title: Low levels of tissue inhibitor of metalloproteinase-2 at birth may be associated with subsequent development of bronchopulmonary dysplasia in preterm infants.
abstract: OBJECTIVE
  Bronchopulmonary dysplasia (BPD) is characterized by inflammation with proteolytic damage to the lung extracellular matrix. The results from previous studies are inconsistent regarding the role of proteinases and antiproteinases in the development of BPD. The aim of the present study was to investigate whether matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-1 levels in the serum of preterm infants at birth are related to the development of BPD.
  
  
  METHODS
  Serum was collected from 62 preterm infants at birth and analyzed for MMP-8, MMP-9, TIMP-2, and TIMP-1 by using enzyme-linked immunosorbent assay. MMPs and TIMPs were compared in BPD (n=24) and no BPD groups (n=38). Clinical predictors of BPD (sex, birth weight, gestational age, etc.) were assessed for both groups. The association between predictors and outcome, BPD, was assessed by using multivariate logistic regression.
  
  
  RESULTS
  Sex, birth weight, and mean gestational age were similar between the groups. BPD preterm infants had significantly lower TIMP-2 levels at birth compared with no BPD preterm infants (138.1±23.0 ng/mL vs. 171.8±44.1 ng/mL, P=0.027). No significant difference was observed in MMP-8, MMP-9, and TIMP-1 levels between the two groups. Multivariate logistic regression analysis indicated that the TIMP-2 levels were predictive of BPD after adjusting for sex, birth weight, gestational age, proteinuric preeclampsia, and intraventricular hemorrhage (β=-0.063, P=0.041).
  
  
  CONCLUSIONS
  Low TIMP-2 serum levels at birth may be associated with the subsequent development of BPD in preterm infants.
authors.affiliation: Graduate School, CHA University, Pocheon, Korea.
authors.forename: Choae
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, CHA University Bundang Medical Center, Seongnam, Korea.
authors.forename: Jaewoo
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Pediatrics, CHA University Gangnam Medical Center, Seoul, Korea. ; CHA University School of Medicine, Pocheon, Korea.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Kangwon National University School of Medicine, Chuncheon, Korea.
authors.forename: Eun Sun
authors.initials: ES
authors.lastname: Kim
authors.affiliation: CHA University School of Medicine, Pocheon, Korea. ; Department of Obstetrics and Gynecology, CHA University Gangnam Medical Center, Seoul, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: CHA University School of Medicine, Pocheon, Korea. ; Department of Obstetrics and Gynecology, CHA University Gangnam Medical Center, Seoul, Korea.
authors.forename: Yeon Kyung
authors.initials: YK
authors.lastname: Cho
authors.affiliation: CHA University School of Medicine, Pocheon, Korea. ; Department of Obstetrics and Gynecology, CHA University Gangnam Medical Center, Seoul, Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Cha
authors.affiliation: Department of Pediatrics, CHA University Bundang Medical Center, Seongnam, Korea. ; CHA University School of Medicine, Pocheon, Korea.
authors.forename: Man Yong
authors.initials: MY
authors.lastname: Han
authors.affiliation: Department of Pediatrics, CHA University Bundang Medical Center, Seongnam, Korea. ; CHA University School of Medicine, Pocheon, Korea.
authors.forename: Kyu Hyung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, CHA University Gangnam Medical Center, Seoul, Korea. ; CHA University School of Medicine, Pocheon, Korea.
authors.forename: Youn Ho
authors.initials: YH
authors.lastname: Sheen
keywords: Bronchopulmonary dysplasia; Matrix metalloproteinases; Premature infants; Tissue inhibitor of metalloproteinase