Preterm prelabor rupture of the membranes: A disease of the fetal membranes

Preterm prelabor rupture of the membranes (pPROM) remains a significant obstetric problem that affects 3–4% of all pregnancies and precedes 40–50% of all preterm births. pPROM arises from complex, multifaceted pathways. In this review, we summarize some old concepts and introduce some novel theories related to pPROM pathophysiology. Specifically, we introduce the concept that pPROM is a disease of the fetal membranes where inflammation–oxidative stress axis plays a major role in producing pathways that can lead to membrane weakening through a variety of processes. In addition, we report microfractures in fetal membranes that are likely sites of tissue remodeling during gestation; however, increase in number and morphometry (width and depth) of these microfractures in pPROM membranes suggests reduced remodeling capacity of membranes. Microfractures can act as channels for amniotic fluid leak, and inflammatory cell and microbial migration. Further studies on senescence activation and microfracture formation and their role in maintaining membrane homeostasis are needed to fill the knowledge gaps in our understanding of pPROM as well as provide better screening (biomarker and imaging based) tools for predicting women at high risk for pPROM and subsequent preterm birth.