Abstract: Three studies with 1306 women are included in the review and compared intramuscular versus intravenous oxytocin administered just after the birth of the anterior shoulder or soon after the birth of the baby. Studies were carried out in hospital settings in Turkey and Thailand and recruited women with singleton, term pregnancies. Overall, the included studies were at moderate risk of bias: none of the studies provided clear information on allocation concealment or attempted to blind staff or women. For GRADE outcomes the quality of the evidence was very low, with downgrading due to study design limitations and imprecision of effect estimates. Only one study reported severe postpartum haemorrhage (blood loss 1000 mL or more) and showed no clear difference between the intramuscular and intravenous oxytocin groups (risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.04; 256 women; very low-quality evidence). No woman required hysterectomy in either group in one study (no estimable data, very low-quality evidence), and in another study one woman in each group received a blood transfusion (RR 1.00, 95% CI 0.06 to 15.82; 256 women; very low-quality evidence). Other important outcomes (maternal death, hypotension, maternal dissatisfaction with the intervention and neonatal jaundice) were not reported by any of the included studies. There were no clear differences between groups for other prespecified secondary outcomes reported (postpartum haemorrhage 500 mL or more, use of additional uterotonics, retained placenta or manual removal of the placenta). Very low-quality evidence indicates no clear difference between the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Appropriately designed randomised trials with adequate sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such studies could be large enough to detect clinically important differences in major side effects that have been reported in observational studies and should also consider the acceptability of the intervention to mothers and providers as important outcomes.

Plain-language summary: We searched for evidence on 7 September 2017 and identified three studies (together including 1306 women) comparing intramuscular versus intravenous administration of oxytocin to women during or immediately after the birth of the baby. Studies were carried out in hospitals in Turkey (two) and Thailand (one) and recruited women having only one baby, at term (not early or late). The methods that the studies used to divide women into treatment groups were not clear, and in all three included studies women and staff would have been aware of which treatment they received. This may have had an impact on results and means we cannot be confident in the evidence. The included studies did not report several important outcomes. Only one study reported severe blood loss (a litre or more) after birth and showed that there may be little or no difference between giving intramuscular and intravenous oxytocin. None of the women in one study needed surgery to remove their uterus (womb) after either intramuscular or intravenous oxytocin, and in another study two women needed a blood transfusion, one after intramuscular oxytocin and one after intravenous oxytocin. The quality of the evidence was low or very low, so we had very little confidence in the results. The studies did not report other important outcomes, such as death of the mother, low blood pressure, mothers' dissatisfaction with intramuscular or intravenous oxytocin, and number of babies with jaundice (yellowing of the skin). We found little or no clear difference between intramuscular and intravenous oxytocin for blood loss of 500 mL or more, use of additional drugs to reduce bleeding, and the placenta either not being delivered naturally or having to be removed by doctors. The findings from the three included studies did not clearly show which method of giving oxytocin was better for the mother or baby and more research is needed to answer this question. There was only a small number of included studies and our important outcomes did not occur very often, so there was insufficient evidence to decide whether intramuscular or intravenous oxytocin is more effective and safer for women in the third stage of labour.