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Meta-Analysis
. 2019 Apr 29;4(4):CD001808.
doi: 10.1002/14651858.CD001808.pub3.

Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage

Jennifer A Salati  1 , Sebastian J Leathersich, Myfanwy J Williams, Anna Cuthbert, Jorge E Tolosa
Affiliations
Meta-Analysis

Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage

Jennifer A Salati et al. Cochrane Database Syst Rev. .

Abstract

Background: Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a prophylactic uterotonic, early umbilical cord clamping and controlled cord traction to facilitate placental delivery. The choice of uterotonic varies across the globe and may have an impact on maternal outcomes. This is an update of a review first published in 2001 and last updated in 2013.

Objectives: To determine the effectiveness of prophylactic oxytocin to prevent PPH and other adverse maternal outcomes in the third stage of labour.

Search methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (6 March 2019) and reference lists of retrieved studies.

Selection criteria: Randomised, quasi- or cluster-randomised trials including women undergoing vaginal delivery who received prophylactic oxytocin during management of the third stage of labour. Primary outcomes were blood loss 500 mL or more after delivery, need for additional uterotonics, and maternal all-cause mortality.

Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted data, and assessed trial quality. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach.

Main results: This review includes 24 trials, with 23 trials involving 10,018 women contributing data. Due to many trials assessed at high risk of bias, evidence grade ranged from very low to moderate quality.Prophylactic oxytocin versus no uterotonics or placebo (nine trials)Prophylactic oxytocin compared with no uterotonics or placebo may reduce the risk of blood loss of 500 mL after delivery (average risk ratio (RR) 0.51, 95% confidence interval (C) 0.37 to 0.72; 4162 women; 6 studies; Tau² = 0.10, I² = 75%; low-quality evidence), and blood loss 1000 mL after delivery (RR 0.59, 95% CI 0.42 to 0.83; 4123 women; 5 studies; low-quality evidence). Prophylactic oxytocin probably reduces the need for additional uterotonics (average RR 0.54, 95% CI 0.36 to 0.80; 3135 women; 4 studies; Tau² = 0.07, I² = 44%; moderate-quality evidence). There may be no difference in the risk of needing a blood transfusion in women receiving oxytocin compared to no uterotonics or placebo (RR 0.88, 95% CI 0.44 to 1.78; 3081 women; 3 studies; low-quality evidence). Oxytocin may be associated with an increased risk of a third stage greater than 30 minutes (RR 2.55, 95% CI 0.88 to 7.44; 1947 women; 1 study; moderate-quality evidence), however the confidence interval is wide and includes 1.0, indicating that there may be little or no difference.Prophylactic oxytocin versus ergot alkaloids (15 trials)It is uncertain whether oxytocin reduces the likelihood of blood loss 500 mL (average RR 0.84, 95% CI 0.56 to 1.25; 3082 women; 10 studies; Tau² = 0.14, I² = 49%; very low-quality evidence) or the need for additional uterotonics compared to ergot alkaloids (average RR 0.89, 95% CI 0.43 to 1.81; 2178 women; 8 studies; Tau² = 0.76, I² = 79%; very low-quality evidence), because the quality of this evidence is very low. The quality of evidence was very low for blood loss of 1000 mL (RR 1.13, 95% CI 0.63 to 2.01; 1577 women; 3 studies; very low-quality evidence), and need for blood transfusion (average RR 1.37, 95% CI 0.34 to 5.51; 1578 women; 7 studies; Tau² = 1.34, I² = 45%; very low-quality evidence), making benefit of oxytocin over ergot alkaloids uncertain. Oxytocin probably increases the risk of a prolonged third stage greater than 30 minutes (RR 4.69, 95% CI 1.63 to 13.45; 450 women; 2 studies; moderate-quality evidence), although it is uncertain if this translates into increased risk of manual placental removal (average RR 1.10, 95% CI 0.39 to 3.10; 3127 women; 8 studies; Tau² = 1.07, I² = 76%; very low-quality evidence). Oxytocin may make little or no difference to risk of diastolic blood pressure > 100 mm Hg (average RR 0.28, 95% CI 0.04 to 2.05; 960 women; 3 studies; Tau² = 1.23, I² = 50%; low-quality evidence), and is probably associated with a lower risk of vomiting (RR 0.09, 95% CI 0.05 to 0.14; 1991 women; 7 studies; moderate-quality evidence), although the impact of oxytocin on headaches is uncertain (average RR 0.19, 95% CI 0.03 to 1.02; 1543 women; 5 studies; Tau² = 2.54, I² = 72%; very low-quality evidence).Prophylactic oxytocin-ergometrine versus ergot alkaloids (four trials)Oxytocin-ergometrine may slightly reduce the risk of blood loss greater than 500 mL after delivery compared to ergot alkaloids (RR 0.44, 95% CI 0.20 to 0.94; 1168 women; 3 studies; low-quality evidence), based on outcomes from quasi-randomised trials with a high risk of bias. There were no maternal deaths reported in either treatment group in the one trial that reported this outcome (RR not estimable; 1 trial, 807 women; moderate-quality evidence). Need for additional uterotonics was not reported.No subgroup differences were observed between active or expectant management, or different routes or doses of oxytocin for any of our comparisons.

Authors' conclusions: Prophylactic oxytocin compared with no uterotonics may reduce blood loss and the need for additional uterotonics. The effect of oxytocin compared to ergot alkaloids is uncertain with regards to blood loss, need for additional uterotonics, and blood transfusion. Oxytocin may increase the risk of a prolonged third stage compared to ergot alkaloids, although whether this translates into increased risk of manual placental removal is uncertain. This potential risk must be weighed against the possible increased risk of side effects associated with ergot alkaloids. Oxytocin-ergometrine may reduce blood loss compared to ergot alkaloids, however the certainty of this conclusion is low. More high-quality trials are needed to assess optimal dosing and route of oxytocin administration, with inclusion of important outcomes such as maternal mortality, shock, and transfer to a higher level of care. A network meta-analysis of uterotonics for PPH prevention plans to address issues around optimal dosing and routes of oxytocin and other uterotonics.

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Conflict of interest statement

Jennifer Salati: none known.

Sebastian Leathersich: none known.

Myfanwy Williams: is employed by the University of Liverpool as a Research Associate for Cochrane Pregnancy and Childbirth. Her role is supported by the World Health Organization.

Anna Cuthbert: is employed by the University of Liverpool as a Research Associate for Cochrane Pregnancy and Childbirth. Her role was supported by the World Health Organization.

Jorge Tolosa: none known.

Figures

1
1
Study flow diagram
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 3 Oxytocin versus ergot alkaloids, outcome: 3.1 Blood loss 500 mL or more after delivery.
5
5
Funnel plot of comparison: 3 Oxytocin versus ergot alkaloids, outcome: 3.7 Mean blood loss (mL).
1.1
1.1. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 1 Blood loss 500 mL or more after delivery.
1.2
1.2. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 2 Need for additional uterotonics.
1.3
1.3. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 3 Blood loss 1000 mL or more after delivery.
1.4
1.4. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 4 Blood transfusion.
1.5
1.5. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 5 Third stage greater than 30 minutes.
1.6
1.6. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 6 Mean blood loss (mL).
1.7
1.7. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 7 Maternal haemoglobin concentration (Hb) < 7 g/dL 24‐48 hours PP.
1.8
1.8. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 8 Mean length of third stage (minutes).
1.9
1.9. Analysis
Comparison 1 Oxytocin versus no uterotonics or placebo, Outcome 9 Manual removal of the placenta.
2.1
2.1. Analysis
Comparison 2 Oxytocin versus no uterotonics or placebo‐subgroup analyses, Outcome 1 Blood loss 500 mL or more after delivery; active v. expectant management.
2.2
2.2. Analysis
Comparison 2 Oxytocin versus no uterotonics or placebo‐subgroup analyses, Outcome 2 Blood loss 500 mL or more after delivery; IM v. IV oxytocin.
2.3
2.3. Analysis
Comparison 2 Oxytocin versus no uterotonics or placebo‐subgroup analyses, Outcome 3 Blood loss 500 mL or more after delivery; oxytocin dose < 10 IU v. 10 IU.
2.4
2.4. Analysis
Comparison 2 Oxytocin versus no uterotonics or placebo‐subgroup analyses, Outcome 4 Need for additional uterotonics; active v. expectant management.
2.5
2.5. Analysis
Comparison 2 Oxytocin versus no uterotonics or placebo‐subgroup analyses, Outcome 5 Need for additional uterotonics; IM v. IV oxytocin.
2.6
2.6. Analysis
Comparison 2 Oxytocin versus no uterotonics or placebo‐subgroup analyses, Outcome 6 Need for additional uterotonics; oxytocin dose < 10 IU v. 10 IU.
3.1
3.1. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 1 Blood loss 500 mL or more after delivery.
3.2
3.2. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 2 Need for additional uterotonics.
3.3
3.3. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 3 Blood loss 1000 mL or more after delivery.
3.4
3.4. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 4 Blood transfusion.
3.5
3.5. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 5 Third stage > 30 minutes.
3.6
3.6. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 6 Diastolic blood pressure > 100 mm Hg between delivery of the baby and discharge from the labour ward.
3.7
3.7. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 7 Mean blood loss (mL).
3.8
3.8. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 8 Mean length of third stage (minutes).
3.9
3.9. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 9 Manual removal of the placenta.
3.10
3.10. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 10 Vomiting between delivery of the baby and discharge from the labour ward.
3.11
3.11. Analysis
Comparison 3 Oxytocin versus ergot alkaloids, Outcome 11 Headaches between delivery of the baby and discharge from the labour ward.
4.1
4.1. Analysis
Comparison 4 Oxytocin versus ergot alkaloids‐‐subgroup analyses, Outcome 1 Blood loss 500 mL or more after delivery; active v. expectant management.
4.2
4.2. Analysis
Comparison 4 Oxytocin versus ergot alkaloids‐‐subgroup analyses, Outcome 2 Blood loss 500 mL or more after delivery; IM v. IV oxytocin.
4.3
4.3. Analysis
Comparison 4 Oxytocin versus ergot alkaloids‐‐subgroup analyses, Outcome 3 Blood loss 500 mL or more after delivery; oxytocin dose < 10 IU v. 10 IU.
4.4
4.4. Analysis
Comparison 4 Oxytocin versus ergot alkaloids‐‐subgroup analyses, Outcome 4 Need for additional uterotonics; active v. expectant management.
4.5
4.5. Analysis
Comparison 4 Oxytocin versus ergot alkaloids‐‐subgroup analyses, Outcome 5 Need for additional uterotonics; IM v. IV oxytocin.
4.6
4.6. Analysis
Comparison 4 Oxytocin versus ergot alkaloids‐‐subgroup analyses, Outcome 6 Need for additional uterotonics; oxytocin dose < 10 IU v. 10 IU.
5.1
5.1. Analysis
Comparison 5 Oxytocin + ergometrine versus ergot alkaloids, Outcome 1 Blood loss 500 mL or more after delivery.
5.2
5.2. Analysis
Comparison 5 Oxytocin + ergometrine versus ergot alkaloids, Outcome 2 Manual removal of the placenta.
5.3
5.3. Analysis
Comparison 5 Oxytocin + ergometrine versus ergot alkaloids, Outcome 3 Mean blood loss (mL).
5.4
5.4. Analysis
Comparison 5 Oxytocin + ergometrine versus ergot alkaloids, Outcome 4 Maternal all‐cause mortality.
6.1
6.1. Analysis
Comparison 6 Oxytocin + ergometrine versus ergot alkaloids‐‐subgroup analyses, Outcome 1 Blood loss 500 mL or more after delivery; active v. expectant management.
6.2
6.2. Analysis
Comparison 6 Oxytocin + ergometrine versus ergot alkaloids‐‐subgroup analyses, Outcome 2 Blood loss 500 mL or more after delivery; IM v. IV oxytocin.
7.1
7.1. Analysis
Comparison 7 Oxytocin versus no uterotonics or placebo‐‐subgroup analyses, Outcome 1 Blood loss 500 mL or more after delivery; active v. expectant management.
7.2
7.2. Analysis
Comparison 7 Oxytocin versus no uterotonics or placebo‐‐subgroup analyses, Outcome 2 Blood loss 500 mL or more after delivery; IM v. IV oxytocin.
7.3
7.3. Analysis
Comparison 7 Oxytocin versus no uterotonics or placebo‐‐subgroup analyses, Outcome 3 Blood loss 500 mL or more after delivery; oxytocin dose < 10 IU v. 10 IU.
7.4
7.4. Analysis
Comparison 7 Oxytocin versus no uterotonics or placebo‐‐subgroup analyses, Outcome 4 Need for additional uterotonics; active v. expectant management.
7.5
7.5. Analysis
Comparison 7 Oxytocin versus no uterotonics or placebo‐‐subgroup analyses, Outcome 5 Need for additional uterotonics; IM v. IV oxytocin.
7.6
7.6. Analysis
Comparison 7 Oxytocin versus no uterotonics or placebo‐‐subgroup analyses, Outcome 6 Need for additional uterotonics; oxytocin dose < 10 IU v. 10 IU.
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References

References to studies included in this review

Abdel‐Aleem 2010 {published data only}
    1. Abdel‐Aleem H, Singata M, Abdel‐Aleem M, Mshweshwe N, Williams X, Hofmeyr GJ. Uterine massage to reduce postpartum hemorrhage after vaginal delivery. International Journal of Gynecology & Obstetrics 2010;111(1):32‐6. - PubMed
Adhikari 2007 {published data only}
    1. Adhikari S, Rana A, Bista KD. Active management of third stage of labour: comparison between prophylactic intramuscular methylergometrine and intramuscular oxytocin. Nepal Journal of Obstetrics and Gynaecology 2007;2(2):24‐8.
Bader 2000 {published data only}
    1. Bader W, Ast S, Hatzmann W. The significance of acupuncture in the third stage of labour. Deutsche Zeitschrift fur Akupunktur 2000;43:264‐8.
    1. Bader W, Ast S, Reinehr J, Hackmann J, Hatzmann W. Oxytocin versus Akupunktur in der Plazentarperiode ‐ eine prospektiv randomisierte Studie [abstract]. Geburtshilfe und Frauenheilkunde 2000;60 Suppl 1:S73.
Bonham 1963 {published data only}
    1. Bonham DG. Intramuscular oxytocics and cord traction in third stage of labour. Brtish Medical Journal 1963;2:1620‐3. - PMC - PubMed
Boopathi 2014 {published data only}
    1. Boopathi A, Nayak SR, Rao A, Rao B. Oxytocin versus methylergometrine in the active management of third stage of labour. Open Journal of Obstetrics and Gynecology 2014;4:666‐71.
De Groot 1996 {published data only}
    1. Groot AN, Roosmalen J, Dongen PW, Borm GF. A placebo‐controlled trial of oral ergometrine to reduce postpartum hemorrhage. Acta Obstetricia et Gynecologica Scandinavica 1996;75:464‐8. - PubMed
Dhananjaya 2014 {published data only}
    1. Dhananjaya BS, Charishma S. Comparative study of efficacy and safety of intramuscular oxytocin with intramuscular methylergometrine in the active management of third stage of labour. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2014;5(3):734‐9.
Ezeama 2014 {published data only}
    1. Ezeama CO, Eleje GU, Ezeama NN, Igwegbe AO, Ikechebelu JI, Ugboaja JO, et al. A comparison of prophylactic intramuscular ergometrine and oxytocin for women in the third stage of labor. International Journal of Gynecology and Obstetrics 2014;124(1):67‐71. - PubMed
Francis 1965 {published data only}
    1. Francis HH, Miller JM, Porteous CR. Clinical trial of an oxytocin‐ergometrine mixture. Australian & New Zealand Journal of Obstetrics and Gynaecology 1965;5:47‐51. - PubMed
Fugo 1958 {published data only}
    1. Fugo NW, Dieckmann WJ. A comparison of oxytocic drugs in the management of the placental stage. American Journal of Obstetrics and Gynecology 1958;76:141‐6. - PubMed
Ilancheran 1990 {published data only}
    1. Ilancheran A, Ratnam SS. Effect of oxytocics on prostaglandin levels in the third stage of labour. Gynecologic and Obstetric Investigation 1990;29:177‐80. - PubMed
Jago 2007 {published data only}
    1. Jago AA, Ezechi OC, Achinge GI, Okunlola MA. Effect of oxytocics on the blood pressure of normotensive Nigerian parturients. Journal of Maternal‐Fetal & Neonatal Medicine 2007;20(9):703‐5. - PubMed
Jerbi 2007 {published data only}
    1. Jerbi M, Hidar S, Elmoueddeb S, Chaieb A, Khairi H. Oxytocin in the third stage of labor. International Journal of Gynecology & Obstetrics 2007;96(3):198‐9. - PubMed
McGinty 1956 {published data only}
    1. McGinty LB. A study of the vasopressor effects of oxytocics when used intravenously in the third stage of labour. Western Journal of Surgery 1956;64:22‐8. - PubMed
Modi 2014 {published data only}
    1. Modi V, Goel JK, Kashyap A, Arya SB, Kar J, Goel R. Active management of third stage of labor: A comparison of various uterotonic. Journal of South Asian Federation of Obstetrics and Gynaecology ‐ SAFOG 2014;6(3):151‐5.
Moodie 1976 {published data only}
    1. Moodie JE, Moir DD. Ergometrine, oxytocin and extradural analgesia. British Journal of Anaesthesia 1976;48:571‐4. - PubMed
Nordstrom 1997 {published data only}
    1. Nordstrom L, Fogelstam K, Fridman G, Larsson A, Rydhstroem H. Routine oxytocin in the third stage of labour: a placebo controlled randomised trial. British Journal of Obstetrics and Gynaecology 1997;104:781‐6. - PubMed
Orji 2008 {published data only}
    1. Orji E, Agwu F, Loto O, Olaleye O. A randomized comparative study of prophylactic oxytocin versus ergometrine in the third stage of labor. International Journal of Gynecology & Obstetrics 2008;101(2):129‐32. - PubMed
Pierre 1992 {published data only}
    1. Pierre F, Mesnard L, Body G. For a systematic policy of iv oxytocin inducted placenta deliveries in a unit where a fairly active management of third stage of labour is yet applied: results of a controlled trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 1992;43:131‐5. - PubMed
Poeschmann 1991 {published data only}
    1. Poeschmann RP, Doesburg WH, Eskes TK. A randomized comparison of oxytocin, sulprostone and placebo in the management of the third stage of labour. British Journal of Obstetrics and Gynaecology 1991;98:528‐30. - PubMed
Saito 2007 {published data only}
    1. Saito K, Haruki A, Ishikawa H, Takahashi T, Nagase H, Koyama M, et al. Prospective study of intramuscular ergometrine compared with intramuscular oxytocin for prevention of postpartum hemorrhage. Journal of Obstetrics and Gynaecology Research 2007;33(3):254‐8. - PubMed
Singh 2009 {published data only}
    1. Singh G, Radhakrishnan G, Guleria K. Comparison of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor. International Journal of Gynecology & Obstetrics 2009;107(2):130‐4. - PubMed
Sorbe 1978 {published data only}
    1. Sorbe B. Active pharmacologic management of the third stage of labor. A comparison of oxytocin and ergometrine. Obstetrics & Gynecology 1978;52:694‐7. - PubMed
Vaughan Williams 1974 {published data only}
    1. Vaughan Williams CA, Johnson A, Ledward R. A comparison of central venous pressure changes in the third stage of labour following oxytocic drugs and diazepam. Journal of Obstetrics and Gynaecology of the British Commonwealth 1974;81:596‐9. - PubMed

References to studies excluded from this review

Barbaro 1961 {published data only}
    1. Barbaro CA, Smith GO. Clinical trial of SE505 ‐ a new oxytocic mixture. Australian and New Zealand Journal of Obstetrics and Gynaecology 1961;1:147‐50.
Boucher 2004 {published data only}
    1. Boucher M, Nimrod C, Tawagi G. Carbetocin IM injection vs oxytocin IV infusion for prevention of postpartum hemorrhage in women at risk following vaginal delivery. American Journal of Obstetrics and Gynecology 2001;185(6 Pt 2):A494.
    1. Boucher M, Nimrod CA, Tawagi GF, Meeker TA, Rennicks, White RE, et al. Comparison of carbetocin and oxytocin for the prevention of postpartum hemorrhage following vaginal delivery:a double‐blind randomized trial. Journal of Obstetrics & Gynaecology Canada: JOGC 2004;26(5):481‐8. - PubMed
Dickinson 2009 {published data only}
    1. Dickinson JE, Doherty DA. Optimization of third‐stage management after second‐trimester medical pregnancy termination. American Journal of Obstetrics and Gynecology 2009;201(3):303.e1‐7. - PubMed
Docherty 1981 {published data only}
    1. Docherty PW, Hooper M. Choice of an oxytocic agent for routine use at delivery. Journal of Obstetrics and Gynaecology 1981;2:60.
Dommisse 1980 {published data only}
    1. Dommisse J. The routine use of oxytocic drugs in the third stage of labour [letter]. South African Medical Journal 1980;46:549. - PubMed
Dumoulin 1981 {published data only}
    1. Dumoulin JG. A reappraisal of the use of ergometrine. Journal of Obstetrics and Gynaecology 1981;1:178‐81.
Friedman 1957 {published data only}
    1. Friedman EA. Comparative clinical evaluation of postpartum oxytocics. Journal of Obstetrics and Gynecology 1957;73:1306‐13. - PubMed
Gerstenfeld 2001 {published data only}
    1. Gerstenfeld T, Wing D. Rectal misoprostol versus intravenous oxytocin for the prevention of postpartum hemorrhage after vaginal delivery. American Journal of Obstetrics and Gynecology 2001;185:878‐82. - PubMed
Hacker 1979 {published data only}
    1. Hacker NF, Biggs JS. Blood pressure changes when uterine stimulants are used after normal delivery. British Journal of Obstetrics Gynaecology 1979;86:633‐6. - PubMed
Hoffman 2006b {published data only}
    1. Hoffman M, Castagnola D, Naqvi F. A randomized trial of active versus expectant management of the third stage of labor [abstract]. American Journal of Obstetrics and Gynecology 2006;195(6 Suppl 1):S107.
    1. Hoffman M, Naqvi F, Sciscione A. A randomized trial of active versus expectant management of the third stage of labor. American Journal of Obstetrics and Gynecology 2004;191(6 Suppl 1):S82.
Howard 1964 {published data only}
    1. Howard WF, McFadden PR, Keettel WC. Oxytocic drugs in fourth stage of labor. JAMA 1964;189:411‐3. - PubMed
Huh 2000 {published data only}
    1. Huh W, Chelmow D, Malone FD. A randomized, double‐blinded, placebo controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage. American Journal of Obstetrics and Gynecology 2000;182(1 Pt 2):S130. - PubMed
Irons 1994 {published data only}
    1. Irons DW, Sriskandabalan P, Bullough CH. A simple alternative to parenteral oxytocics for the third stage of labor. International Journal of Gynecology & Obstetrics 1994;46:15‐8. - PubMed
Jackson 2001 {published data only}
    1. Jackson KJ, Allbert J, Schemmer G, Elliot M, Humphrey A, Taylor J. A randomized controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage. American Journal of Obstetrics and Gynecology 2001;185:873‐7. - PubMed
Jans 2017 {published data only}
    1. Jans S, Herschderfer KC, Diem MT, Aitink M, Rijnders M, Pal‐Bruin K, et al. LENTE study: effectiveness of prophylactic intramuscular oxytocin during third stage of labour amongst low risk women. A randomized controlled trial. 31st International Confederation of Midwives Triennial Congress. Midwives ‐ Making a Difference in the World; 2017 June 18‐22; Toronto, Canada. 2017:Abstract no: P1.063.
Khan 1997 {published data only}
    1. Khan GQ, John IS, Chan T, Wani S, Doherty T. Controlled cord traction versus minimal intervention techniques in delivery of the placenta: a randomized controlled trial. American Journal of Obstetrics and Gynecology 1997;177(4):770‐4. - PubMed
Kundodyiwa 2001 {published data only}
    1. Kundodyiwa T, Majoko F, Rusakaniko S. Misoprostol versus oxytocin in the third stage of labor. International Journal of Gynecology & Obstetrics 2001;75:235‐41. - PubMed
Lokugamage 2001 {published data only}
    1. Lokugamage A, Paine M, Bassaw‐Balroop K, Sullivan K, El‐Refaey H, Rodeck C. Active management of the third stage at caesarean section: a randomised controlled trial of misoprostol versus syntocinon. Australian and New Zealand Journal of Obstetrics & Gynaecology 2001;41(4):411‐4. - PubMed
    1. Lokugamage AU, Paine M, Bassau‐Balroop H, El‐Refaey K, Sullivan K, Rodek C. Active management of the third stage at caesarean section: misoprostol vs syntocinon. XVI FIGO World Congress of Obstetrics & Gynecology. 2000 Sept 3‐8; Washington DC, USA 2000; Book 2:54. - PubMed
Muller 1996 {published data only}
    1. Muller R, Beck G. Active management of the third stage of labour. 19th Swiss Congress of the Swiss Society of Gynecology and Obstetrics; 1996 June; Interlaken, Switzerland. 1996.
Neri‐Mejia 2016 {published data only}
    1. Neri‐Mejia M, Pedraza‐Aviles AG. Active management of the third stage of labor: three schemes of oxytocin: randomised clinical trial. Ginecologia y Obstetricia De Mexico 2016;84(5):306‐13. - PubMed
Newton 1961 {published data only}
    1. Newton M, Mosey LM, Egli GE, Gifford WB, Hull CT. Blood loss during and immediately after delivery. Obstetrics & Gynecology 1961;17:9‐18. - PubMed
Nieminen 1963 {published data only}
    1. Nieminen U, Jarvinen PA. A comparative study of different medical treatments of the third stage of labour. Annales Chirurgiae et Gynaecologiae Fenniae 1963;53:424‐9. - PubMed
Nuamsiri 2016 {published data only}
    1. Nuamsiri T, Kaewkiattikun K. Prevention of postpartum hemorrhage with oxytocin versus ergometrine plus oxytocin in the third stage of labor. Thai Journal of Obstetrics and Gynaecology 2016;24:97‐103.
    1. Nuamsiri T, TCTR20150820001. Prevention of postpartum hemorrhage with oxytocin versus ergometrine plus oxytocin in the third stage of labor. http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&.... (20 May 2015) 2015. [TCTR20150820001]
Oguz Orhan 2014 {published data only}
    1. Oguz Orhan E, Dilbaz B, Aksakal SE, Altinbas S, Erkaya S. Prospective randomized trial of oxytocin administration for active management of the third stage of labor. International Journal of Gynecology and Obstetrics 2014;127(2):175‐9. - PubMed
Parsons 2004 {published data only}
    1. Parsons S, Ntumy YM, Walley RL, Wilson JB, Crane JM, Matthews K, et al. Rectal misoprostol vs intramuscular oxytocin in the routine management of the third stage of labour. 30th British Congress of Obstetrics and Gynaecology; 2004 July 7‐9; Glasgow, UK 2004;18. 2004.
Porter 1991 {published data only}
    1. Porter KB, O'Brien WF, Collins MK, Givens P, Knuppel R, Bruskivage L. A randomized comparison of umbilical vein and intravenous oxytocin during the puerperium. Obstetrics & Gynecology 1991;78:254‐6. - PubMed
Quibel 2016 {published data only}
    1. Quibel T, Ghout I, Goffinet F, Salomon LJ, Fort J, Javoise S, et al. Active management of the third stage of labor with a combination of oxytocin and misoprostol to prevent postpartum hemorrhage: a randomized controlled trial. Obstetrics and Gynecology 2016;128(4):805‐11. - PubMed
Ramirez 2001 {published data only}
    1. Ramirez O, Benito V, Jimenez R, Valido C, Hernandez C, Garcia J. Third stage of labour: active or expectant management? preliminary results. Journal of Perinatal Medicine 2001;Suppl 1(Pt 2):364.
Rouse 2011 {published data only}
    1. Rouse D, Abramovici A, Szychowski J, Seals S, Andrews W, Hauth J, et al. Oxytocin dose‐regimens to prevent uterine atony after vaginal delivery: does treatment efficacy vary by risk status?. American Journal of Obstetrics and Gynecology 2011;204(1 Suppl):S50‐S51.
Sariganont 1999 {published data only}
    1. Sariganont J. Comparative study between syntocinon and methergin in prevention of postpartum hemorrhage. Thai Journal of Obstetrics and Gynaecology 1999;11(4):248.
Schaefer 2004 {published data only}
    1. Schaefer A, Klein L, Wolfe P, Heindricks G, Downs L, Guinn D. Double blind rct of early versus traditional oxytocin management in the third stage to prevent blood loss. American Journal of Obstetrics and Gynecology 2004;191(6 Suppl 1):S69.
Schemmer 2001 {published data only}
    1. Schemmer G. A randomized controlled trial comparing prophylactic administration of oxytocin before and after placental delivery in the prevention of postpartum hemorrhage [abstract]. American Journal of Obstetrics and Gynecology 2001;184(1):S20. - PubMed
Sharma 2014 {published data only}
    1. Sharma M, Kaur P, Kaur K, Kaur A, Kaur PK, Kaur MM. A comparative study of oxytocin/misoprostol/methylergometrine for active management of the third stage of labor. Journal of Obstetrics and Gynecology of India 2014;64(3):175‐9. - PMC - PubMed
Soiva 1964 {published data only}
    1. Soiva K, Koistinen O. Clinical experience with simultaneous intramuscular injection of oxytocin and methylergometrine. Annales Chirurgiae et Gynaecologiae 1964;53:173‐86. - PubMed
Soriano 1995 {published data only}
    1. Soriano D, Dulitzki M, Schiff E, Barkai G, Seldman DS. A randomized prospective trial of oxytocin plus ergometrin vs oxytocin alone for prevention of postpartum hemorrhage. American Journal of Obstetrics and Gynecology 1995;172:361. - PubMed
Stanton 2010 {published data only}
    1. Stanton C, NCT01108302. Assessing the effectiveness, safety and feasibility of expanding use of oxytocin in uniject™ by auxiliary nurse midwives to prevent postpartum hemorrhage: a community‐based cluster randomized trial in Bagalkot, India. clinicaltrials.gov/show/NCT01108302 (first received 21 April 2010).
Stanton 2012 {published data only}
    1. Stanton CK, Newton S, Mullany LC, Cofie P, Agyemang CT, Adiibokah E, et al. Impact on postpartum hemorrhage of prophylactic administration of oxytocin 10 IU via Uniject by peripheral health care providers at home births: Design of a community‐based cluster‐randomized trial. BMC Pregnancy and Childbirth 2012;12:42. - PMC - PubMed
Stanton 2013 {published data only}
    1. Stanton C, NCT01108289. The oxytocin initiative: determining the effect of prophylactic administration of oxytocin in uniject™ by a community health officer on postpartum hemorrhage at home births in four districts in. clinicaltrials.gov/ct2/show/record/NCT01108289 (first received 21 April 2010).
    1. Stanton CK, Newton S, Mullany LC, Cofie P, Tawiah Agyemang C, Adiibokah E, et al. Effect on postpartum hemorrhage of prophylactic oxytocin (10 IU) by injection by community health officers in Ghana: a community‐based, cluster‐randomized trial. PLOS Medicine 2013;10(10):e1001524. - PMC - PubMed
Stearn 1963 {published data only}
    1. Stearn RH. Syntometrine in the management of the third stage of labour. Journal of Obstetrics and Gynaecology of the British Commonwealth 1963;70:593‐6. - PubMed
Suhrabi 2013 {published data only}
    1. Suhrabi Z, IRCT201304146790N6. Comparision the effect of dextrose and oxytocine on bleeding rate in 3th stage of labor in women who hospitalized in Shahid Mustafa Khomeini (PBUH) of Ilam city. en.irct.ir/trial/7202 (first received 26 May 2013).
Sunil 2016 {published data only}
    1. Sunil Kumar KS, Shyam S, Batakurki P. Carboprost versus oxytocin for active management of third stage of labor: a prospective randomized control study. Journal of Obstetrics and Gynaecology of India 2016;66(Suppl 1):S229‐34. - PMC - PubMed
Symes 1984 {published data only}
    1. Symes JB. A study on the effect of ergometrine on serum prolactin levels following delivery. Journal of Obstetrics and Gynaecology 1984;5:36‐8. [Record 2022]
Tessier 2000 {published data only}
    1. Tessier JL, Davies GAL, Woodman MC, Lipson A. Maternal hemodynamics after oxytocin bolus versus infusion in the third stage of labor. American Journal of Obstetrics and Gynecology 2000;182(1 Pt 2):S128. - PubMed
Thornton 1988 {published data only}
    1. Thornton S, Davison JM, Baylis PH. Plasma oxytocin during third stage of labour: comparison of natural and active management. BMJ 1988;297:167‐9. - PMC - PubMed
Tita 2012 {published data only}
    1. Tita A, NCT00790062. Comparison of the effectiveness of 3 different dose regimens of oxytocin in preventing uterine atony and postpartum hemorrhage during vaginal delivery. https://clinicaltrials.gov/show/NCT00790062 (first received 13 November 2008).
    1. Tita AT, Szychowski JM, Rouse DJ, Bean CM, Chapman V, Nothern A, et al. Higher‐dose oxytocin and hemorrhage after vaginal delivery: A randomized controlled trial. Obstetrics and Gynecology 2012;119(2 Pt 1):293‐300. - PMC - PubMed
    1. Wetta L, Szychowski J, Seals S, Mancuso M, Hauth J, Tita A. Risk factors for uterine atony at vaginal delivery: a comprehensive evaluation. American Journal of Obstetrics and Gynecology 2011;204(1 Suppl):S71‐2. - PMC - PubMed
    1. Wetta LA, Szychowski JM, Seals S, Mancuso MS, Biggio JR, Tita AT. Risk factors for uterine atony/postpartum hemorrhage requiring treatment after vaginal delivery. American Journal of Obstetrics and Gynecology 2013;209(1):51e1‐6. - PMC - PubMed
Vasegh 2005 {published data only}
    1. Vasegh FR, Bahiraie A, Mahmoudi M, Salehi L. Comparison of active and physiologic management of third stage of labor. HAYAT: Journal of Tehran Faculty of Nursing & Midwifery 2005;10(23):102.
Yuen 1995 {published data only}
    1. Yuen PM, Chan NST, Yim SF, Chang AM. A randomised double blind comparison of Syntometrine and Syntocinon in the management of the third stage of labour. British Journal of Obstetrics and Gynaecology 1995;102:377‐80. - PubMed

References to studies awaiting assessment

Draycott 2014 {published data only}
    1. Draycott T, NCT02216383. Intramuscular oxytocics: a comparison study of intramuscular carbetocin, syntocinon and syntometrine for the third stage of labour following vaginal birth. clinicaltrials.gov/ct2/show/record/NCT02216383 (first received 15 August 2014).
Narenji 2012 {published data only}
    1. Narenji F. Comparison the effect of intramuscular injection of oxytocin and nipple stimulation on the third stage of delivery length and bleeding. irct.ir/trial/10487 (first received 25 June 2012).
Shahbazian 2013 {published data only}
    1. Shahbazian N, IRCT201106143756N2. Comparison of the effects of intramuscular methylergonovine, intravascular oxytocin, and sublingual prostaglandin (misoprostol) in active management of the third stage of labor. en.irct.ir/trial/3866 (first received 20 September 2011).
    1. Shahbazian N, Saadati N, Nezhad, Fathi L. Comparison of the effects of intramuscular methylergonovine, intravascular oxytocin, and sublingual misoprostol in active management of the third stage of labor. Jundishapur Scientific Medical Journal 2013;12(5):559‐605.
Suthutvoravut 2012 {published data only}
    1. Suthutvoravut S, TCTR20120000012. Comparison of postpartum blood loss between intravenous oxytocin and intravenous methylergometrine maleate during third stage of labor. clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fullt... (first received 5 August 2012).

References to ongoing studies

Hermesch 2014 {published data only}
    1. Hermesch A, NCT02221830. Postpartum hemorrhage prevention in patients with preeclampsia (PHP3 Study). clinicaltrials.gov/ct2/show/record/NCT02221830 (first received 20 August 2014). [NCT02221830]
Yogev 2014 {published data only}
    1. Yogev Y, NCT02319707. Management of the third stage of labor. clinicaltrials.gov/ct2/show/NCT02319707 (first received 18 December 2014).

Additional references

Al Kadri 2011
    1. Al Kadri HM, Al Anazi BK, Tamim HM. Visual estimation versus gravimetric measurement of postpartum blood loss: a prospective cohort study. Archives of Gynecology and Obstetrics 2011;283(6):1207‐13. - PubMed
Begley 2019
    1. Begley CM, Gyte GML, Devane D, McGuire W, Weeks A, Biesty LM. Active versus expectant management for women in the third stage of labour. Cochrane Database of Systematic Reviews 2019, Issue 2. [DOI: 10.1002/14651858.CD007412.pub5] - DOI - PMC - PubMed
Borovac‐Pinheiro 2018
    1. Borovac‐Pinheiro A, Pacagnella RC, Cecatti JG, Miller S, Ayadi AM, Souza JP, et al. Postpartum hemorrhage: new insights for definition and diagnosis. American Journal of Obstetrics and Gynecology 2018;219(2):162‐8. - PubMed
De Groot 1998
    1. Groot AN, Dongen PW, Vree TB, Hekster YA, Roosmalen J. Ergot alkaloids. Current status and review of clinical pharmacology and therapeutic use compared with other oxytocics in obstetrics and gynecology. Drugs 1998;56(4):523‐35. - PubMed
Dildy 2004
    1. Dildy GA, Paine AR, George NC, Velasco C. Estimating blood loss: can teaching significantly improve visual estimation?. Obstetrics and Gynecology 2004;104(3):601‐6. - PubMed
Du Vigneaud 1953
    1. Du Vigneaud V, Ressler C, Tippet S. The sequence of amino acids in oxytocin with a proposal for the structure of oxytocin. Journal of Biological Chemistry 1953;205:949. - PubMed
Embrey 1963
    1. Embrey MP, Barber DT, Scudamore JH. Use of syntometrine in prevention of post partum haemorrhage. British Medical Journal 1963;1:1387‐9. - PMC - PubMed
Gallos 2018
    1. Gallos ID, Papadopoulou A, Man R, Athanasopoulos N, Tobias A, Price MJ, et al. Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis. Cochrane Database of Systematic Reviews 2018, Issue 12. [DOI: 10.1002/14651858.CD011689.pub3] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Hoffman 2006a
    1. Hoffman M, Castagnola D, Naqvi F. A randomized trial of active versus expectant management of the third stage of labor [abstract]. American Journal of Obstetrics and Gynecology 2006;195(6 Suppl 1):S107.
Hogan 2010
    1. Hogan MC, Foreman KJ, Naghavi M, Ahn SY, Wang M, Makela SM, et al. Maternal mortality of 181 countries, 1980‐2008: a systemic analysis of progress towards Millennium Development Goals 5. Lancet 2010;375(9726):1609‐23. - PubMed
Kassebaum 2016
    1. Kassebaum NJ, Barber RM, Bhutta ZA, Dandona L, Gething PW, Hay SI, et al. Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388(10053):1775‐812. - PMC - PubMed
Liabsuetrakul 2018
    1. Liabsuetrakul T, Choobun T, Peeyananjarassri K, Islam QM. Prophylactic use of ergot alkaloids in the third stage of labour. Cochrane Database of Systematic Reviews 2018, Issue 6. [DOI: 10.1002/14651858.CD005456.pub3] - DOI - PMC - PubMed
Meher 2018
    1. Meher S, Cuthbert A, Kirkham JJ, Williamson P, Abalos E, Aflaifel N, et al. Core outcome sets for prevention and treatment of postpartum hemorrhage: an international Delphi consensus study. British Journal of Obstetrics and Gynaecology 2018;126(1):83‐93. [DOI: 10.1111/1471-0528.15335] - DOI - PubMed
Moir 1932
    1. Moir JC. The action of ergot preparation on the puerperal uterus. British Medical Journal 1932;1:1119‐22. - PMC - PubMed
Moir 1955
    1. Moir JC. The history of present day use of ergot. Canadian Medical Association Journal 1955;72:727‐34. - PMC - PubMed
Mori 2012
    1. Mori R, Nardin JM, Yamamoto N, Carroli G, Weeks A. Umbilical vein injection for the routine management of third stage of labour. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/14651858.CD006176.pub2] - DOI - PubMed
Novikova 2015
    1. Novikova N, Hofmeyr GJ, Cluver C. Tranexamic acid for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews 2015, Issue 6. [DOI: 10.1002/14651858.CD007872.pub3] - DOI - PubMed
Pantoja 2016
    1. Pantoja T, Abalos E, Chapman E, Vera C, Serrano VP. Oxytocin for preventing postpartum haemorrhage (PPH) in non‐facility birth settings. Cochrane Database of Systematic Reviews 2016, Issue 4. [DOI: 10.1002/14651858.CD011491.pub2] - DOI - PMC - PubMed
RevMan 2014 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Say 2014
    1. Say L, Chou D, Gemmill A, Tuncalp O, Moller A, Daniels J, et al. Global cause of maternal death: a WHO systematic analysis. Lancet 2014;2(6):e323‐e333. - PubMed
Stafford 2008
    1. Stafford I, Dildy GA, Clark SL, Belfort MA. Visually estimated and calculated blood loss in vaginal and cesarean delivery. American Journal of Obstetrics and Gynecology 2008;199(5):519.e1‐7. - PubMed
Su 2012
    1. Su LL, Chong YS, Samuel M. Carbetocin for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews 2012, Issue 4. [DOI: 10.1002/14651858.CD005457.pub4] - DOI - PubMed
Toledo 2007
    1. Toledo P, McCarthy RJ, Hewlett BJ, Fitzgerald PC, Wong CA. The accuracy of blood loss estimation after simulated vaginal delivery. Anesthesia Analgesia 2007;105(6):1736‐40. - PubMed
Tunçalp 2012
    1. Tunçalp Ö, Hofmeyr GJ, Gülmezoglu AM. Prostaglandins for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews 2012, Issue 8. [DOI: 10.1002/14651858.CD000494.pub4] - DOI - PMC - PubMed
WHO 2012
    1. World Health Organization. WHO recommendations for the prevention and treatment of postpartum haemorrhage. https://apps.who.int/iris/bitstream/handle/10665/75411/9789241548502_eng.... Geneva: World Health Organization, (date accessed 27 August 2018).
WHO 2018
    1. World Health Organization. WHO recommendations for the prevention of postpartum haemorrhage. https://afro.who.int/sites/default/files/2017‐06/WHO_MPS_0706_engPPH.pdf. Geneva: World Health Organization, (accessed 1 February 2019).

References to other published versions of this review

Cotter 2001
    1. Cotter AM, Ness A, Tolosa JE. Prophylactic oxytocin for the third stage of labour. Cochrane Database of Systematic Reviews 2001, Issue 4. [DOI: 10.1002/14651858.CD001808] - DOI - PubMed
Elbourne 1988
    1. Elbourne D, Prendiville W, Chalmers I. Choice of oxytocic preparation for routine use in the management of the third stage of labour: an overview of evidence from controlled trials. British Journal of Obstetrics and Gynaecology 1988;95(1):17‐30. - PubMed
Prendiville 1988b
    1. Prendiville W, Elbourne D, Chalmers I. The effect of routine oxytocic administration in the management of the third stage of labour: an overview of the evidence from controlled trials. British Journal of Obstetrics and Gynaecology 1988;95(1):3‐16. - PubMed
Prendiville 1989
    1. Prendiville WJ, Elbourne DR. Care during the third stage of labour. In: Chalmers I, Enkin M, Keirse MJNC editor(s). Effective Care in Pregnancy and Childbirth. Vol. 2, Oxford: Oxford University Press, 1989:1145‐69.
Westhoff 2013
    1. Westhoff G, Cotter AM, Tolosa JE. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage. Cochrane Database of Systematic Reviews 2013, Issue 10. [DOI: 10.1002/14651858.CD001808.pub2] - DOI - PubMed

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