Synergy and interactions among biological pathways leading to preterm premature rupture of membranes

Reprod Sci. 2014 Oct;21(10):1215-27. doi: 10.1177/1933719114534535. Epub 2014 May 19.


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.

Keywords: PPROM; abruption; chorioamnion; chorioamnionitis; fetal membranes; inflammation; intraamniotic infection; oxidative stress; preterm birth; preterm premature rupture of membranes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Female
  • Fetal Membranes, Premature Rupture / diagnosis*
  • Fetal Membranes, Premature Rupture / metabolism*
  • Humans
  • Oxidative Stress / physiology*
  • Pregnancy
  • Signal Transduction / physiology*

Supplementary concepts

  • Preterm Premature Rupture of the Membranes