W J Prendiville’s research while affiliated with Coombe Women & Infants University Hospital and other places

Background: Postpartum haemorrhage is a leading cause of maternal morbidity and mortality. Active management of the third stage of labour, including use of a uterotonic agent, has been shown to reduce blood loss. Misoprostol (a prostaglandin E1 analogue) has been suggested for this purpose because it has strong uterotonic effects, can be given orally, is inexpensive, and does not need refrigeration for storage. We did a multicentre, double-blind, randomised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour. Methods: In hospitals in Argentina, China, Egypt, Ireland, Nigeria, South Africa, Switzerland, Thailand, and Vietnam, we randomly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly, according to routine practice, plus corresponding identical placebos. The medications were administered immediately after delivery as part of the active management of the third stage of labour. The primary outcomes were measured postpartum blood loss of 1000 mL or more, and the use of additional uterotonics without an unacceptable level of side-effects. We chose an upper limit of a 35% increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence, which was assessed by the confidence interval of the relative risk. Analysis was by intention to treat. Findings: 9264 women were assigned misoprostol and 9266 oxytocin. 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded. 366 (4%) of women on misoprostol had a measured blood loss of 1000 mL or more, compared with 263 (3%) of those on oxytocin (relative risk 1.39 [95% CI 1.19-1.63], p<0.0001). 1398 (15%) women in the misoprostol group and 1002 (11%) in the oxytocin group required additional uterotonics (1.40 [1.29-1.51], p<0.0001). Misoprostol use was also associated with a significantly higher incidence of shivering (3.48 [3.15-3.84]) and raised body temperature (7.17 [5.67-9.07]) in the first hour after delivery. Interpretation: 10 IU oxytocin (intravenous or intramuscular) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital settings where active management is the norm.

Many maternal deaths across the world result from complications of the third stage of labour (when the placenta is delivered). OBJECTIVES: To examine the effect of oxytocin given prophylactically in the third stage of labour on maternal and neonatal outcomes. SEARCH STRATEGY: Relevant trials were identified in the Cochrane Collaboration Controlled Trials Register and the Pregnancy and Childbirth Review Group's Specialised Register of Controlled Trials. Date of last search: May 2001. SELECTION CRITERIA: All acceptably randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where oxytocin was given prophylactically for the third stage of labour. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for relevance and methodological quality, and extracted data. Analysis was by intention to treat. Subgroup analyses were based on extent of selection bias, oxytocin in the context of active or expectant management of the third stage, and timing of administration. Results are presented as relative risks, and weighted mean difference, both with 95% confidence intervals using a fixed effects model. MAIN RESULTS: In seven trials involving over 3000 women in hospital and/or developed country settings, prophylactic oxytocin showed benefits (reduced blood loss (relative risk (RR) for blood loss > 500 ml 0.50; 95% confidence interval (CI) 0.43, 0.59) and need for therapeutic oxytocics (RR 0.50; 95% CI 0.39, 0.64).) compared to no uterotonics, although there was a non-significant trend towards more manual removal of the placenta (RR 1.17; 95% CI 0.79, 1.73) which was most marked in the expectant management subgroup, and blood transfusions (RR 1.30; 95% CI 0.50, 3.39) in the trials with more manual removals of the placenta). In six trials involving over 2800 women, there was little evidence of differential effects for oxytocin versus ergot alkaloids, except ergot alkaloids are associated with more manual removals of the placenta (RR 0.57; 95% CI 0.41, 0.79), and with the suggestion of more raised blood pressure (RR 0.53; 95% CI 0.19, 1.58) than with oxytocin. In five trials involving over 2800 women, there was little evidence of a synergistic effects of adding oxytocin to ergometrine versus ergometrine alone. For all other outcomes in the comparisons either there are no data or the number of adverse events is very small, and so definite conclusions cannot be drawn. REVIEWER'S CONCLUSIONS: There are strong suggestions of benefit for oxytocin in terms of postpartum haemorrhage, and the need for therapeutic oxytocics, but without sufficient information about other outcomes and side-effects it is difficult to be confident about the trade-offs for these benefits, especially if the risk of manual removal of the placenta may be increased. There seems little evidence in favour of ergot alkaloids alone compared to either oxytocin alone, or to Syntometrine, but the data are sparse. More trials are needed in domiciliary deliveries in developing countries, which shoulder most of the burden of third stage complications.

Many maternal deaths across the world result from complications of the third stage of labour (when the placenta is delivered). To examine the effect of oxytocin given prophylactically in the third stage of labour on maternal and neonatal outcomes. Relevant trials were identified in the Cochrane Collaboration Controlled Trials Register and the Pregnancy and Childbirth Review Group's Specialised Register of Controlled Trials. Date of last search: May 2001. All acceptably randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where oxytocin was given prophylactically for the third stage of labour. Two reviewers independently assessed studies for relevance and methodological quality, and extracted data. Analysis was by intention to treat. Subgroup analyses were based on extent of selection bias, oxytocin in the context of active or expectant management of the third stage, and timing of administration. Results are presented as relative risks, and weighted mean difference, both with 95% confidence intervals using a fixed effects model. In seven trials involving over 3000 women in hospital and/or developed country settings, prophylactic oxytocin showed benefits (reduced blood loss (relative risk (RR) for blood loss > 500 ml 0.50; 95% confidence interval (CI) 0.43, 0.59) and need for therapeutic oxytocics (RR 0.50; 95% CI 0.39, 0.64).) compared to no uterotonics, although there was a non-significant trend towards more manual removal of the placenta (RR 1.17; 95% CI 0.79, 1.73) which was most marked in the expectant management subgroup, and blood transfusions (RR 1.30; 95% CI 0.50, 3.39) in the trials with more manual removals of the placenta). In six trials involving over 2800 women, there was little evidence of differential effects for oxytocin versus ergot alkaloids, except ergot alkaloids are associated with more manual removals of the placenta (RR 0.57; 95% CI 0.41, 0.79), and with the suggestion of more raised blood pressure (RR 0.53; 95% CI 0.19, 1.58) than with oxytocin. In five trials involving over 2800 women, there was little evidence of a synergistic effects of adding oxytocin to ergometrine versus ergometrine alone. For all other outcomes in the comparisons either there are no data or the number of adverse events is very small, and so definite conclusions cannot be drawn. There are strong suggestions of benefit for oxytocin in terms of postpartum haemorrhage, and the need for therapeutic oxytocics, but without sufficient information about other outcomes and side-effects it is difficult to be confident about the trade-offs for these benefits, especially if the risk of manual removal of the placenta may be increased. There seems little evidence in favour of ergot alkaloids alone compared to either oxytocin alone, or to Syntometrine, but the data are sparse. More trials are needed in domiciliary deliveries in developing countries, which shoulder most of the burden of third stage complications.

The routine prophylactic administration of an oxytocic agent is an integral part of active management of the third stage of labour. These agents help prevent postpartum haemorrhage. The objective of this review was to assess the effects of ergometrine-oxytocin (syntometrine) with oxytocin alone in reducing the risk of postpartum haemorrhage (blood loss of equal to or greater than 500 millilitres) and other maternal and neonatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group trials register. Trials of oxytocic drugs (syntometrine or oxytocin) in women having the third stage of labour managed actively. Eligibility, trial quality assessment and data extraction were done independently by three reviewers. Study authors were contacted for additional information. Six trials were included. Compared with oxytocin, ergometrine-oxytocin (syntometrine) was associated with a small reduction in the risk of postpartum haemorrhage (odds ratio 0.74, 95% confidence interval 0.65 to 0.85). This advantage was smaller but still significant when 10 international units of oxytocin was used. There was no difference seen between the groups using either five or 10 international units for blood loss equal to or greater than 1000 millilitres. Adverse effects of vomiting and hypertension were associated with the use of ergometrine-oxytocin. No significant differences were found in other maternal or neonatal outcomes. The use of the combination preparation syntometrine (oxytocin and ergometrine) as part of the routine active management of the third stage of labour appears to be associated with a statistically significant reduction in the risk of postpartum haemorrhage when compared to oxytocin where blood loss is less than 1000ml. No difference was seen between the groups using either five or 10 international units for blood loss equal to or greater than 1000 millilitres. This needs to be weighed against the more common adverse effects associated with the use of syntometrine.

Active management of the third stage of labour reduces blood loss and haemorrhage after birth. The third stage of labour is that period from the birth of the baby until delivery of the placenta. Uterine muscles contract to stop maternal blood loss once the placenta separates. If this process does not work efficiently, the mother can haemorrhage. The review of trials found that active management of the third stage of labour, including drug administration, early cord clamping and controlled cord traction was more effective than expectant management, using none of these. Some of the drugs can cause side effects of nausea and vomiting. No effects were apparent for the baby.

This paper concerns itself with the use of oxytocic therapy as part of the routine management of the third stage of labour. It attempts to answer three different questions: (1) do oxytocics reduce the risk of post partum haemorrhage (PPH) when used during the routine management of the third stage of labour? (2) does the clinical package of active management reduce the risk of PPH (3) which is the best oxytocic to use during routine active management of the third stage? It attempts to answer these questions by presenting the evidence from formal meta-analytical reviews of the randomised controlled trials of the pertinent intervention and by presenting the results of the two trials that were undertaken as a result of the hypotheses which were generated from the formal reviews.

To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. Double blind, randomised controlled trial. Two metropolitan teaching hospitals in Perth, Western Australia. All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. Postpartum haemorrhage, nausea, vomiting, and increased blood pressure. 3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure. There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose-response for oxytocin may be warranted.

The paper describes the technique of 'LLETZ' (large loop excision of the transformation zone), a new method of management for women with an abnormal cervical smear which offers the advantages of conization with those of local destruction. A large loop of thin wire forms a diathermy electrode that allows deep excision of the transformation zone with minimal tissue damage. The tissue removed can be examined histologically. The technique was used to investigate and treat 111 women with abnormal smears referred to the Bristol Royal Infirmary during 1986. Microinvasive disease was revealed in one woman where it was not suspected by cytology or colposcopic examination. Of 102 women followed up for at least 1 year by cytology, colposcopy and, where appropriate, histology, two women were found to have residual/recurrent cervical intraepithelial neoplasia.

Mothers and midwives who had participated in the Bristol randomized controlled trial of active versus physiologic management of the Third Stage of Labor were asked for their views. One hundred ninety-one mothers (11% of the total randomized) and 49 midwives completed self-administered questionnaires. Both mothers and midwives commented adversely about the length of the third stage under physiologic management. In general, their views were in accord with the conclusions of the main trial (based on clinical data, including maternal blood loss, length of third stage, need for therapeutic oxytocic agents, and specified neonatal morbidity) in favor of continuing with the current practice of active management.