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Timing of prophylactic uterotonics for the third stage of labour after vaginal birth

RHL Commentary by Qureshi Z and Lubano K

1. INTRODUCTION

Postpartum hemorrhage (PPH) is a major contributor to maternal mortality and morbidity. In Africa, one third of maternal mortality is attributed to PPH (1). Active management of the third stage of labour (AMTSL) is an effective intervention to prevent PPH resulting from uterine atony. AMTSL comprises the following series of interventions: (i) administration of a prophylactic uterotonic; (ii) controlled cord traction; and (iii) uterine massage after delivery of the placenta. AMTSL has been shown to reduce the incidence of severe PPH by approximately 60%–70% (2, 3, 4).

It has been recommended that administration of the prophylactic uterotonic should take place within 1 minute of delivery of the baby (2). However, in practice, in most busy maternity units, this is often not feasible because most deliveries are attended by only one health-care professional. The timing of oxytocin administration has implications for maternal blood loss, neonatal blood volume or haemodynamics, and health-care resources needed at the time of birth. This Cochrane review was conducted to evaluate the effects of the timing of administration of prophylactic uterotonics (before versus after delivery of the placenta) on outcomes related to the third stage of labour (5).

2. METHODS OF THE REVIEW

The authors planned to include randomized controlled trials that had compared administration of a uterotonic before and after placental delivery for the management of the third stage of labour. The methods used to search for trials and to evaluate trial quality and analyse the data were adequate. The primary maternal outcome assessed was PPH (estimated or measured blood loss greater than 500 ml). Secondary maternal outcomes ranged from severe PPH (estimated or measured blood loss greater than 1000 ml) to severe maternal morbidity and death. There were also five neonatal outcomes.

3. RESULTS OF THE REVIEW

Three hospital-based trials with 1667 participants met the inclusion criteria. Two had been conducted in the USA and one in the Philippines. The dose and route of administration of oxytocin varied in the three trials. In one of them, 20 IU of oxytocin (administered as a continuous intravenous infusion) was compared in women randomly allocated to receive a uterotonic after the second (delivery of anterior shoulder) or the third stage of labour. In the second trial, 20 IU of oxytocin (in a 500 ml crystalloid intravenous bolus) was given intravenously at delivery of the anterior shoulder or after delivery of the placenta. In the third trial, 10 IU of oxytocin was given intramuscularly at delivery of the anterior shoulder or immediately after delivery of the placenta.

Administration of oxytocin before and after the expulsion of the placenta did not significantly influence: (i) the incidence of PPH [risk ratio (RR) 0.81, 95% confidence interval (CI) 0.62–1.04]; (ii) the incidence of retained placenta (RR 1.54, 95% CI 0.76–3.11); (iii) the duration (in minutes) of the third stage of labour [mean difference (MD) −0.30, 95% CI −0.95 to 0.36]; (iv) postpartum blood loss (ml) (MD 22.32, 95% CI −58.21 to 102.86); (v) changes in haemoglobin concentration (g/dl) (MD 0.06, 95% CI −0.60 to 0.72); (vi) blood transfusion (RR 0.79, 95% CI 0.23–2.73); (vii) the use of additional uterotonics (RR 1.10, 95% CI 0.80–1.52); (viii) the incidence of maternal hypotension (RR 2.48, 95% CI 0.23–26.70; one trial, 130 women); and (ix) the incidence of severe PPH (RR 0.98, 95% CI 0.48–1.98; one trial, 130 women). No data on other maternal or neonatal outcome measures were available

4. DISCUSSION

Administration of oxytocin before or after placental expulsion does not significantly influence the major clinical outcomes such as the incidence of PPH. This is an important finding because a previous (now withdrawn) systematic reviews (3) had found a trend towards an increased rate of placental retention following active management of the third stage of labour in which uterotonic drugs had been administered prior to or at the beginning of the third stage of labour in women at low risk of haemorrhage. The administration of oxytocin after expulsion of the placenta has the advantage of reducing the risk of over-infusion of placental blood to the baby. There is already evidence to show the beneficial effects of delaying cord clamping and of cord drainage (6, 7). Delaying the administration of oxytocin until after delivery of the placenta would add to these benefits and help in normalizing the birth process, while preserving the known prophylactic effects of such interventions. This review also found that administration of oxytocin before or after the delivery of the placenta had no significant effect on the duration of the third stage of labour.

4.1. APPLICABILITY OF THE RESULTS

The three trials included in this review were conducted in the USA and the Philippines. There is no reason to believe that the results would be different in other regions of the world. However, the findings of the review need to be interpreted with caution owing to the relatively small sample sizes in the included studies. Administering a uterotonic drug after delivery of the placenta reduces any potential risk to the baby from excessive transfer of placental blood to the baby during delayed cord clamping. In under-resourced settings it is recommend that, if it is not already the routine practice, the option of administering a uterotonic after delivery of the placenta may be adopted.

4.2. IMPLEMENTATION OF THE INTERVENTION

In settings where AMTSL using oxytocin is the norm, there is no evidence from this review to recommend a change in practice. In health-care facilities considering the introduction of AMTSL, education and training of health-care staff would be necessary to ensure that they have the skills to implement the policy. The capacity to use injectable uterotonics needs to be available for emergencies related to PPH. The feasibility of using an injectable uterotonic must take into account the availability of trained health-care personnel and health-care facilities for the administration of uterotonics. The cost of oxytocin and syringes is relatively low. WHO recommends a 10 IU dose (given intramuscularly or intravenously) of oxytocin in AMTSL (8).

4.3. IMPLICATIONS FOR RESEARCH

All three included studies were of a high quality in terms of methodological rigour, but the number of available studies in this area is limited. The lack of significant results in this review may well be due to the small number of available studies and small sample sizes. Also, the majority of the participants in the studies included in this review received intravenous infusion of oxytocin. The effect of administration of intramuscular uterotonic drugs (the WHO recommended dose of 10 IU of oxytocin) before and after delivery of the placenta should be investigated. In addition, none of the available studies provided information on neonatal outcomes, which should also be investigated in well designed large multi-centre studies in both under-resourced and well-resourced settings.

References

• Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. The Lancet 2006;367:1066-1074.
• Prevention and treatment of post-partum haemorrhage: new advances for low resource settings. Joint statement. International Confederation of Midwives (ICM) International Federation of Gynaecology and Obstetrics (FIGO). Available at: http://www.pphprevention.org/files/FIGO-ICM_Statement_November2006_Final.pdf
• Prendiville WJP, Elbourne D, McDonald SJ. Active versus expectant management in the third stage of labour. Cochrane Database of Systematic Reviews 2009;Issue 3. Art. No.: CD000007; DOI: 10.1002/14651858.CD000007.pub2 (review withdrawn).
• WHO recommendations for the prevention of postpartum haemorrhage. Geneva: World Health Organization; 2007. http://whqlibdoc.who.int/hq/2007/WHO_MPS_07.06_eng.pdf
• Soltani H, Hutchon DR, Poulose TA. Timing of prophylactic uterotonics for the third stage of labour after vaginal birth. Cochrane Database of Systematic Reviews 2010;Issue 8. Art. No.: CD006173; DOI: 10.1002/14651858.CD006173.pub2.
• McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database of Systematic Reviews 2008;Issue 2. Art. No.: CD004074; DOI: 10.1002/14651858.CD004074.pub2.
• Soltani H, Dickinson F, Symonds IM. Placental cord drainage after spontaneous vaginal delivery as part of the management of the third stage of labour. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD004665. DOI: 10.1002/14651858.CD004665.pub2.
• WHO recommendations for the prevention of postpartum haemorrhage. Geneva: World Health Organization; 2007.

This document should be cited as: Qureshi Z and Lubano K. Uterine Timing of prophylactic uterotonics for the third stage of labour after vaginal birth: RHL commentary (last revised: 1 July 2011). The WHO Reproductive Health Library; Geneva: World Health Organization.