Pathophysiology of preterm birth. Clinical relevence

Increased uterine contractility at term and preterm results from activation and then stimulation of the myometrium. Activation can be provoked by mechanical stretch of the uterus, and by an endocrine pathway resulting from increased activity of the fetal hypothalamic-pituitary-adrenal (HPA) axis. In fetal sheep increased cortisol regulates PGHS-2 expression in the placenta in an estrogen independent manner, resulting in increased levels of PGE(2) in the fetal circulation. Later increases in maternal uterine expression of PGHS-2 require estrogen and lead to increased concentrations of PGF(2alpha) in the maternal circulation. In women, cortisol also contributes to increased PG production in fetal tissues through upregulation of PGHS-2 and down regulation of 15-OH PG dehydrogenase (PGDH). The effect of cortisol on chorion expression of PGDH reverses a tonic stimulatory effect of progesterone. By competing with progesterone inhibition cortisol also increases expression of placental CRH. Other agents such as pro-inflammatory cytokines similarly upregulate PGHS-2 and decrease expression of PGDH, indicating the presence of several mechanisms by which labor at term or preterm may be initiated. These different mechanisms need to be considered in the development of strategies for the detection and management of the patient in preterm labor.