Preterm premature rupture of fetal membranes is responsible for 30% to 40% of preterm
deliveries. Fetal membranes are composed primarily of collagen. Matrix metalloproteinases
are enzymes capable of degrading extracellular matrix macromolecules, including collagens.
Expression of matrix metalloproteinase-9 (gelatinase B, 92 kd) and its tissue inhibitor
(tissue inhibitor of metalloproteinase-1) has been localized in amnion and chorion.
The objective of this study was to determine whether rupture of fetal membranes and
intrauterine infection are associated with changes in the expression of matrix metalloproteinase-9
and tissue inhibitor of metalloproteinase-1.
Two hundred one women in the following categories had amniotic fluid retrieved: (1)
preterm labor and intact membranes in the presence (n = 42) or absence (n = 21) of
microbial invasion of the amniotic cavity, (2) preterm premature rupture of the membranes
with (n = 29) or without (n = 23) microbial invasion of the amniotic cavity, and (3)
term gestation with intact membranes (n = 50) or with premature rupture of the membranes
(n = 40). Women in groups 1 and 2 were matched for gestational age at amniocentesis.
Microbial invasion of the amniotic cavity was defined by a positive amniotic fluid
culture for micro-organisms. Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1
were measured with use of sensitive and specific immunoassays that were validated
for amniotic fluid.
Spontaneous rupture of membranes at term is associated with a significant increase
in the amniotic fluid concentrations of matrix metalloproteinase-9 (premature rupture
of membranes, no labor: median 3.9 ng/mL, range 2. 7 to 11.1 ng/mL vs no premature
rupture of membranes, no labor: median <0.4 ng/mL, range <0.4 to 22.4 ng/mL; P <.001).
Patients with preterm premature rupture of the membranes had higher median matrix
metalloproteinase-9 concentrations than those with preterm labor and intact membranes
who were delivered at term (7.6 ng/mL, range <0.4 to 230.81 ng/mL vs <0.4 ng/mL, range
<0.4 to 1650 ng/mL; P =.06). Women with microbial invasion of the amniotic cavity
had higher median matrix metalloproteinase-9 concentrations than did those without
microbial invasion regardless of membrane status (preterm labor: 54.5 ng/mL, range
<0.4 to 3910 ng/mL vs <0.4 ng/mL, range <0. 4 to 1650 ng/mL; P <.01; preterm premature
rupture of membranes: 179. 8 ng/mL, range <0.4 to 611 ng/mL vs 7.6 ng/mL, range <0.4
to 230.81; P <.001).
Our data support a role for matrix metalloproteinase-9 in the mechanisms responsible
for membrane rupture in term and preterm gestations.