Neutrophil phenotypes in prolonged labor: Implications for therapeutic strategies

Prolonged labor, defined as labor extending beyond 20 hours for nulliparas and 14 hours for multiparas, poses significant risks to both maternal and neonatal health. The inflammatory response plays a crucial role in the pathophysiology of prolonged labor, with neutrophils being key players in this process. Neutrophils, the most abundant leukocytes, exhibit diverse phenotypes and functions in response to prolonged labor, influencing both the onset and progression of labor through their inflammatory actions. Classical neutrophils (N1) are involved in acute inflammatory responses, aiding in tissue remodeling and labor onset, but their prolonged activation can lead to tissue damage. Regulatory neutrophils (N2), which produce anti-inflammatory cytokines, help resolve inflammation and facilitate labor progression. Low-density granulocytes and aged neutrophils, associated with chronic inflammation and impaired function respectively, contribute to labor complications. The balance among these neutrophil phenotypes is crucial for maintaining a controlled inflammatory response during labor. Therapeutic strategies targeting neutrophil recruitment, NETosis, and cytokine production hold promise for managing prolonged labor. Modulating chemokine pathways, regulating NET formation, and balancing cytokine profiles may reduce inflammation and improve labor outcomes. Further research into the mechanisms of neutrophil regulation and the development of targeted therapies is essential for mitigating the adverse effects of prolonged labor and enhancing maternal and neonatal health.