Epidural analgesia, intrapartum hyperthermia, and neonatal brain injury: a systematic review and meta-analysis

Abstract

Background: Epidural analgesia is associated with intrapartum hyperthermia, and chorioamnionitis is associated with neonatal brain injury. However, it is not known if epidural hyperthermia is associated with neonatal brain injury. This systematic review and meta-analysis investigated three questions: (1) does epidural analgesia cause intrapartum hyperthermia, (2) is intrapartum hyperthermia associated with neonatal brain injury, and (3) is epidural-induced hyperthermia associated with neonatal brain injury? Methods: PubMed, ISI Web of Knowledge, The Cochrane Library, and Embase were searched from inception to January 2020 using Medical Subject Headings (MeSH) terms relating to epidural analgesia, hyperthermia, labour, and neonatal brain injury. Studies were reviewed independently for inclusion and quality by two authors (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach). Two meta-analyses were performed using the ManteleHaenszel fixed effect method to generate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Forty-one studies were included for Question 1 (646 296 participants), 36 for Question 2 (11 866 021 participants), and two studies for Question 3 (297 113 participants). When the mode of analgesia was randomised, epidural analgesia was associated with intrapartum hyperthermia (OR: 4.21; 95% CI: 3.48e5.09). There was an association between intrapartum hyperthermia and neonatal brain injury (OR: 2.79; 95% CI: 2.54e2.3.06). It was not possible to quantify the association between epidural-induced hyperthermia and neonatal brain injury. Conclusions: Epidural analgesia is a cause of intrapartum hyperthermia, and intrapartum hyperthermia of any cause is associated with neonatal brain injury. Further work is required to establish if epidural-induced hyperthermia is a cause of neonatal brain injury.

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

“…Epidural analgesia of greater duration not only is associated with a de facto higher dose of local anaesthetic but could impair heat loss by extended sympathetic blockade, promoting the same effect, suggested elsewhere as one likely explanation for epidural hyperthermia. 18 …”

“…One previous review has found evidence for an association between maternal hyperthermia from any cause and neonatal morbidity, with a greater impact in pre-term infants. 18 However, evidence to link epidural-related fever with neonatal brain injury is currently insufficient. 18 Prematurity is an established risk factor for neonatal brain injury and although it is likely the aetiology differs to that of intrapartum fever, the risks associated with fever development may potentiate mechanisms of injury in the premature neonatal brain.…”

“… 18 However, evidence to link epidural-related fever with neonatal brain injury is currently insufficient. 18 Prematurity is an established risk factor for neonatal brain injury and although it is likely the aetiology differs to that of intrapartum fever, the risks associated with fever development may potentiate mechanisms of injury in the premature neonatal brain. 93 Therefore, these population characteristics mean the results of our review are not generalisable to all population groups; specifically, they cannot be applied to women with pre-term labours.…”

“…ERMF is an under-researched problem; previous systematic reviews focused on confirming the association between epidural analgesia and the development of maternal fever, 16 , 17 or evaluating the consequences of fever on the mother and neonate. 17 , 18 Another systematic review compared the use of intravenous remifentanil as an alternative to epidural analgesia, 19 but methods of preventing or treating fever when an epidural is already placed, or is inevitable because of analgesia requirements, have not been systematically reviewed. The aim of this systematic review is to evaluate the RCT evidence of the comparative effectiveness of interventions to prevent or treat the development of ERMF.…”

Current Resources for Evidence‐Based Practice, May/June 2021

“…Epidural analgesia is selected by 7 of every 10 of those in labor, making it by far the most common form of pain relief in labor 1 . What are the potential adverse effects of epidural analgesia in labor besides the potential of maternal hypotension resulting in the need for an emergent cesarean? 2,3 This meta‐analysis by Morton and colleagues addresses maternal hyperthermia from epidural analgesia and what, if any, effect this has on the neonatal brain 4 …”