We subsequently reexamined mean maternal tympanic temperature over time stratified by ultimate intrapartum fever status (Fig. 2). We restricted our analysis to the first 4 hours after epidural analgesia to pinpoint thermoregulatory changes rather than acquired infection. In the 77 women (77.8%) who remained afebrile, epidural analgesia was not associated with any temperature increase during the 4 hours after catheter placement (P=.26). In contrast, in the subset of 22 women who subsequently became febrile, mean maternal temperature rose dramatically after initiation of epidural analgesia. This increase was significant as early as 1 hour after catheter placement (P<.05). Over the 4-hour interval, the rise in mean maternal tympanic temperature was 1.3ºF (0.33ºF per hour). In comparison to the unstratified temperature curve, the magnitude of the standard error bars indicates less variability within each subgroup.
To our knowledge, this study represents the largest prospective cohort with hourly evaluation of maternal temperature after epidural analgesia (MEDLINE search January 1966 to November 2006; keywords: “hyperthermia,” “temperature,” “fever,” “epidural analgesia,” “labor”). When the cohort is examined as a whole, our results closely resemble the findings of Camann et al (1.3ºF versus 1.1ºF over 8 hours).6 However, the larger size of our cohort allowed us to present a stratified analysis that reveals a bimodal temperature response among nulliparous patients receiving epidural analgesia. The majority of women do not demonstrate an increase in mean tympanic temperature after epidural analgesia. In contrast, a minority subset of women demonstrates a brisk temperature response of higher magnitude than has been previously reported (0.33ºF per hour). Our findings do not support the current theory of a universal perturbation in maternal thermoregulation after epidural analgesia. Hyperthermia appears to be an abnormal response that occurs only in a relatively small subset of women at term. Our recent randomized controlled trial demonstrating that prophylactic maternal methylprednisolone (100 mg intravenously every 4 hours) reduced the rate of intrapartum fever after epidural analgesia by more than 90% also suggests an inflammatory, rather than a thermoregulatory, etiology.7
Of equal interest, those women who respond to epidural analgesia with hyperthermia do so immediately. A significant increase in maternal temperature was observed just 1 hour after epidural placement. This early onset of maternal temperature response precedes the accumulation of other maternal exposures to known risk factors for chorioamnionitis (eg, vaginal exams, prolonged membrane rupture). This rapid temperature rise suggests that factors which mediate alterations in maternal temperature response are already present in early labor and that identification of women at risk of subsequent fever may be possible. Although the two subsets of women receiving epidural analgesia appear clinically similar, they may have subclinical alterations in serum or cerebral spinal fluid markers, including altered levels of pro- or anti-inflammatory cytokines. Of note, women with the tumour necrosis factor (TNF) α Δ308 polymorphism, which increases levels of this pro-inflammatory cytokine, have an increased risk of intrapartum fever (24.4%) compared with controls with a relative risk of 3.3 (95% confidence interval 1.3–7.1).8 Currently, our group is actively investigating underlying maternal inflammatory balance to develop a strategy for early identification of women at high risk for subsequent intrapartum fever.
Early identification is critical if intervention to prevent fetal exposure to intrauterine hyperthermia and inflammation is found to be beneficial. Recent reports of neonatal hypothermia to treat hypoxic encephalopathy have refocused clinical attention on the interrelationship between fetal and neonatal brain temperature and the extent of brain injury after a hypoxic insult.9,10 Fetal hyperthermia at term (potentially in combination with intrauterine inflammation) is associated with a more than 4-fold increased risk of neonatal encephalopathy,11 and a 4- to 9-fold increased risk of cerebral palsy.12,13 Most recently, data has linked fetal cytokine polymorphisms, including heterozygous carriage of the Δ308 polymorphism of TNF α, to an increased risk of cerebral palsy in term infants.14 The fetal contribution to maternal temperature response is not known, but is an active area of research. Alternatively, fetal cytokine polymorphisms may reflect inherited maternal polymorphisms.
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