Prophylactic interventions after delivery of placenta for reducing bleeding during the postnatal period

Haemorrhage following childbirth (postpartum haemorrhage) is a major cause of maternal death and health problems in resource-poor settings in both low- and high-income countries. Postpartum haemorrhage is defined as blood loss from the genital tract of more than 500 mL, generally occurring within the first 24 hours after delivering the placenta and occasionally between 24 hours and six to 12 weeks. Possible causes are the uterus (womb) failing to contract after delivery (uterine atony), a retained placenta, inverted or ruptured uterus, and cervical, vaginal, or perineal lacerations. To address these issues, the joint policy statements between the International Confederation of Midwives, the International Federation of Gynecology and Obstetrics, and the World Health Organization recommend 'active management of third stage of labour', which includes the administration of a uterotonic drug (intravenous oxytocin), just before or just after delivery in order to help the uterine muscles to contract. The use of oral uterotonic drugs such as methylergometrine for the prevention of postpartum haemorrhage after delivery of the placenta is not recommended in the joint policy statements. Yet orally delivered uterotonic drugs, such as ergot alkaloids (including methylergometrine), herbal therapies, or homeopathic remedies are easy-to-administer agents that may be considered as possible alternatives after delivery of the placenta in developing countries, as in Japan. We set out to determine whether such agents are effective in preventing haemorrhage after childbirth. We found a total of five randomised clinical trials (involving 1466 women). In three of the trials (involving 1268 women), oral methylergometrine was compared with placebo (two trials) or the Japanese traditional herbal medicine Kyuki-chouketsu-in (one trial). The other two trials (involving 198 women) did not report information on relevant outcomes of interest for this review. Overall, there was no clear evidence that prophylactic oral methylergometrine was effective in reducing haemorrhage after childbirth. The trials were not of good quality and adverse events were not well-reported. We did not find any completed trials looking at the effectiveness of homeopathic remedies in reducing haemorrhage after childbirth. The effectiveness of such remedies warrants further investigation.

Authors' conclusions: 

There was insufficient evidence to support the use of prophylactic oral methylergometrine given after delivery of the placenta for the prevention of PPH. Additionally, the effectiveness of prophylactic use of herbal medicine or homeopathic remedies for PPH is still unclear as we could not find any clear evidence. Trials to assess the effectiveness of herbal medicines and homeopathic remedies in preventing PPH are warranted.

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Background: 

There are several Cochrane systematic reviews looking at postpartum haemorrhage (PPH) prophylaxis in the third stage of labour and another Cochrane review investigating the timing of prophylactic uterotonics in the third stage of labour (i.e. before or after delivery of the placenta). There are, however, no Cochrane reviews looking at the use of interventions given purely after delivery of the placenta. Ergometrine or methylergometrine are used for the prevention of PPH in the postpartum period (the period after delivery of the infant) after delivery of the placenta in some countries. There are, furthermore, no Cochrane reviews that have so far considered herbal therapies or homeopathic remedies for the prevention of PPH after delivery of the placenta.

Objectives: 

To assess the effectiveness of available prophylactic interventions for PPH including prophylactic use of ergotamine, ergometrine, methylergometrine, herbal therapies, and homeopathic remedies, administered after delivery of the placenta, compared with no uterotonic agents as well as with different routes of administration for prevention of PPH after delivery of the placenta.

Search strategy: 

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013), The Food and Drug Administration (FDA) (USA),  Medicines and Healthcare Products Regulatory Agency (MHRA) (UK), European Medicines Agency (EMA) (EU), Pharmaceuticals and Medical Devices Agency (PMDA) (Japan),  Therapeutic Goods Administration (TGA) (Australia), ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform (ICTRP), University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; Japan), Japan Pharmaceutical Information Center Clinical Trials Information (Japic-CTI; Japan), Japan Medical Association Clinical Trial Registration (JMACCT CTR; Japan) (all on 30 April 2013) and reference lists of retrieved studies

Selection criteria: 

All randomised or quasi-randomised controlled trials comparing prophylactic ergotamine, ergometrine, methylergometrine, herbal therapies, and homeopathic remedies (using any route and timing of administration) during the postpartum period after delivery of the placenta with no uterotonic agents or trials comparing different routes or timing of administration of ergotamine, ergometrine, methylergometrine, herbal therapies, and homeopathic remedies, during the postpartum period after delivery of the placenta.

Data collection and analysis: 

Two review authors independently assessed trial eligibility and the methodological quality of trials, extracted data using the agreed form. Data were checked for accuracy.

Main results: 

Five randomised studies involving 1466 women met the inclusion criteria. All studies were classified as having an unclear risk of bias. Two studies (involving 1097 women) compared oral methylergometrine with a placebo, and one (involving 171 women) compared oral methylergometrine with Kyuki-chouketsu-in, a Japanese traditional herbal medicine. The remaining two studies (involving 198 women) did not report the outcomes of interest for this review. None of the included studies reported primary outcomes prespecified in the review protocol (blood loss of 1000 mL or more over the period of observation, maternal death or severe morbidity). Overall, there was no clear evidence of differences between groups in the following PPH outcomes: blood loss of 500 mL or more (risk ratio (RR) 1.45; 95% confidence interval (CI) 0.39 to 5.47, two studies), amount of lochia during the first 72 hours of the puerperium (mean difference (MD) -25.00 g; 95% CI -69.79 to 19.79, one study), or amount of lochia by four weeks postpartum (MD -7.00 g; 95% CI -23.99 to 9.99).

The Japanese study with a relatively small sample size comparing oral methylergometrine with a Japanese traditional herbal medicine found that oral methylergometrine significantly increased the blood haemoglobin concentration at day one postpartum (MD 0.50 g/dL; 95% CI 0.11 to 0.89) compared to herbal medicine. Adverse events were not well-reported in the included studies. We did not find any studies comparing homeopathic remedies with either a placebo or no treatment.