Jack Moodley

Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial

BACKGROUND Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate. METHODS Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat. FINDINGS Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89). INTERPRETATION Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.ARTICLES Summary Background Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.

Intensive care unit morbidity and mortality from eclampsia: an evaluation of the Acute Physiology and Chronic Health Evaluation II score and the Glasgow Coma Scale score.

Objective: To determine the maternal morbidity and mortality in patients with eclampsia admitted to an intensive care unit (ICU), and to establish the efficacy of the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the organ system failure score as defined by Knaus, and the Glasgow Coma Scale (GCS) score in predicting outcome. Design: Retrospective analysis of a 3.5‐yr period. Setting: Surgical ICU in a university hospital. Patients: A total of 105 patients who were admitted with a diagnosis of eclampsia were studied. Interventions: None. Measurements and Main Results: The data captured included the reason for admission, maternal age, gestational age, parity, number of seizures, duration of ICU stay, anticonvulsant therapy, drug therapy, GCS score, APACHE II score, and the occurrence of organ failure. Of the 126 patients with eclampsia who were admitted to the ICU, records of 105 patients (83%) were found. The overall mortality was 10.5% (n = 11). The mean age, gestation, parity, number of preadmission seizures, and duration of stay were similar in survivors and nonsurvivors. Although the APACHE II score was significantly higher in nonsurvivors, multiple logistic regression analysis suggested that the goodness‐of‐fit scores for GCS and APACHE II were similar (38.29 vs. 38.01). The GCS scores of survivors were significantly higher than those of nonsurvivors (10.61 vs. 5.0; p < .001). Respiratory failure was the most common organ failure in both groups. The mean number of organ failures was higher in nonsurvivors compared with survivors (2.9 vs. 1.3; p < .001). An occurrence of more than two organ failures that persisted for >48 hrs was invariably associated with a fatal outcome. Anticonvulsant therapy consisted of magnesium sulfate or phenytoin and a midazolam infusion. Only one patient (0.9%) had a seizure, and this occurred en route to the ICU. No seizures occurred after admission to the ICU. Conclusions: The organ system failure score and the GCS score are good predictors of outcome in eclampsia. Apart from the GCS score, other variables in the APACHE II score are not valuable for outcome prediction. The low GCS score in nonsurvivors suggests that closer attention to the neurologic management may be beneficial. A prospective study is indicated to validate these findings.

HIV and maternal mortality: turning the tide

This article discusses the risks associated with pregnancy-related death in women infected with HIV in comparison with that in non-infected women.

Severe obstetric morbidity.

Obstetric morbidity is an important marker of the quality of obstetric care. This review explores the definition, incidence and significance of obstetric morbidity. Some topical issues related to obstetric morbidity are discussed. In addition, the importance of long-term morbidity and violence against women is highlighted.

Evaluation of standard and modified severity of illness scores in the obstetric patient

PURPOSE To test discrimination and calibration of APACHE-II and SAPS-II risk prediction scores in a cohort of obstetric patients, and to evaluate the effect of modifying these scores for the physiological changes in pregnancy. MATERIALS AND METHODS A retrospective review of obstetric patients, 12 weeks gestation to 48 hours postpartum, admitted to the ICU for more than 24 hours. APACHE-II and SAPS-II, and versions modified for the physiological changes of pregnancy, were evaluated by receiver operating characteristic (ROC) curves and standardized mortality ratios (SMR). Multivariable analysis identified other parameters associated with mortality. RESULTS Data were obtained from 332 patients from 5 countries, with a mortality rate of 12%. Mean (± SD) APACHE-II score was 16.8 ± 6.1 and SAPS-II score 26.5 ± 15.8. Good discrimination was demonstrated with area under the ROC curves of 0.82 and 0.78 respectively, with no improvement after modification for altered maternal physiology. APACHE-II overestimated mortality, with an SMR of 0.43 (0.52 after including diagnostic weighting) compared with 0.89 for SAPS-II. Bilirubin, albumin and Glasgow Coma Scale were independently associated with mortality. CONCLUSION APACHE-II and SAPS-II are good discriminators of illness severity and may be valuable for comparing obstetric cohorts, but APACHE-II significantly over-estimates mortality.

A Review of the Management of Eclampsia: Practical Issues

We reviewed 90 cases of eclampsia, an obstetric emergency associated with high blood pressure and convulsions, treated in two hospitals in Durban, South Africa. We present a protocol for the management of eclampsia based on this review and extensive clinical experience on this subject, which includes hemodynamic stabilization of the mother, prevention of recurrent convulsions, prompt delivery, and intensive monitoring in the immediate post-partum period.

COMPARISON OF THE EFFICACY OF CONTINUOUS FUROSEMIDE AND LOW-DOSE DOPAMINE INFUSION IN PREECLAMPSIA/ECLAMPSIA-RELATED OLIGURIA IN THE IMMEDIATE POSTPARTUM PERIOD

Aim: To compare the efficacy of furosemide infusion with that of low-dose dopamine infusion in improving urine output and subsequent renal function in preeclamptic/eclamptic patients with oliguria in the immediate postpartum period. Design: Prospective randomised single blind clinical trial. Setting: Obstetric High Care Unit of King Edward VIII Hospital, a large referral tertiary hospital. Method: Eighty postpartum patients with severe preeclampsia/eclampsia with oliguria were enrolled. Hypovolaemia was corrected under central venous pressure (CVP) monitoring and urine output monitored for 4 hr. Patients who remained oliguric were randomly assigned to a continuous infusion of low-dose dopamine (3 μg/kg/min), or furosemide 5 mg/hr infusion, for 12 hr. In patients with no response after 12 hr, the drugs were switched and continued for a further 12 hr. A subgroup of patients who responded 4 hr after correction of hypovolaemia was observed for 12 hr. The primary outcome measured involved the comparison in urine output between the different drug regimes and the number of patients requiring haemodialysis. Secondary outcome measures involved assessment of serum urea and creatinine values in the two treatment groups. Results: Of the 80 patients enrolled, 20 improved their urine outputs within the 4-hr observation period. Sixty patients were randomised to furosemide or low-dose dopamine infusion. There was no statistical significant difference in the mean hourly urine output, rate of change in urine output over time and the mean urea or creatinine levels between the treatment groups. Ten percent of patients that failed on furosemide primarily, and 8.5% of patients that failed on initial low-dose dopamine, received haemodialysis. The difference in demographic and clinic data between these groups was not statistically significant. Conclusion: Administration of continuous infusion of furosemide showed comparable efficacy to low-dose dopamine infusion in ameliorating oliguria in severe preeclampsia/eclampsia post delivery; there was no difference in the percentage of patients that required haemodialysis in either group.

Maternal death and caesarean section in South Africa: Results from the 2011 - 2013 Saving Mothers Report of the National Committee for Confidential Enquiries into Maternal Deaths

BACKGROUND In the latest (2011-2013) Saving Mothers report, the National Committee for Confidential Enquiries into Maternal Deaths in South Africa (SA) (NCCEMD) highlights the large number of maternal deaths associated with caesarean section (CS). The risk of a woman dying as a result of CS during the past triennium was almost three times that for vaginal delivery. Of all the mothers who died during or after a CS, 3.4% died during the procedure and 14.5% from haemorrhage afterwards. Including all cases of death from obstetric haemorrhage where a CS was done, there were 5.5 deaths from haemorrhage for every 10,000 CSs performed. OBJECTIVE To scrutinise the contribution or effect of the surgical procedure on the ultimate cause of death by a cross-cutting analysis of the 2011-2013 national data. METHODS Data from the 2011-2013 triennial review were entered into an Excel database and analysed on a national and provincial basis. RESULTS There were 1,243 maternal deaths where a CS was the mode of delivery and 1 471 deaths after vaginal delivery. More mothers died as a result of CS in the provinces where there is a low overall CS rate. The following CS categories were identified as specific problems: bleeding during or after CS, pre-eclampsia and eclampsia, anaesthesia-related deaths, pregnancy-related sepsis and acute collapse and embolism. CONCLUSION This is an area of concern, and a concentrated effort should be done to make CS in SA safer. Several recommendations are

The role of angiogenic, anti-angiogenic and vasoactive factors in pre-eclamptic African women: early- versus late-onset pre-eclampsia

Abstract The pathogenesis and aetiology of pre-eclampsia (PE) is still unclear. We investigated the role of angiogenic, anti-angiogenic and vasoactive factors in black South African women with early- and late-onset PE. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), soluble vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) levels were determined using the ELISA technique, and placental mRNA expression levels of sFlt-1, VEGF, PlGF and AT1 receptors were determined using real-time PCR. Serum sFlt-1 levels were significantly elevated and PlGF significantly reduced in early-onset PE compared to the normotensive group. Placental VEGF mRNA expression levels were significantly reduced in the late-onset preeclamptic group compared with the normotensives. The placental mRNA expression of AT1 receptor in the late-onset pre-eclamptic group was relatively raised compared to the normotensives, suggesting hypersensitivity to pressor agents. We believe that the excess of serum sFlt-1 and reduced VEGF and PlGF levels favour an anti-angiogenic state and endothelial dysfunction leading to PE, and that the aetiology and pathogenesis of early- and late-onset PE differ.

Combined oral contraceptives and cervical cancer

Purpose of review The issue of whether there might be an increased risk of cervical cancer associated with the use of oral contraceptives has been debated for decades. Early studies found a modest association with long-term use. A literature review was performed over the past 3 years, to establish whether there is any new evidence linking cervical cancer with the use of oral contraceptives. Recent findings A new analysis from eight studies conducted by the International Agency for Research on Cancer and a systematic review of cervical cancer and the use of hormonal contraceptives are two recent major epidemiological links strongly suggesting the increased risk of cervical cancer (up to twofold), but only for women who were both long-term users (5 years or more) and who had persistent human papilloma virus infections of the cervix. Summary These findings seem biologically plausible, but weighing the various risks and benefits, the World Health Organization does not recommend any change in oral contraceptive use or practice.