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Different interventions have been proposed for the management of the third stage of labour. Active management includes a group of interventions such as administration of a prophylactic uterotonic at or after delivery of the baby, early cord clamping and cutting and controlled cord traction to deliver the placenta. On the other hand, expectant management means waiting for the signs of separation of the placenta and its spontaneous delivery, and late cord clamping, which is clamping the umbilical cord when cord pulsation has ceased (hands-off approach). These two approaches Active versus expectant management for the third stage of labour were compared in the review.

One of the components of the active management approach is the administration of a prophylactic uterotonic at or after delivery of the baby. The use of prophylactic oxytocin, regardless of other aspects of third stage management, was evaluated in the review entitled Prophylactic use of oxytocin in the third stage of labour. Prostaglandins compared either with placebo/no treatment or with another uterotonic were evaluated in the review entitled Prostaglandins for prevention of postpartum haemorrhage. Another comparison was between Syntometrine® (oxytocin + ergot) and oxytocin) alone.

Active management of the third stage of labour was evaluated in five trials that included nearly 6500 women in maternity hospitals. Active management was associated with a lower incidence of blood loss, postpartum haemorrhage (PPH), need for blood transfusion, prolonged third stage of labour and maternal anaemia, but it was also associated with an increased risk of maternal nausea, vomiting and raised blood pressure (when ergot preparations were used). There were no apparent adverse effects on the baby.

Prophylactic use of oxytocin in the third stage of labour review includes comparisons of: (i) oxytocin versus placebo/no uterotonics; (ii) oxytocin versus ergot alkaloids (ergometrine); and (iii) oxytocin plus ergometrine (Syntometrine®) versus ergometrine alone in the management of the third stage of labour.

The use of oxytocin halves the risk of PPH of >500 ml of blood loss and decreases the risk of severe PPH (blood loss >1000 ml) compared with placebo/no uterotonics. These results are consistent even if oxytocin is used as part of the active management approach or on its own without other components of active management. A significant reduction in the use of additional uterotonics was also found. No differences were seen in the need for blood transfusion or manual removal of the placenta in the pre-specified subgroups.

Sufficient information is not available on other outcomes and side-effects, as well as on the effects on the baby.

Prostaglandins for prevention of postpartum haemorrhage. Prophylactic use of prostaglandins was compared with either no uterotonics/placebo or with other uterotonics for the management of the third stage of labour. Prostaglandins included oral and rectal misoprostol and intramuscular prostaglandins (PGF2alpha and PGE2). All of these drugs were analysed separately, while oxytocin, Syntometrine® and ergometrine were grouped as “conventional injectable uterotonics”. The authors identified severe PPH (blood loss > 1000 ml) and the use of additional uterotonics as the most clinically relevant outcomes.

Results of studies comparing oral or rectal misoprostol with no uterotonic/placebo are equivocal and come from small trials showing effects in different directions. Side-effects were more common, as expected, and consistent across trials in the misoprostol group.

The rate of severe PPH and the use of additional uterotonics were statistically significantly higher with 600 µg of misoprostol compared with conventional injectable uterotonics. These results are dominated by the large WHO trial but other trials showed the same trend (1). No significant differences were found with lower doses (i.e. 500 µg or 400 µg) in severe PPH. Possible reasons could be related to the fewer numbers of women studied. The use of additional uterotonics was also significantly higher with 400 µg of misoprostol compared with conventional injectable uterotonics.

Compared with other uterotonics, intramuscular prostaglandins were associated with reduced blood loss. Other outcomes occurred infrequently for any reliable conclusions to be drawn.

Prostaglandin-related side-effects—especially shivering, pyrexia, nausea, vomiting and diarrhoea—were frequent and consistent across trials.

Prophylactic Syntometrine® versus oxytocin for delivery of the placenta.

The use of Syntometrine®, as part of the active management of the third stage of labour, is associated with a significant reduction in the incidence of PPH (blood loss >500 ml) compared with oxytocin alone, irrespective of the dose (5 IU or 10 IU). No difference was observed in severe PPH (blood loss >1000 ml). However, the addition of ergometrine increases the incidence of high blood pressure and vomiting, and these harmful effects should be taken into account in determining the best therapy. A useful tool to assess the practical clinical benefits of a therapy is the Number-Needed-to-Treat (NNT) (2). The main results of the review can be summarized as follows: when 100 women are treated with oxytocin plus ergometrine rather than oxytocin alone, 3 additional episodes of blood loss >500 ml will be prevented, but at the same time, 1 additional case of high blood pressure and 10 additional cases of vomiting, will be observed.

All adequately controlled trials that could be identified have been included in these reviews. Trials were evaluated for methodological quality and appropriateness of inclusion. The methods of the reviews are generally sound. The reviewers conducted some sub-group analyses to identify if certain aspects of management (such as components of active management), doses of uterotonics or risk profile of women affect the results.

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