Evidence for the participation of interstitial collagenase (matrix metalloproteinase 1) in preterm premature rupture of membranes

OBJECTIVE: Rupture of membranes is thought to result from the effects of ph ysical forces in localized areas of the membranes weakened by the degradati on of structural collagens. Matrix metalloproteinases are enzymes that degr ade extracellular matrix components and have been implicated in membrane ru pture. The objective of this study was to determine whether spontaneous rup ture of membranes is associated with a change in the amniotic fluid concent ration of interstitial collagenase (matrix metalloproteinase 1 [MMP-1]), a major collagenase. STUDY DESIGN: A cross-sectional study was conducted to determine MMP-1 conc entrations in amniotic fluid from 353 women in the following categories: (1 ) term with intact membranes not in labor and in labor, (2) preterm labor w ho delivered at term, (3) preterm labor who delivered preterm without micro bial invasion of the amniotic cavity, (4) preterm labor who delivered prete rm with microbial invasion of the amniotic cavity, (5) preterm premature ru pture of membranes with and without microbial invasion of the amniotic cavi ty, (6) term premature rupture of membranes not in labor and in labor, and (7) mid trimester of pregnancy. Microbial invasion of the amniotic cavity w as determined by an amniotic fluid culture positive for microorganisms. MMP -1 concentrations in amniotic fluid were determined by means of sensitive a nd specific immunoassays. RESULTS: (1) MMP-1 was detectable in 81.3% of amniotic fluid samples (287/3 53), and its concentrations increased with advancing gestational age (r = 0 .4; P < .001). (2) Preterm premature rupture of membranes was associated wi th a significant increase in the median amniotic fluid concentration of MMP -1 (P = .02). (3) Women with term premature rupture of membranes had a sign ificantly lower amniotic fluid MMP-1 concentration than those with intact m embranes at term not in labor (P < .001). (4) Microbial invasion of the amn iotic cavity in patients in preterm labor with intact membranes and in pati ents with preterm premature rupture of membranes was also associated with s ignificant increases in the median amniotic fluid MMP-1 concentrations (P < .05 and P < .01, respectively). (5) Patients with preterm premature ruptur e of membranes and microbial invasion of the amniotic cavity had a signific antly higher median amniotic fluid MMP-1 concentration than those with inta ct membranes and microbial invasion of the amniotic cavity (P = .01). (6) N either term nor preterm parturition was associated with changes in amniotic fluid MMP-1 concentrations (P = .6 and P = .3, respectively). CONCLUSION: (1) Collagenase 1 (MMP-1) is a physiologic constituent of amnio tic fluid. (2) Preterm premature rupture of membranes (in both the presence and absence of infection) was associated with an increase in the amniotic fluid MMP-1 concentrations. (3) Neither term nor preterm parturition was as sociated with a significant increase in the amniotic fluid concentration of MMP-1.