Maternal Epidural Steroids to Prevent Neonatal Exposure to Hyperthermia and Inflammation

Abstract

Background Epidural analgesia is associated with a fourfold increased rate of intrapartum fever. The likely pathophysiology is a noninfectious maternal inflammatory activation. Safe interventions to reduce maternal and neonatal exposures to intrapartum fever and inflammation are needed. Objective The purpose of this study was to determine if prophylactic epidural steroids decrease fetal exposure to hyperthermia and inflammatory cytokines following epidural analgesia. Study Design This is a randomized, double-blinded, placebo controlled trial. Term nulliparous women requesting epidural analgesia received 80 mg methylprednisolone or preservative-free normal saline via the epidural catheter at placement. The primary outcome was maternal temperature >100.4°F. Secondary outcomes included fetal exposure to inflammation as assessed by cord blood interleukin-6 (IL-6) levels and rates of funisitis. Power analysis estimated a sample size requirement of 276, but new Food and Drug Administration (FDA) recommendations advising a black box warning on epidural steroids resulted in early study termination. Results A total of 116 subjects were enrolled: 58 treatments and 58 placebos. There was no difference in the rate of maternal intrapartum fever or cord blood IL-6 levels between treatment arms. No complications listed in the FDA warning occurred. Conclusion Prophylactic epidural methylprednisolone was not effective in reducing intrapartum fever or neonatal inflammation following epidural analgesia. Alternate mechanisms and preventative strategies should be considered.

Inflammation and Epidural-Related Maternal Fever: Proposed Mechanisms

“…Dexamethasone administered via epidural infusion (mean total dose 5.8 mg (range: 3.4-14.2 mg)) was also associated with a reduction in maternal temperature rise and lower plasma IL-6 levels 40 , although a subsequent study has failed to replicate these findings. 41 . Taken together, these trials of anti-inflammatory steroid therapy suggest that pro-inflammatory pyrogen release is suppressed.…”

Interventions for the prevention or treatment of epidural-related maternal fever: a systematic review and meta-analysis

“…Fifty-nine records were screened at full text, of which 37 were eligible for inclusion. Reasons for exclusion at full text included non-RCTs, 29 , 30 , 31 , 32 , 33 , 34 , 35 results not being available, 36 , 37 , 38 , 39 incorrect population or intervention, 40 , 41 , 42 or no outcome data on the incidence of intrapartum fever. 43 , 44 , 45 , 46 A further four excluded records were trial protocols for eligible RCTs but had no published results.…”

Combined spinal-epidural analgesia and epidural analgesia induced maternal fever with a similar timing during labor-A randomized controlled clinical trial

“…Lots of evidence has proved that ERMF results from a high serum concentration of pro-inflammatory cytokines such as IL-6, IL-1 beta , and TNF alpha ( 9 ). It has been proved that the increases in cytokines were induced by non-infectious factors ( 10 , 23 – 25 ). Local anesthetics were thought to be able to induce the production of these pro-inflammatory cytokines by the injuries they caused to human umbilical vein endothelial cells and human placental trophoblasts ( 26 ).…”