The Pathophysiology of Spontaneous Preterm Birth: Emerging Mechanisms Reviewed by the Preterm Birth International Collaborative

Around 10% of global births are preterm (before 37 weeks of gestation), posing a significant challenge to maternal and neonatal health. Preterm infants face an increased risk of mortality and long-term health complications, impacting their survival and development across all life stages. Despite decades (~ 80 years) of research, effective methods to predict and prevent idiopathic or spontaneous preterm birth remain limited. Therefore, a deeper understanding of the pathophysiology of spontaneous preterm birth is warranted. This review explores some aspects of recent progress in unravelling the complex pathophysiology of both normal and preterm human birth. We present parturition as an inflammatory event, triggered by stressors affecting the uterine reproductive tissues (myometrium, decidua, and cervix), and involving multiple endocrine and paracrine pathways. These pathways, along with signals from fetal membrane senescence and the vaginal microbiome, contribute to labor induction. Proposed perspectives in parturition research include using mathematical modeling and machine learning (artificial intelligence) to map pregnancy trajectories and identify patient phenotypes associated with preterm birth risk. Additionally, incorporating preterm birth history into routine life course medical surveillance for affected individuals and their offspring is recommended. Finally, increased investment and prioritization from national funding bodies, along with greater support for international collaborations, are essential to identify the causes of preterm birth across multiple populations and develop new, effective treatments.