Preterm prelabour rupture of the fetal membranes (PPROM) and premature cervical dilatation are driven by bacterial-induced inflammation, often resulting in late miscarriage, preterm birth, chorioamnionitis and early onset neonatal sepsis (EONS). The vaginal microbiome is considered a key determinant of pregnancy outcome but relatively little is known about its composition in these adverse pregnancy events. PPROM is treated with erythromycin, whilst the management of premature cervical dilatation is contentious, including expectant management with bed-rest or emergency cervical cerclage.
This thesis aimed to; 1) prospectively profile vaginal bacterial composition using next generation sequencing prior to and following PPROM and emergency cerclage, 2) examine the impact of erythromycin on vaginal bacterial composition, 3) investigate the anti-inflammatory properties of erythromycin in vaginal epithelial cells (VEC) and amniocytes and 4) retrospectively analyse the success of emergency cerclage.
Vaginal bacterial communities deficient in Lactobacillus spp. were observed prior to PPROM in a quarter of cases and 40% of women presenting with premature cervical dilatation. Erythromycin treatment exacerbated Lactobacillus spp. depletion creating vaginal communities enriched with pathobionts associated with subsequent funisitis and EONS and did not inhibit inflammation in VECs or amniocytes in-vitro.
Emergency cerclage was successful in 66% of cases. Cervical dilatation > 2cm, CRP >10mg/dL, the presence of G. vaginalis and maternal symptoms were all associated with poor outcomes.
The data presented in this thesis demonstrate that reduced Lactobacillus spp. abundance is a risk factor for subsequent PPROM, premature cervical dilatation, chorioamnionitis and EONS.
Modification of Lactobacillus spp. deplete communities in early pregnancy and alternative treatment strategies following PPROM may improve pregnancy outcomes. Emergency cervical cerclage is a successful procedure in the majority of cases and should be considered as first line treatment for premature cervical dilatation, especially in women with minimal cervical dilatation, low CRP and an absence of G. vaginalis.