Preterm premature rupture of membranes (PPROM) occurs in 1% to 2% of births. 
Impact of PPROM is greatest in low- and middle-income countries where 
prematurity-related deaths are most common. Recent investigations identify 
cytokine and matrix metalloproteinase activation, oxidative stress, and 
apoptosis as primary pathways to PPROM. These biological processes are initiated 
by heterogeneous etiologies including infection/inflammation, placental 
bleeding, uterine overdistention, and genetic polymorphisms. We hypothesize that 
pathways to PPROM overlap and act synergistically to weaken membranes. We focus 
our discussion on membrane composition and strength, pathways linking risk 
factors to membrane weakening, and future research directions to reduce the 
global burden of PPROM.