant hospitalized women on bed rest: a longitudinal study.

BACKGROUND: While approximately 700,000 women experience pregnancy complications and are treated with bed rest in the hospital each year, little is known about negative affect in these women. OBJECTIVES: The study purpose was to describe dysphoria, a composite of symptoms of negative affect across the antepartum and postpartum and to identify the relationship between dysphoria and the length of pre-admission home bed rest, hospital bed rest, and maternal and fetal/neonatal indices of risk. METHODS: The convenience sample for this longitudinal repeated measures study consisted of 63 high-risk pregnant women admitted on antepartum bed rest to one of three university-affiliated hospitals. Women were included if they were diagnosed with (a) preterm labor, (b) premature rupture of membranes, (c) incompetent cervix, (d) placenta previa, (e) placental abruption or multiple gestation, and (f) did not have a psychiatric disorder. The Multiple Affect Adjective Checklist-Revised (MAACL-R) was used to assess dysphoria. Obstetric risk status was assessed by both the Hobel and Creasy Risk Assessment tools. RESULTS: Dysphoria was highest upon hospital admission and decreased significantly across time (F (5) = 23.58, p <.001). Positive Affect-Sensation Seeking significantly increased across time (F (5) = 53.16, p <.001). Dysphoria scores were significantly greater for those with highest Hobel obstetric risk scores (F (1, 60) = 4.53, p =.037). Antepartum dysphoria was not correlated with gestational age upon hospital admission, length of bed rest, or Creasy risk status. However, gestational age at birth was significantly correlated with postpartum dysphoria. DISCUSSION: The stimulus for antepartum dysphoria is unclear. However, postpartum dysphoria appears to be related to indicators of the infant's state of health at birth.

Abruptio Placentae↗

The molecular changes during placental detachment.

OBJECTIVES: RCAS1 is a membrane protein that plays a role in the maintenance of maternal immune tolerance during pregnancy. The work presented here demonstrates the results of RCAS1 expression in placenta in cases of placental abruption and patients with retained placental tissue during the third stage of labor. STUDY DESIGN: The placenta tissue samples were obtained during vaginal and cesarean delivery (derived from 117 pregnancies). Pregnant women were divided into four groups according to the onset of labor and the time of placental detachment in term labors. The samples were analyzed by the Western blot method. Statistical analysis was performed using the Shapiro-Wilk procedure. The Mann-Whitney test and Student's t-test were applied to compare the differences between parametric data. RESULTS: The average relative amount of RCAS1 observed in those patients with retained placental tissue was statistically significantly higher than in the patients with placental abruption. CONCLUSION: The differences observed in placental RCAS1 levels confirm the participation of this protein in the inhibition of maternal immune response during gestation. The present results also indicate that RCAS1 participates in the changes in the maternal immune system that take place during parturition and reinforce its potential involvement in the mechanism of placental abruption.

Abruptio Placentae↗

Spectral Doppler index mapping of the umbilicoplacental circulation and pregnancy outcome.

OBJECTIVE: To determine the value of Doppler measurements obtained by a new multigate Doppler modality, the spectral Doppler index mapping (SDIM) technique, to predict adverse outcome among pregnant women with normal conventional umbilical artery (UA) Doppler indices. DESIGN: A cross-sectional prospective cohort study. SUBJECTS: 183 women with well-dated singleton pregnancies who underwent prenatal ultrasound examination between 18 and 40 weeks of gestation were included in the study. At the time of the initial Doppler examination, all patients had normal UA and uterine artery Doppler indices, size appropriate for gestational age, no evidence of fetal anomalies or fetal distress. METHODS: SDIM data included the distribution curves of the pulsatility indices (PI) as well as the mean of the PI detected in the placenta and in the umbilical cord. The mean PI values were also calculated using conventional spectral Doppler sonography. Logistic regression analysis was used to control for gestational age while assessing various Doppler variables in predicting outcome. RESULTS: Adverse outcomes occurred in 26.6% of the pregnancies. In pregnancies with adverse outcome, the umbilicoplacental PI gradient was significantly lower (0.10 vs. 0.28, p < 0.003), the maximum intraplacental PI value was higher (1.28 vs. 1.16, p = 0.031), and there was a greater proportion with skewed UA distribution curves. Using forward stepwise logistic regression to compare the predictive value of the conventional Doppler ultrasound with SDIM, we found that the most accurate predictors of adverse outcome were the maximum intraplacental PI value (p < 0.028), skewed distributions (p = 0.002) and the gradient between the umbilical and intraplacental PI distributions (p = 0.006). CONCLUSIONS: Our results suggest that the SDIM system may enhance the ability of Doppler technology to predict obstetrical outcomes in patients with normal UA Doppler indices.

Abruptio Placentae↗

Uterine allergy: a cause of preterm birth?

OBJECTIVE: To identify the origin of eosinophils in cases of eosinophil-associated preterm delivery. METHODS: From an established set of 465 consecutive non-anomalous singleton infants delivered at 22-32 weeks' gestation, we retrieved 161 cases of preterm delivery following spontaneous onset of preterm labor, 78 cases with maternal preeclampsia, 33 cases of abruption, and 193 cases of premature rupture of membranes (PROM). Charts were reviewed, and the placenta, umbilical cord, and membranes were examined histologically. In cases with extravascular eosinophils showing evident gradient toward the amniotic cavity, the origin of the eosinophils (fetal or maternal) was determined by the proximity to fetal or maternal vessels. RESULTS: Histologic evidence of an eosinophilic gradient toward the amniotic cavity was present only in the fetal (including umbilical cord and chorion) compartments. This eosinophilic gradient was present in 19% (90 of 465) of preterm delivery cases and was significantly more common in cases of PROM (54 of 193, 28%) and preterm labor (34 of 161, 21%) than abruption (two of 33, 6%) and preeclampsia (none of 78) (P < .001). In 84 of 90 cases (93%), the eosinophilic gradient was present along with multiple histologic indicators of acute intrauterine inflammation. CONCLUSION: An eosinophilic gradient toward the amniotic cavity, present in nearly a fifth of cases of preterm delivery, is probably of fetal origin, making it unlikely that a maternal "allergy-like" mechanism is a cause of preterm delivery.

Abruptio Placentae↗

[Premature separation of the placenta--etiology and risk factors].

OBJECTIVE: Placental abruption complicates approximately 1% of all pregnancies and remains a significant cause of both maternal and fetal morbidity and mortality. Several risk factors are associated with this complications, but a clear causal relation is diffucult to establish. THE AIM OF THE STUDY: The aim of the study was to determine and identify risk factors for placental abruption. DESIGN: Retrospective cohort study. SETTING: Dept. of Obstetrics and Gynaecology, Medical Faculty of Palacký University, Olomouc. SUBJECT AND METHOD: Retrospectively gathered cohort of 180 women was compared to 198 healthy women. We have focused on anthropometric, sociodemographic, behavioral, obstetric and fetal parameters. Statistical evaluation was done by Statsoft, Inc. (2001) Statistika CZ (Software system data analysis), version 6. RESULTS: The incidence of the placental abruption was 0.89%. We have confirmed the following risk factors as statistically significant (p values are given): Low-degree education (0.00002), prepregnancy weight of the mother (0.00), weight gain in pregnancy (0.00), higher parity (0.0272), smoking (0.03847), preeclampsia (0.00889), chorioamnionitis (0.00), premature rupture of membranes (0.00), recurrent spontaneous abortions (0.00), positive family history of deep venous thrombosis (0.0007) and intrauterine growth retardation (0.0386). CONCLUSION: Placental abruption has a large number of potential risk factors. The true biological cause and its etiopathogenic role is still to be elucidated.

Abruptio Placentae↗

Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua.

Recent evidence has linked preterm premature rupture of the fetal membranes (PPROM) to placental abruption. Because neutrophils are a rich source of proteases that can degrade extracellular matrix in abruption-associated PPROM, we examined whether decidual neutrophil infiltration complicates abruption-associated PPROM. Accordingly, immunostaining for the neutrophil marker CD15 was performed in placentas obtained after overt abruption (decidual hemorrhage) with or without PPROM and in control placentas. Abruptions were associated with a marked decidual neutrophil infiltration that peaked after PPROM, whereas decidua from gestational age-matched controls were virtually devoid of neutrophils. Neutrophil infiltrates co-localized with fibrin deposition. Because abruptions elicit intense decidua-enhanced thrombin production, we examined the regulation of abruption-induced neutrophil infiltration. Expression of the primary neutrophil chemoattractant interleukin-8 (IL-8) was evaluated in leukocyte-free term decidual cells incubated with estradiol (E2; control) or with E2+medroxyprogesterone acetate (to mimic pregnancy)+/-thrombin. After 24 hours, enzyme-linked immunosorbent assay measurements indicated that thrombin (0.1 to 2.5 U/ml) elicited a dose-dependent elevation in secreted IL-8 (P<0.05) with 2.5 U/ml of thrombin increasing IL-8 levels by >14-fold in E2 and E2+medroxyprogesterone incubations. Results were validated by Western blot and quantitative reverse transcriptase-polymerase chain reaction. In summary, thrombin-enhanced IL-8 expression in term decidual cells may explain how abruption-associated PPROM promotes decidual neutrophil infiltration.

Abruptio Placentae↗

Placental abruption.

Placental abruption complicates about 1% of pregnancies and is a leading cause of vaginal bleeding in the latter half of pregnancy. It is also an important cause of perinatal mortality and morbidity. The maternal effect of abruption depends primarily on its severity, whereas its effect on the fetus is determined both by its severity and the gestational age at which it occurs. Risk factors for abruption include prior abruption, smoking, trauma, cocaine use, multifetal gestation, hypertension, preeclampsia, thrombophilias, advanced maternal age, preterm premature rupture of the membranes, intrauterine infections, and hydramnios. Abruption involving more than 50% of the placenta is frequently associated with fetal death. The diagnosis of abruption is a clinical one, and ultrasonography and the Kleihauer-Betke test are of limited value. The management of abruption should be individualized on a case-by-case basis depending on the severity of the abruption and the gestational age at which it occurs. In cases where fetal demise has occurred, vaginal delivery is preferable. Disseminated intravascular coagulopathy should be managed aggressively. When abruption occurs at or near term and maternal and fetal status are reassuring, conservative management with the goal of vaginal delivery may be reasonable. However, in the presence of fetal or maternal compromise, prompt delivery by cesarean is often indicated. Similarly, abruption at extremely preterm gestations may be managed conservatively in selected stable cases, with close monitoring and rapid delivery should deterioration occur. Most cases of placental abruption cannot be predicted or prevented. However, in some cases, maternal and infant outcomes can be optimized through attention to the risks and benefits of conservative management, ongoing evaluation of fetal and maternal well-being, and through expeditious delivery where appropriate.

Abruptio Placentae↗

[The perinatal factors associated with the development of neonatal RDS in cases of placenta previa].

Sixty-two cases of preterm placenta previa were managed in our hospital since September, 1979 through August, 1983. These were reviewed and analysed retrospectively for the perinatal factors in terms of the development of respiratory distress syndrome (RDS). Conservative management was employed in 56 cases (90%), which consisted of antepartum blood transfusion (7 cases: 11.3%), tocolysis for inhibition of premature labor (37 cases: 59.7%), and prenatal steroid administration (8 cases: 12.9%). Nineteen cases (31%) were delivered from 28 to 33 weeks, 20 cases (32%) from 34 to 36 weeks, and 23 cases (37%) after 37 weeks. When regular uterine contractions occurred at less than 10 minute intervals at the initiation of tocolysis, the majority of the cases had to be delivered within 7 days or less. Ten of the 39 preterm neonates in this study developed clinical RDS. All of these were delivered at between 28 and 33 weeks, associated with neonatal asphyxia. Three perinatal factors were significantly associated with the development of clinical RDS in comparison with the control group of non-RDS preterm neonates. These were neonatal asphyxia, maternal bleeding (greater than 500 ml) and no prenatal steroid administration.

Abruptio Placentae↗