Preterm birth remains an important global problem, and an important contributor to under-5 mortality. Reducing spontaneous preterm birth rates at the global level will require the early identification of patients at risk of preterm delivery in order to allow the initiation of appropriate prophylactic management strategies. Ideally these strategies target the underlying pathophysiologic causes of preterm labor. Prevention, however, becomes problematic as the causes of preterm birth are multifactorial and vary by gestational age, ethnicity, and social context. Unfortunately, current screening and diagnostic tests are non-specific, with only moderate clinical risk prediction, relying on the detection of downstream markers of the common end-stage pathway rather than identifying upstream pathway-specific pathophysiology that would help the provider initiate targeted interventions. As a result, the available management options (including cervical cerclage and vaginal progesterone) are used empirically with, at best, ambiguous results in clinical trials. Furthermore, the available screening tests have only modest clinical risk prediction, and fail to identify most patients who will have a preterm birth. Clearly defining preterm birth phenotypes and the biologic pathways leading to preterm birth is key to providing targeted, biomolecular pathway-specific interventions, ideally initiated in early pregnancy Pathway specific biomarker discovery, together with management strategies based on early, mid-, and-late trimester specific markers is integral to this process, which must be addressed in a systematic way through rigorously planned biomarker trials.

Biomedical Research Center University Hospital Hradec Kralove Hradec Kralove Czechia

Department of Genetics and Bioinformatics Domain of Health Data and Digitalization Norwegian Institute of Public Health Oslo Norway

Department of Obstetrics and Gynaecology The University of Pretoria School of Medicine Pretoria South Africa

Department of Obstetrics and Gynecology and of Global Health University of Washington Seattle WA United States

Department of Obstetrics and Gynecology Brigham and Women's Hospital and Harvard Medical School Boston MA United States

Department of Obstetrics and Gynecology Faculty of Medicine Hradec Kralove Charles University Prague Hradec Kralove Czechia

Department of Obstetrics and Gynecology Sahlgrenska Academy Gothenburg University Gothenburg Sweden

Department of Obstetrics and Gynecology The University of Texas Medical Branch at Galveston Galveston TX United States

Department of Women and Children's Health Faculty of Life Sciences and Medicine School of Life Course Sciences King's College London London United Kingdom

Department of Women and Children's Health Faculty of Life Sciences and Medicine School of Life Course Sciences St Thomas' Hospital Campus King's College London London United Kingdom

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