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A Double-Blinded, Randomized Controlled Trial of Oxytocin at the Beginning versus the End of the Third Stage of Labor for Prevention of Postpartum Hemorrhage
Abstract
The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage.
Patients with documented singleton pregnancies were randomly assigned to two groups. The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta. The second received the opposite medication sequence. The study was double blinded. Blood loss was measured by weighing all fluids collected, visual estimation, and serial blood counts.
27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta. Oxytocin given after placenta delivery resulted in lower blood loss (345 vs. 400 ml, p = 0.28), lower collection bag weight (763 vs. 833 g, p = 0.55), lower change in HgB (-1.26 vs. -1.32 g, p = 0.86), lower DeltaHCT (-3.43 vs. -3.64%, p = 0.85), and a shorter third stage of labor duration (8.6 vs. 9.2 min, p = 0.75). The incidence of postpartum hemorrhage, defined as estimated blood loss >500 ml (0 vs. 14.8%) was significantly lowered with oxytocin following placental delivery (p = 0.049).
In our study, postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery.
... 16 Various researches are conducted to find out the effective and convenient time of administration of oxytocin during delivery which will prevent PPH and also bring out operational feasibility. 1,[16][17][18][19] But there is scarcity of the same in Bankura district of West Bengal. With this backdrop, the present study had been taken up to find out the ideal timing of oxytocin administration in the "active management of third stage of labour" to prevent postpartum haemorrhage. ...
... Nadim AA et al, Jackson KW et al, Soltani H et al, in their previous researches similarly found that timing of administration of oxytocin had no impact in the change of occurrence of the event of PPH, while Huh WK et al, reported that incidence of PPH was found to be significantly lower in the group when oxytocin was administered after placental delivery. 1,16,17,20 However, in this study when mean blood loss amount had been compared between the two groups, it was clearly evident that mean blood loss was significantly less if oxytocin administered before placental delivery than after placental delivery. Similar findings had been demonstrated in previous researches by Mohamadian S et al, Orhan EO et al. 18,19 Timing of administration of oxytocin remained a matter of debate since it had become an important drug to prevent occurrence of an event of PPH. ...
... 16 Various researches are conducted to find out the effective and convenient time of administration of oxytocin during delivery which will prevent PPH and also bring out operational feasibility. 1,[16][17][18][19] But there is scarcity of the same in Bankura district of West Bengal. With this backdrop, the present study had been taken up to find out the ideal timing of oxytocin administration in the "active management of third stage of labour" to prevent postpartum haemorrhage. ...
... Nadim AA et al, Jackson KW et al, Soltani H et al, in their previous researches similarly found that timing of administration of oxytocin had no impact in the change of occurrence of the event of PPH, while Huh WK et al, reported that incidence of PPH was found to be significantly lower in the group when oxytocin was administered after placental delivery. 1,16,17,20 However, in this study when mean blood loss amount had been compared between the two groups, it was clearly evident that mean blood loss was significantly less if oxytocin administered before placental delivery than after placental delivery. Similar findings had been demonstrated in previous researches by Mohamadian S et al, Orhan EO et al. 18,19 Timing of administration of oxytocin remained a matter of debate since it had become an important drug to prevent occurrence of an event of PPH. ...
Background: PPH is the prime cause of maternal mortality worldwide. The incidence of PPH can be drastically combatted by application of uterotonic in active management of third stage labour. Timing of its administration is a matter of concern. This study aimed to assess whether timing of administration of oxytocin would have any impact on incidence or mean blood loss of PPH.Methods: It was a single blinded randomized controlled trial conducted in the department of Obstetrics and Gynecology, Bankura Sammilani Medical College for 6 months where 100 antenatal mothers admitted for normal delivery in labour room were allocated randomly in study and control group considering inclusion and exclusion criteria. Incidence of PPH and mean blood loss had been identified clinically by following them for 24 hours.Results: Only 9% of study population had experienced PPH. There was no statistically significant difference in incidence of PPH with difference in timing of administration of oxytocin (p >0.05). But there was statistically significant decrease in mean blood loss if oxytocin was administered before the placental delivery. The mean blood loss with oxytocin administered before placental delivery was 296.8 ml (102.45) and after placental delivery was 452.0 (128.87) ml respectively.Conclusions: Policy makers should keep in mind not only the incidence of PPH, but the mean blood loss amount too in a setting where anaemia in pregnancy is quite prevalent.
... Fujimoto et al. [11] reported significantly decreased postpartum bleeding risk in a group who received oxytocin after delivery of the anterior shoulder. By contrast, Huh et al. [12] stated that postpartum blood loss was less and the third stage was shorter when oxytocin (10 IU intramuscular) was administered after delivery of the placenta than when it was administered after delivery of the fetal anterior shoulder. Jackson et al. [13] administered 20 IU of oxytocin in crystalloid solution by intravenous bolus upon delivery of either the fetal anterior shoulder or placenta, and found no significant difference between the two groups with respect to the incidence of PPH, rate of retained placenta, or duration of the third stage. ...
... The UK National Institute for Health and Care Excellence guideline for intrapartum care [9] recommends the administration of 10 IU of intramuscular oxytocin during the Fujimoto et al. [11] reported significantly decreased postpartum bleeding risk in a group who received oxytocin after delivery of the anterior shoulder. By contrast, Huh et al. [12] stated that postpartum blood loss was less and the third stage was shorter when oxytocin (10 IU intramuscular) was administered after delivery of the placenta than when it was administered after delivery of the fetal anterior shoulder. Jackson et al. [13] administered 20 IU of oxytocin in crystalloid solution by intravenous bolus upon delivery of either the fetal anterior shoulder or placenta, and found no significant difference between the two groups with respect to the incidence of PPH, rate of retained placenta, or duration of the third stage. ...
Objective
: To determine the most efficient route and timing of oxytocin administration for active management of the third stage of labor.
Methods
: A prospective randomized study was done at one center in Ankara, Turkey, between January and October 2010. Women with a singleton pregnancy (> 37 weeks) who had a live vaginal birth were randomly allocated to four groups: iv-A (intravenous oxytocin after delivery of the fetus), iv-B (when anterior shoulder seen), im-A (intramuscular oxytocin after delivery), and im-B (when anterior shoulder seen). Postpartum blood loss within the first hour, hemoglobin, hematocrit, and duration of the third stage were compared.
Results
: A total of 600 eligible women were recruited; 150 were assigned to each group. Postpartum blood loss, prepartum and postpartum hemoglobin and hematocrit, and need for additional uterotonics were similar among groups (P > 0.05). The duration of the third stage of labor and changes in hemoglobin and hematocrit were significantly reduced in group iv-B (P < 0.05). Among women not exposed to oxytocin before delivery, postpartum blood loss was significantly lower in group iv-B (P = 0.019). Labor augmentation was related to significantly increased postpartum blood loss in all groups except iv-A.
Conclusion
: Although postpartum blood loss was similar in all groups, early intravenous administration seemed to have beneficial effects.
... However, it does reduce the bleeding intensity and hemorrhage frequency, which was also in harmony with our study [34]. Methylergonovine and oxytocin are stimulators of uterine contraction that act directly on uterine smooth muscle and peripheral vasculature, especially uterine vessels, and thus reduce bleeding [35,36]. ...
Objective
The complications associated with miscarriages have surfaced as a major concern in maintaining women’s physical and mental health. The present study evaluated the efficacy of three medication regimes for the complete expulsion of retained intrauterine tissues in patients who underwent a miscarriage.
Methods
In this randomized clinical trial, 90 patients participated with their gestational age below 12 weeks, each having undergone a recent miscarriage. After being screened for underlying diseases and coagulative blood disorders, they were randomly allocated into three groups. For the first group, labeled as the control group, misoprostol was administered alone. In contrast, the combination of misoprostol plus methylergometrine and misoprostol plus oxytocin was prescribed for the second and third groups, respectively. Further, the data obtained were analyzed by descriptive and inferential statistics using Stata software version 14.
Results
The mean age of participants and gestational age were 29.76 ± 5.53 years and 8.23 ± 2.29 weeks, respectively. There was no significant difference between the three treatment groups regarding the amount of bleeding after the abortion(P = 0.627). Regarding pain severity, the group that received Misoprostol plus Methylergometrine had less pain intensity than the other two groups(p = 0.004). The mean rate of RPOC expulsion was in the Misoprostol plus Oxytocin (9.68 ± 10.36) group, Misoprostol plus Methylergometrine (11.73 ± 12.86), and Misoprostol groups (19.07 ± 14.31)(p = 0.013). The success rate in outpatient medical abortion in the misoprostol plus oxytocin and misoprostol plus methylergonovine group was 93.33%, but in patients treated by misoprostol alone was 83.33%.
Conclusion
The effectiveness of the drugs in the two drug groups combined with oxytocin and methylergometrine is higher than the misoprostol group alone. An outpatient approach was deemed more satisfactory against surgical maneuvers and hospitalizations by patients since family support influenced their pain coping mechanism.
Trial registration
The trial was registered in the Iranian registry of clinical trials on 04/10/2019. (https://fa.irct.ir/trial/34519; registration number: IRCT20150407021653N19).
... Further initial prophylaxis involves treatment with oxytocin (19), either 20 units in one liter of IV fluid or 10 units intramuscularly. The timing of this therapy remains a matter of some debate, and local practice methods often govern whether it is administered after cord clamp or following delivery of the placenta (20)(21)(22). ...
... IV administration may have a clinical advantage, as it leads to a faster response and a higher peak in plasma oxytocin levels [12][13][14]; however, IM injection confers practical advantages, requiring fewer skills and less equipment to administer, making it a more serviceable option in a wider array of settings [9,15]. Despite many discussions of the clinical importance of route [9,[15][16][17][18][19][20][21][22][23][24][25], differences in efficacy remain largely uninvestigated. The few published studies investigating route are inconsistent, with two showing reduced blood loss associated with IV administration [24,25] and two others showing no difference between IV and IM administration [20,21]. ...
Background
Oxytocin for postpartum hemorrhage (PPH) prophylaxis is commonly administered by either intramuscular (IM) injection or intravenous (IV) infusion with both routes recommended equally and little discussion of potential differences between the two. This trial assesses the effectiveness and safety of 10 IU oxytocin administered as IM injection versus IV infusion and IV bolus during the third stage of labor for PPH prophylaxis.
Methods
In two tertiary level Egyptian maternity hospitals, women delivering vaginally without exposure to pre-delivery uterotonics were randomized to one of three prophylactic oxytocin administration groups after delivery of the baby. Blood loss was measured 1 h after delivery, and side effects were recorded. Primary outcomes were mean postpartum blood loss and proportion of women with postpartum blood loss ≥500 ml in this open-label, three-arm, parallel, randomized controlled trial.
Results
Four thousand nine hundred thirteen eligible, consenting women were randomized. Compared to IM injection, mean blood loss was 5.9% less in the IV infusion arm (95% CI: -8.5, − 3.3) and 11.1% less in the IV bolus arm (95% CI: -14.7, − 7.8). Risk of postpartum blood loss ≥500 ml in the IV infusion arm was significantly less compared to IM injection (0.8% vs. 1.5%, RR = 0.50, 95% CI: 0.27, 0.91). No side effects were reported in any arm.
Conclusions
Intravenous oxytocin is more effective than intramuscular injection for the prevention of PPH in the third stage of labor. Oxytocin delivered by IV bolus presents no safety concerns after vaginal delivery and should be considered a safe option for PPH prophylaxis.
Trial registration
clinicaltrials.gov #NCT01914419, posted August 2, 2013.
... As all infants had immediate cord clamping (27), this finding is consistent with the view that delayed cord clamping causes placenta to infant blood transfusion. There is also evidence that oxytocin administration after delivery of the placenta is associated with less maternal blood loss than administration before delivery of the placenta (28) and that early administration of oxytocin may increase the risk of a retained placenta (29). Perhaps, therefore, it is time to revisit how the third stage of labour is managed with reference to the timing of oxytocin administration and umbilical cord clamping so that both maternal and neonatal outcomes are considered. ...
The transition to newborn life at birth involves major cardiovascular changes that are triggered by lung aeration. These include a large increase in pulmonary blood flow (PBF), which is required for pulmonary gas exchange and to replace umbilical venous return as the source of preload for the left heart. Clamping the umbilical cord before PBF increases reduces venous return and preload for the left heart and thereby reduces cardiac output. Thus, if ventilation onset is delayed following cord clamping, the infant is at risk of superimposing an ischemic insult, due to low cardiac output, on top of an asphyxic insult. Much debate has centered on the timing of cord clamping at birth, focusing mainly on the potential for a time dependent placental to infant blood transfusion. This has prompted recommendations for delayed cord clamping for a set time after birth in infants not requiring resuscitation. However, recent evidence indicates that ventilation onset before cord clamping mitigates the adverse cardiovascular consequences caused by immediate cord clamping. This indicates that the timing of cord clamping should be based on the infant's physiology rather than an arbitrary period of time and that delayed cord clamping may be of greatest benefit to apneic infants.Pediatric Research (2015); doi:10.1038/pr.2015.21.
... One study reported that early administration did not increase the risk of manual removal of the placenta and that PPH was prevented equally eff ectively; the uterotonic agent can thus be administered either before or aft er delivery of the placenta (Jackson et al., 2001). Another study showed less frequent PPH when oxytocin was administered aft er placenta delivery (Huh et al., 2004). ...
... A escolha do medicamento uterotônico e de sua via de administração (parenteral, oral ou retal) requer maiores estudos (9)(10)(11)(12)(13)(14) . Os efeitos adversos da ocitocina (9-10) -tido hoje como o ocitócico de escolha na maior parte das maternidades -são bastante conhecidos (vômitos, náuseas, cefaleia, intoxicação hídrica), porém se comparada à ergometrina (maior de elevação dos índices pressóricos) seus danos maternos e fetais podem ser menores (6,15) . ...
OBJETIVO: Descrever as práticas obstétricas e os resultados maternos e neonatais de dois Centros de Parto Normal do Município de São Paulo, comparandose as unidades intra e extra-hospitalares. MÉTODOS: Estudo observacional, transversal e retrospectivo com dados secundários provenientes de 192 prontuários das instituições envolvidas. As variáveis de estudo foram as práticas selecionadas para o parto normal: a utilização de ocitocina, o tipo de rompimento das membranas amnióticas, a realização de episiotomia ou perineotomia e o tempo de permanência materna e neonatal. Foi elaborado um instrumento informatizado para coleta de dados com base nas variáveis de estudo. Os dados foram tratados através de análise estatística multivariada. RESULTADOS: O centro de parto normal intra-hospitalar utilizou com maior frequência às intervenções relacionadas à utilização de ocitocina, rompimento artificial de membranas amnióticas e tempo de permanência materna e neonatal superior às 48h, após o parto. O centro de parto normal extra-hospitalar apresentou maior frequência de parturientes com períneo íntegro após o parto, rompimento de membranas de maneira espontânea e tempo de permanência materna e neonatal inferior a 48 horas pós-parto. Os resultados maternos e neonatais não evidenciaram complicações relacionadas às práticas utilizadas. CONCLUSÃO: As práticas obstétricas pouco diferiram, comparando-se os dois tipos de Centros de Parto Normal; ambos seguem as recomendações da Organização Mundial de Saúde e aplicam as intervenções somente nos casos indicados.
... A escolha do medicamento uterotônico e de sua via de administração (parenteral, oral ou retal) requer maiores estudos (9)(10)(11)(12)(13)(14) . Os efeitos adversos da ocitocina (9-10) -tido hoje como o ocitócico de escolha na maior parte das maternidades -são bastante conhecidos (vômitos, náuseas, cefaleia, intoxicação hídrica), porém se comparada à ergometrina (maior de elevação dos índices pressóricos) seus danos maternos e fetais podem ser menores (6,15) . ...
OBJETIVO: Descrever as práticas obstétricas e os resultados maternos e neonatais de dois Centros de Parto Normal do Município de São Paulo, comparandose as unidades intra e extra-hospitalares. MÉTODOS: Estudo observacional, transversal e retrospectivo com dados secundários provenientes de 192 prontuários das instituições envolvidas. As variáveis de estudo foram as práticas selecionadas para o parto normal: a utilização de ocitocina, o tipo de rompimento das membranas amnióticas, a realização de episiotomia ou perineotomia e o tempo de permanência materna e neonatal. Foi elaborado um instrumento informatizado para coleta de dados com base nas variáveis de estudo. Os dados foram tratados através de análise estatística multivariada. RESULTADOS: O centro de parto normal intra-hospitalar utilizou com maior frequência às intervenções relacionadas à utilização de ocitocina, rompimento artificial de membranas amnióticas e tempo de permanência materna e neonatal superior às 48h, após o parto. O centro de parto normal extra-hospitalar apresentou maior frequência de parturientes com períneo íntegro após o parto, rompimento de membranas de maneira espontânea e tempo de permanência materna e neonatal inferior a 48 horas pós-parto. Os resultados maternos e neonatais não evidenciaram complicações relacionadas às práticas utilizadas. CONCLUSÃO: As práticas obstétricas pouco diferiram, comparando-se os dois tipos de Centros de Parto Normal; ambos seguem as recomendações da Organização Mundial de Saúde e aplicam as intervenções somente nos casos indicados.
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.
Background:
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic agents can prevent PPH, and are routinely recommended. The current World Health Organization (WHO) recommendation for preventing PPH is 10 IU (international units) of intramuscular or intravenous oxytocin. There are several uterotonic agents for preventing PPH but there is still uncertainty about which agent is most effective with the least side effects. This is an update of a Cochrane Review which was first published in April 2018 and was updated to incorporate results from a recent large WHO trial.
Objectives:
To identify the most effective uterotonic agent(s) to prevent PPH with the least side effects, and generate a ranking according to their effectiveness and side-effect profile.
Search methods:
We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (24 May 2018), and reference lists of retrieved studies.
Selection criteria:
All randomised controlled trials or cluster-randomised trials comparing the effectiveness and side effects of uterotonic agents with other uterotonic agents, placebo or no treatment for preventing PPH were eligible for inclusion. Quasi-randomised trials were excluded. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved.
Data collection and analysis:
At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. Secondary outcomes included blood loss and related outcomes, morbidity outcomes, maternal well-being and satisfaction and side effects. Primary outcomes were also reported for pre-specified subgroups, stratifying by mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of administration. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available agents.
Main results:
The network meta-analysis included 196 trials (135,559 women) involving seven uterotonic agents and placebo or no treatment, conducted across 53 countries (including high-, middle- and low-income countries). Most trials were performed in a hospital setting (187/196, 95.4%) with women undergoing a vaginal birth (71.5%, 140/196).Relative effects from the network meta-analysis suggested that all agents were effective for preventing PPH ≥ 500 mL when compared with placebo or no treatment. The three highest ranked uterotonic agents for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, misoprostol plus oxytocin combination and carbetocin. There is evidence that ergometrine plus oxytocin (RR 0.70, 95% CI 0.59 to 0.84, moderate certainty), carbetocin (RR 0.72, 95% CI 0.56 to 0.93, moderate certainty) and misoprostol plus oxytocin (RR 0.70, 95% CI 0.58 to 0.86, low certainty) may reduce PPH ≥ 500 mL compared with oxytocin. Low-certainty evidence suggests that misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin.All agents except ergometrine and injectable prostaglandins were effective for preventing PPH ≥ 1000 mL when compared with placebo or no treatment. High-certainty evidence suggests that ergometrine plus oxytocin (RR 0.83, 95% CI 0.66 to 1.03) and misoprostol plus oxytocin (RR 0.88, 95% CI 0.70 to 1.11) make little or no difference in the outcome of PPH ≥ 1000 mL compared with oxytocin. Low-certainty evidence suggests that ergometrine may make little or no difference to this outcome compared with oxytocin meanwhile the evidence on carbetocin was of very low certainty. High-certainty evidence suggests that misoprostol is less effective in preventing PPH ≥ 1000 mL when compared with oxytocin (RR 1.19, 95% CI 1.01 to 1.42). Despite the comparable relative treatment effects between all uterotonics (except misoprostol) and oxytocin, ergometrine plus oxytocin, misoprostol plus oxytocin combinations and carbetocin were the highest ranked agents for PPH ≥ 1000 mL.Misoprostol plus oxytocin reduces the use of additional uterotonics (RR 0.56, 95% CI 0.42 to 0.73, high certainty) and probably also reduces the risk of blood transfusion (RR 0.51, 95% CI 0.37 to 0.70, moderate certainty) when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe morbidity as these outcomes were rare in the included randomised trials where they were reported.The two combination regimens were associated with important side effects. When compared with oxytocin, misoprostol plus oxytocin combination increases the likelihood of vomiting (RR 2.11, 95% CI 1.39 to 3.18, high certainty) and fever (RR 3.14, 95% CI 2.20 to 4.49, moderate certainty). Ergometrine plus oxytocin increases the likelihood of vomiting (RR 2.93, 95% CI 2.08 to 4.13, moderate certainty) and may make little or no difference to the risk of hypertension, however absolute effects varied considerably and the certainty of the evidence was low for this outcome.Subgroup analyses did not reveal important subgroup differences by mode of birth (caesarean versus vaginal birth), setting (hospital versus community), risk of PPH (high versus low risk for PPH), dose of misoprostol (≥ 600 mcg versus < 600 mcg) and regimen of oxytocin (bolus versus bolus plus infusion versus infusion only).
Authors' conclusions:
All agents were generally effective for preventing PPH when compared with placebo or no treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional desirable effects compared with the current standard oxytocin. The two combination regimens, however, are associated with significant side effects. Carbetocin may be more effective than oxytocin for some outcomes without an increase in side effects.
Background:
Previous research has shown that the prophylactic use of uterotonic agents in the third stage of labour reduces postpartum blood loss and moderate to severe postpartum haemorrhage (PPH). PPH is defined as a blood loss of 500 mL or more within 24 hours after birth. This is one of a series of systematic reviews assessing the effects of prophylactic use of uterotonic drugs; in this review prophylactic ergot alkaloids as a whole, and different regimens of administration of ergot alkaloids, are compared with no uterotonic agents. This is an update of a Cochrane Review which was first published in 2007 and last updated in 2011.
Objectives:
To determine the effectiveness and safety of prophylactic use of ergot alkaloids in the third stage of labour by any route (intravenous (IV), intramuscular (IM), or oral) compared with no uterotonic agents, for the prevention of PPH.
Search methods:
For this update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (19 September 2017); we also searched reference lists of retrieved studies.
Selection criteria:
We included all randomised controlled trials or cluster-randomised trials comparing prophylactic ergot alkaloids by any route (IV, IM, or oral) with no uterotonic agents in the third stage of labour among women giving birth vaginally.
Data collection and analysis:
Two review authors independently assessed trials for inclusion, extracted data and checked them for accuracy; they also assessed the risk of bias in included studies. Two review authors assessed the quality of the evidence using the GRADE approach.
Main results:
There were eight included studies: three studies had a low risk of bias and five studies had high risk of bias. The studies compared ergot alkaloids with no uterotonic agents, with a total of 2031 women in the ergot alkaloids group and 1978 women in the placebo or no treatment group. Seven studies used the IV/IM route of administration and one study used the oral route.Ergot alkaloids (any route of administration) versus no uterotonic agentsUse of ergot alkaloids in the third stage of labour decreased mean blood loss (mean difference (MD) -80.52 mL, 95% confidence interval (CI) -96.39 to -64.65 mL; women = 2718; studies = 3; moderate-quality evidence); decreased PPH of at least 500 mL (average risk ratio (RR) 0.52, 95% CI 0.28 to 0.94; women = 3708; studies = 5; I2 = 83%; low-quality evidence); increased maternal haemoglobin concentration (g/dL) at 24 to 48 hours postpartum (MD 0.50 g/dL, 95% CI 0.38 to 0.62; women = 1429; studies = 1; moderate-quality evidence); and decreased the use of therapeutic uterotonics (average RR 0.37, 95% CI 0.15 to 0.90; women = 2698; studies = 3; I2 = 89%; low-quality evidence). There were no clear differences between groups in severe PPH of at least 1000 mL (average RR 0.32, 95% CI 0.04 to 2.59; women = 1718; studies = 2; I2 = 74%; very low-quality evidence). The risk of retained placenta or manual removal of the placenta, or both, were inconsistent with high heterogeneity. Ergot alkaloids increased the risk of elevated blood pressure (average RR 2.60, 95% CI 1.03 to 6.57: women = 2559; studies = 3; low-quality evidence) and pain after birth requiring analgesia (RR 2.53, 95% CI 1.34 to 4.78: women = 1429; studies = 1; moderate-quality evidence) but there were no differences between groups in vomiting, nausea, headache or eclamptic fit.Results for IV/IM ergot alkaloids versus no uterotonic agents were similar to those for the main comparison of ergot alkaloids administered by any route, since most of the studies (seven of eight) used the IV/IM route. Only one small study (289 women) compared oral ergometrine with placebo and it showed no benefit of ergometrine over placebo. No maternal adverse effects were reported.None of the studies reported on any of our prespecified neonatal outcomes AUTHORS' CONCLUSIONS: Prophylactic IM or IV injections of ergot alkaloids may be effective in reducing blood loss, reducing PPH (estimated blood loss of at least 500 mL), and increasing maternal haemoglobin. Ergot alkaloids may also decrease the use of therapeutic uterotonics, but adverse effects may include elevated blood pressure and pain after birth requiring analgesia. There were no differences between groups in terms of other adverse effects (vomiting, nausea, headache or eclamptic fit). There is a lack of evidence on the effects of ergot alkaloids on severe PPH, and retained or manual removal of placenta. There is also a lack of evidence on the oral route of administration of ergot alkaloids.
Background:
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality worldwide. Prophylactic uterotonic drugs can prevent PPH, and are routinely recommended. There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best.
Objectives:
To identify the most effective uterotonic drug(s) to prevent PPH, and generate a ranking according to their effectiveness and side-effect profile.
Search methods:
We searched Cochrane Pregnancy and Childbirth's Trials Register (1 June 2015), ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for unpublished trial reports (30 June 2015) and reference lists of retrieved studies.
Selection criteria:
All randomised controlled comparisons or cluster trials of effectiveness or side-effects of uterotonic drugs for preventing PPH.Quasi-randomised trials and cross-over trials are not eligible for inclusion in this review.
Data collection and analysis:
At least three review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for preventing PPH ≥ 500 mL and PPH ≥ 1000 mL as primary outcomes. We performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available drugs. We stratified our primary outcomes according to mode of birth, prior risk of PPH, healthcare setting, dosage, regimen and route of drug administration, to detect subgroup effects.The absolute risks in the oxytocin are based on meta-analyses of proportions from the studies included in this review and the risks in the intervention groups were based on the assumed risk in the oxytocin group and the relative effects of the interventions.
Main results:
This network meta-analysis included 140 randomised trials with data from 88,947 women. There are two large ongoing studies. The trials were mostly carried out in hospital settings and recruited women who were predominantly more than 37 weeks of gestation having a vaginal birth. The majority of trials were assessed to have uncertain risk of bias due to poor reporting of study design. This primarily impacted on our confidence in comparisons involving carbetocin trials more than other uterotonics.The three most effective drugs for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination. These three options were more effective at preventing PPH ≥ 500 mL compared with oxytocin, the drug currently recommended by the WHO (ergometrine plus oxytocin risk ratio (RR) 0.69 (95% confidence interval (CI) 0.57 to 0.83), moderate-quality evidence; carbetocin RR 0.72 (95% CI 0.52 to 1.00), very low-quality evidence; misoprostol plus oxytocin RR 0.73 (95% CI 0.60 to 0.90), moderate-quality evidence). Based on these results, about 10.5% women given oxytocin would experience a PPH of ≥ 500 mL compared with 7.2% given ergometrine plus oxytocin combination, 7.6% given carbetocin, and 7.7% given misoprostol plus oxytocin. Oxytocin was ranked fourth with close to 0% cumulative probability of being ranked in the top three for PPH ≥ 500 mL.The outcomes and rankings for the outcome of PPH ≥ 1000 mL were similar to those of PPH ≥ 500 mL. with the evidence for ergometrine plus oxytocin combination being more effective than oxytocin (RR 0.77 (95% CI 0.61 to 0.95), high-quality evidence) being more certain than that for carbetocin (RR 0.70 (95% CI 0.38 to 1.28), low-quality evidence), or misoprostol plus oxytocin combination (RR 0.90 (95% CI 0.72 to 1.14), moderate-quality evidence)There were no meaningful differences between all drugs for maternal deaths or severe morbidity as these outcomes were so rare in the included randomised trials.Two combination regimens had the poorest rankings for side-effects. Specifically, the ergometrine plus oxytocin combination had the higher risk for vomiting (RR 3.10 (95% CI 2.11 to 4.56), high-quality evidence; 1.9% versus 0.6%) and hypertension [RR 1.77 (95% CI 0.55 to 5.66), low-quality evidence; 1.2% versus 0.7%), while the misoprostol plus oxytocin combination had the higher risk for fever (RR 3.18 (95% CI 2.22 to 4.55), moderate-quality evidence; 11.4% versus 3.6%) when compared with oxytocin. Carbetocin had similar risk for side-effects compared with oxytocin although the quality evidence was very low for vomiting and for fever, and was low for hypertension.
Authors' conclusions:
Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current standard oxytocin. Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin. Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies. Carbetocin had the most favourable side-effect profile amongst the top three options; however, most carbetocin trials were small and at high risk of bias.Amongst the 11 ongoing studies listed in this review there are two key studies that will inform a future update of this review. The first is a WHO-led multi-centre study comparing the effectiveness of a room temperature stable carbetocin versus oxytocin (administered intramuscularly) for preventing PPH in women having a vaginal birth. The trial includes around 30,000 women from 10 countries. The other is a UK-based trial recruiting more than 6000 women to a three-arm trial comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018.Consultation with our consumer group demonstrated the need for more research into PPH outcomes identified as priorities for women and their families, such as women's views regarding the drugs used, clinical signs of excessive blood loss, neonatal unit admissions and breastfeeding at discharge. To date, trials have rarely investigated these outcomes. Consumers also considered the side-effects of uterotonic drugs to be important but these were often not reported. A forthcoming set of core outcomes relating to PPH will identify outcomes to prioritise in trial reporting and will inform futures updates of this review. We urge all trialists to consider measuring these outcomes for each drug in all future randomised trials. Lastly, future evidence synthesis research could compare the effects of different dosages and routes of administration for the most effective drugs.
Objective:
Postpartum hemorrhage is still the most significant cause of maternal mortality and morbidity worldwide. Our aim was to evaluate the effect of timing of oxytocin administration on postpartum hemorrhage incidence in parturients with low-risk for postpartum hemorrhage.
Study design:
A randomized controlled trial was completed on 343 women at a level-three care hospital. In group 1, 10 IU of oxytocin was injected intramuscularly within the first minute following the delivery of the fetus. Group 2 received 10 IU of intramuscular oxytocin immediately following placental delivery. The primary outcome parameters were the incidence of postpartum hemorrhage and the measured blood loss.
Results:
The rate of postpartum hemorrhage, defined as estimated blood loss >500 mL, did not differ significantly between the two groups (7/172 (4.1%) in group 1 vs. 10/171 (5.8%) in group 2, P = .45). The mean blood loss did not differ significantly between the two groups (192.18 ± 135.7 in group 1 vs. 198.92 ± 165.4 mL in group 2, P = .68). The duration of the third stage was significantly shorter in group 1. There were no significant differences between the two groups with respect to the mean changes in hemoglobin and hematocrit, postpartum 24th hour hemoglobin and hematocrit, the additional use of oxytocin, manual expulsion of placenta, curettage, blood transfusion demand, uterine atony, and lengthening of the third stage.
Conclusion:
In a level-three care hospital, timing of intramuscular oxytocin administration did not influence the incidence of postpartum hemorrhage in women with low risk of postpartum hemorrhage.
Background and purpose: Postpartum hemorrhage is one of the most common causes of maternal deaths worldwide. Most deaths associated with hemorrhage occur due to delay in diagnosis and proper management of bleeding. This study aimed to evaluate the accuracy of postpartum hemorrhage estimation using artificial blood. Materials and methods: This descriptive study was performed in 92 midwifery students, in Mashhad School of Nursing, 2013. The samples were selected using convenience sampling. Data was collected through questionnaires and objective structured clinical examination. Scenes similar to postpartum hemorrhage were created using artificial blood in six stations. The students saw each station and estimated the volume of blood. Data was analyzed applying central tendency and dispersion indices, paired T-test, and chi-square in SPSS V.16. Results: Accuracy of visual estimation of blood loss was between 2- 20%. In estimation of postpartum hemorrhage it was found that about 40.21% of the students have underestimated, 10.34% had accurate estimation of blood loss and 49.45% estimated higher volume of postpartum hemorrhage than their actual volume. Conclusion: Visual estimation of blood loss was not accurate in most of the subjects. Authorities should focus more on skills and competencies required for accurate estimation of blood loss after delivery by revising the educational curriculum. © 2015, Mazandaran University of Medical Sciences. All rights reserved.
Postpartum hemorrhage is the most important reason for maternal mortality. In developed countries, the reason of 13% of maternal deaths is postpartum hemorrhage while this percentage reaches more than 30% in other countries. In this study, the effect of oxytocin use in different times at the 3
In the study, 89 pregnant women to whom oxytocin was administered after placenta separation were studied in Group 1, 89 pregnant women were included in Group 2, and oxytocin was administered after delivery of the shoulder. The levels of hemoglobin and hematocrit before and after delivery were quantified.
The biochemical parameters were examined, there was no significant statistical differences in the levels of hemoglobin and hemotocrit before delivery between the two groups. When compared to Group 1, Δ-hemoglobin (P=>0.001), Δ-hematocrit (P=>0.001), the change between the prepartum and postpartum hemoglobin percentage (P
Background:
Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage (PPH) greater than 1000 mL. One aspect of the active management protocol is the administration of prophylactic uterotonics, however, the type of uterotonic, dose, and route of administration vary across the globe and may have an impact on maternal outcomes.
Objectives:
To determine the effectiveness of prophylactic oxytocin at any dose to prevent PPH and other adverse maternal outcomes related to the third stage of labour.
Search methods:
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013).
Selection criteria:
Randomised or quasi-randomised controlled trials including pregnant women anticipating a vaginal delivery where prophylactic oxytocin was given during management of the third stage of labour. The primary outcomes were blood loss > 500 mL and the use of therapeutic uterotonics.
Data collection and analysis:
Two review authors independently assessed trials for inclusion, assessed trial quality and extracted data. Data were checked for accuracy.
Main results:
This updated review included 20 trials (involving 10,806 women). Prophylactic oxytocin versus placebo Prophylactic oxytocin compared with placebo reduced the risk of PPH greater than 500 mL, (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.38 to 0.74; six trials, 4203 women; T² = 0.11, I² = 78%) and the need for therapeutic uterotonics (RR 0.56; 95% CI 0.36 to 0.87, four trials, 3174 women; T² = 0.10, I² = 58%). The benefit of prophylactic oxytocin to prevent PPH greater than 500 mL was seen in all subgroups. Decreased use of therapeutic uterotonics was only seen in the following subgroups: randomised trials with low risk of bias (RR 0.58; 95% CI 0.36 to 0.92; three trials, 3122 women; T² = 0.11, I² = 69%); trials that performed active management of the third stage (RR 0.39; 95% CI 0.26 to 0.58; one trial, 1901 women; heterogeneity not applicable); trials that delivered oxytocin as an IV bolus (RR 0.57; 95% CI 0.39 to 0.82; one trial, 1000 women; heterogeneity not applicable); and in trials that gave oxytocin at a dose of 10 IU (RR 0.48; 95% CI 0.33 to 0.68; two trials, 2901 women; T² = 0.02, I² = 27%). Prophylactic oxytocin versus ergot alkaloids. Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL (RR 0.76; 95% CI 0.61 to 0.94; five trials, 2226 women; T² = 0.00, I² = 0%). The benefit of oxytocin over ergot alkaloids to prevent PPH greater than 500 mL only persisted in the subgroups of quasi-randomised trials (RR 0.71, 95% CI 0.53 to 0.96; three trials, 1402 women; T² = 0.00, I² = 0%) and in trials that performed active management of the third stage of labour (RR 0.58; 95% CI 0.38 to 0.89; two trials, 943 women; T² = 0.00, I² = 0%). Use of prophylactic oxytocin was associated with fewer side effects compared with use of ergot alkaloids; including decreased nausea between delivery of the baby and discharge from the labour ward (RR 0.18; 95% CI 0.06 to 0.53; three trials, 1091 women; T² = 0.41, I² = 41%) and vomiting between delivery of the baby and discharge from the labour ward (RR 0.07; 95% CI 0.02 to 0.25; three trials, 1091 women; T² = 0.45, I² = 30%). Prophylactic oxytocin + ergometrine versus ergot alkaloids: There was no benefit seen in the combination of oxytocin and ergometrine versus ergometrine alone in preventing PPH greater than 500 mL (RR 0.90; 95% CI 0.34 to 2.41; five trials, 2891 women; T² = 0.89, I² = 80%). The use of oxytocin and ergometrine was associated with increased mean blood loss (MD 61.0 mL; 95% CI 6.00 to 116.00 mL; fixed-effect analysis; one trial, 34 women; heterogeneity not applicable).In all three comparisons, there was no difference in mean length of the third stage or need for manual removal of the placenta between treatment arms.
Authors' conclusions:
Prophylactic oxytocin at any dose decreases both PPH greater than 500 mL and the need for therapeutic uterotonics compared to placebo alone. Taking into account the subgroup analyses from both primary outcomes, to achieve maximal benefit providers may opt to implement a practice of giving prophylactic oxytocin as part of the active management of the third stage of labour at a dose of 10 IU given as an IV bolus. If IV delivery is not possible, IM delivery may be used as this route of delivery did show a benefit to prevent PPH greater than 500 mL and there was a trend to decrease the need for therapeutic uterotonics, albeit not statistically significant.Prophylactic oxytocin was superior to ergot alkaloids in preventing PPH greater than 500 mL; however, in subgroup analysis this benefit did not persist when only randomised trials with low risk of methodologic bias were analysed. Based on this, there is limited high-quality evidence supporting a benefit of prophylactic oxytocin over ergot alkaloids. However, the use of prophylactic oxytocin was associated with fewer side effects, specifically nausea and vomiting, making oxytocin the more desirable option for routine use to prevent PPH.There is no evidence of benefit when adding oxytocin to ergometrine compared to ergot alkaloids alone, and there may even be increased harm as one study showed evidence that using the combination was associated with increased mean blood loss compared to ergot alkaloids alone.Importantly, there is no evidence to suggest that prophylactic oxytocin increases the risk of retained placenta when compared to placebo or ergot alkaloids.More placebo-controlled, randomised, and double-blinded trials are needed to improve the quality of data used to evaluate the effective dose, timing, and route of administration of prophylactic oxytocin to prevent PPH. In addition, more trials are needed especially, but not only, in low- and middle-income countries to evaluate these interventions in the birth centres that shoulder the majority of the burden of PPH in order to improve maternal morbidity and mortality worldwide.
Challenging the current National Institute for Clinical Excellence guidelines (NICE 2007), this paper will identify and discuss the evidence to support a care pathway for delayed active management of the third stage of labour, which promotes a delay in the administration of the uterotonic drug and delayed cord clamping (DCC). Current evidence highlights that clamping and cutting the umbilical cord once pulsation has ceased allows the baby to receive additional blood from the placenta, which in turn increases the baby's blood volume and significantly reduces instances of anaemia. The research available to support DCC and the benefits this provides to the newborn with little adverse effect to the mother could possibly be enough to change current practice to create Delayed Active Management as a third stage option for women.
Although the focus at delivery may naturally shift to infant transition, continued maternal vigilance during stage 3 is imperative to accomplish a safe outcome for the mother and her newborn. The third stage of labor is a normal physiological progression of birth that may be compounded by serious complications. The most common complication is postpartum hemorrhage due to uterine atony. Clinicians choose either active management or expectant management for stage 3 to prevent excessive maternal blood loss. Rapid identification and response to a postpartum hemorrhage are critical. A multidisciplinary perinatal team at a large Midwest tertiary center led the transition from an expectant to an active-management protocol within the obstetric service. Outcomes included a decrease in the postpartum hemorrhage rate and decreased usage of additional uterotonic medications during the immediate recovery period.
Active management of the third stage of labour has been shown to reduce the risk of postpartum haemorrhage. It usually involves clamping and cutting the cord, administration of uterotonic drugs and controlled cord traction (inserting pressure on the uterus and pulling the cord mainly with the sign of placental separation). Although active management has been shown to reduce the risk of postpartum haemorrhage, it may have an impact on the well-being of the mother and baby in terms of the amount of blood that has been transfused to the baby before the separation of the placenta. The optimum timing of uterotonic administration (before or after placental expulsion) can have a major role in this process and it has not been systematically investigated previously. This review of three trials (1671 participants) found that routine administration of oxytocin with the anterior shoulder compared with use of oxytocin after delivery of the placenta did not have any influence on the amount of bleeding postpartum or retained placenta. The route of administration of oxytocin in two of the three included studies was through intravenous infusion. Cord management at delivery was consistent with double clamping and immediate cutting after delivery of the baby. Application of controlled cord traction was slightly different among the included studies. In two of the studies, the placenta was delivered with controlled cord traction when signs of placental separation were present. Fundal pressure on the uterus was used in one study from the beginning to ensure continued uterine contraction. Oxytocin was the only uterotonic assessed. There were no assessments of any impact on neonatal health. More well designed studies using consistent approaches in this area of the management of the third stage of labour are required.
Postpartum hemorrhage (PPH) remains a significant contributor to maternal morbidity and mortality throughout the world. The majority of research on this topic has focused on efforts to prevent PPH. Sound data exist that active management of the third stage of labor can reduce the occurrence of PPH. Although there remains debate regarding the optimal protocol for active management, it appears at this time that oxytocin is the preferable uterotonic to use. Misoprostol may be a reasonable option where parenteral administration of an uterotonic is not feasible. There is little evidence to guide treatment decisions should PPH occur.
Prophylactic oxytocin is fine before or after placental delivery. Timing alone doesn't influence the drug's efficacy in preventing postpartum bleeding (recommendation based on randomized controlled trial and prospective cohort studies).
Very little is known about possible association of nevi and melasma. The study objective was to determine if there is an association between melasma and existence of different kinds of nevi.
In a case-control study, 120 female melasma patients referred to dermatology clinic of Ardabil and 120 patients referred to other specialty clinics who lacked melasma were enrolled after matching for age. Number of different types of nevi including lentigines and melanocytic nevi were compared between case and control group patients. Data were entered into the computer and analyzed by SPSS 13 statistical software.
Mean number of lentigines was 25.5 in melasma group compared to 8 in control group(P < 0.01). Mean number of melanocytic nevi was 13.2 in cases compared to 2.8 in control group(P < 0.001). Multivariate analysis showed that existence of freckles, lentigines and more than three melanocytic nevi were positively related to developing melasma. The chance of melasma increased up to 23 times for patients having more than three melanocytic nevi. Congenital nevi were observed among 10% both in case and control groups. Campbell de morgan angiomas were seen among 26 patients(21.8%) in case group compared to 6 patients(5%) in control group.
Existence of lentigines and melanocytic nevi increases chance of having melasma.
The third stage of labour is the period from birth of the baby to the expulsion of the placenta and membranes. As the placenta separates, there is inevitably some blood loss from the placental site until the muscles of the uterus clamp the blood vessels. Fit, healthy women cope with this normal blood loss without problems, but where poor nutrition, poor sanitation and limited or no access to clinical care are complications of pregnancy, severe morbidity and mortality can result from excessive blood loss at birth. This is very common in low- and middle-income countries. Active intervention, called 'active management of third stage', is recommended for the third stage of labour to reduce excess blood loss. Active intervention incorporates (1) the administration of a uterotonic drug, given either just before or just after the baby is born to help the muscles of the uterus contract; (2) early cord clamping; and (3) the use of controlled cord traction to deliver the placenta. This review of studies looked at the use of one group of uterotonic drugs called ergot alkaloids, e.g. ergometrine, as part of this active management. The review found six trials involving 3941 women receiving ergometrine by mouth (orally), into the muscle (intramuscularly (IM)) or into the vein (intravenously (IV)). Evidence indicates that the oral route was not very effective. The IV route, although it reduced blood loss, was associated with the adverse effects of raised blood pressure and pain due to uterine contraction, and so is unlikely to be used. The IM route showed benefit in terms of reducing blood loss, and although there were adverse effects similar to those associated with the IV route, these were less common. So, while the ergot alkaloid group of drugs given IM is an option, there are other drugs, namely oxytocin, syntometrine and prostaglandins (which are assessed in other Cochrane reviews), that can be used and may be preferable.
The EUropean Project on obstetric Haemorrhage Reduction: Attitudes, Trial, and Early warning System (EUPHRATES) is a set of five linked projects, the first component of which was a survey of policies for management of the third stage of labour and immediate management of postpartum haemorrhage following vaginal birth in Europe.
The objectives were to ascertain and compare policies for management of the third stage of labour and immediate management of postpartum haemorrhage in maternity units in Europe following vaginal birth.
Survey of policies.
The project was a European collaboration, with participants in 14 European countries.
All maternity units in 12 countries and in selected regions of two countries in Europe.
A postal questionnaire was sent to all or a defined sample of maternity units in each participating country.
Stated policies for management of the third stage of labour and the immediate management of postpartum haemorrhage.
Policies of using uterotonics for the management of the third stage were widespread, but policies about agents, timing, clamping and cutting the umbilical cord and the use of controlled cord traction differed widely. For immediate management of postpartum haemorrhage, policies of massaging the uterus were widespread. Policies of catheterising the bladder, bimanual compression and in the choice of drugs administered were much more variable.
Considerable variations were observed between and within countries in policies for management of the third stage of labour. Variations were observed, but to a lesser extent, in policies for the immediate management of postpartum haemorrhage after vaginal birth. In both cases, policies about the pharmacological agents to be used varied widely.
To evaluate the effect of timing of episiotomy repair on peripartum blood loss.
In this case-controlled study, nulliparous women were grouped as: group 1: no episiotomy (control; n = 82); group 2: midline episiotomy repair after placental removal (n = 76); group 3: midline episiotomy repair before placental removal (n = 78); group 4: mediolateral episiotomy repair after placental removal (n = 84), and group 5: mediolateral episiotomy repair before placental removal (n = 80). Hemoglobin and hematocrit values were evaluated at admission and 24 h postpartum.
The reductions in hemoglobin and hematocrit in all episiotomy groups (groups 2-5) were significantly more than that of control (group 1) (p < 0.05). There was no difference among midline episiotomy groups (groups 2 and 3) whereas a significant difference existed among mediolateral groups (groups 4 and 5) (p < 0.05). When episiotomy repair was done after placental removal, there was a significant difference between midline and mediolateral techniques (groups 2 and 4) (p < 0.05). When repair was done before placental removal, there was no difference in the amount of blood loss regardless of technique (between groups 3 and 5).
Episiotomy should be avoided to decrease the amount of peripartum blood loss. However, if mediolateral episiotomy is to be performed, it should be repaired before placental removal to decrease the amount of peripartum blood loss.
To determine the safety and efficacy of intramuscular oxytocin plus ergometrine compared to intravenous oxytocin for prevention of postpartum haemorrhage, and the significance of administration at the end of the second stage of labour compared with that after the third stage.
A prospective cohort study.
A university affiliated tertiary medical centre.
Two thousand one hundred and eighty-nine women delivering singletons during 40 consecutive weeks.
Postpartum haemorrhage (> 500 ml), prolonged third stage (> 30 min), retained placenta (> 60 min), elevated blood pressure (systolic > 150 mmHg, diastolic > 100 mmHg).
The rate of postpartum haemorrhage was not significantly different for oxytocin-ergometrine compared with oxytocin, when administered at the end of the second stage of labour (odds ratio 1.10, 95% confidence interval (CI) 0.75-1.61) or after the third stage (odds ratio 0.95, 95% CI 0.68-1.34). The patients receiving oxytocics at the end of the second stage of labour had significantly lower rates of postpartum haemorrhage, for both oxytocin-ergometrine (odds ratio 0.69, 95% CI 0.49-0.98) and oxytocin (odds ratio 0.60, 95% CI 0.41-0.87), compared with those treated after the third stage.
Administration of oxytocin alone is as effective as the use of oxytocin plus ergometrine in the prevention of postpartum haemorrhage, but associated with a significantly lower rate of unpleasant maternal side effects. Oxytocics administered after delivery of the fetal head compared with after the placental expulsion are associated with a significantly lower rate of postpartum haemorrhage.
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.
Recent claims that routine active management of the third stage of labour increases rather than decreases maternal and neonatal morbidity have prompted us to conduct a systematic review of the relevant controlled trials. In this paper we have analysed data derived from a total of nine published reports of controlled trials in which an oxytocic drug was compared with either a placebo or no routine prophylactic. Oxytocic drugs used routinely appear to reduce the risk of postpartum haemorrhage by about 40% (typical odds ratio 0.57, 95% confidence interval 0.44-0.73) implying that for every 22 women given such an oxytocic, one postpartum haemorrhage could be prevented. The available data are insufficient to assess the possible effects of this policy on the incidence of retained placenta, hypertension and other possible adverse effects.
To assess postpartum care at an international level, we reviewed published literature on postpartum maternal deaths.
Meta-analysis was used to summarize the literature reviewed. Postpartum deaths in developing countries were compared with those in the United States.
In both developing countries and the United States, > 60% of maternal deaths occurred in the postpartum period; 45% of postpartum deaths occurred within 1 day of delivery, > 65% within 1 week, > 80% within 2 weeks. In developing countries, 80% of postpartum deaths caused by obstetric factors occurred within 1 week.
The first 24 h postpartum and the first postpartum week is the high risk of postpartum deaths, and the risk remains significant until the second week after delivery. In developing countries, hemorrhage, pregnancy-induced hypertension complications, and obstetric infection are commonest causes of postpartum deaths. We suggest primary prevention, early detection, and secondary prevention of postpartum deaths.
To determine if the timing of the administration of prophylactic oxytocin influences the incidence of postpartum hemorrhage caused by uterine atony, retained placenta, and third-stage duration.
Parturients who presented for vaginal delivery were randomized in a double-blinded fashion to receive oxytocin, 20 units in a 500-mL crystalloid intravenous bolus, beginning upon delivery of either the fetal anterior shoulder or placenta. For all patients, the third stage of labor was managed with controlled cord traction until placental expulsion, followed by at least 15 seconds of fundal massage. Patients were excluded if they had a previous cesarean section, multiple gestation, antepartum hemorrhage, or bleeding disorder.
A total of 1486 patients were enrolled: 745 in the before-placenta group and 741 in the after-placenta group. The groups were similar with respect to gestational age, fetal weight, labor duration, maternal age, parity, and ethnicity. The incidence of postpartum hemorrhage did not differ significantly between the two groups (5.4% vs 5.8%; crude OR, 0.92; 95% CI, 0.59 to 1.43). There were no significant differences between the two groups with respect to incidence of retained placenta (2.4% vs 1.6%; OR, 1.49; 95% CI, 0.72 to 3.08), or third-stage duration (7.7 minutes vs 8.1 minutes; P =.23).
The administration of prophylactic oxytocin before placental delivery does not reduce the incidence of postpartum hemorrhage or third-stage duration, when compared with giving oxytocin after placental delivery. Early administration, however, does not increase the incidence of retained placenta.