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Treatment of severe preeclampsia remote from term: a clinical dilemma.

UNLABELLED: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. Women with severe preeclampsia are usually delivered without delay. In recent years, a new approach in the treatment of women with severe preeclampsia remote from term has been advocated by several investigators worldwide. This approach advocates conservative management in a selected group of women with severe preeclampsia remote from term with the aim of improving perinatal outcome without compromising maternal safety. In most studies, patients who were candidates for conservative management had a blood pressure of more than 160/110, whereas in some studies, women with heavy proteinuria were also considered suitable. Only very few studies have supported conservative management in patients with signs and symptoms of HELLP syndrome. It is imperative to carefully balance maternal and fetal risks before choosing conservative management in severe preeclampsia remote from term. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand which patients are most likely to benefit from conservative management of severe preeclampsia remote from term, what the conservative management of severe preeclampsia remote from term entails, and what are the benefits of conservative management of preeclampsia remote form term.

Adrenal Cortex Hormones↗

The severity of polyhydramnios, estimated fetal weight and preterm delivery are independent risk factors for the presence of congenital malformations.

OBJECTIVE: To evaluate maternal and fetal factors associated with congenital malformations in patients with polyhydramnios. STUDY DESIGN: The study group consisted of 275 singleton pregnancies with an amniotic fluid index (AFI) >25.0 cm. An equal number of controls were matched for maternal age, gravidity, parity and gestational age. The proportion of cases and controls with malformations was compared. Polyhydramnios cases were categorized into three groups by severity: mild (AFI 25-30 cm), moderate (AFI: 30.1-35.0 cm) and severe (AFI >35.1 cm). Among cases, logistic regression analysis was utilized to estimate the risk for fetal congenital malformations in relation to severity of polyhydramnios, estimated fetal weight, maternal diabetic status and gestational age at delivery. RESULTS: Congenital malformations were detected in 40 of 275 cases (14.5%) with polyhydramnios and in 9 cases (3.3%) of the control group (p < 0.01). The relative risks of congenital malformations increased with the severity of polyhydramnios: 3.2 (95% CI 1.5-6.8), 5.7 (95% CI 2. 4-13.3) and 13.1 (95% CI 5.8-29.5) for mild, moderate and severe polyhydramnios, respectively. Congenital malformations among polyhydramnios cases were present in 54.5% of small-for-gestational age fetuses, in contrast to 12.7% for average-for-gestational age fetuses and 10.8% for large-for-gestational age fetuses (p < 0.001). Maternal diabetic status did not significantly affect the fetal anomaly rate once polyhydramnios was detected. Premature newborns in the polyhydramnios group had a higher malformation rate (24%) than did term newborns (11.3%) (p < 0.02). In the study group, multiple logistic analysis confirmed the significance of severe polyhydramnios, small-for-gestational age status and preterm delivery as independent contributors to the malformation risk. CONCLUSIONS: Polyhydramnios (AFI >35 cm), small-for-gestational age fetus and preterm delivery are independent risk factors for congenital malformations.

Birth Weight↗

Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment.

The inherited thrombophilias--deficiencies of protein C, protein S, and antithrombin III--and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (P=0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (P=0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of >1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE.

Adult↗

Neurodevelopmental outcome in children with intrauterine growth retardation: a 3-year follow-up.

The study was designed to detect early clinical predictors of developmental outcome in children with intrauterine growth retardation. Eighty-five children with intrauterine growth retardation were followed up prospectively to 3 years of age, using biometric parameters, perinatal risk questionnaires, and neurodevelopmental evaluations. Forty-two children served as controls. A significant difference in neurodevelopmental score at 3 years of age was noted between the intrauterine growth retardation and control groups (P < .001). In the intrauterine growth retardation group, the clinical parameters that most significantly correlated with outcome were cephalization index (head circumference:birthweight ratio), neonatal risk score, and birthweight. The best predictor of 3-year outcome was the cephalization index (P < .01). The children with intrauterine growth retardation with neonatal complications had significantly lower IQ scores (P < .05) and a poorer neurodevelopmental outcome (P < .01) than those without complications. Children with intrauterine growth retardation are at higher risk for developmental disabilities than are controls, especially in the presence of neonatal complications and a high cephalization index.

Case-Control Studies↗

Outcome of pregnancy in three patients with primary antiphospholipid syndrome after stroke.

OBJECTIVE: Ischemic stroke is the most common neurological manifestation in patients with antiphospholipid syndrome (APS). Pregnancy in APS patients markedly increases the risk of thrombosis. There is no data on pregnancy outcome in patients with APS with a history of an ischemic stroke. We report our experience with three APS patients with a history of stroke who had successful pregnancies and deliveries. PATIENTS: Three patients with APS and previous stroke were treated with small doses of aspirin and anticoagulants during pregnancy. RESULTS: The patients remained free of attacks of cerebral ischemia during their pregnancies and at follow-up periods of 1 to 4 years. CONCLUSIONS: Successful pregnancy and delivery is possible in APS patients with a history of stroke, treated with low-dose aspirin and anticoagulants. A previous episode of cerebral ischemia should not be considered an absolute contraindication for an APS patient to become pregnant.

Adult↗

Obstetric outcome after RhD and Kell testing.

The study was conducted to report on the use of molecular biology methods and pregnancy outcome in women sensitized to either Rhesus D (RhD) or Kell 1 (K1) antigens. Paternal RhD genotype was determined by DNA amplification of an RhD-specific sequence from single sperm cells. Paternal Kell phenotype was determined by serologic assays using peripheral blood samples, and the fetal RhD or Kell-type status were established by the polymerase chain reaction (PCR) with amniotic cells. Thirteen women (14 pregnancies, one with twins) sensitized to RhD and four sensitized to K1 antigens, comprised the study group. All had paternal heterozygosity to either D or K1 antigens. Nine fetuses were RhD positive and five were RhD negative. An additional woman underwent early spontaneous abortion. The nine RhD-positive fetuses underwent a total of 41 invasive procedures. One fetus with hydrops fetalis died in utero after intrauterine blood transfusion. All the remaining RhD-positive fetuses were delivered after 33 weeks gestation, and all those who were RhD negative were delivered at term. Four women were sensitized to the K1 antigen; in three, the fetus was found to be K1 negative, and in one, K1 positive, necessitating intrauterine blood transfusion. In all cases, the results of RhD or K1 genotype analyses from amniotic fluid were compatible with fetal/neonatal red blood cell RhD or Kell phenotypes. In conclusion, the use of molecular biology techniques represents a major advance in the clinical management of RhD and Kell alloimmunization.

Amniotic Fluid↗

Increased xanthine oxidase during labour--implications for oxidative stress.

Xanthine dehydrogenase/oxidase (XDH/XO) produces uric acid. When in the oxidase form, this production is coupled with the generation of free radicals. Hypoxia-reperfusion enhances conversion of XDH to XO. Since the placenta is exposed to short periods of hypoxia reperfusion during labour, 17 placentae of pregnancy terminated by elective caesarean section and five placentae of pregnancies terminated by caesarean section during labour were examined for XDH/XO activity. It was found that XO activity was higher in the placentae of labouring women (P = 0.003), which suggests that labour enhances conversion of XDH to XO, facilitating free radical production.

Adult↗

Vascular endothelial growth factor is increased in patients with preeclampsia.

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

Adult↗

The underlying cause of polyhydramnios determines prematurity.

The preterm delivery rate in polyhydramnios is higher than in the normal population. We conducted this study to determine if different aetiologies for polyhydramnios have different frequencies of preterm delivery. Three hundred and forty women with a singleton pregnancy and polyhydramnios were included in the study group. A delivery was considered premature if it occurred before 37 weeks' gestation. Preterm deliveries occurred in 14.1 per cent of patients with unexplained polyhydramnios, 27.7 per cent of patients with insulin-dependent diabetes mellitus (IDDM), and in 36 per cent of pregnancies with congenital malformations. The prevalence of preterm delivery was significantly greater for the subgroups with IDDM (P = 0.02) and congenital malformations (P = 0.001), when compared with patients with idiopathic polyhydramnios. The prevalence of preterm delivery in patients with gestational diabetes mellitus was no greater than for the population at large. The underlying cause of polyhydramnios is a major factor in determining when delivery will occur.

Congenital Abnormalities↗

Low-molecular-weight heparin during pregnancy and delivery: preliminary experience with 41 pregnancies.

OBJECTIVE: To describe experience with 41 pregnancies treated with the low-molecular-weight heparin enoxaparin. METHODS: The medical charts of 34 women (a total of 41 pregnancies) treated between January 1992 and March 1995 with the low-molecular-weight heparin enoxaparin were reviewed. Most patients (87.5%) received one daily 40-mg injection. In all cases, treatment was continued throughout labor, delivery, and the immediate postpartum period. RESULTS: Therapy was administered for 5-280 days (median 91). One case of a thromboembolic event was recorded during treatment. No systemic or local side effects were reported. During pregnancy, only one patient had mild vaginal bleeding, which resolved spontaneously while therapy was continued. There was no excessive intrapartum bleeding in any of these patients, whether delivered vaginally or abdominally. During treatment, 19 of the 34 patients underwent 24 surgical procedures, including 13 cesarean deliveries, without excessive bleeding. Epidural anesthesia was used during labor in nine of the patients, with no specific complications. The corrected perinatal mortality rate, (ie, the rate of fetal death after 24 weeks' gestation plus neonatal death, excluding a neonate with multiple anomalies) for those neonates delivered after 24 weeks' gestation was 2.7%. There were no cases of intraventricular hemorrhage in any of the neonates. CONCLUSION: This preliminary series, the largest reported to date, demonstrates the relative safety and efficacy of low-molecular-weight heparin therapy in pregnancy and delivery.

Adult↗

Hyperuricemia and xanthine oxidase in preeclampsia, revisited.

Hyperuricemia is associated with the severity of preeclampsia and with fetal outcome. Traditionally the high uric acid concentration in preeclampsia has been attributed soley to renal dysfunction. Preeclampsia is also characterized by increased free radical formation and elevated oxidative stress. Xanthine dehydrogenase/oxidase produces uric acid. Xanthine dehydrogenase/oxidase is present as two isoforms in vivo. Uric acid production is coupled with formation of reactive oxygen species when the enzyme is in the oxidase form. Several factors can increase the holoenzyme activity and the conversion of xanthine dehydrogenase/oxidase to its oxidase form. These factors include hypoxia-reperfusion, cytokines, and increased substrate availability (xanthine and hypoxanthine). Preeclampsia is characterized by hyperuricemia and signs of increased formation of reactive oxygen species and decreased levels of antioxidants. Preeclampsia is also characterized by shallow implantation, producing a relatively hypoxic maternal-fetal interface, and increased turnover of trophoblast tissue, which can result in higher xanthine and hypoxanthine concentrations and higher levels of circulating cytokines. These mechanisms can lead to increased production of uric acid and free radicals and contribute to the hyperuricemia and increased oxidative stress present in preeclampsia.

Female↗

Aspergillosis in systemic lupus erythematosus.

Infection is the major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although various fungi account for a substantial number of these lethal infections, aspergillosis, an important opportunistic infection in immunosuppressed patients, is described rarely. Only 23 cases have been reported in the English-language medical literature. Risk factors for acquiring aspergillosis in these patients were high grade disease activity, granulocytopenia, use of steroids and other immunosuppressive treatment and presence of bacterial infection. The diagnosis in most patients was delayed and they died. Here, we describe three SLE patients with invasive aspergillosis. Features of our patients' diseases were similar to those reported previously. Aspergillosis appeared while they had active SLE treated with high dose corticosteroids. In 2 patients the fungal infection was systemic and diagnosed post mortem. Both were leukopenic and had concurrent bacterial infection and one received amphotericin B prior to death. In the third, the infection was localized to a transplanted kidney and was cured by nephrectomy. Aspergillosis should be suspected in patients with active SLE, who are immunocompromised and sustain concomitant bacterial infections. The currently poor prognosis may be improved with more aggressive diagnostic investigation and treatment.

Adolescent↗

The effect of amniotic sheet orientation on subsequent maternal and fetal complications.

The purpose of this investigation was two-fold, first, to determine the incidence of amniotic sheets in our obstetric population; and, second, to elucidate the maternal and fetal complications associated with this particular finding. In this retrospective study, we searched the computerized records of the ultrasound department for the presence of amniotic sheets in singleton pregnancies from 1 March 1991 to 17 September 1993. Sonographic criteria for an amniotic sheet included the findings that (1) a reflective membrane attached to the placenta at one end or the other, with measurable thickness, was identified traversing the amniotic fluid; and (2) the fetus was not attached to the membrane, and fetal ability to move without restriction was ascertained. An amniotic sheet was identified in 79 of 17,553 examinations (0.45%) performed between 12 and 28 weeks' gestation. Two subsets of amniotic sheets were identified: perpendicular and not perpendicular. The sheets in the first subset were orientated perpendicular to the placental surface and were more likely to be associated with an abnormal presentation at delivery (p < 0.001) and a history of pelvic inflammatory disease, but not with a history of prior Cesarean section, or previous dilatation and curettage. The second subset of amniotic sheets were non-perpendicular, either oblique or parallel, in orientation to the placental surface and were associated with fewer maternal complications. Of the study group, 40.7% had a history of vaginal bleeding. The incidence of vaginal bleeding was not significantly different between those patients with perpendicular or those with non-perpendicular amniotic sheets. We conclude that perpendicular, in contrast to non-perpendicular, amniotic sheets are more commonly associated with breech presentation at term and a past history of pelvic inflammatory disease.

Amnion↗

Vibroacoustic stimulation enhances visualization of the four-chamber cardiac view in the third trimester.

The objective of this study was to determine whether vibroacoustic stimulation would improve the visualization rate of the four-chamber cardiac view. Patients between 26 and 42 weeks' gestation were considered to be candidates for this study if the amniotic fluid index (AFI) was between 8.0 and 24.0 cm, no malformations were detected on a careful fetal anatomical survey and a four-chamber cardiac view was not obtainable. Once a four-chamber view was considered to be not obtainable due to fetal position, the patient was asked to withdraw a sealed envelope and was assigned to either the study or the control group. The 164 study patients received one to three 3-s vibroacoustic stimulations. Five minutes later a second attempt was made to visualize the four-chamber view adequately. The control group consisted of another 198 subjects in whom a four-chamber view could not be obtained. The control group did not receive vibroacoustic stimulation. A similar 5-min time interval was allowed to elapse before an attempt was made to visualize the four-chamber view. The study and control groups were similar with respect to fetal presentation, placental location, fetal weight category, biophysical profile score, gestational age, AFI and estimated fetal weight. The rate of the four-chamber view was significantly higher among fetuses receiving vibroacoustic stimulation (20.1%), in comparison to the control group (11.1%) (p = 0.019). Successful repositioning was more likely among fetuses with estimated fetal weight between 2251 and 3050 g, and at a gestational age between 33.1 and 37.0 weeks. We conclude that in a selected group of patients vibroacoustic stimulation can be used to enhance visualization of the four-chamber view.

Female↗

Prospective study of incidence and predisposing factors for clavicular fracture in the newborn.

OBJECTIVE: To determine the incidence of clavicular fracture, associated fetal and maternal risk factors and its connection with quality care control. SUBJECTS AND METHODS: A total of 3030 newborns delivered vaginally were evaluated for clavicular fractures by three separate physicians. The study group included all newborns with fractured clavicle. A control group consisted of 52 newborns delivered vaginally with no history of fractures. Maternal records were evaluated for possible predisposing factors. RESULTS: Forty-six (l.5%) newborns were found to have clavicular fractures. When compared to the control group, they were found to have a higher birthweight (3710+/-352gm vs 3235+/-405gm) an older maternal age (30.5+/-5 bs 27.7+/-6), a longer second stage of labor (34 min vs 23 min), higher rate of instrumental deliveries (13/46 vs 6/52) and shoulder dystocia (6/46 vs 1/52). Nearly 80% of newborns with clavicular fractures weighed less than 4000 gm. Multivariate analysis demonstrated two independent variables; birthweight over 3500 gm and maternal age >29. CONCLUSION: Clavicular fractures are associated with higher birthweight, older maternal age, longer second stage of labor, instrumental deliveries and shoulder dystocia. However, in most cases this injury cannot be predicted prior to delivery and thus cannot be an indicator of quality control.

Apgar Score↗

Severity of polyhydramnios does not affect the prevalence of large-for-gestational-age newborn infants.

The purpose of this study was to evaluate the relationship between the severity of polyhydramnios with or without maternal diabetes and the prevalence of large-for-gestational-age newborn infants. A case control design was used. The study group consisted of 275 singleton pregnancies with an amniotic fluid index > or = 25.0 cm. An equal number of controls was matched for maternal age, gravidity, parity, and gestational age. Polyhydramnios was categorized into three groups by severity: mild (amniotic fluid index 25 to 30 cm.); moderate (amniotic fluid index, 30.1 to 35.0 cm); and severe (amniotic fluid index > or = 35.1 cm). Among our study group, 72.7%, 19.7%, and 7.6% of cases had mild, moderate, and severe polyhydramnios, respectively. Patients with polyhydramnios had a significantly higher prevalence of large-for-gestational-age neonates (27%) than did controls (10%) (P < 0.001). No correlation was seen between the severity of polyhydramnios and neonatal delivery weight. The prevalence of gestational and class > or = B diabetes mellitus was significantly higher among patients with polyhydramnios (17.7%) than among controls (7%) (P < 0.003). Once polyhydramnios was diagnosed sonographically, however, maternal diabetic status did not affect the prevalence of large-for-gestational-age newborn infants. We conclude that the prevalence of large-for-gestational-age neonates is 2.7 times greater when polyhydramnios is present than when the amniotic fluid volume is normal. Neither the severity of polyhydramnios nor the presence of maternal diabetes mellitus strengthens the relationship between polyhydramnios and large-for-gestational-age newborn infants.

Case-Control Studies↗