Abstract: Twelve trials involving 3285 healthy women at low risk of excessive bleeding undergoing elective CS (nine trials, 2453 participants) or spontaneous birth (three trials, 832 participants) satisfied inclusion criteria and contributed data to the analysis. All participants received routine prophylactic uterotonics in accordance with the local guideline in addition to TA or placebo or no intervention. Overall, included studies had moderate risk of bias for random sequence generation, allocation concealment, blinding, selective reporting and low risk of bias for incomplete data. The quality of evidence was also as assessed using GRADE. Blood loss greater than 400 mL or 500 mL, and more than 1000 mL was less common in women who received TA versus placebo or no intervention (risk ratio (RR) 0.52, 95% confidence interval (CI) 0.42 to 0.63, six trials, 1398 women; moderate quality evidence) and (RR 0.40, 95% CI 0.23 to 0.71, six trials, 2093 women; moderate quality evidence), respectively. TA was effective in decreasing the incidence of blood loss greater than 1000 mL in women who had undergone CS (RR 0.43, 95% CI 0.23, 0.78, four trials, 1534 women), but not vaginal birth (RR 0.28, 95% CI 0.06, 1.36, two trials 559 women). The effect of TA on blood loss greater than 500 mL or 400 mL was more pronounced in the group of women having vaginal birth than in women who had CS. Mean blood loss (from delivery until two hours postpartum) was lower in women who received TA versus placebo or no intervention (mean difference MD - 77.79 mL, 95% CI -97.95, -57.64, five trials, 1186 women) and this effect was similar following vaginal birth and CS. Additional medical interventions (moderate quality evidence) and blood transfusions were less frequent in women receiving TA versus placebo or no interventions. Mild side effects such as nausea, vomiting, dizziness were more common with the use of TA (moderate quality evidence). The effect of TA on maternal mortality, severe morbidity and thromboembolic events is uncertain (low quality evidence). TA (in addition to uterotonic medications) decreases postpartum blood loss and prevents PPH and blood transfusions following vaginal birth and CS in women at low risk of PPH based on studies of mixed quality. There is insufficient evidence to draw conclusions about serious side effects, but there is an increase in the incidence of minor side effects with the use of TA. Effects of TA on thromboembolic events and mortality as well as its use in high-risk women should be investigated further.

Plain-language summary: TA decreased blood loss greater than 400 mL or greater than 500 mL and this effect was more apparent with vaginal births. The studies had methodological shortcomings. Blood loss greater than 1000 mL decreased with the use of TA in six trials (2093 women), however, the difference was most obvious in caesarean section (two trials, 1400 women) and not in vaginal birth in which there were few such outcomes (one trial, 439 women). Mean blood loss decreased with the use of TA by 77 mL, overall (five studies, 1186 women) and with both vaginal and caesarean section births. This finding was based on studies with methodological limitations. The studies were too small to detect the effect of TA on maternal death or blood clots. Mild side effects, which include diarrhoea, nausea and vomiting, were more common in women who received TA versus placebo or no intervention. No differences in blood loss and side effects were found when two different doses of TA were evaluated. Further larger studies are needed to investigate the effects of TA on maternal deaths and formation of clots in the blood (thromboembolism).