Neutrophil to Lymphocyte Ratio Values in Late Preterm and Term Patients with Evidence of Chorioamnionitis on Placental Histopathology: A Retrospective Cohort Study

Introduction: Neutrophil to lymphocyte ratio (NLR) is an inexpensive biomarker that may aid in the prediction of adverse pregnancy outcomes, though data remains sparse at this time. Previously published research regarding chorioamnionitis almost exclusively focuses on preterm labor and preterm prelabor rupture of membranes before 34 weeks of gestation and suggests an increase in NLR in those patients with chorioamnionitis identified on placental histopathologic examination. However, chorioamnionitis in the late preterm and term timeframe also represents a significant source of maternal and neonatal morbidity. Therefore, the primary aims of the study were to: 1) compare obstetric admission NLR values among those with and without evidence of histopathologic chorioamnionitis 2) evaluate the efficacy of NLR in identifying histopathologic chorioamnionitis and 3) compare NLR values pre- and postdelivery in the setting of a placental histopathologic chorioamnionitis diagnosis in patients beyond 34 weeks of gestation. Methods: A retrospective electronic chart review was performed at an American urban safety net hospital. Institutional review board approval was obtained (UMKC #2093657), and patient consent was waived due to the retrospective nature of the review. Obstetric encounters were included if a complete blood count (CBC) with differential was performed on admission and postpartum, the subject underwent a trial of labor, a placental histopathologic examination was performed, and delivery occurred beyond 34 0/7 weeks of gestation. Subjects were excluded if an extrauterine infection was present during the hospitalization or the subject received corticosteroids within two weeks of delivery. Postdelivery placentas were examined by the University’s pathology department. Statistical analyses were performed with receiver operator curves, Mann-Whitney U test, and Wilcoxon Signed-Rank Test where applicable, with a significance level p < 0.05. Results: Three hundred seventy-nine patient encounters were reviewed, with only 30.1% of all encounters with placental histopathology available. A total of 58 subjects met the inclusion criteria and 14 additional subjects were excluded due to extrauterine infection (n=1), SARS-CoV-2 diagnosis (n=5), and late preterm steroids administration (n=8). There was no difference between those subjects with and without histopathologic chorioamnionitis in median gestational age at the time of delivery (39 0/7 versus 39 1/7 weeks of gestational, p=0.960), median time of admission CBC collection to delivery (0.98 versus 0.98 days, p=0.340), and timing of collection of postpartum CBC (1.0 versus 1.0 days postpartum, p=0.631). Predelivery neutrophil to lymphocyte ratio values were compared in subjects with and without histopathologic chorioamnionitis and there was no significant difference in median values (4.11 versus 4.52, p=0.683). The predelivery NLR predicted the presence of chorioamnionitis poorly (AUC 0.518, 95% CI 0.326, 0.711, p=0.843). The postdelivery NLR was a slightly better predictor of chorioamnionitis (AUC 0.634, 95% CI 0.454, 0.815, p=0.147), but did not reach statistical significance. Although there was no significant difference in postpartum NLR values in those with and without chorioamnionitis on final histopathology (6.73 versus 4.63, p=0.147), the value was notably higher in the former. When the antepartum and postpartum NLR were compared across individual subjects in a paired fashion, there was a significantly higher postpartum NLR in those subjects both with and without chorioamnionitis on final histopathology (with chorioamnionitis: antepartum median 4.52 versus postpartum 6.73, p=0.012, n=15; without chorioamnionitis: antepartum median 4.11 versus postpartum 4.63, p=0.043, n=29). Conclusion: Though predelivery NLR is a poor predictor of chorioamnionitis, significantly higher postpartum NLR values in the sample population suggest an increase in NLR for all laboring patients, but a more pronounced increase occurs in those with inflammatory placental findings. While the study is limited by a heterogeneous sample population, nonparametric evaluation, and small sample sizes, the data does add to the paucity of preexisting literature that seeks to utilize NLR in the prediction of chorioamnionitis during the labor course. Larger longitudinal studies may help better characterize the rising NLR values over the course of labor and delivery as seen in our study. Neutrophil to lymphocyte ratio values across the spectrum of disease states and gestational ages in pregnancy may help isolate other inflammatory processes that impact perinatal outcomes.