Epidural-related maternal temperature elevation is associated with an increased risk of adverse neonatal outcomes, a retrospective cohort study involving more than 3,200 women has shown.
Because randomized and observational studies consistently demonstrate an association between epidural use and maternal fever during labor – with greater than 90% of fever in labor related to epidural use in low-risk women at term, the findings are concerning, Elizabeth A. Greenwell, Sc.D., of the Harvard School of Public Health, Boston, and her colleagues reported Jan. 30 in Pediatrics. Dr. Greenwell is currently a postdoctoral fellow at the University of Colorado at Denver.
Of 3,209 women in the study population, 2,784 received epidural anesthesia and 425 did not. A temperature greater than 99.5 F developed after admission for delivery in 1,246 (44.8%) of those who received an epidural and in 62 (14.6%) of those who did not. A temperature greater than 100.4° F developed during labor in 535 (19.2%) of those who received epidural anesthesia and in 10 (2.4%) of those who did not.
In the absence of intrapartum temperature, no significant differences were seen in regard to adverse neonatal outcomes between those who did and did not receive epidural anesthesia. However, a trend was seen between the maximum maternal temperature and a significant increase in the incidence of hypotonia, assisted ventilation, 1- and 5-minute Apgar scores less than 7, and early-onset seizures in those with temperature elevation who received an epidural, the investigators said (Pediatrics 2012;129:e447-54).
On regression analysis, the risk of these adverse outcomes was two- to six-fold greater among infants born to women with a fever greater than 101° F.
For example, the proportion of infants with transitional hypotonia increased from 10.8% to 25.2% when maternal temperature was less than or equal to 99.5 F, compared with a temperature greater than 101° F. Similarly, the proportion of infants with hypotonia lasting greater than 15 minutes increased from 0.6% to 2.5% when maternal temperature was less than or equal to 99.5 F, compared with a temperature greater than 101° F, they said.
"Maternal fever exceeding 101 F was associated with a twofold increase in the risk of transitional hypotonia, a threefold increased risk of hypotonia lasting greater than 15 minutes, and a twofold increased risk for assisted ventilation. ... Infants of mothers with fever greater than 101° F were also 6.5 times more likely to have a seizure compared with infants of mothers with a maximum temperature less than or equal to 99.5 ° F," they said.
Study participants were low-risk nulliparous women with singleton pregnancies who were delivered at 37 or more weeks’ gestation in 2000, and who had their temperature recorded. Those with a temperature above 99.5° F at admission were excluded, as were those who received spinal anesthesia and those with infants who had conditions that might be associated with adverse neonatal outcomes.
The findings suggest that epidural analgesia without accompanying maternal fever does not have an immediate effect on neonatal status, but that epidural analgesia with fever could have an impact on the fetus.
"Our finding of an increase in unexplained seizures among infants of women with fever greater than 101° F is of concern," they said, noting that even though the findings were based on a relatively small number of seizures (n = 8), the finding is consistent with other studies demonstrating a link between intrapartum maternal fever and neonatal encephalopathy.
"Studies hypothesizing an association between neonatal encephalopathy or seizures and intrapartum maternal fever have assumed the fever resulted from infection such as chorioamnionitis. However, data suggest that among women delivering at term, most fever is related to epidural use rather than infection," they said.
Findings in this study also support those from prior studies suggesting an association between maternal fever and neonatal stroke in term infants, which along with other data demonstrating that clinical chorioamnionitis – primarily diagnosed by the presence of intrapartum fever – is associated with a substantially increased risk of cerebral palsy in term infants suggest that "exposure to intrapartum fever may not only increase the risk of adverse effects at birth but could potentially contribute to the development of long-term neurologic morbidity," they said.
The mechanism by which epidural analgesia may cause maternal fever, and by which fever might increase risk for adverse neonatal outcomes, remains unclear, they said, noting: "Our recent work, as well as that of others, suggests an inflammatory response accompanying epidural-related fever. ...
"Cytokines released in response to inflammation or infection can act as mediators of neurologic injury, and have been linked to neonatal encephalopathy and brain damage in newborns," they explained.