6 Weakening and Rupture of Human Fetal Membranes – Biochemistry and Biomechanics N. Rangaswamy 1 , D. Kumar 1 , R.M. Moore 1 , B.M. Mercer 2 , J.M. Mansour 3 , R. Redline 4 and J.J. Moore 1,2 1 Department of Pediatrics, 2 Department of Reproductive Biology, 3 Department of Mechanical and Aerospace Engineering, 4 Department of Pathology, Case Western Reserve University, Cleveland, OH, USA 1. Introduction In spite of advances in the quality of prenatal care, management of high-risk pregnancies and treatment strategies targeting prevention of preterm births, the rate of preterm births in the US has continued to rise over the last two decades and is associated with high mortality and morbidity. Care of preterm infants also poses a significant financial burden on limited health care resources. Infants born at less than 37 weeks gestation account for 69% of all US infant deaths and their care has been modestly estimated at 26 billion dollars per year (Behrman et al., 2006; MacDorman et al., 2008). Preterm Premature Rupture of Membranes (PPROM) causes 30 - 40% of all preterm births and is disproportionately distributed such that African Americans suffer twice the rate of PPROM than Caucasians (Goldenberg et al., 1996a). Although some limited success has been achieved in the treatment of iatrogenic fetal membrane (FM) rupture resulting from amniocentesis or fetal surgery (Quintero et al., 1999; Young et al., 2000; O’Brien et al., 2001; Bilic et al., 2010), there has been no success in the repair of spontaneously ruptured FM, as occurs with PPROM (Quintero et al., 1998; Sciscione et al., 2001; Young et al., 2004b; Devlieger et al., 2006). Recent progress in the understanding of the biochemically-mediated processes which lead to FM weakening and rupture suggests that inhibition of these processes may be possible. This generates hope that many cases of PPROM may ultimately be preventable (R.M. Moore et al., 2009b, 2010; Kumar et al., 2011). 2. New techniques used in the studies on FM rupture 2.1 Mapping procedure We have developed and utilized a systematic procedure to map the rupture strength of FM over its entire topographic surface, thereby identifying relatively weak areas for further biochemical, proteomic, and sophisticated biomechanical testing.