The mechanical role of the cervix in pregnancy

Abstract

Appropriate mechanical function of the uterine cervix is critical for maintaining a pregnancy to term so that the fetus can develop fully. At the end of pregnancy, however, the cervix must allow delivery, which requires it to markedly soften, shorten and dilate. There are multiple pathways to spontaneous preterm birth, the leading global cause of death in children less than 5 years old, but all culminate in premature cervical change, because that is the last step in the final common pathway to delivery. The mechanisms underlying premature cervical change in pregnancy are poorly understood, and therefore current clinical protocols to assess preterm birth risk are limited to surrogate markers of mechanical function, such as sonographically measured cervical length. This is what motivates us to study the cervix, for which we propose investigating clinical cervical function in parallel with a quantitative engineering evaluation of its structural function. We aspire to develop a common translational language, as well as generate a rigorous integrated clinical-engineering framework for assessing cervical mechanical function at the cellular to organ level. In this review, we embark on that challenge by describing the current landscape of clinical, biochemical, and engineering concepts associated with the mechanical function of the cervix during pregnancy. Our goal is to use this common platform to inspire novel approaches to delineate normal and abnormal cervical function in pregnancy.

Keywords: Cervix; Pregnancy; Preterm birth.

Fig. 1

Biological length scales in the human cervix. (A) The location of the uterine cervix based on segmentation of magnetic resonance imaging (MRI) data of a 20 week pregnant patient (Fernandez et al., 2015). (B) Collagen fiber directionality of an axial slice of a nonpregnant (NP) cervix imaged via optical coherence tomography (Gan et al., 2014). (C) NP cervical collagen fiber imaged via second harmonic generation (Myers et al., 2009). (D) NP cervical crosslink density (mole-per-mole basis with collagen) content, pyridinoline (PYD), deoxypyridinoline (DPD), dihydroxylysinonorleucine (DHLNL), pentosidine [PEN] (Zork et al., 2015).

Fig. 2

Cervical deformation patterns and clinical definitions: Cervical length is clinically measured as the portion of the cervix that is closed. Effacement progresses in normal pregnancy when the fetal head descends and shortens the cervix. Funneling is a pathologic condition related to an abnormal cervical deformation pattern when the membranes slip into the inner canal and the cervix prematurely shortens.

Fig. 3

Closure pressure p_cl of nonpregnant (NP), pregnant (months 2–9, n=50) and post-partum (PP) patients are shown as vertical bars, crosses indicate cervical length (CL, second vertical axis). Standard deviations are indicated as vertical lines. On the right: maximum logarithmic strains (LE) in the aspiration experiment calculated by finite element analysis (axisymmetric model with a neo-Hookean material, from Badir et al., 2013a, with the aspirated tissue in the middle and the aspirator edge as horizontal line next to it). Reproduced with permission from Badir et al. (2013a,. (For interpretation of the references to color in this figure caption, the reader is referred to the web version of this article.)

Fig. 4

Comparing fiber composite material models proposed in Myers et al. (2015) and Liao et al. (2014) for the human cervix. Principal strain magnitude and directionality are calculated within a thick-walled cylinder (inner radius=8 mm, outer radius=28 mm, length=38 mm) under compressive longitudinal pressure for an elliptically-shaped continuous fiber distribution (EFD) material model (Myers et al., 2015) fit to NP and PG ex vivo mechanical data and a 3-fiber family model fit to PG in vivo pressure-dilation data (Liao et al., 2014). The EFD material produces a more uniform strain pattern compared to the 3-fiber family model, where the 3-fiber family model produces a twist of the cylinder under uniform compression. The two models predict similar levels of longitudinal compression for the term pregnant condition. However, the two models predict different patterns of strain, where the 3-fiber family model produces a larger gradient of strain through the thickness of the cylinder.