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

Soon Sup Shim; Hye Sim Kang; Young Hee Maeng; Young Don Kim

doi:10.14734/kjp.2015.26.1.58

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

Original Article

Korean J Perinatol 2015;26(1):58-66.

Published online: 20 March 2015

DOI: https://doi.org/10.14734/kjp.2015.26.1.58

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

Soon Sup Shim, M.D.¹, Hye Sim Kang, M.D.¹, Young Hee Maeng, M.D.², Young Don Kim, M.D., Ph.D.^3,

¹Department of Obstetrics and Gynecology, Jeju National University School of Medicine, Jeju, Korea

²Department of Pathology, Jeju National University School of Medicine, Jeju, Korea

³Department of Pediatrics, Jeju National University School of Medicine, Jeju, Korea

Correspondence to: Young Don Kim, M.D., Ph.D., Department of Pediatrics, Jeju National University School of Medicine, Ara 1-dong 1753-3, Jeju-si, Jeju Special Self-Governing Province 690-767, South Korea, Tel: +82-64-717-2087, Fax: +82-64-717-1097, E-mail: cardios@hanmail.net

Received 8 December 2014 Revised 12 February 2015 Accepted 17 February 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Keywords: Umbilical cord blood, Chorioamnionitis, Funisitis, Bronchopulmonary dysplasia, Tumor necrosis factor-α, Matrix metalloproteinase, Intercellular adhesion molecule

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Fig. 1.

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).

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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