Cervical etiology of spontaneous preterm birth

Abstract

The cervix functions as a barrier between the uterus and vagina and keeps the uterus closed until term so that the fetus can develop. For delivery the cervix must soften and dilate, and finally reconstitute to close the uterus. This complex process involves precisely timed activation of molecular and microstructural events. Spontaneous preterm birth (sPTB) can result from aberrant timing of these events in the cervix. Unfortunately, the pathophysiology of sPTB due to cervical causes remains unclear and thus our treatment options remain limited - even if all appropriate candidates were identified and correctly treated with currently available interventions, the rate of sPTB would only be reduced by 5%. Very recent molecular and microstructural investigation is challenging prevailing concepts about cervical remodeling in pregnancy. We believe that progress toward novel, targeted solutions for the diverse pathways to sPTB entails a paradigm shift in which the overlapping and complex interactions between the cervix, uterus, membranes, fetus, placenta, and surrounding (structural and molecular) environment are suitably honored.

Keywords: Cervical insufficiency; Cervical microstructural assessment; Cervical remodeling; Cervical ripening; Spontaneous preterm birth.

Fig. 1

The three-zone theory of the cervical collagen network: inner and outer zones contain mostly collagen fibers that are oriented parallel to the endocervical canal, and a middle zone contains collagen fibers that are circumferentially oriented around the endocervical canal.

Fig. 2

Second harmonic generation microscopy image of human cervical tissue showing the complex collagen network. The right side of the image shows longitudinal sections taken from the endocervical canal, with the distal cervix on the left and proximal on the right. The left side of the image shows transverse sections taken from midway between the distal and proximal ends of the cervix (upper: anterior cervix; lower: posterior cervix).

Fig. 3

The emerging view of uterine and cervical smooth muscle cell (SMC) architecture. The area of the internal os contains circumferential SMCs that are contractile and resemble a “sphincter.” These SMCs express gap junctions which are a means to directly communicate with uterine SMCs.

Fig. 4

Cervical remodeling. HPA axis, hypothalamic–pituitary–adrenal axis; PPROM, preterm premature rupture of membranes; PTL, preterm labor; sPTB, spontaneous preterm birth.