Korean J Perinatol.  2015 Mar;26(1):58-66. 10.14734/kjp.2015.26.1.58.

Umbilical Cord Blood Matrix Metalloproteinase-9 Levels are associated with Funisitis

• Shim SS
• Kang HS
• Maeng YH
• Kim YD

• KMID: 2072338
• DOI: http://doi.org/10.14734/kjp.2015.26.1.58

Abstract

PURPOSE
Intrauterine inflammation (IUI) is a leading cause of preterm delivery. Although matrix metalloproteinase-8 (MMP-8) and intercellular adhesion molecule-1 (ICAM-1) are known to be related with IUI, it has not been fully elucidated whether MMP-9 or ICAM-3 is associated with IUI. We performed this study to determine whether the levels of tumor necrosis factor-alpha (TNF-alpha), MMP-9 and ICAM-3 in umbilical cord blood of preterm infants are associated with chorioamnionitis, funisitis or bronchopulmonary dysplasia.
METHODS
Eighty-two pairs of pregnant women and their preterm newborns <35 weeks gestation were enrolled. Levels of TNF-alpha, MMP-9 and ICAM-3 in umbilical cord blood were measured using immunoassays and compared with results of histological examination of placenta and clinical data of the study participants.
RESULTS
The level of MMP-9 in umbilical cord blood was significantly associated with the presence of funisitis (P =0.007). The level of TNF-alpha in umbilical cord blood was significantly associated with the development of bronchopulmonary dysplasia (P =0.030). However, presence of chorioamnionitis or funisitis was not associated with development of bronchopulmonary dysplasia. With the establishment of receiver operating characteristic (ROC) curve, the best cut-off value for umbilical blood MMP-9 was 99.42 pg/mL in identification of funisitis. The area under a constructed ROC curve for prediction of funisitis was 0.847 (standard error, 0.112; 95% confidence interval, 0.750-0.917).
CONCLUSION
Measurement of MMP-9 concentration in umbilical cord blood may be an alternative way to predict whether a preterm infant has been exposed to IUI. Further study with larger numbers of subjects will be necessary to elucidate the association between the presence of IUI and neonatal adverse outcome.

Keyword

Umbilical cord blood; Chorioamnionitis; Funisitis; Bronchopulmonary dysplasia; Tumor necrosis factor-alpha; Matrix metalloproteinase; Intercellular adhesion molecule

MeSH Terms

Bronchopulmonary Dysplasia
Chorioamnionitis*
Female
Fetal Blood*
Humans
Immunoassay
Infant, Newborn
Infant, Premature
Inflammation
Intercellular Adhesion Molecule-1
Matrix Metalloproteinase 8
Matrix Metalloproteinase 9*
Placenta
Pregnancy
Pregnant Women
ROC Curve
Tumor Necrosis Factor-alpha
Intercellular Adhesion Molecule-1
Matrix Metalloproteinase 8
Matrix Metalloproteinase 9
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1. Comparison of matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-3 (ICAM-3) and tumor necrosis factor-α (TNF-α) level in umbilical cord blood according to the presence or absence of funisitis. Infants from mother with funisitis had a significantly higher level of MMP-9 than those without funisitis (P=0.007).

• 

  Fig. 2. Comparison of matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-3 (ICAM-3) and tumor necrosis factor-α (TNF- α) level in umbilical cord blood according to the presence or absence of bronchopulmonary dysplasia (BPD). Infants with BPD had a significantly higher level of TNF-α than those without funisitis (P=0.030). Although the median level of ICAM-3 in infants with BPD was lower than those without BPD, there was no statistical significance when the gestational age was adjusted as a cofounding factor.

• 

  Fig. 3. Receiver operating characteristic curves for identification of the presence of funisitis. Area under the curve for umbilical matrix metalloproteinase-9 level: 0.847 (95% confidence interval: 0.750–0.917, P=0.0019).

Reference

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