Association between oxytocin exposure in the second stage of labor and postpartum hemorrhage among nulliparous patients with neuraxial analgesia

Abstract Objective Oxytocin is often used in the second stage of labor and despite studies demonstrating dose‐dependent oxytocin receptor desensitization, the relationship between second stage exposure and postpartum hemorrhage (PPH) risk is not well established. We sought to evaluate the relationship between second‐stage oxytocin exposure and postpartum bleeding outcomes. Study design Secondary analysis of a multicenter randomized controlled trial of term singleton nulliparous patients with neuraxial analgesia comparing immediate versus delayed pushing in the second stage. Estimated cumulative second‐stage oxytocin exposure was calculated as the product of oxytocin dose at complete dilation and second‐stage duration and was modeled continuously per 100‐milliunit (mU) increase. The primary outcome was a maternal composite consisting of PPH, blood transfusion, or additional uterotonic administration. Modified Poisson regression with robust variance estimation was used to estimate risk ratios (RRs) and adjusted risk ratios (aRRs), controlling for randomized pushing assignment, admission diagnosis, and prolonged second‐stage duration. Exploratory analyses evaluated estimated blood loss (EBL) as a continuous outcome; sensitivity analyses examined categorical exposure groups using median cumulative dose defined as no exposure (0 mU), low exposure (<816 mU), and high exposure (≥816 mU). Results A total of 2302 participants were included from the parent trial. Each 100‐mU increase in estimated second‐stage oxytocin exposure was associated with a 2.5% higher risk of the primary maternal composite outcome (aRR, 1.025, 95% confidence interval [CI], 1.014–1.036; p < 0.001) and a 2.7% higher risk of PPH (aRR, 1.027, 95% CI, 1.015–1.038; p < 0.001). In exploratory analyses, increasing exposure was associated with greater EBL (aRR, 1.008, 95% CI, 1.006–1.010; p < 0.001). Categorical sensitivity analyses demonstrated similar findings, with high exposure associated with a 60% higher risk of the primary maternal composite outcome and a 63% higher risk of PPH compared with no exposure. Conclusion Greater cumulative second‐stage oxytocin exposure was associated with increased maternal morbidity, particularly postpartum hemorrhage, with findings supporting a dose–response relationship.