Micromechanical Mechanisms of Fetal Membrane Failure

Premature birth is a major public health problem accounting for over 13,000 deaths and 30,000 surviving infants with life-long morbidity yearly. Preterm premature rupture of the fetal membranes (FM) is the initiating event leading to preterm birth of 40% of these premature infants. The mechanisms which cause FM failure and thereby rupture are not understood. A "weak zone" in the FM region overlying the cervix has recently been discovered, which demonstrates both biophysical weakness and concomitant biochemical evidence of tissue remodeling and apoptosis. This "weak zone" has been the subject of limited biomechanical investigation. A full understanding of FM failure requires a complete characterization of structural and biomechanical behavior of the FM at near/full term under sub-failure (forces well below that which induce rupture) and failure conditions as well as elucidating the biological factors which modulate its failure. The goals of this study were to (1) characterize the sub-failure structure-strength behavior of the FM under physiological loading conditions, (2) implement a structural constitutive model to investigate the sub-failure responses of FM, and (3) characterize the structural/strength sequelae during failure of the FM in the "non-weak" regions. The first two aims of this study established the baseline structure-strength relation of "non-weak zone" FM tissue. Specifically, the stress-strain relationship from an unloaded state up to failure was established. It was found that the FM behaves as an effectively isotropic material and that collagen fibers of the FM are recruited rapidly once they are loaded, which may be an important mechanism in the facilitation of FM rupture. Finally, a novel membrane inflation device revealed that upon loading, there was a small increase in collagen fiber alignment, although not significant, and there was no change in collagen fiber direction. More importantly, FM failure occurs catastrophically, suggesting that particular collagen fibers are not predisposed to failure. The results obtained in this study further our understanding of this unique physiological event, failure, and provide a basis for establishing how the structure-function relationship of the FM is altered the "weak zone," which has unique mechanical properties that facilitates membrane rupture