The Role of the Endocannabinoid, Anandamide in Parturition and in the Prediction of Preterm Labour

Preterm birth is responsible for 75% of the perinatal mortality and morbidity. There is a trend towards an increase in its prevalence. Until now screening and prevention programmes have not been that successful due to limited knowledge of the basic molecular mechanisms of labour. As a result the predictive markers of preterm birth are not that effective raising the need for novel biomarkers. The endogenous endocannabinoid N-arachidonoylethanolamine (anandamide; AEA) acts as a ligand for cannabinoid receptors CB[subscript 1], CB[subscript 2].and non-CB[subscript 1] and non-CB[subscript 2] receptors. There is lack of knowledge on the role of anandamide in pregnancy and labour in humans. However the fact that smoking of exogenous cannabinoids such as marijuana is associated with preterm birth suggests a role for the endocannabinoids in labour. Plasma AEA was shown to increase 3.7 fold with labour. The aim of this thesis was to develop an improved method for the measurements of plasma AEA and to investigate further its role in labour and to measure its level in a cohort of women at high risk of delivering preterm. This led to the development of UPLC-MS/MS method of measuring plasma AEA. In women undergoing induction of labour, plasma AEA level was found to be elevated 1.5 fold in active labour (1.82±0.87nM) in comparison to levels in the non-labouring phase (1.20 ± 0.57nM) (P<0.0001). In women at high risk of delivering preterm the plasma AEA levels were significantly elevated in those who delivered within 6 weeks of sampling compared to women who delivered at term (P=0.01). A plasma AEA level of 1.10nM, predicted preterm delivery at <37 weeks of gestation with a sensitivity of 66.6% and specificity of 81.8%. Plasma AEA levels were not found to be significantly elevated in women delivering preterm amongst women presenting with threatened preterm labour. However a small sample size could have contributed to this result. The mean plasma AEA level was significantly elevated in women who had a positive fetal fibronectin test when compared to those who tested negative suggesting a relationship between the two. These data provide additional evidence that plasma AEA plays a significant role in labour and it could be used as a predictor of preterm delivery.