Prophylactic Methylergonovine and Oxytocin Compared With Oxytocin Alone in Patients Undergoing Intrapartum Cesarean Birth: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether the administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents. METHODS: This was a single-center, placebo-controlled, randomized trial of patients undergoing intrapartum cesarean birth. Patients were randomly allocated to receive intravenous oxytocin 300 mL/minute plus intramuscular methylergonovine 0.2 mg (1 mL) or intravenous oxytocin 300 mL/minute plus intramuscular normal saline (1 mL). The primary outcome was the receipt of additional uterotonic agents. Secondary outcomes included surgeon assessment of uterine tone, incidence of postpartum hemorrhage, quantitative blood loss, and blood transfusion. To detect a twofold decrease in the need for additional uterotonic agents (assuming a 42% baseline) with a two-sided type 1 error of 5% and power of 80%, a sample size of 76 patients per group was required. RESULTS: From June 2019 through February 2021, 80 patients were randomized to receive methylergonovine plus oxytocin and 80 were randomized to receive to oxytocin alone. Significantly fewer patients who were allocated to the methylergonovine group received additional uterotonic agents (20% vs 55%, relative risk [RR] 0.4, 95% CI 0.2-0.6). Participants receiving methylergonovine were more likely to have satisfactory uterine tone (80% vs 41%, RR 1.9, 95% CI 1.5-2.6), lower incidence of postpartum hemorrhage (35% vs 59%, RR 0.6, 95% CI 0.4-0.9), lower mean quantitative blood loss (967 mL vs 1,315 mL; mean difference 348, 95% CI 124-572), and a lower frequency of blood transfusion (5% vs 23%, RR 0.2, 95% CI 0.1-0.6). CONCLUSION: The administration of prophylactic methylergonovine in addition to oxytocin in patients undergoing intrapartum cesarean birth reduces the need for additional uterotonic agents. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03904446.

Eclampsia with RCVS: Postpartum seizure provoked by methergine.

BACKGROUND: Eclampsia is a pregnancy complicationcharacterized bygeneralized tonic-clonicconvulsions.Not all seizures in pregnancy are eclamptic, and othercauses include epilepsy, infection,stroke,tumor, and ruptured aneurysm. CASE: A 19-year-old G1P0 presentedinlabor at term. She had a generalized tonic-clonicseizure one hour aftervaginaldelivery for which she received methergine for uterine atony. Seizure activity resolved with lorazepam and magnesium sulfate for presumed eclampsia.Brain imaging revealedvasoconstriction of theleftposterior cerebral artery and blood in the subarachnoid space,andshewas diagnosed with eclampsia with reversible cerebral vasoconstrictive syndrome (RCVS). CONCLUSION: RCVS isapregnancy-related cause of seizure that should remain on the differential for any patient presenting with a seizure in the peripartum period, especially with use of vasoconstrictive agents. Management is controversial but involves calcium channel blockers and magnesium sulfate, as well as avoidance of vasoconstrictive agents.

Pharmaco-vigilance of oral MethylErgometrine prescriptions for delayed and secondary postpartum haemorrhage.

Objectives The objectives of this study were to quantify the prescription of oral methergin tablets in a busy Women's Hospital, assess the stated indications for such prescription and highlight the issues and safety profile of Methergin use especially in the postpartum patient. Methods Review of prescription data for oral Methergin and the corresponding annual figures on primary and secondary postpartum hemorrhage. Results Over a period of 5 years, oral Methergin prescriptions for delayed and secondary postpartum hemorrhage constituted less than 1% of the overall prescription in Obstetrics and Gynaecology, which ranged between 1214 and 2085 per year. The numbers were too few to ascertain any relationship with both types of postpartum hemorrhage. Although stated on the relevant Patient Information leaflet, no local or regional guideline on its use exist. Conclusions Specific and random trend monitoring of medications for continuing safety profile, risk benefit issues, or unapproved indication, may help in identifying, preventing and mitigating any medication safety matters. Clinical pharmacists in collaboration with physicians are well placed in conducting such pharmacovigilance activities to improve medication safety.

Efficacy of methylergometrine during the early puerperium: a randomized double-blind placebo-controlled clinical trial.

Objective: To determine if oral methylergometrine administration during the first 10 d following spontaneous vaginal delivery has any beneficial effect on the increase of hemoglobin levels.Methods: This was a parallel group double-blind placebo-controlled clinical trial conducted at single center university hospital in Italy. Participants were puerperal women, who delivered singleton gestation with spontaneous vaginal delivery at term. Participants were randomized into a 1:1 ratio to receive either 0.125 mg methylergometrine per os twice a day or placebo for 10 d. Hemoglobin levels were recorded on the day of delivery and after 10 d. The primary outcome was the variation in hemoglobin levels between the first and the 10th day of treatment.Results: From December 2012 to October 2015, 220 agreed to take part in the study, underwent randomization, and were enrolled and followed-up. Of the randomized women, 110 (50%) were randomized to the methylergometrine group and 110 (50%) to the placebo group. No women were excluded after randomization or lost to follow-up (100%). We found no significant difference in the median variation of hemoglobin levels between the intervention and the placebo groupConclusions: The use of 10 d oral methylergometrine in puerperal women was not associated with any benefit in the variation of hemoglobin levels from delivery to 10 d after delivery.Key MessageMethylergometrine in puerperal women was not associated with any benefit.

Inadvertent Methylergonovine Administration to a Neonate.

BACKGROUND Methylergonovine is an ergot alkaloid used to treat post-partum hemorrhage secondary to uterine atony. Mistaking methylergonovine for vitamin K with accidental administration to the neonate is a rare iatrogenic illness occurring almost exclusively in the delivery room setting. Complications of ergot alkaloids in neonates include respiratory depression, seizures, and death. CASE REPORT A term infant was inadvertently given 0.1 mg of methylergonovine intramuscularly in the right thigh. The error was only noted when the vial of medication was scanned, after administration, identifying it as methylergonovine rather than vitamin K. The local poison center was notified, and the infant was transferred to the neonatal intensive care unit for observation. Two hours after transfer, the infant was noted to have oxygen desaturations and required oxygen via nasal cannula. Supplemental oxygen was continued for 4 hours until the neonate was able to maintain normal oxygen saturations in room air. Feeding was started by 10 hours of life, and the infant was discharged home in good condition after a 72-hour stay without further complications. CONCLUSIONS Because of the potential for serious adverse events, vigilance is required to prevent accidental administration of methylergonovine to the neonate as a result of possible confusion with vitamin K in the early post-partum period.

Exposure to methylergonovine maleate as a cause of sirenomelia.

BACKGROUND: Sirenomelia is a rare, but deadly condition characterized by fusion of the lower limbs, lower spinal column defects, severe malformations of the urogenital and lower gastrointestinal tract, and an aberrant abdominal umbilical artery. METHODS: The two main hypotheses, not mutually exclusive, that have been advanced to explain the pathogenesis of sirenomelia are the blastogenetic theory and the vascular disruption theory. RESULTS: We describe a case of sirenomelia, probably associated with the use of methylergonovine maleate, an ergot alkaloid, during the first weeks of pregnancy. CONCLUSION: On the basis of the mechanisms of vascular disruption and early administration of methylergonovine maleate at a critical stage of organogenesis, we conclude that exposure to methylergonovine maleate could be the cause of the development of sirenomelia. Birth Defects Research (Part A) 106:643-647, 2016. © 2016 Wiley Periodicals, Inc.

The Effect of the Combined Use of Methylergonovine and Oxytocin during Caesarean Section in the Prevention of Post-partum Haemorrhage.

We aimed to show to patients the benefit of post-partum haemorrhage prophylaxis treatment and the effectiveness as a uterotonic agent of the combined use of methylergonovine and oxytocin infusion in the prevention of haemorrhage during and after Caesarean section, by comparison with a control group which received oxytocin infusion only. Two groups of patients undergoing Caesarean section at the same clinic were included in the study. A combination of methylergonovine and oxytocin was administered to the first group during the intra-operative and post-operative periods. The second group did not receive methylergonovine and was administered only with oxytocin infusion in the intra-operative and post-operative periods. Pre-operative and post-operative haemogram readings were taken for all patients in each of the groups for comparison. No difference was found between the two groups with regard to mean ages and pre-operative haemogram values. The decrease in post-operative haemoglobin values for the group administered with methylergonovine maleate and oxytocin was found to be significantly greater than for the group administered with oxytocin only. Results indicated that prophylactic methylergonovine treatment was clearly successful for the patients and no adverse side effects were found. The routine use of methylergonovine and oxytocin infusion in combination during the intra-operative period of Caesarean section reduced the level of post-partum haemorrhage considerably. We believe that this procedure will also reduce the risk of uterine atony, but clearly, prospective studies will be necessary in future to confirm this assumption.

Inadvertent oral administration of methylergometrine maleate to children in the first months of life: from surveillance to prevention.

PURPOSE: Methylergometrine maleate is an ergot alkaloid frequently used in obstetrics for prevention and treatment of post partum haemorrhage. Accidental administration of this medicine to newborns can cause severe effects and should be carefully prevented. The present paper is aimed at describing the main characteristics of cases accidentally exposed to this medicine in Italy before and after Novartis, the manufacturer of Methergin®, a widely used methylergometrine maleate-containing gynecological medication, decided to withdraw the drop preparation from the European market. METHODS: The study design is a case-series study. The database of the National Poison Control Centre of Milan was searched retrospectively (from 1 January 2005 to 31 December 2011) and prospectively (from 1 January 2012 to 31 December 2013) in order to provide a descriptive analysis of the main characteristics of cases unintentionally exposed to methylergometrine maleate and to document the impact of Novartis' decision. RESULTS: In the first period under study (2005-2011), a total of 642 cases of exposure to methylergometrine maleate were identified. Most of them were children aged <1 year (No. 483, 75%). Patients aged 1-2 and 3-5 years accounted for 13% (No. 85) and 9% (No. 56) of cases, respectively. Among children aged <1 year, about 76% (No. 368) were exposed during the first month of life, including 44% (No. 211) of cases exposed in the first week of life. The main cause of exposure was medication error (No. 432, 89%), mainly due to oral administration of methyltergometrine maleate in place of a paediatric preparation (No. 469, 97%). About 14% of these cases suffered clinical effects as a consequence of the exposure. Severity of poisoning was minor in 45 cases, moderate in 12, and severe in one case. The main cause of exposure among children aged 1-2 and 3-5 years was uncontrolled access to the medicine, accounting for 78% (No. 66) and 77% (No. 43) of cases, respectively. Some 9% (No. 8) of cases aged 1-2 years and 7% (No. 4) of those aged 3-5 years developed signs/symptoms possibly related to the exposure. For all of them, severity of clinical effects was low, but one case suffered moderate effects. Exposure to the medicine in drops was reported for 87% (No. 74) and 84% (No. 47) of cases aged 1-2 and 3-5 years, respectively. In 2012-2013 a total of 25 cases were observed. Among them, two patients were aged <1 year (8%). Both cases occurred in 2012 and were inadvertently administered the medicine in drops still available (present) in the home. Fourteen (56%) and 8 (32%) cases were aged 1-2 and 3-5 years, respectively. All of them were exposed to the tablet formulation following uncontrolled access to the medicine. CONCLUSIONS: The observations here reported indicate that having different formulations for methylergometrine maleate-containing products intended for the mother and paediatric medicines can successfully prevent medication error due to medicine exchange in the first months of life.

Management of methylergonovine induced respiratory depression in a newborn with naloxone.

INTRODUCTION: We report a case of a female neonate who developed respiratory depression following the unintentional administration of methylergonovine. The respiratory depression appeared to improve after the administration of bag mask ventilation, stimulation, and naloxone; and the baby was able to be managed without endotracheal intubation and prolonged positive-pressure ventilation. CASE: A full-term female neonate was delivered vaginally without issue. Approximately 10 min after delivery, the infant was inadvertently administered 0.1 mg of methylergonovine intramuscularly instead of vitamin K. Thirty minutes later the child developed cyanotic extremities and respiratory depression with an oxygen saturation of 75%. Naloxone, 0.4 mg IM, was recommended to mitigate respiratory depression. Within 5 min the patient's respirations improved to 40 breaths per minute, cyanosis improved, and she began resisting ventilations and crying loudly. The child continued to improve and was back to baseline that evening. DISCUSSION: Methylergonovine toxicity in neonates has been commonly associated with respiratory depression necessitating ventilatory support. In consideration of chemical structural similarity between methylergonovine and morphine, as well as signs/symptoms consistent with opioid-induced respiratory depression, naloxone was suggested. CONCLUSION: It appears that naloxone may reverse methylergonovine toxicity in neonates. The identification of a safe and potentially useful antidote to mitigate respiratory depression, potentially avoiding the need for intubation and more invasive interventions in this patient population is important.

Comparison the effects of oxytocin and methylergonovine in elective caesarean section under spinal anesthesia.

PURPOSE: In order to prevent postpartum hemorrhage in caesarean section under spinal anesthesia, patients routinely receive oxytocin. In this study we compared the efficacy of Methylergonovine and Oxytocin on hemodynamic stability and bleeding amount in caesarean section. MATERIALS AND METHODS: In this randomised controlled trial study, 80 patients candidate for elective caesarean section under spinal anesthesia divided to two groups: 40 patients in control group received oxytocin and 40 ones in case group received methylergonovine. RESULTS: There was no differences between groups in Mean age, baseline hemodynamic values, after spinal anesthesia and recovery (except diastolic blood pressure min 20), time of uterine atony, dizziness; nausea and vomiting. After drug administration (oxytocin and methylergonovine), systolic blood pressure in minutes 1, 10, 15 and diastolic blood pressure in minutes 1, 3, 20 increased in case group statistically more than control group. In control group, heart rate in minutes 1, 5 increased significantly more than the other group. Mean arterial blood pressure in minutes 1, 3, 5, 10, 15 reduced significantly more than in control group. Need to vasoconstrictor drug statistically was less in case group (p < 0.0001). CONCLUSION: Methylergonovine induced significantly more hemodynamic stability. Adverse effects were similar between two groups. We recommend the use of methylergonovine in patients with caesarean section under spinal anesthesia because of its hemodynamic stability and low need to vasoconstrictor drugs.

Reversible cerebral vasoconstriction syndrome with limb myoclonus following intravenous administration of methylergometrine.

Neurological deficits associated with methylergometrine have been reported primarily as a result of reversible cerebral vasoconstriction syndromes (RCVS). RCVS are characterized by reversible multifocal vasoconstrictions of the cerebral arteries heralded by acute severe headache with or without neurological deficits. Here, we present the first case of suspected RCVS with transient limb myoclonus following the intravenous administration of methylergometrine during cesarean section. A 31-year-old woman who received slowly infused intravenous methylergometrine during a cesarean section suddenly reported severe occipital headache after 40 min, followed by apnea and unconsciousness for 8 min. A second administration of methylergometrine to treat the weakness of her uterine contractions resulted in a repeated loss of consciousness within minutes and the development of limb myoclonus. No abnormalities were detected by brain computerized tomography, magnetic resonance imaging, and electroencephalogram. She fully recovered spontaneously within 12 h. We consider that the transient limb myoclonus in our patient appeared as a result of RCVS caused by the intravenous administration of methylergometrine.

Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study.

BACKGROUND: Methylergonovine is an ergot alkaloid widely used in postpartum women. It is also an active metabolite of methysergide and previous studies suggest that it could be effective against refractory headache and cluster headache. The purpose of the present study was to assess the potential therapeutic effectiveness of methylergonovine in the emergency treatment of severe migraine. METHODS: One hundred and twenty five female patients with migraine attending the emergency department received 0.15 mg of methylergonovine intravenously. Pain intensity, heart rate, blood pressure, and methylergonovine side effects were checked 5, 10, 15, 30 and 60 minutes after drug administration. An additional 0.075 mg dose of methylergonovine was administered to those patients who did not experienced relevant pain relief 15 minutes after dosing. RESULTS: Pain intensity decreased markedly from the first minutes after dosing, the 74.4% of patients being pain free at 60 minutes. Only seven patients required an additional dose of methylergonovine. Nausea and vomiting were the most relevant side effects related with methylergonovine administration (84% of patients). A substantial decrease (10 to 25 mmHg) in systolic blood pressure values was observed in 56% of the patients. A significant correlation (p < 0.0001) was found between the decrease in pain intensity and the reduction of systolic blood pressure. CONCLUSION: Although limited by the non-controlled design of the study, our data suggest that intravenous methylergonovine can be an effective and safe drug in the management of severe migraine attacks in the emergency room.

Comparison of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor.

OBJECTIVE: To compare the efficacy and adverse effects of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor (AMTSL). METHODS: A double-blind randomized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either: 400 microg or 600 microg of sublingual misoprostol, 5 IU of intravenous oxytocin, or 200 microg of intravenous methylergometrine. The primary outcome measure was blood loss in the third and fourth stage of labor; secondary measures were duration of the third stage of labor, changes in hemoglobin levels, and adverse effects. RESULTS: Patients who received 600 microg of misoprostol had the lowest blood loss (96.05+/-21.1 mL), followed by 400 microg of misoprostol (126.24+/-49.3 mL), oxytocin (154.7+/-45.7 mL), and methylergometrine (223.4+/-73.7 mL) (P<0.01). Shortest mean duration of the third stage of labor (5.74 minutes) was with 600 microg of misoprostol, while methylergometrine had the longest (6.83 minutes) (P<0.05). Pyrexia was observed in the misoprostol groups, and raised blood pressure in the methylergometrine group (P<0.001). The 24-hour postpartum hemoglobin level was similar among the groups (P>0.05). CONCLUSION: Administration of 600 microg of sublingual misoprostol was more effective than 400 microg of misoprostol, intravenous oxytocin, and intravenous methylergometrine for AMTSL.

Acute myocardial infarction following oral methyl-ergometrine intake.

Ergot derivatives are frequently administrated during cesarean delivery, induced abortion, or post-partum hemorrhage to promote uterine contractions. Ergot derivatives may also induce coronary spasm and intravenous ergonovine is used in cardiac catheterization laboratories as a diagnostic agent. Serious ischemic cardiac events related to ergonovine are rare and have most often been described after intravenous use. We report the case of a 38-year-old woman with a ST elevation myocardial infarction (STEMI) few days after artificially induced abortion by oral prescription of methylergometrine. Coronary angiography performed 2 days after onset of chest pain did not reveal any abnormalities of the coronary arteries but a provocative test using intravenous methylergometrine was positive with reproduction of chest pain, ECG changes and with a significant narrowing localized on the second segment of the left anterior descending artery at the angiogram. Thus, since methylergometrin may clearly induce coronary spasm when prescribed orally, chest pain occurring under oral treatment should require immediate attention even if atypical or in the absence of cardiovascular risk factors.

Low-dose sublingual misoprostol versus methylergometrine for active management of the third stage of labor.

OBJECTIVE: To compare the efficacy and side-effects of low-dose sublingual misoprostol and i.v. methylergometrine for active management of the third stage of labor. METHODS: The study subjects were three hundred low-risk women with term pregnancy and spontaneous onset of labor. These women received either one (100 microg/tablet) or two tablets of misoprostol (200 microg) sublingually or 1 mL (200 microg) of methylergometrine, i.v. injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were the need for additional oxytocic drugs, blood loss >or=500 mL, change in hemoglobin levels and side-effects. RESULTS: Post-partum hemorrhage (>or=500 mL blood loss) did not occur in any of the women, but above-average bleeding occurred in 2.0% of cases in groups I, II (sublingual misoprostol 100 microg and 200 microg respectively) and III (methylergometrine), despite additional oxytocics used in 5.0%, 4.0% and 3.0% cases in groups I, II and III respectively (P>0.05). The change in hemoglobin levels at 24 h post-partum were 0.8%, 0.7% and 0.8% in groups I, II and III respectively (P>0.05). CONCLUSION: A low dose of sublingual misoprostol appears to be as effective as a low dose of i.v. methylergometrine in the prevention of post-partum hemorrhage in low-risk cases. So given the advantages of its stability at room temperature, low cost and easy route of administration, misoprostol appears to be a better choice, and a low dose is enough. However, larger studies in low-risk as well as high-risk cases are needed to advocate routine use of a low dose at the primary level.

Oral misoprostol for the prevention of primary post-partum hemorrhage during third stage of labor.

AIM: To assess the effectiveness of oral misoprostol compared with methylergometrine in the prevention of primary post-partum hemorrhage during the third stage of labor. METHODS: This was a randomized controlled trial of 864 singleton low-risk pregnant women. The outcomes were total blood loss, duration of the third stage of labor and peripartal change in hematocrit. Comparisons were by the chi2-test and Student t-test. Relative risks were calculated for side-effects profile. A P-value of less than 0.05 was statistically significant. RESULTS: The biodata of all the participants were similar. The mean blood loss for the misoprostol and methylergometrine groups was 191.6 +/- 134.5 mL and 246.0 +/- 175.5 mL, respectively (95% CI: -79.3 to -39.5 mL). The mean duration of the third stage of labor was 19.6 +/- 2.4 min and 9.4 +/- 3.3 min in the misoprostol and methylergometrine groups, respectively (95% CI: 9.82-10.58 min). More subjects had blood loss >500 mL, 42 (9.7%) versus 6 (1.4%), and peripartal hematocrit change greater than 10%, 38 (8.8%) versus 5 (1.2%), in the methylergometrine group than in the misoprostol group, respectively. Also, more subjects received additional oxytocic in the methylergometrine group, compared to the misoprostol group (80 [18.5%] versus 33 [7.6%] patients, respectively). CONCLUSIONS: Orally administered misoprostol was more effective in reducing blood loss during the third stage of labor than intramuscular methylergometrine. However, there were more subjects in the misoprostol group in whom duration of the third stage of labor was greater than 15 min and who also had manual placental removal than in the methylergometrine group.

A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active management of third stage of labour.

To compare active management of third stage of labour with 15-methyl prostaglandin F2alpha (PGF2alpha) and conventional management with methylergometrine as prophylaxis for postpartum hemorrhage, a randomised comparative study was carried out at Calcutta National Medical College and Hospital, Kolkata on 100 women. They were randomly allotted to one of the two groups. Group A included 50 women who received 15-methyl PGF2alpha (125 microg) intramusculary at the time of delivery of the anterior shoulder and group B included 50 women who underwent conventional management of the third stage of labour where methylergometrine 0.2 mg was given after delivery of placenta. Main outcome measured were duration of third stage, amount of bleeding and side-effects. The present study showed that there were significent reduction of the duration of third stage as well as reduction of amount of bleeding particularly when 125 microg of 15-methyl PGF2alpha was given intramuscularly at the time of delivery of the anterior shoulder in comparison to coventional method of management of third stage of labour with methylergometrine. Placental expulsion occurred within 4 minutes in group A and 16.5 minutes in group B. The amount of bleeding following delivery was 95.6 ml in average in group A and 249.6 ml in average in group B. 15-methyl PGF2alpha (125 microg) is certainly effective in prevention of postpartum haemorrhage particularly in developing country like India where this complication contributes a major factor for maternal mortality.

Prevention of postpartum hemorrhage by uterotonic agents: comparison of oxytocin and methylergometrine in the management of the third stage of labor.

OBJECTIVES: To determine the efficacy of intravenous oxytocin administration compared with intravenous methylergometrine administration for the prevention of postpartum hemorrhage (PPH), and the significance of administration at the end of the second stage of labor compared with that after the third stage. METHODS: A prospective study was undertaken: two major groups (oxytocin group and methylergometrine group) of 438 women with singleton pregnancy and vaginal delivery were studied during a 15-month period. These two groups were subdivided into three subgroups: 1. intravenous injection (two minutes) group immediately after the delivery of the fetal anterior shoulder, 2. intravenous injection (two minutes) group immediately after the delivery of the placenta, and 3. drip infusion (20 min) group immediately after the delivery of the fetal head. In each group, quantitative postpartum blood loss, frequencies of blood loss >500 ml, and need of additional uterotonic treatment were evaluated. RESULTS: As compared with methylergometrine, oxytocin administration was associated with a significant reduction in postpartum blood loss and in frequency of blood loss >500 ml. The risk of PPH was significantly reduced with intravenous injection of oxytocin after delivery of the fetal anterior shoulder, compared with intravenous injection of oxytocin after expulsion of the placenta (OR 0.33, 95%CI 0.11-0.98) and intravenous injection of methylergometrine after delivery of the fetal anterior shoulder (OR 0.31, 95%CI 0.11-0.85). CONCLUSIONS: Intravenous injection of 5 IU oxytocin immediately after delivery of fetal anterior shoulder is the treatment of choice for prevention of PPH in patients with natural course of labor.