The effect of magnesium on matrix metalloproteinase-9 activity in umbilical cord blood at delivery of pregnancies complicated by chorioamnionitis

Abstract

ACTIVITY IN UMBILICAL CORD BLOOD AT DELIVERY OF PREGNANCIES COMPLICATED BY CHORIOAMNIONITIS PETER NAPOLITANO, PATRICK MCNUTT, JAMES WRIGTH, BOBBY HOWARD, ANDREA FISK, PETER NIELSEN, NATHAN HOELDTKE, Madigan Army Medical Center, Obstetrics and Gynecology, Division Maternal-Fetal Medicine, Tacoma, WA Madigan Army Medical Center, Clinical Investigations, Tacoma, WA Madigan Army Medical Center, Obstetrics & Gynecology, Division Maternal-Fetal Medicine, Tacoma, WA Tripler Army Medical Center, OBGYN, Division MFM, Honolulu, HI OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) is an inflammatory cytokine that is increased in preterm intrauterine infection and may be associated with the development of cerebral palsy. Our objective was to determine umbilical cord serum concentrations of MMP-9 in term pregnancies complicated by chorioamnionitis compared to controls, and to determine if magnesium alters MMP-9 enzymatic activity. STUDY DESIGN: Umbilical cord serum was obtained from 6 term pregnancies with chorioamnionitis and 5 term pregnancies without chorioamnionitis. Samples were analyzed using MMP-9 activity assay (Amersham Biosciences) for total enzyme and percent active enzyme. The MMP-9 was then exposed to magnesium (Mg), at concentrations of 6.0 mg/dl and 60.0 mg/dl, and the enzyme activity was re-evaluated. All results are reported as the mean ± SEM. RESULTS: There was no difference in cord serum concentrations of MMP-9 between pregnancies with chorioamnionitis and normal controls (40.8 ± 9.9 ng/ml versus 28.0 ± 1.5 ng/ml, p = 0.26). There was no difference in endogenous MMP-9 enzyme activity between groups (p = 0.78). There was a 40% drop in total measured MMP-9 enzyme activity (p < 0.0001) at a Mg concentration of 6.0 mg/dl and a 97% drop (p < 0.0001) at a Mg concentration of 60.0 mg/dl. CONCLUSION: In term pregnancies the presence of clinical chorioamnionitis does not appear to affect the level of MMP-9 found in umbilical cord blood. However, there is a significant decrease in total measured MMP-9 enzyme activity upon in vitro exposure to Mg at a concentration therapeutically achieved in obstetrics. This decreased activity may be due to Mg competitively inhibiting zinc dependent MMP-9 activity, and this may be one mechanism to explain the association of in utero Mg exposure with a decreased incidence of cerebral palsy in preterm delivery.