Postpartum haemorrhage (PPH) is the leading cause of maternal morbidity and mortality worldwide. The burden of PPH mortality and morbidity is concentrated in low-resource settings. PPH is traditionally defined as estimated blood loss (EBL) ≥500mL from the genital tract during the puerperium and complicates approximately 6% of births annually. Severe PPH (EBL ≥1000mL) complicates one to 2% of births. Due to the subjective nature of estimating blood loss in labour, the definition of PPH has been updated and now includes signs of clinical shock regardless of the volume of EBL.
PPH is difficult to predict and occurs frequently in women without identifiable risk factors. Thus, preventative care with active management of the third stage of labour, including uterotonic agents to promote uterine contraction, is required. There are many uterotonic agents, all with differing effectiveness and maternal side effect profiles.
In general, systematic reviews (SR) and meta-analyses (MA) of randomised controlled trials (RCTs) provide the highest level of evidence and certainty of a particular treatment's effect size. MA with individual participant data (IPD-MA) allows assessment of the trustworthiness of RCT data. Here, authors reported an IPD-MA assessing the effectiveness of oxytocin for preventing PPH.
Of 14 eligible RCTs, four provided IPD (n=4304; 51.7% received oxytocin and 48.4% received placebo or no intervention). Meta-analysis of IPD showed that oxytocin decreased the risk of PPH ≥500mL (aOR 0.59; 95% CI 0.46 to 0.74) and PPH ≥1000mL (aOR 0.51; 95% CI 0.32 to 0.80). Of 10 RCTs that did not share data, seven met trustworthiness criteria while three did not. Trustworthy IPD and aggregate data (AD) from RCTs meeting trustworthiness criteria (n=6003) showed that oxytocin significantly reduced the rate of PPH ≥500mL (aOR 0.53; 95% CI 0.45 to 0.62) and PPH ≥1000mL (aOR 0.59; 95% CI 0.48 to 0.71). RCTs not meeting trustworthiness criteria reported a larger risk reduction of oxytocin for PPH ≥500mL (n=1027; aOR 0.37; 95% CI 0.03 to 4.03) and PPH ≥1000mL (n=1157; aOR 0.13; 95% CI 0.01 to 1.45).
Jointly considering the results of IPD-MA and AD-MA of all RCTs meeting trustworthiness criteria, authors found that oxytocin administered in the third stage of labour significantly decreases the risk of PPH and severe PPH. Three RCTs did not meet the pre-defined trustworthiness criteria; meta-analysis of these RCTs was difficult to interpret given the overall low PPH event rates and wide CIs.
Analysis of trustworthy data confirms that oxytocin significantly reduces the risk of PPH and severe PPH compared to no intervention and is associated with improved maternal safety outcomes. Twenty-one percent of RCTs did not meet predefined trustworthiness criteria, elucidating the importance of integrity assessment in evidence synthesis.
Source: Madeline Flanagan, Arsheeya Rattan, Ling Shan Au; BJOG: An International Journal of Obstetrics & Gynaecology, 2025; 0:1–10 https://doi.org/10.1111/1471-0528.18279
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