NYMC Faculty Publications

Fetal and Maternal Inflammatory Response in the Setting of Maternal Intrapartum Fever With and Without Clinical and Histologic Chorioamnionitis

Author Type(s)


Journal Title

American Journal of Obstetrics & Gynecology MFM

First Page


Document Type


Publication Date



Obstetrics and Gynecology


BACKGROUND: Both infectious and noninfectious causes of maternal fever have been linked to adverse neonatal outcomes including low Apg0ar scores, respiratory distress, hypotonia, and neonatal seizures. Even in the absence of infection, the occurrence of intrapartum fever is a strong risk factor for poor long-term neonatal developmental outcomes, including encephalopathy, cerebral palsy, and neonatal death. OBJECTIVE: The primary objective of this study was to compare intrapartum and postpartum maternal and fetal umbilical cord serum levels of cytokines RANTES, interferon-ɣ, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-13, and tumor necrosis factor-α among nonfebrile patients, febrile patients without clinical chorioamnionitis, and febrile patient with clinical chorioamnionitis. STUDY DESIGN: This study was conducted at the Richmond University Medical Center from May 15, 2020 to July 16, 2019. During this time, we recruited 30 nonfebrile patients at >36 gestational weeks who were in labor and collected umbilical cord and pre- and postdelivery maternal serum samples to evaluate the cytokine levels. Placentas were collected for pathologic review and to evaluate the histopathologic findings. These results were compared with 121 patients who developed a fever of >38°C during labor. The febrile patients were further divided based on the presence or absence of clinical chorioamnionitis. A secondary analysis was performed based on the presence of absence of histologic chorioamnionitis. Statistical analysis was performed using IBM Statistical Package for the Social Sciences version 25.0. For the 3 group comparisons, a P value of <.017 was considered statistically significant after application of a Bonferroni correction. RESULTS: A total of 151 patients were included in the study; 30 were nonfebrile patients, 46 were febrile patients with a diagnosis of clinical chorioamnionitis, and 75 were febrile patients without clinical chorioamnionitis. Compared with nonfebrile patients, umbilical cord serum interferon-ɣ, interleukin-1β, interleukin-6, interleukin-8, RANTES, and tumor necrosis factor-α levels were elevated in the presence of maternal hyperthermia irrespective of the diagnosis of clinical chorioamnionitis. Interleukin-6 umbilical cord levels were more than doubled from 63.60 pg/mL (6.09-1769.03 pg/mL) in febrile patients with no clinical chorioamnionitis to 135.77 pg/mL (1.86-6004.78 pg/mL) in febrile patients with clinical chorioamnionitis, making it the only cytokine that was significantly different between these 2 groups. When comparing the intrapartum maternal serum, we found a significant elevation in the interleukin-10, RANTES, and tumor necrosis factor-α levels in the febrile group irrespective of the presence of clinical chorioamnionitis when compared with the nonfebrile group. In the postpartum maternal blood evaluations, tumor necrosis factor-α was the only cytokine that was significantly higher in febrile patients than in nonfebrile controls. CONCLUSION: In the setting of intrapartum fever, maternal cytokine profiles were similar irrespective of the diagnosis of clinical chorioamnionitis. Even in the absence of clinical or histologic chorioamnionitis, maternal hyperthermia induced elevations in fetal cytokines.