Maintenance of High Risk Pregnancies: Role of Prostaglandins and Other Mediators

Summary: The initiation of a complex cascade of events resulting in the delivery of a healthy newborn appears to involve the integrated actions of the fetus, mother and the placenta. Many putative factors have already been extensively reviewed. Instead of concentrating on the action of estrogen and progesterone, the role of regulators of myometrial activity such as prostaglandins as well as the fetal pituitary‐adrenal system, oxytocin, corticosteroids, leukotrienes, platelet activating factor, endotoxin and cytokines to name a few, will be discussed. Nevertheless, there is an increasing weight of evidence suggesting that many of the above agonists converge upon a final pathway of prostaglandin production which subsequently increases myometrial responsiveness. Prostaglandins are involved at levels of myometrial regulation such as myometrial gap junction formation, intracellular calcium flux modulation, synchronisation of myometrial contraction via interaction with oxytocin thus having stimulatory effects on uterine contractility, as well as cervical maturation (via PGE 2 ). Importantly, there has been clinical benefit of a more thorough understanding of the physiology of rnyometrial regulation at the time of partuition. The approach to the treatment of preterm delivery has improved, eventhough the exact mechanism(s) and cause(s) of this phenomenon remain an enigma. Current tocolytic therapy is not generally prophylactic but commences after labour, contractions and cervical dilatation are underway. Key regulatory pathways have been pin‐pointed that present opportunity for tocolysis including:‐ c‐AMP inhibition of contraction by (3‐mimetic agents, inhibition of calmodulin‐calcium function, inhibition of calcium influx by calcium channel blockers, inhibition of prostaglandin production, modulation of rnyometrial function by peptide hormones or antagonists (e.g. relaxin, VIP and oxytocin antagonists). New pathways and regulators may lead to further specific therapy. For example, Platelet Activating Factor may be one area of increased consideration; Changes in intracellular calcium concentrations in uterine muscle are clearly important in muscle contraction and Platelet Activating Factor increases cytosolic calcium concentration.