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.

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.

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.

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.

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.

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.

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.

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 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.

Thrombophilia and pregnancy.

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.

Third-trimester unexplained intrauterine fetal death is associated with inherited thrombophilia.

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.

Inherited thrombophilia and poor pregnancy outcome.

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.

Neurodevelopmental and cognitive assessment of children born growth restricted to mothers with and without preeclampsia.

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.

Pregnancy-induced hypertension is associated with elevation of aggregability of red blood cells.

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.