Refining Pharmacologic Research to Prevent and Treat Spontaneous Preterm Birth

Preterm birth (PTB), delivery prior to 37 weeks’ gestation, is the leading cause of mortality among non-anomalous neonates. Survivors carry an increased risk for lifelong intellectual, physical, and social disabilities compared with their term counterparts (Russell et al., 2007; Bodeau-Livinec et al., 2008; Vohr, 2013; Manuck et al., 2014a, 2016b; Natarajan and Shankaran, 2016). In the US alone, more than 450,000 babies are born too soon and ∼25,000 die as a result (Hamilton et al., 2015). Approximately two-thirds of all PTBs are spontaneous PTB (SPTB), and occur following preterm premature rupture of membranes, cervical insufficiency, and/or uterine contractions leading to cervical dilation. To reduce the burden of SPTB, interventions must target both prematurity prevention prior to the onset of symptoms and acute treatment once the process of acute preterm labor has begun. Research efforts to develop treatments to improve neonatal outcomes have met some success [e.g., 17-alpha hydroxprogesterone caproate for recurrent SPTB prevention (Meis et al., 2003), antenatal corticosteroid treatment to prevent sequelae of prematurity (Roberts and Dalziel, 2006; Gyamfi-Bannerman and Thom, 2016)]. However, our ability to effectively prevent and treat SPTB remains limited. Of the available treatment options, significant inter-individual variation is appreciated. The reasons for this response variation are poorly understood and represent a critical knowledge gap contributing to thousands of SPTB every year. Refinement of patient selection for available drugs, or changing the form or dose of medication has the potential for large impact on therapeutic efficacy. Here we highlight two examples of medications currently used to reduce SPTB and discuss how cutting edge approaches may improve outcomes (Table 1).