Abstract:
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 nonspecific, 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.
