687 - Serum Matrix Metalloproteinase-7 (MMP-7) Levels in Premature Infants without Biliary Atresia

Publication Number: 1664.687

Cindy Zou, Goryeb Children's Hospital, Morristown, NJ, United States; Elizabeth A. Eckman, MidAtlantic Neonatology Associates, Morristown, NJ, United States; Reva-Jillene Rogerson, Goryeb Children's Hospital, Morristown, NJ, United States; Aimee Herdt, MidAtlantic Neonatology Associates, Morristown, NJ, United States; Naureen Memon, Goryeb Children's Hospital, Morristown, NJ, United States

Background: Matrix metalloproteinase-7 (MMP-7) is a promising biomarker for the diagnosis of biliary atresia (BA) in term infants. Produced by cholangiocytes during bile duct injury and fibrosis, MMP-7 reflects the underlying disease process; however, it is not entirely specific to BA. Elevated levels have been reported in other inflammatory and fibrotic conditions, including congenital heart disease, pulmonary hypertension, idiopathic pulmonary fibrosis, and systemic disorders involving epithelial injury. This limitation is particularly relevant in preterm infants, who commonly experience comorbidities, such as BPD, NEC, sepsis, that may independently increase MMP-7. As a result, the diagnostic performance of MMP-7 for BA in premature infants remains uncertain.

Objective: Our study aims to evaluate MMP-7 levels in the preterm population between 31-60 days of life (DOL) and to assess whether gestational age (GA), postnatal age (PNA), or common preterm conditions affect serum levels.

Design/Methods: Preterm infants enrolled in the neonatal biobank study at a single center NICU were selected for MMP-7 analysis if they had at least 1 plasma sample stored between 31 and 60 DOL. Additional samples stored between DOL 10 and 85 were included from a subset of study infants (n=9). In total, MMP-7 concentration was measured in 58 plasma samples from 25 infants using a commercially available sandwich ELISA (R&D Systems DMP700). Spearman's rank correlation test was performed in GraphPad Prism to analyze the relationship between MMP-7 concentration, GA, and PNA.

Results: Patient characteristics are shown in Table 1. MMP-7 levels were not correlated with GA (Spearman r = -0.12, P = 0.61). MMP-7 levels in preterm infants (Fig 1) were elevated in the first postnatal month and decreased over time (Spearman r = -0.72, P< 0.0001). To compare MMP-7 levels in preterm infants with proposed diagnostic cutoffs for BA, samples were grouped by DOL 0-30, 31-60, 61-90 (Fig 2). 67% of infants at DOL 0-30 and 44% at DOL 31-60 had MMP-7 levels exceeding the cutoffs proposed by Jiang et al (2024) in a large study of term infants with cholestasis. 48% at any age had MMP-7 levels classified as indeterminate by the clinical laboratory at CMC Dallas, and only one infant (with severe BPD) had a level exceeding this range.

Conclusion(s): To our knowledge, this is the first study to evaluate MMP-7 levels in a dedicated cohort of preterm infants. Common preterm morbidities did not consistently affect MMP-7 values, though isolated elevations were observed in two infants. These findings indicate that MMP-7 may still have diagnostic utility in preterm infants.

Table 1. Demographic and clinical characteristics of preterm infants enrolled in the MMP7 study


Figure 1: Plasma MMP-7 concentration in preterm infants without biliary atresia
MMP-7 was measured by sandwich ELISA in plasma from preterm infants (n=25) between DOL 10-85. MMP-7 concentration was inversely correlated with postnatal age (Spearman r = -0.72, P= <0.0001). Data were fit to a second order polynomial curve (solid line) with automatic outlier elimination of points >99th percentile. Dotted lines indicate the 95% prediction band.

Figure 2: Plasma MMP-7 concentration in preterm infants relative to proposed diagnostic cutoffs for biliary atresia
Data shown in Figure 1 were grouped by age range to facilitate comparison with proposed diagnostic cutoffs for biliary atresia in term infants. MMP-7 concentrations within the shaded range (17-68 ng/ml) are reportedly indeterminate for biliary atresia in term infants, while concentrations above 68 ng/ml have 95% specificity (Children's Medical Center, Dallas) Laboratory). Dotted lines indicate proposed diagnostic cutoffs for biliary atresia in the 0-30d age range (28 ng/ml) and 31-60d age range (18 ng/ml) from a large study of Chinese infants with cholestasis (Jiang et al 2024).
Boxes = 25th-75th percentiles, line = median, whiskers = min-max.