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Preeclampsia with severe features and other severe placenta-mediated complications may be life threatening to mother and fetus, especially when they are recurrent. Recurrence of pregnancy complications is common, however, when combined treatment with low molecular weight heparin and low dose aspirin fails, there are not any proven therapeutic options for prevention of recurrence of obstetrical complications.We aimed to determine the impact of adding pravastatin to low molecular weight heparin and low dose aspirin for improving pregnancy outcome in women with severe recurrent placenta-mediated complications.A retrospective study of 32 women with severe recurrent placenta-mediated complications (preeclampsia with severe features, placental abruption, severe intrauterine growth retardation or intra uterine fetal death) in spite of treatment with low molecular weight heparin and low dose aspirin in previous pregnancy. All women were treated in the index pregnancy with 20 mg pravastatin starting at 12 weeks, with low molecular weight heparin and low dose aspirin. Antiphospholipid syndrome was evident for 10 of the 32 women.In the index pregnancy, only one woman had recurrence of severe placenta-mediated complications. Gestational age at delivery in the index pregnancy compared to previous pregnancy when women were treated with low molecular weight heparin and low dose aspirin was 36.5 ± 1.7 vs. 32 ± 3.6 weeks, and mean birth weight 2691 ± 462 vs. 1436 ± 559 grams, compared to previous pregnancy when women were treated with low molecular weight heparin and low dose aspirin (Additive treatment with pravastatin to low molecular weight heparin and low dose aspirin may be a promising option in cases of previous severe recurrent placenta-mediated complications.

Introduction The association between the degree of isolated gestational proteinuria and pre-eclampsia with severe features and other placental mediated complications is controversial. The aim of this study was to evaluate whether a higher isolated proteinuria level is associated with an increased frequency of pre-eclampsia with severe features. Material and methods This retrospective cohort study included pregnant women who were past 24 weeks of gestation and were diagnosed as having new-onset proteinuria ≥300 mg in a 24-hour urine collection. Exclusion criteria included diagnosis of preeclampsia within 72 hours from admission, chronic renal disease, or chronic hypertension. The study population was divided into tertiles by proteinuria level and the association with preeclampsia with severe features was assessed in both bivariable and multivariable analysis. The main outcome measures was the development of pre-eclampsia with severe features. Results Overall, 165 women were diagnosed with isolated gestational proteinuria, and 38 (23.0%) of them developed pre-eclampsia with severe features. Women in increasing proteinuria tertile were more likely to develop pre-eclampsia with severe features (5.5%, 21.8%, 41.8%; P = .004). A multivariable logistic regression model controlling for background characteristics as well as gestational age at diagnosis, blood pressure, and kidney and liver function tests showed an increased risk of 14% to develop pre-eclampsia with severe features for every 500 mg rise in proteinuria level (adjusted odds ratio = 1.14, 95% confidence interval 1.03-1.27). Conclusions A higher isolated gestational proteinuria level was associated with an increased risk to develop pre-eclampsia with severe features among pregnant women past 24 weeks of gestation.

Background: Major liver resection during pregnancy is extremely rare. When required, the associated physiologic and anatomic changes pose specific challenges and greater risk for both mother and fetus Materials and methods: Three cases of major liver resection during pregnancy due to different etiologies are presented. The relevant literature is reviewed and discussed. Results: We present 3 cases of major liver resection due to giant liver hemangioma with Kasabach-Merrit syndrome, giant hydatid cyst, and intrahepatic cholangiocarcinoma, at gestational week (GW) 17, 19, and 30, respectively. All patients had an uneventful postoperative course, continued the pregnancy and gave birth at GW 38. Conclusion: Major liver resection can be performed safely during pregnancy. A multidisciplinary team of surgeons, anesthesiologists and gynecologists, in a highly experienced tertiary hepatobiliary center, should be involved.

Objective: To evaluate whether medical personnel differ from the general population in obstetrical and perinatal outcomes. Materials and methods: The participants comprised 46 physicians and 116 nurses employed at one medical center who gave birth in its maternity hospital. General medical and obstetrical data on their latest (“index”) pregnancy and delivery were extracted from real-time computerized patient files. The control group included 162 women who gave birth during the same period in the same hospital. Results: The study group had significantly more deliveries, cesarean sections, and terminations of pregnancy prior to the index pregnancy. The medical personnel conceived significantly more often with assisted reproductive technologies (ART) (18.8% vs. 8% for controls, Pnd/3rd trimester bleeding or chorioamnionitis (42.5% vs. 29% for controls, P Conclusions: Medical personnel utilized ART more frequently and had more pregnancy complications as well as a lower incidence of VBAC than non-personnel. Neonatal outcomes were similar for both groups.

The objective of this study is to investigate the prevalence of elevated factor VIII activity among women with severe complications of pregnancy. The study group included 49 patients with a previous history of pregnancy complications: severe preeclampsia (n = 9); intrauterine fetal death (IUFD) (n = 9); severe intrauterine fetal growth restriction (IUGR) (n = 12); IUGR and preeclampsia (n = 7); preeclampsia and placental abruption (n = 2); IUFD and IUGR (n = 5); and abruptio placenta (n = 5). The control group included 49 healthy women who had had at least one normal pregnancy. Seventeen women of the study group (34.6%) had elevated factor VIII activity compared to one woman (2.1%) in the control group (P < 0.05). The mean level of factor VIII was 159 ± 52% and 88 ± 17.4% of normal activity (mean ± SD, t-test, P < 0.05). Importantly, 10 women of the study group (20.4%) had only elevated factor VIII activity with no other known thrombophilia compared to one woman (2.1%) in the control group (P < 0.05). Elevated plasma activity of factor VIII might be a risk factor for severe pregnancy complications.

The aim of this study was to investigate the effect of low molecular weight heparin (LMWH) on incidence of adverse outcome in women with thrombophilias and previous severe pregnancy complications.The study included 116 women with history of severe preeclampsia, fetal growth restriction (FGR) ≤5th percentile, severe placental abruption and stillbirth 20 weeks carrying factor V Leiden or prothrombin mutations, or protein S or C deficiency. Eighty-seven women referred to us for follow-up were treated with LMWH starting from weeks 5-15 (study group, A). Twenty-nine non-treated women referred only for delivery in our institution constituted the control group (B).The incidence of severe pregnancy complications in previous pregnancies was similar in both groups. Following treatment with LMWH, the incidence of severe preeclampsia was 4.6% in group A compared to 21% in group B, p = 0.007. The incidence of FGR was 2.3% in group A compared to 21% in group B, p = 0.03. The incidence of stillbirth or placental abruption was 0% in group A compared to 7% in group B, p = 0.06. The total incidence of adverse outcome was 7% in group A compared to 55% in group B, p = 0.0001.LMWH treatment of women with previous severe pregnancy complications and thrombophilias significantly reduces the rate of recurrence.

Introduction The majority of women with preeclampsia have increased proteinuria. However, the 2013 Task Force on Hypertension in Pregnancy suggested that the degree of proteinuria is no longer a severe feature of preeclampsia due to a minimal correlation between proteinuria levels and pregnancy outcome. This change has brought about even more uncertainty regarding the clinical significance of isolated proteinuria in the development of pre-eclampsia. Objective To investigate the association between the severity of isolated proteinuria and later development of severe preeclampsia and other placental mediated complications. Methods Pregnant women with new onset proteinuria levels exceeding 300 mg in 24-h urine collection, who were referred to our institution between 2014 and 2017 were approached. Exclusion criteria included immediate diagnosis of preeclampsia, chronic renal disease or chronic hypertension. 104 women met inclusion criteria and were followed throughout pregnancy and until after delivery. Results Overall, 29 of 104 (28%) women developed severe preeclampsia. The rate of severe preeclampsia was significantly higher in women with proteinuria ⩾3 g⧹24 h (57.1%) compared to women with proteinuria ± 2 for women with ⩾3 g ⧹ 24 h, versus 36.4 ± 1 for women with 3 g ⧹ 24 h, (p 0.01). The median time interval (days) between the diagnosis of proteinuria and presentation of severe preeclampsia was not significantly different between women with ⩾ 3 g ⧹ 24 h (15) and 3 g ⧹ 24 h (17). Discussion Isolated proteinuria > 3 g ⧹ 24h is a significant risk factor for severe preeclampsia and HELLP syndrome with a rapid and earlier progression to clinical disease.

Stillbirth is a major obstetric complication, with 3.2 million stillbirths worldwide and 26,000 stillbirths in the United States every year. The Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop from October 22-24, 2007, to review the pathophysiology of conditions underlying stillbirth to define causes of death. The optimal classification system would identify the pathophysiologic entity initiating the chain of events that irreversibly led to death. Because the integrity of the classification is based on available pathologic, clinical, and diagnostic data, experts emphasized that a complete stillbirth workup should be performed. Experts developed evidence-based characteristics of maternal, fetal, and placental conditions to attribute a condition as a cause of stillbirth. These conditions include infection, maternal medical conditions, antiphospholipid syndrome, heritable thrombophilias, red cell alloimmunization, platelet alloimmunization, congenital malformations, chromosomal abnormalities including confined placental mosaicism, fetomaternal hemorrhage, placental and umbilical cord abnormalities including vasa previa and placental abruption, complications of multifetal gestation, and uterine complications. In all cases, owing to lack of sufficient knowledge about disease states and normal development, there will be a degree of uncertainty regarding whether a specific condition was indeed the cause of death. (Obstet Gynecol 2009,114:901-14)

To assess the outcome of induced deliveries with IUGR. We reviewed the computerized files of parturients who underwent inducted labor because of IUGR (

Objective In our previous studies we have shown that the process of term labor is associated with oxidative stress, as indicated by increased susceptibility of maternal serum lipids to copper induced peroxidation. In order to continue evaluating the role of oxidative stress in the labor process, we next tested whether term premature rupture of the membranes (PROM) is also associated with increased susceptibility of maternal serum lipids to copper induced peroxidation. Design A controlled prospective study. Setting Tertiary care centre. Population 31 healthy women with term PROM and 19 healthy pregnant women with intact membranes. The women were matched for maternal and gestational age. Methods Venous blood was drawn from the women (up to 6h after rupture of the membranes and prior to labor in the PROM group), and the kinetics of copper-induced oxidation of serum lipids ex vivo were monitored spectroscopically at 37°C by continuous recording of absorbance at 245nm. Results The lag phase, reflecting resistance of serum lipids to oxidation, was similar in the PROM group when compared to the control group (43.7±3.2 versus 41.9±1.6min, P =0.61). However, the maximal rate of oxidation ( V max ) and the maximal accumulation of absorbing products (OD max ) were shorter in the PROM group when compared to the control group (5.14±0.26 versus 6.29±0.4010 −3 OD 245 nm/min, P =0.016; 0.61±0.03 versus 0.71±0.04 OD 245 nm, P =0.07). Conclusion As opposed to term labor, term PROM is not associated with increased maternal systemic oxidative stress when compared to normal pregnant women. The role for oxidative stress in preterm PROM warrants further studies.

To examine maternal and neonatal outcomes of isolated proteinuria and define maternal characteristics for progression to pre-eclampsia.Retrospective cohort study. Data from all hospitalized pregnant women between 2009 and 2014 with new onset isolated proteinuria of over 300 mg/24 h at admission were obtained. Follow-up was performed from the time of admission to the hospital to the time of discharge postpartum. Obstetrical, maternal and neonatal outcomes were obtained.Ninety-five pregnant women diagnosed with new onset isolated proteinuria were followed to term. Thirteen women developed pre-eclampsia during pregnancy and eight developed pre-eclampsia postpartum. Maternal characteristics for progression to pre-eclampsia were greater maximal values of proteinuria. Earlier pre-eclampsia onset was associated with early-onset proteinuria and multiple gestation. Although greater values of proteinuria were associated with increased risk for intrauterine growth restriction and lower Apgar scores, maternal outcome was favorable, regardless of pre-eclampsia progression. Isolated proteinuria progressing to pre-eclampsia was associated with late pre-eclampsia onset and favorable maternal and neonatal outcomes.A significant proportion of women with new onset isolated proteinuria will develop pre-eclampsia. In these women, close follow-up is recommended until after delivery.

Preeclampsia, intrauterine growth restriction and placental abruption greatly contribute to maternal and fetal morbidity and mortality. Thrombophilia is an inherited or acquired condition that predisposes individuals to venous and/or arterial thrombosis. Recently, three important inherited thrombophilias have been discovered. An inherited mutation in the gene coding for coagulation factor V (factor V Leiden), and a mutation in prothrombin that is associated with higher plasma levels of prothrombin. Both mutations result in an increased susceptibility to develop venous thrombosis. Hyperhomocysteinemia, which is associated with mutations in the gene for methylenetetrahydrofolate reductase, is a risk factor for venous and arterial thrombosis. The presence of antiphospholipid antibodies, an acquired thrombophilic condition, is associated with venous and arterial thrombosis. The term placental vasculopathy, is used to describe pathological placental changes that have been associated with preeclampsia, intrauterine growth restriction, placental abruption and fetal loss. The known thrombotic nature of the placental vasculopathy and the increased thrombotic risk with the presence of thrombophilias suggest, a cause-and-effect relationship between inherited and acquired thrombophilias and a number of severe obstetric complications. Testing patients with these complications for thrombophilias may have therapeutic implications for future pregnancies.

Background. Several reports suggest preeclampsia to be associated with oxidative stress. In view of potential experimental artifacts in these studies, we tested the effect of preeclampsia on the oxidizibility of maternal serum lipids, using an optimized ex vivo method. Methods. This prospective study included 28 pregnant women with preeclampsia and 28 women matched for maternal and gestational age with normal pregnancies. Venous blood was drawn from the consenting women. Serum levels of lipid peroxidation products and the kinetics of copper-induced oxidation ex vivo were monitored spectroscopically by continuous recording of absorbance at 245 nm. Results. The initial optical density (OD) at 245 nm, attributed to preformed products of lipid peroxidation, was higher in the women with preeclampsia than in the controls (1.26 ± 0.02 vs. 1.17 ± 0.02 OD units; p = 0.01). The lag phase preceding oxidation, reflecting resistance of serum lipids to oxidation, was significantly shorter in the preeclampsia group than...

Gestational vascular complications are a major cause of maternal and fetal morbidity.A growing body of evidence suggests a significant role for inherited thrombophilia in the development of gestational vascular complications. While the majority of women with thrombophilia will have an uneventful gestation, case-control studies demonstrated that thrombophilia is more prevalent in cohorts of women with pregnancy loss and early-onset pre-eclampsia. Placental abruption and severe intrauterine growth restriction (IUGR) may also be associated with thrombophilia. Placental pathological findings in women with thrombophilia are hallmarked by thrombosis and fibrin deposition potentially to a greater degree than in normal pregnancy. Preliminary non-randomized studies suggest a benefit for prophylaxis with unfractionated and low-molecular-weight heparin (LMWH), and prospective randomized trials are in progress to define whether LMWH is effective in preventing pregnancy loss and other gestational vascular complications in women with thrombophilia and previous fetal wastage.

We examined neurological and intellectual outcome of growth-restricted newborns of pregnancies complicated with preeclampsia and without preeclampsia. Seventy-five consecutive growth restricted newborns (5th percentile) were prospectively followed up at 6 months' intervals. Newborns with major congenital malformations and newborns with evident intrauterine viral infection were excluded. At 3 years of age all children had detailed neurological examination and intellectual examination using the Mean developmental index (Stanford Binnet-IQ). Eleven children were born to mother with preeclampsia (ACOG criteria), and 64 were born to mothers without a definite diagnosis of preeclampsia. Gestational age was 34.7 weeks in the preeclamptic group and 37 weeks in the non-preeclamptic group. After adjustment for gestational age, there was no significant difference in the neurological exam score between groups, but the IQ was 85.5 in the preeclamptic group and 96.9 in the non-preeclamptic group (p0.03). We conclude that newborns born growth restricted after pregnancies complicated by preeclampsia have a lower IQ at the age of 3 years compared to growth-restricted babies without preeclampsia.

We investigated whether the presence or absence of physiologic labor may affect the neonatal nucleated red blood cell (RBC) count. We compared absolute nucleated RBC counts taken at approximately 6 hours of life in term infants born by elective cesarean delivery without trial of labor ( n = 32) and in vaginally delivered infants ( n = 28). Venous blood samples were analyzed and differential cell counts were performed manually; absolute nucleated RBC were counted and expressed as an absolute number. There were no significant differences between groups in birth weight, gestational age, maternal age, gravidity, parity, maternal analgesia during labor, 1- and 5-minute Apgar scores, and infant sex. There was a significantly higher hematocrit and RBC count in the vaginally delivered group as compared with the cesarean group. The absolute nucleated RBC, corrected leukocyte and lymphocyte, and platelet counts were strikingly similar in both groups. We conclude that labor does not affect the neonatal nucleated RBC count. This finding supports the speculation that physiologic labor does not induce a fetal hypoxemia severe or prolonged enough to produce hematological evidence of increased erythropoiesis.

To investigate the association between severe mid-trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias.Case-control study.Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel Aviv University.Twenty-six women with severe mid-trimester (22-26 weeks of gestation) IUGR (birthweight3rd centile) and 52 matched multiparous women with normal pregnancies (controls).After excluding pregnancies with vascular maternal disease, chromosomal and structural aberrations and cytomegalovirus infection, 26 women out of 35 with severe mid-trimester IUGR remained and composed the study group. Each was matched for age, ethnicity and smoking status with two healthy women who had normal pregnancies. All the women were tested for genetic and acquired thrombophilias at least eight weeks after delivery.Prevalence of maternal thrombophilias.The frequency of thrombophilias was 69% in the study group compared with 14% in the control group [odds ratio (OR) 4.5; 95% confidence interval (CI) 2.3-9, P0.001]. The frequencies of factor V Leiden mutation, prothrombin gene mutation and protein S deficiency were significantly increased in the study group compared with the control group. The frequency of multiple thrombophilias was 33% in the study group versus none among the controls. Of the 26 pregnancies with severe mid-trimester IUGR, 13 ended in intrauterine fetal death before 25 weeks of gestation: 10 of these women had thrombophilia.Women with mid-trimester severe IUGR have an increased prevalence of inherited and acquired thrombophilias.

Objectives To assess the contribution of additional examiners to: the average discrepancy between estimated and actual fetal weights; the correlation between estimated and actual fetal weights; the reduction in major (> 10%) discrepancies between estimated and actual fetal weights. Design Three experienced sonographers independently measured fetal biparietal diameter, head circumference, abdominal circumference and femur length in 39 fetuses at term. The estimated fetal weights were calculated for each examiner. Fetal biometric measurements were analyzed to obtain the source of differences in estimations among the examiners. Discrepancy, correlation and number of major (> 10%) discrepancies between the estimated and actual fetal weights were calculated for each examiner, and the contribution of additional examiners was analyzed. Results The differences in measurements of the biparietal diameter and femur length were lower than those of the head and abdominal circumferences. For each of the three examiners, the average discrepancy between the estimated and actual fetal weights was 6.1%, 5.9% and 6.3%. When the estimation was based on two examiners, the discrepancy decreased to 4.8–5.6%. The contribution of a third examiner was nil. Major (> 10%) discrepancies between estimated fetal weight and actual birth weight were found in seven, eight and nine estimations of the examiners. Estimation by two examiners decreased the number of major discrepancies, and estimation by all three examiners further decreased by approximately 50% the number of major discrepancies between the estimated and actual fetal weights. Conclusion Measurements by multiple examiners changes only slightly the average number of discrepancies between estimated and actual fetal weights. However, the reduction in major (> 10%) discrepancies is statistically and clinically significant. Copyright © 2002 International Society of Ultrasound in Obstetrics and Gynecology

OBJECTIVE: To determine the risk of thrombophilias in women with unexplained intrauterine fetal deaths (IUFD). METHODS: All women with IUFD at 27 weeks’ gestation or greater were initially assessed during a period of 26 months. Subjects with multiple pregnancies, congenital anomalies, intrauterine infection, chorioamnionitis, immune hydrops, diabetes mellitus, previous thromboembolism, and severe hypertensive disease were excluded. The remaining 40 women with unexplained IUFD (study group) were matched for age and ethnicity with 80 healthy women who had at least one normal pregnancy (control group). All participants were tested at least 2 months after delivery for mutations of factor V Leiden, prothrombin gene, methylenetetrahydrofolate reductase, and for deficiencies of protein S, protein C, and antithrombin III. They were also tested and found to be negative for anticardiolipin antibodies. RESULTS: The gestational age at delivery and birth weight were significantly lower in the study group. The prevalence of inherited thrombophilias was 42.5% in the study group compared with 15% in the control group (odds ratio 2.8, 95% confidence interval 1.5, 5.3, P = .001). The prothrombin mutation and protein S deficiency rates were significantly higher in the study group (odds ratio 2.3, 95% confidence interval 1.3, 4.0, and odds ratio 3.2, 95% confidence interval 2.4, 4.1, respectively). CONCLUSION: Third-trimester IUFD is significantly associated with thrombophilias. These findings suggest that thrombophilia work-ups should be part of IUFD investigations and may have therapeutic and prognostic implications in future pregnancies.

Objective: To investigate placental apoptosis in discordant dichorial twins. Methods: Placental samples were obtained from 7 third-trimester suitable twins. Discordancy was defined as a >25 per cent difference in newborn birth weight. Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end-labelling (TUNEL) methods were used to confirm the incidence of apoptosis. Investigators were blinded to pregnancy outcome. Results: Both methods revealed that the incidence of apoptosis in the placentas of the smaller fetuses was significantly higher than in placentas of the larger fetuses. The incidence of TUNEL-positive cells in the former was 1.4±0.26 per cent: this was significantly higher than the incidence of apoptosis in the placental specimens of the latter (0.9±0.07 per cent, P 0.02 Wilcoxon rank test). The same results were obtained with H&E: the incidence of apoptosis detected in placentas from the former was 1.07±0.1 per cent compared to 0.72±0.08 per cent in those of the latter ( P 0.02 Wilcoxon rank test). Conclusions: Despite similar environment conditions, placental apoptosis is increased in the smaller fetus and thus might play a role in discordancy between twins. Since increased placental apoptosis has also been found in singleton intrauterine growth restriction, this supports the hypothesis that the smaller twin is selectively growth restricted.

OBJECTIVE: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P < .01), more multiple infarcts (P < .05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P < .05). CONCLUSION: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.

OBJECTIVE: To study the state of erythrocyte adhesiveness/aggregation in the peripheral blood of women with pregnancy-induced hypertension as well as in matched controls using a simple slide test and image analysis. METHODS: We recruited 25 women with pregnancy-induced hypertension. Twenty-five age- and gestational age-matched normotensive volunteers took part in the study and served as controls. Blood smears were evaluated by an image analysis system (INFLAMET). Quantitative measures of erythrocyte aggregation were used to describe the state of erythrocyte adhesiveness/aggregation such as vacuum radius, which measures the spaces between the aggregated erythrocytes. The number of participants was established by power analysis (given α of 0.05 and 80% power and considering a minimum difference to detect 4 μm in vacuum radius with a standard deviation of approximately 5). RESULTS: A significant (P = .002) increment in the state of erythrocyte aggregation was noted in the study group compared with the controls, the vacuum radius values being 16.1 ± 1.3 and 10.3 ± 1.2, respectively. Erythrocyte sedimentation rate but not fibrinogen concentration was significantly elevated in the study group. The increased aggregation correlated significantly with fibrinogen concentration, systolic, and diastolic blood pressures. CONCLUSION: We observed increased aggregability of red blood cells in hypertensive conditions of pregnancy. Our findings are significant in that they reveal blood pressure-related increment in red cell adhesiveness/aggregation despite there being no significant increment in clotable fibrinogen concentrations.

Background. It has been reported recently that obstetric complications are associated with thrombophilias. Our objective was to investigate the association between pregnancy complications and the guanine 20210 adenine (G20210A) mutation in prothrombin gene.Methods. Two hundred and twenty-two women (study group) with obstetric complications were tested for the prothrombin mutation. Indications for testing were: severe preeclampsia, mild preeclampsia, intrauterine growth retardation, severe abruptio placentae, unexplained stillbirth, second trimester loss, and three or more consecutive spontaneous abortions. We also tested 156 healthy women who had at least one normal pregnancy and comprised the control group.Results. Demographic data of the study and control groups were similar. Twenty-eight women of the study group (13%) were found to be heterozygous carriers of the 20210 variant of the prothrombin gene compared to five (3.2%) of the control group, p=0.001, odds ratio (OR) 2.9;95% confidence interval (CI)...

The purpose of this work was to evaluate the ability of testing for high-risk human papillomavirus (HPV) types using the hybrid capture technique to predict the presence of cervical intraepithelial neoplasia (CIN) II,III in patients with repeated atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LGSIL) on Pap smears.Hybrid capture testing and tissue biopsy were performed on 503 consecutive women with ASCUS or LGSIL on repeated Pap smears who were referred for colposcopy.A highly significant association (P0.0001) was found between a positive test for high-risk HPV types and CIN II,III, with an 87.0% positive predictive value and a 95.7% negative predictive value. In 226 women with ASCUS on repeated Pap smears, a positive test for high-risk HPV types had a 85.7% sensitivity and a 97% specificity for CIN II,III. In 277 patients with LGSIL on repeated Pap smears, a positive test for high-risk HPV types had an 88.2% sensitivity and a 94.7% specificity for CIN I,II. Reserving colposcopy examination for women who were positive for high-risk HPV types would have reduced the number of referrals for colposcopy to 24.6% and maintained a sensitivity of 87.0% for CIN II,III.A positive hybrid capture test for high-risk HPV types was highly sensitive and specific for the presence of CIN II,III in patients with ASCUS and LGSIL on repeated Pap smears. We believe that improved methodology will eventually enable more selective colposcopy referrals without affecting patient safety among these women.

Objective: To determine whether severe preeclampsia is associated with genetic thrombophilic mutations or other types of thrombophilia. Methods: A case-control study compared 63 consecutive women with severe preeclampsia evaluated at our institution between November 1997 and April 1999 with 126 control women matched for age and ethnicity. All of these women were tested several months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; for deficiencies of protein C, protein S, and antithrombin-III; and for the presence of anticardiolipin antibodies. Results: Thirty-five study women (56%) had a thrombophilic mutation compared with 24 control women (19%), P < .001. Seven other study women (11%) had other thrombophilias, compared with one control woman (0.8%), P < .01. Within the study group, women with thrombophilia delivered at an earlier gestational age, and their neonates’ birth weights were lower compared with those of women without thrombophilia. Conclusion: Because thrombophilia was found in 67% of women with severe preeclampsia, we suggest that women who have severe preeclampsia should be tested for thrombophilia.

Objectives. Loop electrosurgical excision of the transformation zone (LEETZ) was recently associated with relatively high failure rates. We evaluated whether the combination of LEETZ with laser vaporization is superior to LEETZ alone in reducing the rates of recurrent abnormal cytology and residual disease. Methods. The study population included 426 women with histologic diagnosis of cervical intraepithelial neoplasia (CIN) 2–3, of whom 289 (study group) were treated by LEETZ followed by laser vaporization of the crater base and walls and 137 (control group) were treated by LEETZ alone. All women were followed scrupulously at regular intervals for recurrent abnormal cytology and residual disease. The mean follow-up periods were 43 and 59 months for the study and control groups, respectively. Results. Both groups were derived from the same community and were similar in epidemiologic characteristics and disease severity. Although the incidence of positive surgical margins was similar in both groups (10.4 and 9.5% for the study and control groups, respectively), recurrent abnormal cytology (10.2% vs 5.5%, P = 0.07) and histologic residual disease (21.4% vs 0%, P = 0.05) were more frequent among women in the control group. This applied to women with both negative and positive surgical margins. Both study and control women with positive surgical margins, especially at the endocervix, were at higher risk for recurrence. Conclusion. The addition of laser vaporization to LEETZ may improve outcome of both women with positive margins and women with negative margins. Our results support conservative management for all treated women, regardless of cone margin status.

To assess the risk of vaginal birth of breech first twins by Apgar scores and mortality.We did a retrospective case-control analysis of data from 13 centers that allow vaginal birth for breech first twins. We used depressed 5-minute Apgar scores and neonatal mortality as main outcome measures between vaginal (n = 239) and cesarean (n = 374) deliveries of pairs with breech first twins, stratified by parity, birth weights of first twins, and types of cesarean. The 95% power of our sample size (alpha = .05) was sensitive enough to detect differences of 5% of the overall sample and 25-30% of subgroups.Vaginal birth was attempted in 61% of 613 pairs. There were significantly more depressed Apgar scores (P = .008, odds ratio [OR] 2.4, 95% confidence interval [CI] 1.2, 4.7) and neonatal deaths (P.001, OR 9.5, 95% CI 4.0, 23.4) among vaginal births of pairs in whom first twins weighed less than 1500 g but not among the higher-birth-weight cohort (for depressed Apgar scores: P = .76, OR 1.1, 95% CI 0.6, 2.1). Multiparity and elective cesarean seemed to have little influence on outcome measures. Neonatal mortality was associated with extremely preterm twins.There was no evidence that vaginal birth is unsafe, in terms of depressed Apgar scores and neonatal mortality, for breech first twins that weighed at least 1500 g.

Diagnosing retained products of conception in a woman presenting with postpartum or postabortion bleeding presents a clinical challenge. Although ultrasonographic examination may be potentially useful in detecting retained products of conception, its accuracy has not yet been established. Saline infusion sonohysterography is a simple ultrasonographic technique for enhanced transvaginal sonographic imaging of the endometrial cavity by the instillation of saline into the uterine cavity during ultrasonographic evaluation. This technique enhanced our ability to diagnose retained products of conception, and we describe our experience in evacuating them under sonographic guidance while performing saline infusion sonohysterography.

The present study was undertaken to evaluate the efficacy of Stamey bladder neck suspension in preventing post-perative stress urinary incontinence in clinically continent women undergoing surgery for genitourinary prolapse. Thirty clinically continent women with severe genitourinary prolapse were found to have a positive stress test with re-positioning of the prolapse. They all had significant urethrovesical junction hypermobility. In addition to the genitourinary prolapse repair, these patients underwent a prophylactic Stamey procedure to prevent the possible development of post-operative stress urinary incontinence. The mean duration of follow-up was 8+/-4.5 months (range, 3-19 months). Seven (23.30%) patients developed overt post-operative stress urinary incontinence that was confirmed urodynamically. Eleven (36.7%) other patients denied stress incontinence; however, post-operative urodynamics demonstrated sphincteric incontinence. Post-operative complications were uncommon and minor. In conclusion, continent patients with a positive stress test demonstrated on re-positioning of the prolapse during pre-operative urodynamic evaluation are considered to be at high risk of developing post-operative stress urinary incontinence. In these patients, an additional, effective anti-incontinence procedure should be considered during surgical correction of genitourinary prolapse. The Stamey procedure, although simple and safe, does not appear to be the optimal solution to this clinical problem.

Daniel Y, Kupferminc MJ, Baram A, Geva E, Fait G, Lessing JB. A selective increase in plasma soluble vascular cell adhesion molecule-1 levels in preeclampsia. AJRI 1999; 41:407-412 © Munksgaard, Copenhagen PROBLEM: The study was conducted to determine whether altered plasma levels of soluble intercellular adhesion molecule (ICAM)-1 and soluble vascular cell adhesion molecule (VCAM)-I are involved in the pathogenesis of preeclampsia. METHOD OF STUDY: Maternal plasma samples were collected from 20 patients with preeclampsia, 20 matched normotensive patients with uncomplicated pregnancies, and ten healthy nonpregnant women. Samples were assayed for soluble VCAM-I and soluble ICAM- by specific enzyme-linked immunosorbent assay. RESULTS: Both soluble VCAM-I and soluble ICAM-1 were detectable in the plasma of all preeclamptic, normotensive pregnant, and nonpregnant women. The mean plasma level of soluble VCAM-I was significantly higher in preeclamptic women compared to normotensive pregnant women (1831 ng/mL ± 534 ng/mL vs. 1254 ng/mL ± 386 ng/mL, respectively; P

Objective: To determine whether plasma and peritoneal fluid levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) are altered in women with ovarian hyperstimulation syndrome (OHSS). Design: Prospective, case-control study. Setting: Lis Maternity Hospital and the Sara Racine IVF Unit, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Patient(s): The study group comprised 16 women with severe OHSS. The control groups comprised 10 women treated with controlled ovarian hyperstimulation and 8 women with normal findings at diagnostic laparoscopy. Intervention(s): Plasma samples were obtained from the study group and the first control group. Peritoneal fluid samples were obtained during paracentesis from the study group and during diagnostic laparoscopy from the second control group. Main Outcome Measure(s): Samples were assayed by specific ELISA for sVCAM-1 and sICAM-1. Result(s): The mean peritoneal fluid levels of sVCAM-1 and sICAM-1 and the mean plasma levels of sVCAM-1 were significantly higher in the women with OHSS than in the control groups. However, the mean plasma levels of sICAM-1 were comparable. A positive correlation was demonstrated between the levels of sVCAM-1 and plasma E 2 at the time of hCG administration and between the levels of sICAM-1 and number of ova retrieved. Conclusion(s): Our findings suggest that soluble cell adhesion molecules may have a role in the pathogenesis and progression of OHSS.

Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery thrombosis and inadequate placental perfusion. Whether these complications are associated with an increased frequency of thrombophilic mutations is not known.We studied 110 women who had one of the above-mentioned obstetrical complications and 110 women who had one or more normal pregnancies. The women were tested several days after delivery for the mutation of guanine to adenine at nucleotide 1691 [corrected] in the factor V gene (factor V Leiden), the mutation of cytosine to thymine at nucleotide 677 in the gene encoding methylenetetrahydrofolate reductase, and the mutation of guanine to adenine at nucleotide 20210 in the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C, protein S, or antithrombin III and for the presence of anticardiolipin antibodies.The mutation at nucleotide 1691 [corrected] in the factor V gene was detected in 22 of the women with obstetrical complications and in 7 of the women with normal pregnancies (20 percent and 6 percent, respectively; P=0.003). Twenty-four women with complications, as compared with nine women without complications, were homozygous for the C677T mutation in the gene encoding methylenetetrahydrofolate reductase (22 percent and 8 percent, respectively; P=0.005). The G20210A mutation in the prothrombin gene was found in 11 women with complications as compared with 3 women without complications (10 percent and 3 percent, respectively; P=0.03). Overall, 57 women with obstetrical complications had a thrombophilic mutation, as compared with 19 women with normal pregnancies (52 percent and 17 percent, respectively; P0.001). Deficiency of protein S, protein C, or antithrombin III or anticardiolipin antibodies were detected in an additional 14 women with complications, as compared with 1 woman with a normal pregnancy (13 percent and 1 percent, respectively; P0.001).Women with serious obstetrical complications have an increased incidence of mutations predisposing them to thrombosis and other inherited and acquired forms of thrombophilia.

We investigated the role of the fetal immune system in pregnancies complicated by preeclampsia by assessing umbilical cord plasma levels of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). Nineteen nulliparous patients with severe preeclampsia composed the study group (group A). A comparison group was comprised of 19 healthy nulliparous patients with uneventful pregnancies (group B). Mixed umbilical cord blood was collected immediately after delivery. Plasma was prepared and all samples were assayed for TNF-alpha and IL-1beta by specific enzyme-linked immunoassays (ELISAs). Data are presented as the median with range of values. The length of labor was similar in both groups. TNF-alpha was detected less frequently in the umbilical cord plasma of preeclamptic patients than in the umbilical cord plasma of control patients (57.9 vs. 89.5%, p < 0.05), and the concentrations of TNF-alpha were significantly lower in the umbilical cord plasma of the preeclamptic patients [20 pg/ml (0-80 pg/mL) vs. 50 pg/mL (0-310 pg/mL), p < 0.05]. Umbilical cord plasma IL-1beta detection rates and concentrations from the preeclamptic and control patients were similar, [15.8 vs. 5.3%, 0 pg/mL (0-40 pg/mL) vs 0 pg/mL (0-10 pg/mL)]. The lower concentrations of TNF-alpha in umbilical cord plasma of patients with severe preeclampsia suggest that release of TNF-alpha by the fetus and mother are independent and may reflect adaptation of the fetus to reduced placental perfusion in preeclampsia.

A prospective, blind study was carried out on 44 patients to evaluate the most suitable time to perform transvaginal sonohysterography. On the day of arrival at our unit, regardless of their cycle day, the women underwent sonohysterographic evaluation, which was repeated during the first 10 days of the next cycle. Patients with sonohysterographic findings underwent hysteroscopy. According to the timing of the first examination, they were divided into two groups, i.e. group 1 for the first 10 days of the cycle, and group 2 for days 16 through 28. At the end of the study the groups were compared. The results showed a false-positive rate of 27% in group 2, while no false-positive was found in group 1. We concluded that the best time for sonohysterography in patients who still have their menstrual period is during the first 10 days of the cycle.

The study was conducted to determine whether altered plasma concentrations of soluble selectins are involved in the pathogenesis of pre-eclampsia. Maternal plasma samples were collected from 20 patients with pre-eclampsia, and from 20 matched normotensive patients with uncomplicated pregnancies. Samples were assayed for soluble endothelial selectin (sES), platelet selectin (sPS) and leukocyte selectin (sLS) by specific enzyme-linked immunosorbent assay. The three soluble selectins were detectable in the plasma of all pre-eclamptic and control patients. The mean plasma concentrations of sPS and sLS were comparable between the groups. However, the mean plasma concentration of sES was significantly higher in the pre-eclamptic group compared with the control group (61 ng/ml +/- 30 ng/ml compared with 40 ng/ml +/- 17 ng/ml; P < 0.01). The selective increased plasma concentrations of sES in patients with pre-eclampsia provide specific evidence for endothelial activation and may reflect distinct pathways for neutrophil activation in pre-eclampsia.

To evaluate the ability of testing for high-risk human papillomavirus (HPV) using the hybrid capture technique to detect cervical intraepithelial neoplasia (CIN) in patients with repeated low-grade cervical cytologic abnormalities and an adequate and normal colposcopy.Hybrid capture testing and LEETZ were performed on 166 women with repeated low-grade cervical cytologic abnormalities who were referred for colposcopy which was to be adequate and normal.A highly significant correlation (P0.0001) was found between a positive test for high-risk HPV types and the finding of CIN II,III. In 67 women with atypical squamous cells of undetermined significance on repeated cytologic studies, a positive test for high-risk HPV types had a sensitivity and specificity of 90 and 96.5%, respectively, for detecting CIN II,III. In 99 patients with low-grade squamous intraepithelial lesions found on repeated cytologic study, a positive test for high-risk HPV types identified all patients as having CIN II,III on cone biopsy (sensitivity, 100%), with a specificity of 86.4%. Restriction of tissue sampling to women who were positive for high-risk HPV types would have reduced the number of tissue samplings performed to 20.4%, while identifying 20 of 21 patients with biopsy-confirmed CIN II, III.A positive hybrid capture test for high-risk HPV types is highly sensitive and specific for detecting CIN II,III in patients with repeated low-grade cervical cytologic abnormalities and an adequate and normal colposcopy and may be used in the triage of these women before performing tissue sampling.

Objective: The study was conducted to compare maternal and neonatal outcome of two groups of nulliparae with breech presentations, who were selected for vaginal delivery by protocols differing only in their use of X-ray pelvimetry. Study Design: We reviewed all term singleton breech deliveries of nulliparous patients who were eligible for vaginal trial of labour in our Centre between 1992 and 1994. In Group A ( n =85) X-ray pelvimetry was performed, and in Group B ( n =70) it was not. Obstetric management was otherwise similar. Admission to the two departments was on alternate days. Results: The rate of caesarean section was similar in both groups (Group A, 36.4% vs. Group B, 42.8%; P >0.05), however, the indications for caesarean section differed. Neonatal outcome was similar in both groups. Maternal febrile morbidity was higher in Group B patients, especially those who underwent caesarean section after a trial of labour. Conclusion: X-ray pelvimetry in nulliparae with breech presentation is associated with reduced maternal febrile morbidity, but does not improve neonatal outcome.

The study was conducted to compare the neonatal and maternal outcome of breech infants delivered vaginally at term with those delivered by cesarean section. All singleton term breech deliveries between January 1, 1992 and December 31, 1994 were reviewed (n = 496). Criteria for eligibility for vaginal trial of labor included: frank or complete breech presentation, estimated fetal weight of 2000-3800 g, no hyperextension of the fetal head and no history of uterine scar (group A, n = 283) Patients who did not fulfill these criteria, or had an abnormal pelvimetry, were delivered by cesarean section without a trial of labor (group B, n = 213). In group A, 226 patients (80%) delivered vaginally, and 57 (20%) patients underwent a cesarean section; 70%, of the nulliparae and 89%, of the multiparae delivered vaginally. No differences were observed between the groups in gestational week, number of nulliparae, pregnancy complications, and rates of epidural analgesia. However, maternal age and birth weight were significantly higher in group B. No maternal or perinatal mortality occurred. The incidences of 5-min Apgar score

Background. This prospective study was conducted to compare the umbilical cord blood acid-base values of uncomplicated, assisted, vaginal-breech-delivery term neonates with those of uncomplicated, cephalic-vaginal delivery term neonates and to determine whether a different metabolic status should be expected in neonates born by way of uncomplicated vaginal breech delivery. Methods. Umbilical cord artery and vein blood samples were obtained from 30 term neonates with frank or complete breech presentations who were born by uncomplicated assisted vaginal breech delivery. All these neonates had an Apgar score of >7 at 5 min and an uneventful neonatal course (study group). For each neonate in the study group the two consecutive term neonates who were delivered by uncomplicated cephalic spontaneous vaginal delivery, and had uneventful neonatal courses, served as controls (control group). Results. The umbilical cord artery blood pH and pO 2 were significantly lower (p

PROBLEM: This study was conducted to determine whether altered levels of vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of preeclampsia. METHOD OF STUDY: Maternal plasma samples were collected from 19 patients with preeclampsia (group A) either before the onset of labor, or before induction of labor or medical intervention. Plasma samples were also obtained from 19 normotensive patients with uncomplicated pregnancies (group B), who were matched with the patients with preeclampsia for gestational age and parity. Samples were frozen at -70°C until assayed for VEGF by a specific enzyme-linked immunoassay. RESULTS: The mean maternal age was similar in groups A and B. For both groups the VEGF was detectable in all plasma samples. However, the plasma concentrations of VEGF were significantly increased in the group A patients, compared with those in group B (median, 47ng/ml; range, 10.6-72 ng/ml versus median, 13.6 ng/ml; range, 0.66-20 ng/ml; P < 0.001). In group A, a positive correlation was noted between VEGF concentrations and the systolic and diastolic blood pressure (r = 0.56; P = 0.01 and r = 0.48; P = 0.037, respectively). CONCLUSIONS: Maternal plasma VEGF levels were elevated in the patients with preeclampsia and correlated with the severity of hypertension, suggesting a role for VEGF in the pathogenesis of preeclampsia.

The effects of consecutive pregnancies on the course of idiopathic intracranial hypertension (IIH) are unclear in view of the scarce published data.To evaluate the course and management of visual and pregnancy outcomes of consecutive pregnancies with IIH.The medical records of women with IIH in consecutive pregnancies were reviewed for neuro-ophthalmological findings, management, and visual and pregnancy outcomes.The study group comprised eight women with at least two consecutive pregnancies (mean age 27.3 +/- 5.3 years). The mean duration of IIH prior to the first pregnancy was 3.4 +/- 3.16 years. One woman with IIH pre-pregnancy symptoms and three women with clinical features of IIH during the second trimester of pregnancy (gestational week 21.7 +/- 4.04) were treated with acetazolamide (250 mg every 8 hours). Symptoms resolved, resulting in uncomplicated first deliveries for all four. The first deliveries of four other women were by cesarean section due to obstetric indications. Only one woman developed symptoms and signs of IIH during her second pregnancy and was thus treated with acetazolamide. Two women who completed three pregnancies had no IIH symptoms during their pregnancies. The course and outcome of those pregnancies were normal.IIH apparently does not worsen or even become symptomatic in consecutive pregnancies. The appropriate management of IIH in pregnant women is similar to management for non-pregnant women; neither the course nor the obstetric outcome of first and consecutive pregnancies is influenced by the presence of IIH.

Objective : To investigate whether serum and amniotic fluid (AF) levels of soluble tumor necrosis factor receptors and interleukin-6, markers of immune activation and endothelial dysfunction, are altered in patients with severe preeclampsia. Methods : Plasma was collected before induction of labor, at delivery, and postpartum from 19 patients with severe preeclampsia. Amniotic fluid was also obtained in early labor from these patients. Similar samples were obtained from an antepartum control group matched for gestational age and a term control group without preeclampsia. All plasma and AF samples were assayed for p55 and p75 soluble tumor necrosis factor receptors and for interleukin-6 by specific enzyme-linked immunoassays. Levels in preeclamptic patients and the control groups were compared. Results : Levels of both receptors were significantly elevated in AF and all maternal plasma samples except those collected 24 hours postpartum for patients with preeclampsia relative to levels in controls. Interleukin-6 was detected more frequently and in higher concentrations in the plasma collected before labor for preeclamptic patients compared with controls, but no difference was noted in interleukin-6 detection rates or plasma concentrations at delivery. Conversely, AF concentrations of interleukin-6 were significantly reduced in patients with preeclampsia. Conclusion : The increased levels of soluble tumor necrosis factor receptors found in patients with severe preeclampsia may represent a protective response to increased tumor necrosis factor activity and be a marker for immune activation. Increased interleukin-6 concentrations in maternal plasma before labor suggest the involvement of this cytokine as well in the altered immune response and its contribution to endothelial cell dysfunction.

BACKGROUND: We investigated whether hereditary thrombophilia is more prevalent in women with recurrent IVF-embryo transfer failures. METHODS: This case‐control study was conducted in an academic tertiary care hospital and compared 45 women with a history of four or more failed IVF cycles (group A) with 44 apparently healthy women matched for age and ethnic origin (group B). All participants were tested for inherited thrombophilias: mutations of prothrombin, factor V Leiden and methylene tetrahydrofolate reductase (MTHFR), and protein C, protein S and antithrombin III deficiencies. RESULTS: Excluding homozygotic MTHFR, the incidence of thrombophilia in group A, was 26.7% compared with 9.1% in group B (P = 0.003; odds ratio 2.9; 95% confidence interval 1.02‐8.4). The incidence of thrombophilia in women with unexplained infertility in group A was 42.9% (9/21), compared with 18.2% in group B (P < 0.002). CONCLUSIONS: These data suggest that inherited thrombophilia may play a role in the aetiology of repeated IVF failures, particularly in the subgroup with unexplained fertility.