Computational Modeling of Cervical Remodeling During Pre-term Labor

Pre-term labor (PTL) is the leading cause of death for neonates and is on the rise in industrial nations. If it does not cause death, there is a greater chance that physical or intellectual abilities can occur. Normally, the cervix stays closed and firm during the gestation period to keep the baby in a controlled environment and will remodel as labor begins. The cervix goes through two phases, called cervical softening and cervical ripening, that cause the cervix to remodel. Issues in these remodeling phases can lead to PTL. PTL occurs when labor is initiated early in the gestation period, causing pre-mature effacement and dilation of the cervix. Some currently known factors for PTL are cervical remodeling, pro-inflammatory cytokine or fibronectin presence in combination with cervical length, a shortened cervix, and the patient previously going through PTL. Finally, the cervical mucus plug (CMP) is an important feature of the female reproductive environment. This is a viscoelastic material that acts a block to bacteria from entering the cervix. The biophysical properties of the CMP could act as biomarkers for PTL. The goal of this undergraduate research project was to develop a sophisticated computational model that simulates cervical remodeling during PTL and to use this model to investigate how changes in cervical tissue and CMP biophysical properties influence PTL. All factors that make a woman at risk for PTL are not completely understood and efforts are still being made to see what doctors can monitor to try and prevent PTL. Additionally, the role of the CMP in cervical remodeling was investigated and seen if it could be central in preventing PTL. The CMP has not been modeled with the cervix before and is a unique part of the project. A few hypotheses were made during the project, two of which were that alterations in the cervical tissue and the CMP biophysical properties would change the opening of the cervix. Another one made was that the model would support that cervical length has a large influence on cervical opening. Finally the main hypothesis made was the CMP as an overall structure is critical in regulating cervical opening. For the cervical tissue, Poisson’s Ratio, Young’s Modulus, and force were looked at. For the CMP, density, viscosity, and surface tension were tested. After computations, it was found that the Young’s Modulus and force were important factors in preventing PTL for the cervical tissue. The Young’s Modulus in the circumferential direction especially was significant in keeping the cervix from opening. This supported the hypothesis that the cervical tissue properties will play a role in preventing PTL. The viscosity of the CMP started to have an influence on the system at high values. The surface tension may have played a greater role in preventing PTL if there were not limitations in the model. The CMP could not slip along the fluid structure interaction boundary and this could have altered how the properties affected cervical opening. As a result, it was questionable whether these were noteworthy so it did not support the hypothesis that the biophysical properties of the CMP would cause changes to the cervical opening. Similarly, the CMP as a whole did not have a large influence on the preventing PTL, so it proved the main hypothesis that it would to be false. Finally, cervical length was tested and showed that a short cervix is more susceptible to cervical opening. This supported the last hypothesis that the model would verify that cervical length is important. From the cervical length studies, it was also found that the CMP started to have a greater influence with a shorter cervix. This should be kept in mind when proceeding with future steps in the project. An improvement for the project would be to find a way to have the points of the CMP on the fluid structure interface to slip. If this occurred, the results of the properties may have changed. One outlook would be to allow the cervical tissue to efface as well as dilate. Another outlook would be to create a more advanced model that includes the uterus. With the uterus, a pressure could be applied on the inside boundaries like the baby would. This would replace the force that is currently used and would be more anatomically accurate. A final outlook would be to change the viscosity of the CMP from Newtonian to a non-Newtonian shear thinning fluid. The viscosity is a non-linear fluid and the shear dependence of it may be vital in cervical opening and preventing PTL.No embargoAcademic Major: Biomedical Engineerin