Search

OBJECTIVE: We tested whether neonates are subject to oxidative stress by comparing the susceptibility of umbilical blood lipids with copper-induced peroxidation. STUDY DESIGN: Umbilical arterial and venous blood samples were drawn from 32 pregnant women who delivered by elective cesarean section (CS) and from 32 pregnant women who delivered by spontaneous vaginal delivery (SVD) in a tertiary care center. Oxidative stress was evaluated by spectrophotometric monitoring of copper-induced peroxidation of serum samples. RESULTS: The lag preceding lipid peroxidation in umbilical arterial blood was shorter than the lag in umbilical venous blood, irrespective of mode of delivery (14.0+/-1.8 vs 50.6+/-8.25 min, P=.0004 in SVD group; 17.7+/-1.6 vs 39.2+/-7.6 min, P=.006 in CS group). CONCLUSION: Umbilical arterial lipids are more susceptible to peroxidation than umbilical venous lipids, indicating high oxidative stress in the fetal circulation irrespective of mode of delivery. [ABSTRACT FROM AUTHOR]

The study was conducted to investigate the association of placental morphological and histopathological features with term, singleton pregnancies obtained by assisted reproductive technologies (ART). The study group comprised 45 consecutive women with a singleton pregnancy, obtained by ART, who delivered at term. For each subject in the study group, the consecutive, matched-for-age-and-parity woman, with a term singleton, spontaneously conceived pregnancy served as the controls. The placentae of both groups were subject to a detailed morphological and histopathological investigation by one pathologist, who was blinded to specimen origin. Pregnancy complications, fetal weight and perinatal outcome were similar in both groups. No differences in morphological or histopathological features of the placenta were observed between the groups. Nevertheless, the placentae of the study group showed a borderline, significantly higher placental weight and placental:fetal weight ratio, and placental thickness was significantly higher. Abnormal umbilical cord insertion was significantly more prevalent in the study group. Neither the specific ART method employed, nor the infertility factor affected the results, suggesting that multiple embryo transfers and/or ovulation induction protocols may account for these differences. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Background: 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., Objective: 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., Design: 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., Results: 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 ( p  < .001 for both). Of the 17 women with previous preeclampsia with severe features, 15 had no recurrence of preeclampsia and 2 women had mild preeclampsia at term. Of the 8 women with previous severe intrauterine growth retardation, all delivered at significant higher gestational age compare to previous pregnancy, [37.0 ± 1 vs. 34 ± 3 weeks, ( p  < .05)] with higher mean birth-weight [2648 ± 212 vs. 1347 ± 465 grams, ( p  = .05)]. Of the 3 women with previous placental abruption, one delivered at 32 weeks due to non-reassuring fetal heart monitoring, one woman was delivered at 36 weeks due to mild preeclampsia, and one woman underwent elective induction of labor at 37 weeks with no intrauterine growth retardation. Of the 4 women with previous recurrent intrauterine fetal death, 3 women delivered at 37 weeks after elective induction, and one woman at 30 weeks with a birthweight of 960 grams due to severe intrauterine growth retardation., Conclusions: 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 preeclampsia 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 preeclampsia 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-h urine collection. Exclusion criteria included diagnosis of preeclampsia within 72 h 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 preeclampsia with severe features., Results: Overall, 165 women were diagnosed with isolated gestational proteinuria, and 38 (23.0%) of them developed preeclampsia with severe features. Women in the increasing proteinuria tertile were more likely to develop preeclampsia with severe features (5.5%, 21.8%, 41.8%, respectively; p = 0.004). 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 preeclampsia 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 preeclampsia with severe features among pregnant women past 24 weeks of gestation., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

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 three 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 examine maternal and neonatal outcomes of isolated proteinuria and define maternal characteristics for progression to pre-eclampsia., Study Design: 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., Result: 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., Conclusion: 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.

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, P<0.05), and had significantly more obstetrical complications, i.e., premature contractions, gestational diabetes mellitus, preeclamptic toxemia, and 2nd/3rd trimester bleeding or chorioamnionitis (42.5% vs. 29% for controls, P<0.05). The rate of vaginal birth after cesarean delivery (VBAC) was lower in the study group (22.2% vs. 33.3% for controls, P=0.03). There was no difference in gestational age at delivery, birth weight, or adverse neonatal outcome., 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.

Background: The effects of consecutive pregnancies on the course of idiopathic intracranial hypertension (IIH) are unclear in view of the scarce published data., Objectives: To evaluate the course and management of visual and pregnancy outcomes of consecutive pregnancies with IIH., Methods: The medical records of women with IIH in consecutive pregnancies were reviewed for neuro-ophthalmological findings, management, and visual and pregnancy outcomes., Results: 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., Conclusions: 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.

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.

Background: Pregnant women with pathological conditions requiring a neurosurgical intervention pose a unique therapeutic challenge. Changes in normal physiology add to the complexity of patient management. We describe our experience in treating various neurosurgical diseases in parturient women., Methods: Thirty-four pregnant and early postpartum women were treated at our center between 2003 and 2010. The general guideline used in these patients (now deserving re-evaluation based on the presented data) was to postpone surgery until the patient reached term (weeks 34-38 of gestation) unless there was evidence of a life- or function-threatening condition, in which case surgery was promptly performed., Results: Sixteen patients underwent neurosurgical intervention during pregnancy between 11 to 34 weeks of gestation (7 tumor, 3 vascular, 2 VP shunt, 2 spinal, 2 trauma). Thirteen women underwent a neurosurgical procedure after delivery (12 tumor, 1 spine), and 5 women were treated conservatively (2 vascular lesions, 3 trauma). Three patients underwent abortions (one spontaneous and two elective). The other 31 women delivered at 30-42 weeks' gestation. Of 12 patients whose definitive neurosurgical procedure was initially delayed, 5 were not able to complete their pregnancy naturally. Of 21 patients that underwent a cesarean section (CS), 3 were performed urgently. Although two pairs of twins and two singletons had an initial low Apgar score (<7), the outcome for all the neonates was good. Neurosurgical outcome was satisfactory., Conclusions: Our experience demonstrates the safety of neurosurgical intervention and anesthesia during pregnancy. Delaying intervention often resulted in maternal deterioration and urgent intervention. Thus, pregnancy by itself should not be considered a major contraindication for performing a neurosurgical procedure, which should be considered early rather than late in most patients.

Objectives: The aim of this pilot study was to establish reference values for strong ion difference (SID) in umbilical cord blood and investigate the feasibility of evaluating fetal metabolism according to the comprehensive approach to acid-base abnormalities, based on Stewart's physiochemical theory., Study Design: A prospective observational study. Women who underwent an elective cesarean section at term (n=40) were compared to women who completed a normal spontaneous delivery at term (n=40). The primary outcome was the establishment of normal values for SID in the umbilical cord vein. We also compared acid-base variables in the umbilical vein between the groups., Results: The apparent SID in the umbilical vein was 34.61+/-3.92 mequiv./L after normal delivery and 35.98+/-2.56 mequiv./L after elective cesarean section (the effective SID is 37.43+/-1.93 and 38.29+/-2.38 mequiv./L, respectively). The pH values were similar in both groups, but the pCO(2) was significantly higher and the plasma principal weak acids (albumin and phosphate) were significantly lower after cesarean sections., Conclusions: SID enables a comprehensive approach to acid-base abnormalities in the neonate, making it a potential additional tool for evaluating fetal acid-base status.

Objective: To compare selected umbilical cord parameters, especially cord coiling, between breech and vertex presentations., Methods: We prospectively collected umbilical cords from uncomplicated breech and vertex obtained during elective term cesarean deliveries. We compared various cord parameters between the two groups as well as data regarding obstetric history and pregnancy outcome., Results: We evaluated 55 umbilical cords from breech and 55 from vertex deliveries. Umbilical cord length (56.93 cm vs. 63.95 cm, P=0.05), number of coils (5.1+/-0.4 vs. 11.7+/-0.6, P<0.0001) and umbilical cord index (UCI) (0.09 coils/cm vs. 0.18 coils/cm, P<0.0001) were all significantly lower for breech presentations and remained significant following multivariate analysis., Conclusion: We document significant differences in umbilical coiling and the UCI between breech and vertex presentation. The precise reason for these differences is still unclear.

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 degrees C by continuous recording of absorbance at 245 nm., 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+/-1.6 min, 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.

Preeclampsia is a major cause of morbidity and mortality in mothers, fetuses, and neonates worldwide, with 5%-10% of human births being affected. The cause is still uncertain, and many controversies exist concerning its management. Preeclampsia-eclampsia is due to the failure of extra-villous cytotrophoblast to invade the maternal uterine spiral arteries to a sufficient depth, inducing poor vascular exchanges between the mother and the placenta. This physiological endovascular trophoblast invasion represents a remarkable immunological placental-maternal interaction. Recent data strongly indicate an important role for the male partner in the causation of this common pregnancy disorder. This review aims to discuss the relevant literature and to explain how paternal, relational and sexual factors play an important role in the etiology of preeclampsia.

Objective: The objective of this study was to examine the rate of respiratory morbidity in neonates delivered by elective cesarean delivery (ECD) at term, with a definite confirmation of gestational age (GA) by 1st-trimester ultrasound., Methods: Consecutive women carrying a singleton pregnancy and undergoing ECD at term (>38 1/7 weeks), confirmed by 1st-trimester ultrasound, were included in the study group. Multiple gestations, cesarean section (CS) in labor, CS performed after rupture of membranes and induced deliveries were excluded. The control group included women with a singleton pregnancy at term (>38 1/7 weeks) who delivered spontaneously. This group of women was randomly selected during the study period., Results: The study group included 277 women delivered by ECD. The control group consisted of 311 women. Five newborns in the study group and none in the control group were admitted to the neonatal intensive care unit (NICU) due to respiratory disorders (p < 0.02). Excluding diabetic women did not change the results. On multivariate analysis, no other factors were found to independently influence the risk of respiratory complications., Conclusion: In our study, the rate of respiratory morbidity was found to be significantly higher in neonates delivered by ECD compared to those delivered vaginally. The fact that GA was confirmed by 1st-trimester ultrasound makes iatrogenic prematurity an unlikely sole cause for this excess morbidity.

This paper reports a case of S. constellatus chorioamnionitis in a pregnant Crohn's disease patient who was taking azathioprine. Chorioamnionitis is a major cause of perinatal morbidity. Azathioprine, an immunosuppressive antimetabolite, is widely used to treat inflammatory bowel disease. Streptococcus constellatus is a Gram-positive bacterium that has not previously been associated with chorioamnionitis. A high index of suspicion for chorioamnionitis and unusual pathogens should be maintained in the management of obstetric patients on immunosuppressive agents.

Background: Foreign workers in Israel are not covered by the comprehensive medical insurance that all Israelis receive. They have national insurance and injury-related coverage, which does not include routine pregnancy follow-up, Objectives: To compare perinatal outcome between partially insured non-resident migrants in Israel and comprehensively insured Israeli women., Methods: Parameters of perinatal outcome were compared between 16,012 Israeli and 721 foreign women living in Israel. Outcome measures included birth weight, distribution of gestational age at delivery, neonatal complications, cesarean section, neonatal intensive care unit admission, intrauterine fetal death rates, and duration of post-partum hospitalization., Results: Deliveries prior to 28 weeks gestation occurred more frequently among non-residents (1.3% vs. 0.6%, P < 0.001). Gestational diabetes and preeclamptic toxemia were significantly more prevalent among non-residents (3.2% vs. 1.9%, P < 0.05 and 4.9% vs. 3.1%, P < 0.05, respectively). The cesarean rates were 18% and 35% for residents and non-residents, respectively (P < 0.001), and the post-cesarean recovery period was longer among non-residents (4.8 vs. 3.6 days, P < 0.05). The mean birth weight was similar in the two groups (3,214 vs. 3,231 g), although macrosomia (>4,000 g) was more prevalent among non-residents, who also had higher rates of NICU admission ((9.6% vs. 8%, P < 0.05) and intrauterine fetal death (6.6/1,000 vs. 3.7/1,000, P < 0.05)., Conclusions: Non-resident parturients in Israel are more susceptible to an adverse perinatal outcome than their Israeli counterparts. We suggest that government subsidization of non-residents' health expenditures would reduce the differences in perinatal outcome between these two groups.

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.

Objective: Current recommendations are to discontinue low molecular weight heparin (LMWH) at least 24 hours prior to labor induction or administering epidural anesthesia. We assessed the safety of discontinuing LMWH 12-24 hours before delivery., Methods: We evaluated the prevalence of hemorrhagic complications during labor, cesarean or epidural catheter placement in 284 women treated with enoxaparin during pregnancy as compared with 16132 untreated women. Treated participants were divided into subgroups by the various intervals between last LMWH dose hemorrhage-prone events (vaginal delivery,epidural, cesarean etc.). The rate of hemorrhagic complications and hemoglobin values were compared between the study and control groups., Results: Postpartum hemorrhage was uncommon and occurred in 2.1% and 1.9% in study and control groups, respectively (p=0.13). Antenatal as well as postnatal hemoglobin values were very similar for treated and untreated women. No differences were noted between women who discontinued enoxaprin 12-24 hours before labor and those who discontinued treatment later with regard to maternal hemorrhagic complications. No spinal hematomas were report among 12792 treated and un-treated women who had epidural or spinal block. No hemorrhagic neonatal complications were encountered., Conclusion: Discontinuing LMWH more than 12 hours before delivery is safe in relation to maternal hemorrhagic complications.

Background: Thrombophilic risk factors play an important role in the pathogenesis of perinatal stroke and resultant cerebral palsy (CP). The association between thrombophilia and CP caused by etiologies other than stroke is undetermined., Methods: We assessed three genetic thrombophilic markers (mutation of Factor V Leiden [FV G1691A], 677T polymorphism of thermolabile methylenetetrahydrofolate reductase [MTHFR] and G20210A mutation of the prothrombin gene) in 49 pediatric patients with non-stroke CP and compared the findings with 118 apparently healthy controls. CP in the study group was due to periventricular leukomalacia (n=27), intraventricular hemorrhage (n=9), hypoxic ischemic encephalopathy (n=4), prematurity with no apparent complication (n=8) and intrauterine growth retardation (n=1). Twenty-five children had spastic diplegia, 20 had spastic quadriplegia and 4 had spastic hemiplegia. CP was graded as being severe in 26 children (53%)., Results: No significant difference in the prevalence of thrombophilic risk factors was found between the study and control groups. Twelve study children (24.5%) had at least one of the three thrombophilic mutations compared with 27 controls (23%). There was no significant difference in the prevalence of each thrombophilic risk factor in the various etiologic groups and in the subgroups of mild/severe CP and the control group., Conclusion: These findings support the notion that thrombophilia neither contributes to the occurrence nor affects the clinical outcome and severity of non-stroke CP.

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.

Hypercoagulability leading to placental thrombosis has been implicated in severe pregnancy complications. We compared the perinatal outcome in women with severe preeclampsia, intrauterine growth retardation (IUGR) and severe abruptio placentae and multiple acquired and inherited thrombophilias (study group, n=22) to matched women with similar complications and single thrombophilia (control group, n=22). Gestational age at delivery and birth weight were significantly lower in the study group compared to the control group (p<0.01) and among the study women with severe preeclampsia and IUGR. Severe pregnancy complications may occur earlier during pregnancy and more seriously affect perinatal outcome in women with multiple thrombophilias.

Pregnancy is hypercoagulable state. The field of thrombophilia; the tendency to thrombosis, has been developed rapidly and has been linked to many aspects of pregnancy. It is recently that severe pregnancy complications such as severe preeclampsia intrauterine growth retardation abruptio placentae and stillbirth has been shown to be associated with thrombophilia. Recurrent miscarriage and has also been associated with thrombophilia. Finally, thromboembolism in pregnancy as in the non-pregnant state is linked to thrombophilia. In this review all aspects of thrombophilia in pregnancy are discussed, and also all prophylactic and therapeutic implications.

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.

Severe obstetric complications, including preeclampsia, intrauterine growth retardation, abruptio placentae, and stillbirth, constitute a major cause of maternal and perinatal morbidity and death. The etiology of these severe obstetric complications is still unknown. However, the frequent finding of structural and thrombotic changes in placental capillaries, which lead to inadequate fetomaternal circulation and decreased placental perfusion, and the high prevalence of heritable or acquired risk factors for thrombosis found in women with these complications strongly suggest a cause-and-effect relationship. This review describes the recent findings on the association between these obstetric complications and the various thrombophilias, and recent therapeutic approaches. Aspirin, which was regarded as the drug of choice for the prevention of such obstetric complications, has proved to be ineffective in a large clinical trial. The encouraging observations on the efficacy of low-molecular-weight heparins, which are also included in the recently published guidelines of The American College of Chest Physicians, are summarized in this review. However, controlled clinical trials are still necessary to allow the development of better clinical standards.

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 (p<0.03). 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.

Objective: To evaluate the significance of clinical signs and blood indices for the diagnosis of appendicitis during pregnancy., Sample: Of the 40,112 women delivering at our institution (January 1995 to June 2002), 38 women (0.094%) were operated due to the suspicion of appendicitis during pregnancy., Methods: Body temperature, clinical examination, white blood cell counts and lag time from arrival to operation were obtained for each patient. All women were operated with the clinical diagnosis of appendicitis, and their appendices were removed and examined by a pathologist., Results: Inflammatory appendix was discovered in 19 (0.047%) of the pregnancies with subsequent deliveries while a normal appendix was found in 19 of the 38 (50%) appendices removed. The group with normal appendix did not significantly differ from women with inflamed appendix with regard to gestational age at presentation, signs of peritoneal irritation, body temperature, leukocyte count, time elapsed between arrival and surgery, gestational age at delivery and birth weight., Conclusions: The accurate diagnosis of appendicitis during pregnancy is a difficult task requiring a very high level of suspicion and clinical skills and not merely relying upon laboratory and classic signs., (Copyright 2003 S. Karger AG, Basel)

Objective: To investigate the association between severe mid-trimester IUGR, whose causes are unknown in most cases, and maternal thrombophilias., Design: Case-control study., Setting: Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, The Sackler Faculty of Medicine, Tel Aviv University., Population: Twenty-six women with severe mid-trimester (22-26 weeks of gestation) IUGR (birthweight <3rd centile) and 52 matched multiparous women with normal pregnancies (controls)., Methods: 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., Main Outcome Measures: Prevalence of maternal thrombophilias., Results: 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, P < 0.001]. 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., Conclusion: Women with mid-trimester severe IUGR have an increased prevalence of inherited and acquired thrombophilias.

Objective: As a first step towards evaluating the role of oxidative stress in the process of labour, we tested whether term labour is associated with increased oxidisibility of maternal serum lipids., Design: A controlled prospective study., Setting: Tertiary care centre., Population: Twenty healthy women in active labour and 20 healthy pregnant women not in labour (controls) matched for maternal and gestational age., Methods: Venous blood was drawn from women in both groups. Serum levels of lipid peroxidation products and the kinetics of copper-induced oxidation ex vivo were monitored spectroscopically at 37 degrees C by continuous recording of absorbance at 245 nm., Main Outcome Measures: Oxidative stress parameters., Results: The initial optical density (OD) at 245 nm, attributed to preformed dienic hydroperoxides and 7-keto-cholesterol (main products of lipid peroxidation), was higher in the labouring group than in the controls (1.30 +/- 0.11 vs 1.18 +/- 0.09, OD 245 nm, respectively, P < 0.001). The lag phase, reflecting resistance of serum lipids to oxidation, was significantly shorter in the labouring group than in the controls (43.2 +/- 1.4 vs 56.2 +/- 4.7 min, respectively, P = 0.01)., Conclusion: High levels of serum hydroperoxides and decreased resistance of serum lipids to copper-induced peroxidation ex vivo suggest labour to be associated with high oxidative stress. Whether oxidative stress is involved in initiating the labour process or is consequent awaits further studies.

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.

Objectives: To conduct a prospective evaluation of the incidence and neonatal outcome of fetuses with persistent right umbilical vein. This condition had traditionally been considered to be extremely rare and to be associated with a very poor neonatal prognosis, but later evidence has raised some doubts about the veracity of these contentions., Methods: Between August 1995 and November 1998, 8950 low-risk patients were prospectively evaluated at two medical centers. The sonographic diagnosis of a persistent right umbilical vein was made in a transverse section of the fetal abdomen when the portal vein was curved toward the stomach, and the fetal gall bladder was located medially to the umbilical vein., Results: Persistent right umbilical vein was detected in 17 fetuses during the study. Four of them had additional malformations, of which three had been detected antenatally., Conclusions: We established that the incidence of persistent right umbilical vein in a low-risk population is 1 : 526. We believe that the sonographic finding of this anomaly is an indication for conducting targeted fetal sonography and echocardiography. When the persistent right umbilical vein is connected to the portal system and other anomalies are ruled out, the prognosis can generally be expected to be favorable.

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., (Copyright 2002 Elsevier Science Ltd.)

In order to differentiate between the contributions of cellular and plasmatic factors to the elevated aggregation in pregnancy-induced hypertension (PIH), we determined RBC aggregation in autologous plasma and in plasma-free medium. The aggregation was determined as a function of shear stress, to evaluate the strength of the intercellular interaction. These procedures were applied to RBC from PIH women (n=20), normotensive pregnant (NTP) women (n=15), and non-pregnant (control) women (n=15). The average aggregate size (AAS) in plasma for PIH, NTP and control RBC was 38.7+/-3.2, 28.4+/-3.0, and 11.5+/-2.2 (P<0.05, between the three groups), respectively. For the same groups, the aggregation in plasma-free standard medium was 17.3+/-2.0, 12.0+/-1.2 and 10.0+/-1.6 (P<0.05 between PIH and the other two groups), respectively. The contribution of plasma to the elevated aggregation was 75% and 88% for PIH and NTP respectively. Tau(S50), the shear stress required to singly disperse 50% of the RBC population, in plasma and in standard medium, was about the same for PIH and NTP, and both were markedly higher than that for control RBC. These findings suggest that the increased aggregation of RBC from women with PIH, over those at of NTP women, may be due largely to changes in cellular factors and the increased aggregability has the potential to affect blood flow mainly in low-flow states such as in the placental intervillous space.

Objectives: The purpose of the present study was to evaluate whether a gender-related difference exists in first trimester markers used for Down syndrome screening, namely nuchal translucency (NT), maternal serum pregnancy-associated plasma protein-A (PAPP-A), and free beta-human chorionic gonadotrophin (beta-hCG), and whether this has an influence on screening performance., Methods: A total of 1325 patients with a singleton pregnancy underwent combined first trimester screening at 10-13 weeks' gestation. Maternal serum PAPP-A and free beta-hCG were analyzed by fluoroimmunoassay, nuchal translucency (NT) was measured by transvaginal sonography. Only patients with normal outcomes and known fetal gender were included in the study. Data were categorized by gestational age and by fetal gender., Results: There were no significant gender-related differences in NT and PAPP-A levels. However, free beta-hCG was significantly higher (p=0.00004) in the presence of a female fetus than in the presence of a male fetus. Women with female fetuses had a higher median calculated Down syndrome risk (1:5490) compared to those having males (1:6451). This difference was not, however, statistically significant., Conclusion: First trimester free beta-hCG is significantly higher in pregnancies with a female fetus., (Copyright 2001 John Wiley & Sons, Ltd.)

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.

Obstetric complications, such as severe pre-eclampsia, fetal growth restriction, abruptio placentae, or stillbirth are associated with abnormally elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) and beta subunit of human chorionic gonadotrophin (betahCG). This has been attributed to placental abnormalities. Women with thrombophilias have been shown to have abnormalities of the placenta resulting in adverse pregnancy outcome in these patients. The purpose of the present study was to evaluate whether women with pregnancy complications and inherited thrombophilias have abnormally elevated second-trimester MSAFP or betahCG. Sixty-two women with pregnancy complications were tested for inherited thrombophilias several months after delivery. The thrombophilia group included 29 women with pregnancy complications and an inherited thrombophilia and the control group included 33 other patients without thrombophilia. Patients in the thrombophilia group had a higher median MoM MSAFP compared to the controls (1.337 vs. 1.086, p=0.0516). The incidence of abnormally elevated MSAFP (>2.5 MoM) was also significantly higher in the thrombophilia group compared to controls (21% vs. 3%, p=0.04). Neither the median MoM betahCG nor the incidence of abnormally elevated betahCG were significantly different between the groups. We conclude that second trimester MSAFP, but not betahCG, is abnormally elevated in patients with thrombophilia and obstetric complications., (Copyright 2001 John Wiley & Sons, Ltd.)

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 alpha of 0.05 and 80% power and considering a minimum difference to detect 4 microm 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 clottable fibrinogen concentrations.

Combined first trimester screening using pregnancy associated plasma protein-A (PAPP-A), free beta-human chorionic gonadotrophin, and nuchal translucency (NT), is currently accepted as probably the best combination for the detection of Down syndrome (DS). Current first trimester algorithms provide computed risks only for DS. However, low PAPP-A is also associated with other chromosome anomalies such as trisomy 13, 18, and sex chromosome aneuploidy. Thus, using currently available algorithms, some chromosome anomalies may not be detected. The purpose of the present study was to establish a low-end cut-off value for PAPP-A that would increase the detection rates for non-DS chromosome anomalies. The study included 1408 patients who underwent combined first trimester screening. To determine a low-end cut-off value for PAPP-A, a Receiver-Operator Characteristic (ROC) curve analysis was performed. In the entire study group there were 18 cases of chromosome anomalies (trisomy 21, 13, 18, sex chromosome anomalies), 14 of which were among screen-positive patients, a detection rate of 77.7% for all chromosome anomalies (95% CI: 55.7-99.7%). ROC curve analysis detected a statistically significant cut-off for PAPP-A at 0.25 MoM. If the definition of screen-positive were to also include patients with PAPP-A<0.25 MoM, the detection rate would increase to 88.8% for all chromosome anomalies (95% CI: 71.6-106%). This low cut-off value may be used until specific algorithms are implemented for non-Down syndrome aneuploidy., (Copyright 2001 John Wiley & Sons, Ltd.)

Problem: To investigate whether inhibin A, inhibin B, and activin A serum levels are altered in women with preeclampsia., Method of Study: Serum samples of 20 women with preeclampsia (study group) and 20 normotensive pregnant women, matched for maternal and gestational age and parity, were assayed for inhibin A, inhibin B and activin A by specific enzyme-linked immunosorbent assay., Results: Median serum concentrations of inhibin A and activin A were significantly higher among women with preeclampsia than in women with normotensive pregnancies, while inhibin B levels were comparable in both groups. Activin A levels were positively correlated with those of inhibins A and B, and inhibin A levels were positively correlated with diastolic blood pressure and inhibin B concentration in the study group., Conclusions: Inhibin A and activin A, but not inhibin B, serum levels are markedly increased in women with preeclampsia. These hormones might serve as an endocrine marker for preeclampsia.

Objective: To prospectively evaluate the prevalence, presumed etiologies and clinical implications of persistent postpartum urinary retention in modern obstetric practice., Study Design: The study population comprised 8,402 consecutive, unselected parturients delivered in a university-affiliated maternity hospital over a one-year period. If a woman was unable to void spontaneously until the third postpartum day despite intermittent use of a Foley catheter, a diagnosis of persistent postpartum urinary retention was established. Patients were treated by insertion of a Foley catheter for up to two weeks and subsequently by a suprapubic catheter. Obstetric data were collected from the hospital records., Results: Four patients (0.05% of the study population), aged 29-37 years, developed persistent postpartum urinary retention. Risk factors included vaginal delivery after cesarean section, prolonged second stage of labor, epidural analgesia, and delayed diagnosis and intervention. Urodynamic evaluation, performed on two patients one month after removal of the suprapubic catheter, revealed genuine stress incontinence in one and detrusor instability in another. None had had any lower urinary tract symptoms before pregnancy and delivery., Conclusion: Persistent postpartum urinary retention in contemporary obstetric practice is rare but may be associated with long-term bladder dysfunction. Early diagnosis and intervention are required to prevent irreversible bladder damage.

Objective: To assess the hypofibrinolytic 4G/4G mutation of the plasminogen activator inhibitor (PAI-1) gene as a possible factor contributing to severe preeclampsia, abruptio placentae, fetal growth restriction, and stillbirth., Methods: We compared 94 women from a previous report who had obstetric complications to 95 controls with normal pregnancies matched for ethnic background and age. We collected blood and extracted DNA after delivery. All subjects had been tested for thrombophilic mutations factor V Leiden, C677T mutation in the methylenetetrahydrofolate reductase gene, and the G20210A mutation in the prothrombin gene. In the present study we tested for the hypofibrinolytic 4G/4G mutation in the PAI-1 gene., Results: Women who had obstetric complications were more likely than controls to be 4G/4G homozygotes, 32% (30 of 94) women versus 19% (18 of 95) controls, odds ratio (OR) and 95% confidence intervals (CI) 2.0 (1.02, 3.9). Mutations in the PAI-1 gene were independently associated with obstetric complications (OR 1.56, 95% CI 1.005, 2.43). Heterozygosity for the factor V Leiden mutation was more common in the 30 women who had PAI-1 4G/4G than in the 18 4G/4G controls (33% versus 0%, Fisher P =.008). Seventy-six percent of women had some form of thrombophilia or hypofibrinolysis compared with 37% of controls (Fisher P <.001)., Conclusions: Women with severe preeclampsia, abruptio placentae, fetal growth restriction, and stillbirth had increased incidence of the hypofibrinolytic 4G/4G mutation of the PAI-1 gene that is frequently associated with the thrombophilic factor V Leiden mutation, further predisposing them to thrombosis.