Pravastatin is useful for prevention of recurrent severe placenta-mediated complications - a pilot study.

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.

Progression from isolated gestational proteinuria to preeclampsia with severe features.

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.

Major liver resection in pregnancy: three cases with different etiologies and review of the literature.

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.

Personnel-itis: a myth or a pathology? A retrospective analysis of obstetrical and perinatal outcomes for physicians and nurses.

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.

Management and outcome of consecutive pregnancies complicated by idiopathic intracranial hypertension.

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.

Severe pregnancy complications are associated with elevated factor VIII plasma activity.

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.

Neurosurgery and pregnancy.

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.

Low molecular weight heparin treatment during subsequent pregnancies of women with inherited thrombophilia and previous severe pregnancy complications.

OBJECTIVES: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: LMWH treatment of women with previous severe pregnancy complications and thrombophilias significantly reduces the rate of recurrence.

Coiling characteristics of umbilical cords in breech vs. vertex presentation.

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.

Reference values for strong ion difference--a novel tool for fetal metabolic assessment.

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.

Serum lipid oxidizibility in term premature rupture of the membranes.

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.

Neonatal respiratory morbidity after elective cesarean section.

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.

[The male's role in the etiology of preeclampsia].

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.

Chorioamnionitis associated with Crohn's disease and azathioprine treatment: a case report.

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.

Oxidative stress in the fetal circulation does not depend on mode of delivery.

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.

Perinatal outcome among non-residents in Israel.

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.

Role of thrombophilic risk factors in children with non-stroke cerebral palsy.

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.

The safety of low molecular weight heparin therapy during labor.

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.

Perinatal outcome in women with severe pregnancy complications and multiple thrombophilias.

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.