Unlocking the Cervix: Biological Mechanisms and Research Gaps in Preterm Birth

Preterm birth (PTB), defined by the WHO as delivery before 37 completed weeks of gestation, remains a significant global health challenge and the leading cause of neonatal mortality. Despite extensive efforts to prevent PTB, rates have remained stable, largely due to an incomplete understanding of its underlying pathophysiology. While research has traditionally focused on the myometrium and foetal membranes, the cervix's critical role in maintaining pregnancy and initiating labour is increasingly recognized but still often underexplored. This review aims to consolidate current knowledge on cervical function and remodelling during pregnancy and labour while identifying key research gaps and potential intervention strategies. A comprehensive literature review spanning 50 years was conducted using PubMed, identifying 114 studies that met the inclusion criteria. These studies examined cervical function during labour, spontaneous PTB, and the molecular mechanisms involved in cervical remodelling (CR). The review highlights significant molecular differences in cervical remodelling between term and preterm births. Critical processes such as extracellular matrix (ECM) remodelling, immune cell activity, and genetic predispositions vary depending on the specific triggers and gestational age at the onset of labour. Inflammatory responses are especially heightened in preterm births, particularly those driven by infections. However, much of the current data are derived from animal models, which may not accurately represent human physiology. In conclusion, a deeper understanding of the complex molecular mechanisms driving cervical remodelling is crucial to addressing PTB. Future research should prioritize human tissue studies to bridge the gap between animal models and human physiology. Developing targeted interventions that address cervical insufficiency and improve pregnancy outcomes is essential for reducing PTB rates.