Average and time-specific maternal prenatal inflammatory biomarkers and the risk of labor epidural associated fever.

Dominique Y Arce,Olivia J Napoli,Thomas F Mcelrath,Andrea Bellavia,Tamarra James-Todd,John D Meeker,Lawrence C Tsen,David E Cantonwine,Patrick Rozenberg

doi:10.1371/journal.pone.0222958

Abstract

BackgroundThe use of labor epidural analgesia has been associated with intrapartum fever, known as labor epidural associated fever (LEAF). LEAF is most commonly non-infectious in origin and associated with elevated inflammatory cytokines.MethodsThe LIFECODES pregnancy cohort was designed to prospectively collect data to evaluate the association of maternal inflammatory biomarkers with preterm birth in women who delivered between 2007 and 2008 at Brigham and Women’s Hospital. Our secondary analysis of the data from the cohort identified 182 women for whom inflammatory biomarkers (i.e. interleukin-10, interleukin-1β, interleukin-6, tumor necrosis factor-α and C-reactive protein) collected longitudinally over four prenatal visits was available. Maternal temperature and other clinical variables were abstracted from medical records. The primary outcome, the presence of LEAF, was defined as oral temperature ≥ 38°C (≥100.4°F) after epidural analgesia initiation. Multivariable logistic regression estimated the association between inflammatory biomarker concentrations and the odds of developing an intrapartum fever after adjusting for a number of potential confounders.ResultsWomen who developed LEAF were more likely to have a longer duration of epidural analgesia, whereas women who did not develop LEAF were more likely to have induced labor and positive or unknown Group B Streptococcus colonization status. However, no differences were seen by nulliparity, mode of delivery, white blood cell count at admission, baseline temperature, length of rupture of membranes and number of cervical exams performed during labor. Unadjusted and multivariable logistic regression models did not provide evidence for or exclude an association between individual maternal inflammatory biomarkers and the odds of developing LEAF, regardless of visit time-period.ConclusionThe predictive value of maternal inflammatory biomarkers measured during early- and mid-pregnancy for the risk of developing LEAF cannot be excluded.

Highlights

Utilized by more than 70% of women undergoing childbirth in the United States, [1] labor epidural analgesia has been associated with intrapartum fever [2,3]
Women who developed labor epidural associated fever (LEAF) were more likely to have a longer duration of epidural analgesia, whereas women who did not develop LEAF were more likely to have induced labor and positive or unknown Group B Streptococcus colonization status
The predictive value of maternal inflammatory biomarkers measured during early- and midpregnancy for the risk of developing LEAF cannot be excluded

Summary

Introduction

Utilized by more than 70% of women undergoing childbirth in the United States, [1] labor epidural analgesia has been associated with intrapartum fever [2,3]. Labor epidural associated fever (LEAF) affects up to one third of deliveries and is thought to account for approximately 90% of intrapartum fever in low risk nulliparous women at term gestation [3,4]. The etiology of LEAF is most likely a non-infectious inflammatory reaction [10]. Clinical studies supporting this theory include those using methods of fever suppression, including prophylactic intrapartum acetaminophen and dexamethasone administration, and others demonstrating an association of LEAF with baseline and continued elevation of interleukin (IL)-6, a pro-inflammatory cytokine [11,12,13]. LEAF is most commonly non-infectious in origin and associated with elevated inflammatory cytokines

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Results

Conclusion