Systematic Reviews to Inform Practice, May/June 2025

Abstract

Postpartum hemorrhage (PPH) is defined as a blood loss of 500 mL or more within 24 hours of birth.¹ PPH occurs in approximately 1% to 3% of births in the United States.² Globally, 20% of pregnancy-related deaths are attributed to PPH,¹ and in the United States, approximately 11% of pregnancy-related deaths are caused by PPH.³ A factor that may influence the incidence of PPH is the length and course of the third stage of labor, defined as the period from the birth of the newborn to the complete expulsion of the placenta and membranes.⁴ The expected length of the third stage is generally accepted as 30 minutes.⁵ In the case of a prolonged third stage, the recommended management is usually manual removal of the placenta.^{6, 7} Recently, some clinicians and researchers have begun to consider reducing the length of time for expectant management of the third stage of labor and have suggested that manual removal of the placenta is indicated after 20 minutes.^{8, 9} de Vries¹⁰ and colleagues conducted a systematic review and meta-analysis to evaluate the association between the length of the third stage of labor after a vaginal birth and adverse maternal outcomes. They also sought to identify whether the risk of adverse maternal outcomes can be reduced by performing manual removal of the placenta earlier than current clinical practice.

The authors conducted a search of 7 databases and screened the reference lists of national guidelines from high-income countries regarding the prevention of PPH. Randomized trials, comparative studies, and prospective and retrospective cohort trials that were published between January 1, 2000, and June 13, 2023, in English, French, German, Italian, and Dutch languages were eligible for inclusion in the review. The primary outcome of interest was adverse maternal outcomes, defined as any complication occurring to the birthing person during or after birth, such as PPH, blood transfusion, intensive care unit admission, and peripartum hysterectomy. The secondary outcome of interest was the risk of adverse outcome as it related to the length of the third stage of labor. The researchers identified 16 articles that addressed the relationships between the length of the third stage of labor and maternal outcomes and 3 articles that evaluated the association between the timing of the manual removal of the placenta and adverse maternal outcomes. One article measured both outcomes of interest, so a total of 18 articles were included in the full review.

Included studies were conducted in the United States, Australia, Denmark, the Netherlands, Israel, Switzerland, Sweden, Japan, and Egypt, and one study was conducted across multiple countries; the authors do not indicate how many of the 18 studies were conducted in each nation. The risk of bias was rated as low in 1, moderate in 7, and high in 10 studies. Studies that presented an odds ratio (OR) for the likelihood of PPH were included in the meta-analysis, regardless of bias rating.

To examine the association between the length of the third stage of labor and the likelihood of PPH among birthing people with a mixed risk profile when the third stage of labor was measured after 15 minutes, 4 studies were included in the meta-analysis, with a total of 39,324 events or births evaluated. The likelihood of PPH was 5.55 times higher (OR, 5.55; 95% CI, 1.74-17.72) among people who had a third stage of labor that lasted for 15 minutes or longer than in those whose third stage was less than 15 minutes. Another meta-analysis considered hemorrhage in birthing people with a mixed risk profile when the third stage of labor was measured after 30 minutes (5 studies, N = 21,966 events) and found the odds of PPH was significantly higher among those whose third stage was 30 minutes or longer than in those whose third stage was less than 30 minutes (OR, 3.12; 95% CI, 1.83- 5.30). The authors included a variety of additional analyses, some of which do not meet the expectations for meta-analysis due to the number of included studies or the heterogeneity of the outcome measures. The authors also note that the definition of PPH varied among the included studies, with some using a definition of 1000 mL and some using a definition of 500 mL. This is a significant difference when PPH is the key outcome of the analyses. They were not able to reach conclusions about the timing of manual removal of the placenta and the risk of adverse outcomes.

The authors of this systematic review and meta-analysis use the findings of their analyses to propose that the third stage of labor should be redefined as lasting less than 15 minutes, although they note that the associations identified here between the length of third stage and PPH do not imply causality. Additionally, they did not find evidence that manual removal of the placenta, the primary intervention to shorten the third stage of labor, was an effective intervention for reducing adverse maternal outcomes. Although it is likely that when a birthing person experiences a longer third stage of labor, they are more likely to experience a hemorrhage, this may be due to subsequent interventions that occur once a prolonged third stage is diagnosed. The findings here do not indicate that a change in clinical practice is indicated, although the eye-catching title published in one of the leading journals of obstetric practice in the United States does have the potential to influence practice. Until further evidence demonstrates that an intervention that can safely shorten the third stage of labor and reduce the risk of PPH, clinicians will be best served by adhering to current practice guidelines for the management of the third stage of labor.