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The Pathophysiology of Spontaneous Preterm Birth: Emerging Mechanisms Reviewed by the Preterm Birth International
Emmeli Mikkelsen1,2, Emmanuel Amabebe3,4, Andrea Olmos-Ortiz5
1Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Insights
Preterm birth, affecting 10% of global births, lacks effective prediction and prevention methods. Understanding parturition as an inflammatory process is key to developing new treatments for spontaneous preterm birth.
Area of Science:
- Reproductive biology
- Maternal-fetal medicine
- Genetics
Background:
- Approximately 10% of global births are preterm, posing significant maternal and neonatal health challenges.
- Limited progress in predicting and preventing spontaneous preterm birth despite extensive research.
- Spontaneous preterm birth necessitates a deeper understanding of its complex pathophysiology.
Purpose of the Study:
- To review recent advancements in understanding normal and preterm human birth pathophysiology.
- To present parturition as an inflammatory event involving multiple signaling pathways.
- To explore novel research perspectives for preterm birth prediction and prevention.
Main Methods:
- Review of current literature on human parturition.
- Analysis of endocrine, paracrine, and microbiome-related pathways.
- Discussion of mathematical modeling and machine learning applications.
Main Results:
- Parturition is characterized as an inflammatory event impacting uterine tissues.
- Multiple pathways, including fetal membrane senescence and vaginal microbiome, contribute to labor induction.
- Mathematical modeling and AI can identify preterm birth risk phenotypes.
Conclusions:
- Understanding parturition's inflammatory basis is crucial for preterm birth research.
- Integrating preterm birth history into medical surveillance is recommended.
- Increased funding and international collaboration are vital for advancing preterm birth prevention and treatment.
Abstract:
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.
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