Infection-mediated preterm birth: Bacterial origins and avenues for intervention

Preterm birth (PTB) is globally the leading cause of death and disability in children under five years of age. Intra-amniotic infection is well recognised as a major cause of PTB. Importantly, it is the most common cause of extreme PTB (birth prior to 28 weeks gestation), which is frequently associated with a wide range of serious neonatal morbidities. Recent developments in next generation sequencing technologies, combined with many years of culture-based microbiological data have allowed us to gain a deeper understanding of the pathogenesis of infection-mediated PTB. In particular, studies have revealed numerous potential routes to intra-amniotic infection beyond the classically described ascending vaginal route. Currently, antibiotic therapy is standard treatment for suspected or confirmed intra-amniotic infection, although its use in this context has had mixed success due to problems ranging from inappropriate antibiotic selection in relation to the target organism/s, to poor transplacental drug passage. In this review, we will draw together evidence from animal models and human studies to characterise pathways to intra-amniotic infection. We will then thoroughly outline current therapeutic protocols for cases of intra-amniotic infection and suggest potential new avenues for treatment.