Biochemical basis of cervical remodeling in preterm and term labor revealed by Raman spectroscopy

Preterm birth (PTB), affecting approximately 15 million infants annually, is the leading cause of neonatal mortality. However, the underlying mechanisms driving preterm labor (PTL) remain poorly understood. Early detection of biomolecular changes associated with both term and PTL is critical but challenging with current methods. Here, we utilize in vivo Raman spectroscopy (RS) to non‐invasively investigate cervical remodeling in mouse models of PTL induced by inflammatory (lipopolysaccharide ‘LPS’) and hormonal (RU486) pathways, compared with term labor (TL). In vivo RS results revealed etiology‐specific biochemical differences associated with cervical remodeling. LPS‐induced PTL exhibited increased carbohydrate‐associated spectral features, whereas the RU486 model exhibited a distinct protein remodeling pattern that diverged from both LPS‐induced PTL and TL. These biochemical signatures aligned with ex vivo imaging and biomechanical assessments of collagen, elastin, and vascularity. RS differentiated PTL from TL with 86% accuracy, outperforming existing techniques. Collectively, these results demonstrate that PTL is not a single biochemical process but comprises distinct remodeling trajectories that can be detected in vivo prior to labor onset. This work establishes a translational framework for Raman‐based cervical phenotyping, supporting the future development of non‐invasive tools for early PTL detection, etiological stratification, and targeted clinical intervention, to improve maternal and neonatal outcomes.