The pathophysiology of threatened miscarriage and its effect on pregnancy outcome

The presented thesis is an investigation of the incidence and pathophysiology of first trimester threatened miscarriage and its outcomes. First trimester threatened miscarriage is the commonest complication of pregnancy, affecting 10-20% of women with clinically recognised pregnancies, and the incidence and mechanisms for long term adverse outcomes are poorly understood. Early placental development requires a delicate balance between the entry of oxygenated maternal blood and the capacity of the villous trophoblast to metabolise oxygen and eliminate its metabolites (free radicals). There is a rapid increase in placental markers of oxidative stress as the maternal circulation is established, which may serve a physiological role in stimulating placental differentiation, but which equally may result in free radical damage if antioxidant defences are depleted. In normal early pregnancy, the rapid increase in oxygen tension is paralleled by a rise in the expression of placental antioxidant enzymes. Bleeding in early pregnancy could change the delicate equilibrium of placental production of reactive oxygen species and its natural antioxidant defences, leading to disruption of normal development of the early placenta and placental membranes. This disruption results in a range of adverse pregnancy outcomes, from miscarriage in the first trimester, to pre-term pre-labour rupture of the membranes, pre-term labour, fetal growth restriction and pre eclampsia in the third. This study examines in detail the incidence and possible mechanisms of adverse outcome in women with threatened miscarriage and the role of placental function, in terms of placental hormone production and markers of oxidative stress, in both the causation of threatened miscarriage and the subsequent outcome of the pregnancy. It confirms an association between threatened miscarriage and adverse outcome, and provides potential markers of placental damage or stress to add to a growing body of research elucidating the role of oxidative stress in the developing placenta and later pregnancy complications.