Association between the timing of labor epidural analgesia and maternal fever in nulliparous women: a retrospective cohort study

Abstract Background Epidural-related maternal fever has been attributed to non-infectious inflammatory mechanisms and thermoregulatory dysfunction. Its risk is hypothesized to increase with prolonged exposure to epidural analgesia; however, a comprehensive synthesis of evidence regarding the effect of epidural analgesia timing remains lacking. Methods This retrospective cohort study included 2,991 nulliparous women with term singleton pregnancies who received epidural analgesia at a single academic center between 2019 and 2020. Early initiation was defined as 0–2 cm cervical dilation, and late initiation as ≥ 3 cm. The primary outcome was maternal fever (≥ 38 °C). Propensity score matching and multivariable regression were performed to adjust for potential confounders. Results After propensity score matching, the incidence of maternal fever was significantly higher in the early epidural group than in the late epidural group (12.20% vs. 7.30%; P = 0.001). Multivariable logistic regression analysis showed that late initiation of epidural analgesia was associated with a reduced risk of maternal fever (aOR = 0.57, 95% CI, 0.41–0.80; P < 0.001), uterine inertia (aOR = 0.68, 95% CI, 0.48–0.96; P = 0.028), oxytocin use (aOR = 0.73, 95% CI, 0.60–0.88; P = 0.001), cesarean delivery (aOR = 0.51, 95% CI, 0.38–0.69; P < 0.001), and episiotomy (aOR = 0.41, 95% CI, 0.32–0.51; P < 0.001). In addition, late initiation of epidural analgesia was associated with lower log-transformed blood loss during the first 24 hours after delivery (adjusted coefficient = −0.12, 95% CI, −0.17 to −0.07; P < 0.001). Sensitivity analyses yielded consistent findings. Conclusion In this retrospective cohort study of nulliparous women with spontaneous labor, initiation of epidural analgesia (0–2 cm cervical dilation) was associated with an increased risk of intrapartum fever and several adverse maternal outcomes. These findings suggest a potential clinical relevance of epidural timing; however, causal inference cannot be drawn due to the observational study design. Prospective studies are warranted to confirm these associations and further clarify underlying mechanisms.