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Pathophysiology
Preterm births (births taking place before 37 weeks) can be the result of a number of causes such as, in uteruo infection, inflammation, vascular disease and uterine overdistension. The risk of spontaneous preterm birth is increased by a previous preterm birth, black race, periodontal diseases and low maternal body-mass index. Key indicators of preterm birth are short cervical length and a raised cervical-vaginal fetal fibronectin concentration.

Pathophysiology of the fetal membranes, such as microfractures, senescence of cells in the fetal membrane and inflammation can lead to an increased chance of preterm premature rupture of the fetal membranes (pPROM).

Microfractures of the fetal membranes
Throughout gestation the fetal membranes undergo remodelling to allow for the increase in size of the uterus. The remodelling of the fetal membranes occurs at both the level of the cells and the extracellular matrix (ECM). Structural abnormalities such as areas of where collagen has degraded, known as microfractures, have been observed in the amniotic membrane layer.

Microfractures are characterised by:


 * Alterations to or shedding of the epithelial cells of the amnion layer
 * Basement membrane damage or degradation
 * Cells in the ECM migrating
 * The presence of tunnels from the basement membrane to the spongy layer of the amnion

Microfractures of the fetal membranes are seen in pregancies where pPROM has occured. It has been suggested that the presence of more fetal membrane microfractures may mean the fetal membranes may be predisposed for preterm rupture.

Inflammation and senescence of the fetal membranes
Balanced inflammation is an important factor in maintaining fetal membranes by regulating the remodeling. However, if the inflammatory response increases above this level it can have dangerous and potentially fatal effects for the mother and child. These elevated levels of inflammatory molecules in the fetal membrane is called ‘sterile inflammation’. Sterile inflammation can be caused by both microbial infection and non-infectious factors, such as senescence of fetal membranes. Senescence is associated with the aging of actively cycling and dividing cells. As the fetal membrane cells proliferate during remodelling, the telomeres (short length or non-coding DNA on the end of chromosomes that protect essential coding DNA from degradation during replication) shorten as chromosomes can not be copied end-to-end fully. Once the telomeres have reached a critical length the cell can no longer divide and can hence cause telomere-dependent replicative senescence. This should occur naturally at term (37 weeks), as it is an important factor to increase the inflammatory environment in the uterus to initiate parturition. However, fetal membrane senescence can be accelerated by oxidative stress and hence, stimulate sterile inflammation to occur prior to term; consequently, causing preterm birth.