Author Reply

We would like to thank Dr. Jiang and colleagues for their thoughtful comments and for their interest in our study evaluating the role of the neutrophil-to-lymphocyte ratio (NLR) in predicting delivery within 24 h among women with preterm premature rupture of membranes (PPROM) [1]. We are pleased that our work has stimulated further discussion on the role of inflammation in this clinical setting. As noted, infection and inflammation are central mechanisms in the pathophysiology of PPROM and spontaneous preterm birth [2, 3]. In our study, we attempted to account for infection-related confounding by including maternal fever and absolute leukocyte count in the multivariable analysis, alongside NLR and other relevant clinical variables [4]. Even after this adjustment, an elevated NLR remained independently associated with earlier delivery. Regarding gestational age, we agree that its potential impact on NLR values is a significant consideration. To further address this, we performed an additional post hoc analysis examining the correlation between gestational age at admission and NLR values using Spearman's correlation. This analysis demonstrated no significant association (correlation coefficient −0.077, p-value = 0.152), suggesting that gestational age did not materially influence the relationship we observed between NLR and delivery latency. Furthermore, in our Cox regression model, we adjusted for gestational age < 34 weeks, a clinically meaningful threshold given the importance of interventions at this stage, including antenatal corticosteroids for fetal lung maturation, magnesium sulphate for neuroprotection, and consideration of transfer to a tertiary center with a high-level neonatal intensive care unit. After this adjustment, NLR > 10 remained an independent predictor of delivery within 24 h. We acknowledge, as highlighted by Jiang et al., that the predictive performance of NLR alone is limited and should not be viewed as a standalone clinical tool. Instead, we believe our findings support NLR as a readily available biomarker that may reflect underlying inflammatory processes contributing to imminent delivery in the setting of PPROM. Ultimately, confirmation in larger, prospective cohorts, ideally incorporating additional inflammatory markers and stratification by gestational age, will be required to validate and refine these observations. We again thank Jiang and colleagues for their valuable insights and for recognising the clinical potential of our findings. We share their view that further research is needed to strengthen the evidence base and to better define the role of NLR in managing pregnancies complicated by PPROM. All authors contributed to the conception and interpretation of the response. Daniel Gabbai drafted the initial version of the Author's Reply. All authors critically revised the manuscript for important intellectual content and approved the final version. The authors have nothing to report. The authors declare no conflicts of interest. This article is linked to Jiang et al. papers. To view this article, visit https://doi.org/10.1111/1471-0528.70035. No new data were generated for this Author's Reply. Additional analyses were conducted using the data from the original study.