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Term labour (TL) is a complex interplay of maternal and fetal factors which maintains the uterus in a state of quiescence during pregnancy, and then subsequently converts the uterus into a contractile organ which aids to expel the baby. Preterm labour (PTL) is not a single entity but is now recognised as multifactorial disorder and not just the early onset of TL. The aim of this study was to examine the similarities and differences in the molecular pathways of both TL and PTL. Myometrial samples were collected at the time of caesarean section from women in no labour (preterm singleton, preterm twins and term), term early labour, term established labour and PTL (placental abruption, chorioamnionitis PTL, idiopathic PTL and Twins PTL) were used to study pro-labour gene expression using quantitative rtPCR and protein levels/concentrations using Western blotting and multiplexed cytokine assays. Increasing gestation was associated with increased OTR, CX-43, PGDS, PGES-1 and PGES-2 but a decrease in PGFS, PGIS, SRC3 and FKBP5. At the onset of TL (term early labour samples), mRNA expression of PGHS-2 and SRC3 increased while both mRNA expression and protein levels of PGDS, PGIS and PR-B decreased compared to term no labour (TNL). None of the inflammatory chemokines were increased at the onset of term labour compared to TNL. Established labour was associated with a decrease in PGHS-2 (mRNA), increased PGFS and a higher protein concentration of IL-1β, IL-4, IL-6, IL-8, IL-10, CCL-1, CCL-11, CCL-24, CXCL-1, CXCL-5 and CXCL-6 compared to TNL and term early labour. In the preterm labour phenotypes, chorioamnionitis PTL was associated with increased PGHS-2 (mRNA), OTR, PGES-2 and 14 cytokines but a decreased PGDS and CS-43 compared to preterm no labour (PTNL). In contrast, idiopathic PTL, polyhydramnios and abruption PTL was not associated with an increase in cytokines and showed different prolabour gene profiles compared to each other. PTL associated with twins had a less intense inflammatory profile than chorioamnionits PTL. The prolabour gene and inflammatory profile of TL differs in comparison to each of the PTL phenotypes. The inflammation in the myometrium in TL is a consequence rather than the cause of labour while that in PTL is most likely involved in the onset of PTL in phenotypes such as chorioamnionitis or twins PTL.

The immune system during pregnancy undergoes substantial changes to reinforce tolerance of the semi-allogenic foetus until term labour, but disruptions in the immunological balance between innate and adaptive populations can lead to adverse pregnancy outcomes. At present, there are no immunological profiles which can be associated with any aetiology of preterm labour making its prediction difficult. Progesterone is currently being used as a preventative treatment for preterm birth and has been shown to be an effective immune modulator and suppresses inflammation. In myometrial tissue, aminophylline has been shown to enhance the anti-inflammatory effect of progesterone. This project determined cross sectional alterations in systemic and local immune cell phenotypes of women presenting with threatened preterm labour who experienced preterm birth in comparison with term birth pregnancy and secondly, the longitudinal changes in high-risk pregnant women receiving a combination of aminophylline and progesterone intended to prevent preterm labour. Pregnant participants were recruited at Chelsea and Westminster Hospital, maternal blood and cervical mucus were collected at each visit, and leukocytes were extracted for phenotypic and functional analysis using flow cytometry. Functional assays including: LPS-stimulation and intracellular cytokine staining were performed later on frozen cells. A cross-Sectional comparison in innate and adaptive cell populations demonstrated that systemic non-classical monocyte and cytotoxic natural killer cell frequencies were lower in women who experienced preterm labour, furthermore, CD4+ TERMA cell frequency was also lower implying that a dysfunction in innate immunity during pregnancy may suppress an adequate adaptive immune response to upcoming antigen exposure. Longitudinal comparison showed that lower non-classical monocyte frequency and markers of natural killer cell maturity were observed in women treated with aminophylline and progesterone supplementation. Whereas, HLA-DR activation on non-classical monocytes was decreased in women treated with progesterone only. Also, LPS-induced monocytes showed no decrease in IL-8, TNF-α and IL-10 secretion in either treatment group. This suggests that aminophylline may have an antagonistic effect to progesterone rather than enhance it, as shown by reduced proportions of non-classical monocytes and decreased cytotoxic potential of an NK cell subset.