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Anticonvulsants for women with pre-eclampsia.

BACKGROUND: Pre-eclampsia is a relatively common complication of pregnancy. Anticonvulsants are used in the belief they help prevent eclamptic fits and subsequent poor outcomes for mother and infant. OBJECTIVES: The objective of this review was to assess the effects of anticonvulsants for women with pre-eclampsia on the women and their children. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, and the Cochrane Controlled Trials Register, 1999 Issue 3. SELECTION CRITERIA: Randomised trials comparing anticonvulsants with placebo or no anticonvulsants or comparisons of different anticonvulsants in women with pre-eclampsia. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Nine studies were included. Comparing magnesium sulphate with placebo/no anticonvulsant the relative risk (RR) of eclampsia was 0.33, 95% confidence interval (CI) 0.11 to 1.02. There was no significant difference detected in the risk of caesarean section (RR 1.04, 95% CI 0.92 to 1.17). Magnesium sulphate appeared to be better than phenytoin at reducing the risk of eclampsia (RR 0.05, 95% CI 0.00 to 0.84). However there was an increased risk of caesarean section with magnesium sulphate compared to phenytoin (RR 1.21, 95% CI 1.05 to 1. 41). No statistically significant differences were reported for any other clinically important outcomes. Studies comparing magnesium sulphate and diazepam were too small for any reliable conclusions. REVIEWER'S CONCLUSIONS: There is not enough evidence to establish the benefits and hazards of anticonvulsants for women with pre-eclampsia. If an anticonvulsant is used, magnesium sulphate appears to be the best choice.

Anticonvulsants↗

Blood coagulation profile in Indian patients with pre-eclampsia and eclampsia.

Twelve Indian patients with pre-eclampsia, 15 with eclampsia and 15 with normal pregnancy in the third trimester were investigated. A systemic bleeding diathesis was encountered in two patients with eclampsia and in none with pre-eclampsia; two patients with pre-eclampsia, however, had excessive uterine haemorrhage. Coagulation studies showed statistically significant prolongation of thrombin time, elevation of serum fibrinogen degradation products (FDP) and hypofibrinogenaemia in patients with pre-eclampsia as well as eclampsia. In patients with eclampsia, significant thrombocytopenia also occurred. Euglobulin lysis time showed no significant change in patients with pre-eclampsia and eclampsia. There was no significant difference in the coagulation profile between patients with eclampsia and pre-eclampsia, except for more hypofibrinogenaemia in the former. The laboratory findings suggest the occurrence of intravascular coagulation in patients with pre-eclampsia and eclampsia.

Adult↗

Vascular cell adhesion molecule-1 (VCAM-1) and leukocyte activation in pre-eclampsia and eclampsia.

OBJECTIVE: To evaluate the levels of VCAM-1 in pre-eclampsia/eclampsia as a possible marker of leukocyte activation and endothelial damage. METHODS: We performed a case-control study on 25 healthy pregnant women and 35 patients diagnosed as pre-eclampsia or eclampsia which were randomly selected. Peripheral venous blood samples were obtained and serum levels of VCAM-1 were measured by enzyme-linked immunoassay (ELISA). RESULTS: In pre-eclampsia/eclampsia, VCAM-1 levels were higher than in normal pregnancy. Serum concentrations of VCAM-1 were significantly higher in severe pre-eclampsia and eclampsia compared to mild pre-eclampsia or healthy controls. ROC analysis detected that VCAM-1 > or = 450 ng/ml had a sensitivity of 0.79 and a specificity of 0.90 in detecting severe pre-eclampsia and eclampsia. CONCLUSION: This is the first study to correlate VCAM-1 levels with severity of disease in pre-eclampsia. Our findings indicate that increasing levels of soluble VCAM-1 are present in the circulation of patients with severe pre-eclampsia/eclampsia compared to mild pre-eclampsia or healthy pregnant women. Elevated VCAM-1 levels may represent a possible mechanism by which endothelial cells attract leukocytes and cause endothelial cell damage.

Blood Pressure↗

Magnesium sulphate in the treatment of eclampsia and pre-eclampsia: an overview of the evidence from randomised trials.

OBJECTIVE: To evaluate the effectiveness of magnesium sulphate in the treatment of eclampsia and pre-eclampsia by a systematic quantitative overview of controlled clinical trials. DESIGN: Online searching of the MEDLINE database between 1966 and 1995, and scanning of the bibliography of known primary studies and review articles on the use of magnesium sulphate in eclampsia and pre-eclampsia. Study-selection, study quality assessment and data extraction were performed independently by two reviewers under masked conditions. Where possible outcome data from trials were pooled and summarised using the Mantel-Haenszel method. PARTICIPANTS: One thousand seven hundred and forty-three women with eclampsia and 2390 with pre-eclampsia included in nine randomised trials that evaluated the effects of magnesium sulphate. MAIN OUTCOME MEASURES: Seizure activity and maternal death. RESULTS: In eclampsia, recurrence of seizures was less common with magnesium sulphate therapy compared with phenytoin (odds ratio [OR] 0.27, 95% CI 0.17-0.45, P = 0.00) and diazepam (OR 0.41, 95% CI 0.30-0.57, P = 0.00). As indicated by the point estimate, there was a trend towards a reduction in maternal mortality with magnesium sulphate in eclampsia (OR 0.51, 95% CI 0.24-1.07, P = 0.10 versus phenytoin; OR 0.78, 95% CI 0.41-1.45, P = 0.52 versus diazepam). When used for seizure prophylaxis in pre-eclampsia, magnesium sulphate was found to be more effective than phenytoin (OR 0.15, 95% CI 0.03-0.72, P = 0.01). CONCLUSION: Magnesium sulphate is a superior drug in preventing the recurrence of seizures in eclampsia and in seizure prophylaxis in pre-eclampsia.

Anticonvulsants↗

Changing paternity and time since last pregnancy; the impact on pre-eclampsia risk. A study of 547 238 women with and without previous pre-eclampsia.

BACKGROUND: Long time interval between pregnancies has been found to increase the risk of pre-eclampsia in second pregnancy. Our aim was to investigate whether this effect is influenced by a history of pre-eclampsia or a change in paternity. METHODS: We studied 547 238 women with a first and second pregnancy registered in the Medical Birth Registry of Norway, 1967-1998. The relative risk of pre-eclampsia in the second delivery according to time interval between deliveries was estimated as odds ratios (OR) in logistic regression models, controlling for changing paternity, maternal age and calendar time period in women with and without previous pre-eclampsia. RESULTS: A change of paternity for the second pregnancy was associated with a reduced risk of pre-eclampsia after controlling for the time since first delivery (adjusted OR = 0.80, 95% CI : 0.72-0.90), but the interaction between change in paternity and time between deliveries was significant only for women with no previous pre-eclampsia. The interaction between history of pre-eclampsia and time interval between the two deliveries was highly significant, and for women with no previous pre-eclampsia the risk of pre-eclampsia in second pregnancy increased with increasing time interval (for intervals longer than 15 years the adjusted OR was 2.11, 95% CI : 1.75-2.53). For women with previous pre-eclampsia the risk tended to decrease with increasing time interval between deliveries. CONCLUSIONS: The protective impact of a new father for the second pregnancy challenges the hypothesis of primipaternity, and implies that the increase in pre-eclampsia risk ascribed to new father by others is due to insufficient control for interpregnancy interval.

Adult↗

Estimation of cord blood erythropoietin in pre-eclampsia and eclampsia.

OBJECTIVE: The estimation of cord blood erythropoietin in subjects with pre-eclampsia and eclampsia. METHOD: Erythropoietin was measured, using ELISA, in the cord blood of infants born to 83 mothers with pre-eclampsia, and 7 with eclampsia. Another 90 subjects with no evidence of pre-eclampsia or eclampsia were taken as control subjects. Maternal parity, gestational age, blood pressures, 24-h urine protein and Apgar scores of the infants delivered were also noted. RESULT: Cord blood erythropoietin levels were statistically significantly higher (P<0.001) in infants born to mothers with pre-eclampsia and eclampsia. There was a significant positive correlation (P<0.01) between cord blood erythropoietin levels and maternal blood pressure (systolic and diastolic) and albuminuria. A negative correlation (P<0.01) was observed with the birth weights of infants. CONCLUSION: Pre-eclampsia and eclampsia are associated with higher levels of cord blood erythropoietin.

Adult↗

Radical-scavenging antioxidants in pre-eclampsia and eclampsia.

OBJECTIVE: Increased free-radical activity may be implicated in the pathogenesis of pre-eclampsia and knowledge of the response of the antioxidant systems is limited in pre-eclampsia and lacking in eclampsia. Accordingly, this study was initiated to assess total antioxidant status in pre-eclampsia and eclampsia. METHOD: Thirty-five patients with pre-eclampsia (20 mild and 15 severe), 10 patients with eclampsia and 20 normotensive women (controls) with singleton gestations in the third trimester participated in this study. Their freshly drawn blood was assayed for total antioxidant status colorimetrically using incubation mixture of ABTS, a peroxidase (metmyoglobin) and H2O2. In addition, serum fibronectin was determined by radial immunodiffusion. RESULT: Serum total antioxidant status levels in mild and severe pre-eclampsia and eclampsia were significantly lower than that of healthy pregnant women (controls). The mean percent decreases amounted to 22%, 40% and 59%, respectively, indicating the propensity of these patients to oxidative stress. CONCLUSION: These results demonstrate that radical-scavenging antioxidants are consumed by the increased free-radical activity in pre-eclampsia. The mechanisms by which free radicals are involved in endothelial dysfunction and renal injury are explained as evidenced by significant negative correlation of fibronectin and positive correlation of creatinine clearance with total antioxidants.

Adult↗

[Adolescent pregnancy and the development of pre-eclampsia--eclampsia].

The authors aim to investigate the incidence and severity of pre-eclampsia--eclampsia in adolescent pregnancies (age under 17 years) and to evaluate the outcome of pregnancy and birth in this patients. With this purpose we compare obstetric and neonatal results in 528 adolescents aged between 13 and 17 years with the results of a control group of mothers aged between 20 and 24 years. We used clinical observation, laboratory findings, instrumental diagnostics and scoring systems. Data were computer-processed. Pre-eclampsia and eclampsia was diagnosed in 17 cases (3.22%), with mild forms prevailing (2.46%). Eclampsia developed in 4 pregnant (0.76%)-an incidence differing from that cited in the literature. We are impressed by the outmost severity of eclampsia in the adolescents, with 1 case of fatal outcome. Seven of the newborns were retarded. The most frequent indications to caesarean section were placental ablation and foetal distress syndrome. Operative delivery was performed in 41.18%. One case of foetal antenatal death and one death in the early neonatal period were observed, both in mothers with eclampsia. The authors conclude that the incidence of pre-eclampsia and eclampsia in adolescents is lower than in general obstetric population, but if eclampsia develops, it is fulminant and in some cases is fatal for the mother or the foetus. This grave prognosis may be related to inappropriate antenatal care in this patient group.

Adolescent↗

Eclampsia. VII. Pregnancy outcome after eclampsia and long-term prognosis.

OBJECTIVES: Our goal was to report pregnancy outcome and long-term prognosis after eclampsia. STUDY DESIGN: Women whose pregnancies were managed at the E.H. Crump Women's Hospital between August 1977 and April 1989 were studied. A total of 223 women with eclampsia underwent follow-up for an average of 7.2 years. Thirteen had preexisting hypertension and 210 were normotensive (31 were multiparous and 179 were nulliparous). RESULTS: Among these women 23 who were multiparous and 159 who were nulliparous had 366 subsequent pregnancies: 22% of pregnancies were complicated by preeclampsia, 1.9% by eclampsia, and 2.5% by abruptio placentae; 2.7% resulted in perinatal death. Within the nulliparous group, women who had eclampsia before 37 weeks' gestation in the index pregnancy had significantly higher incidences of preeclampsia and poor perinatal outcome in subsequent pregnancies as compared with those who had eclampsia at greater than or equal to 37 weeks' gestation; the highest incidence of obstetric complications occurred in those having eclampsia at less than or equal to 30 weeks. Twenty of the 210 normotensive women (9.5%) had chronic hypertension on follow-up; the highest incidence (17.9%) being in those with eclampsia at less than or equal to 30 weeks and the lowest incidence (4.8%) in those having eclampsia at greater than or equal to 37 weeks. Women with eclampsia who had preeclampsia in subsequent pregnancies had a higher incidence of chronic hypertension as compared with those who were normotensive in subsequent pregnancies (25% vs 2%, p less than 0.0001). Long-term maternal complications included dialysis required in one patient and one case of cardiomyopathy in women with chronic hypertension; there was one maternal death in a women with chronic hypertension. None of the women had evidence of neurologic deficit or seizures during follow-up. CONCLUSIONS: These findings should be used in counseling women who have had eclampsia and are considering future pregnancies.

Adult↗

Family history of pre-eclampsia as a predictor for pre-eclampsia in primigravidas.

OBJECTIVE: To assess the clinical utility of knowledge of a family history of pre-eclampsia as a predictor for the development of pre-eclampsia in primigravid women. METHODS: 368 primigravid women were prospectively recruited from the outpatients department of an obstetric teaching hospital. Details of any family history of pre-eclampsia were obtained from the women and their subsequent obstetric outcomes were observed. RESULTS: Of 368 primigravid women, 34 (9.2%) developed pre-eclampsia. Eighteen (4.9%) women of the total group stated that they had a mother (12), sister (five) or both (one) who had had pre-eclampsia. Of these 18 women, five (27.8%) developed pre-eclampsia. Of the women who had no family history, 29 (8.3%) developed pre-eclampsia (relative risk, RR = 3.4; 95% CI, 1.5-7.6; P = 0.018). Four (22.2%) of the women with a positive family history developed severe pre-eclampsia compared to 18 (5.1%) with a negative family history (RR = 4.3; 95% CI, 1.6-11.5; P = 0.017). CONCLUSIONS: In a primigravida, a family history of pre-eclampsia is associated with a fourfold increased risk of severe pre-eclampsia. This clinical history identifies a group who warrant close clinical surveillance during pregnancy and who may be suitable for trials of prophylactic interventions.

Australia↗

Risk factors for abruptio placentae and eclampsia: analysis of 445 consecutively managed women with severe preeclampsia and eclampsia.

OBJECTIVE: Our purpose was to characterize the clinical presentation or laboratory variables predictive of either abruptio placentae or eclampsia in women with severe preeclampsia. STUDY DESIGN: Prospective collection of perinatal data from 445 consecutively managed women with severe preeclampsia and eclampsia. Univariate analysis was used to determine which of the independent variables were significantly different between the groups (abruptio placentae vs no abruptio placentae; eclampsia vs no eclampsia). Those with significant differences were then entered into multiple logistic regression analysis to determine those characteristics that were independently related to the outcome variable (abruptio placentae or eclampsia). Before multivariate analysis, the independent variables with an interval scale of measurement were converted to a dichotomous scale, with the receiver-operator characteristic curve used to determine a cutoff level. RESULTS: Univariate analysis revealed statistical significance for the following variables associated with eclampsia: uric acid concentration, > 8.1 mg/dL; proteinuria (>3+); headache; visual symptoms; deep tendon reflexes >3+; serum albumin concentration, <3 mg/dL; and serum creatinine concentration, >1.3 mg/dL. However, with subsequent multivariate analysis, only headache and deep tendon reflexes >3+ remained significant. Univariate analysis for variables associated with abruptio placentae revealed an association between bleeding and platelet count <60,000/mm3. There was no association between abruptio placentae and eclampsia and systolic, diastolic, or mean arterial pressure, quantitative proteinuria, epigastric pain, bleeding, gestational age at delivery, history of preeclampsia, or chronic hypertension. CONCLUSION: Quantitative proteinuria and degree of blood pressure elevation were not predictive of either abruptio placentae or eclampsia, as has previously been suggested. The greatest morbidity associated with eclampsia occurred in women with preterm gestations not receiving medical attention.

Abruptio Placentae↗

Maternal and fetal serum nitric oxide (NO) concentrations in normal pregnancy, pre-eclampsia and eclampsia.

OBJECTIVES: To measure the maternal and fetal serum concentrations of total nitrites and nitrates (as an index of nitric oxide production) in normal pregnancy, pre-eclampsia and eclampsia. DESIGN: Three groups of women were studied cross-sectionally: late pregnant women with pre-eclampsia and eclampsia (n=31); normal late pregnant women (n=32); and age-matched healthy non-pregnant women (n=21). Venous blood samples were collected from all women and both maternal and umbilical venous samples were collected from pregnant women. METHODS: Blood samples were assayed for nitric oxide (NO) production by Greiss reaction which measures the combined oxidation products of NO (total nitrites and nitrates). RESULTS: There was a significant increase in serum total nitrites and nitrates concentrations in normal pregnant women than in the serum of age-matched normal non-pregnant women (P<0.0001). Significantly higher total nitrites and nitrates levels were found in the maternal sera of the pre-eclamptic and eclamptic women compared with those of normal pregnant women (P<0.0001). Also, fetal blood levels of total nitrites and nitrates were significantly increased in pre-eclampsia and eclampsia compared with those of normal pregnancy (P<0.0001). CONCLUSIONS: (1) Serum nitric oxide (NO) production is increased in normal pregnancy than in the normal non-pregnancy. (2) Maternal and fetal serum NO levels are increased significantly in pre-eclampsia and eclampsia, which possibly represents a compensatory/protective mechanism to maintain blood flow and limit platelets aggregation in the fetal-maternal circulations. (3) The increase in NO production is directly related to the severity of pre-eclampsia; this would be of diagnostic significance for the prediction of the severity of this syndrome.

Adult↗

Clinical significance of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia.

The aim of this work was to determine the levels of urinary human tissue non-specific alkaline phosphatase (hTNAP) in pre-eclampsia and eclampsia in order to assess renal tubular damage. Urine samples were collected from 26 mild pre-eclamptic, 26 were pre-eclamptic, 20 eclamptic patients and 20 healthy pregnant women (controls) in their late third trimester. Urinary hTNAP/creatinine (hTNAP/cr) in severe pre-eclampsia and eclampsia were significantly higher than in controls. Urinary hTNAP/cr was increased in 23%, 77% and 90% of cases of mild pre-eclampsia, severe pre-eclampsia and eclampsia, respectively, indicating that the increase correlates with the severity of the disease. Marked elevation or urinary hTNAP/cr was also associated with bad fetal outcome. These results provide additional evidence for renal tubular damage in pre-eclampsia and eclampsia.

Adult↗

Maternal transcranial Doppler in pre-eclampsia and eclampsia.

Pre-eclampsia affects 3-7% of women and is associated with significant maternal and perinatal morbidity and mortality. Transcranial Doppler (TCD) has been used in pre-eclampsia/eclampsia to evaluate non-invasively the cerebrovascular hemodynamics in the maternal middle cerebral artery. TCD has demonstrated in pre-eclamptic women maternal cerebral vasospasm, which does not correlate with mean arterial pressure assessed simultaneously. Estimated cerebral perfusion pressure, assessed using a modified formula, has been shown to be increased in women with severe and non-severe pre-eclampsia. However, in severe pre-eclampsia, elevated cerebral perfusion pressure is counterbalanced by increases in cerebrovascular resistance and cerebral blood flow is unaffected. In eclampsia a significant fall in cerebral vascular resistance occurs which, in the presence of increases in cerebral perfusion pressure, leads to hyperperfusion. Cerebral vascular changes to date have not been sensitive enough to predict the development of pre-eclampsia or eclampsia. Longitudinal studies with the aim of predicting the onset of pre-eclampsia and to assess the effects of various drugs on the maternal cerebral circulation need to be designed.

Blood Flow Velocity↗