Journal List > Korean J Perinatol > v.26(1) > 1013784

Shim, Kang, Maeng, and Kim: Umbilical Cord Blood Matrix Metalloproteinase-9 Levels are associated with Funisitis

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-α), 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-α, 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-α 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.

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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).
kjp-26-58f1.tif
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.
kjp-26-58f2.tif
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).
kjp-26-58f3.tif
Table 1.
Clinical characteristics of the study participants
  CA (+) n=22 CA (–) n=60 P value † FN (+) n=5 FN (–) n=77 P value † BPD (+) n=4 BPD (–) n=78 P value †
Mother
 Cesarean section 16 (72.7) 55 (9.7) NS 2 (40) 69 (89.6) 0.016 3 (75) 68 (87.2) NS
 Age (yr) 32.5±4.4 31.6. ±4.3 NS 30.4±5.0 31.9±4.3 NS 29.5±4.7 31.9±4.3 NS
 Serum WBC 10,850.0±3,535.2 9,113.3±2,717.1 1 0.040 1 14,740.0±4,844 9,244.2±2,592. 8 0.000 1 11,625.0±499.2 9,473.4±3,075. 4 NS
 Maternal tachycardia 10 (45.5) 25 (41.7) NS 5 (100) 30 (39.0) 0.012 2 (50) 33 (42.3) NS
 Fetal tachycardia 12 (54.5) 20 (33.3) NS 4 (80) 28 (36.4) NS 2 (50) 30 (38.5) NS
 Funisitis 5 (22.7) 0 (0) 0.001 1 (25) 4 (5.1) NS
 Chorioamnionitis 5 (100) 17 (22.1) 0.001 1 (25) 21 (26.9) NS
 Antibiotics use 11 (50.0) 11 (18.3) 0.010 4 (80) 18 (23.4) 0.017 1 (25) 21 (26.9) NS
 Dexamethasone use 12 (54.5) 19 (31.7) NS 5 (100) 26 (33.8) 0.006 3 (75) 28 (35.9) NS
 PPROM 11 (50.0) 8 (13.3) 0.001 4 (80) 15 (19.5) 0.009 1 (25) 18 (23.1) NS
 PTL with intact membrane 7 (31.8) 16 (26.7) NS 1 (20) 22 (28.6) NS 1 (25) 22 (28.2) NS
 PIH & others 3 (13.6) 13 (21.7) NS 0 (0) 1 (1.3) NS 1 (25) 14 (17.9) NS
Preterm Infant
 Gestational age (week) 31.3±3.1 33.1±2.3 0.012 29.6±3.4 32.8±2.5 0.010 26.3±1.7 32.9±2.3 0.001
 Birth weight (g) 1,670.0±419.8 1,852.7±517.1 NS 1 1,634.0±546.6 1,814.7±495.6 NS 840.0±209.9 1853.1±455.5 0.001
 Male 11 (50.0) 27 (45.0) NS 3 (60) 35 (45.5) NS 2 (50) 36 (46.2) NS
 SGA 13 (92.9) 24 (54.5) 0.020 5 (100) 32 (60.4) NS 1 (33.3) 19 (34.5) NS
 Apgar score at 1 min 6.6±1.6 7.0±1.6 NS 6.7±1.6 7.0±1.7 NS 5.0±0.8 6.8±1.6 0.016
 Apgar score at 5 min 8.2±1.1 8.5±0.9 NS 8.2±1.0 8.8±0.4 NS 7.8±0.5 8.3±1.0 NS
 RDS 9 (40.9) 8 (13.3) 0.012 2 (40) 15 (19.5) NS 4 (100) 13 (16.7) 0.001
 BPD36 (+) 1 (4.5) 3 (5.0) NS 1 (20) 3 (3.9) NS 4 (100) 3 (3.8) 0.001
 PDA 4 (18.2) 4 (6.7) NS 2 (40) 6 (7.8) NS 1 (25) 7 (9.0) NS
 PVL 2 (9.1) 1 (1.7) NS 0 (0) 3 (3.9) NS 0 (0) 3 (3.8) NS

Abbreviation: CA, chorioamnionitis; FN, funisitis; BPD, bronchopulmonary dysplasia

No NEC, sepsis, pneumothorax, pulmonary hemorrhage, severe intraventricular hemorrhage (grade III or IV) and PDA requiring an operative correction were reported.

Mann-WhitneyU test or Fisher's exact test.

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