Measuring MMP-7 levels in dried blood spots appears not feasible for newborn screening of biliary atresia.

OBJECTIVE: Biliary atresia (BA) is an obstructive cholangiopathy of the newborn. Early diagnosis improves outcomes, but due to rarity and nonspecific presentation, referral is often delayed. Incorporation of BA into newborn screening (NBS) using dried blood spots (DBS) is desirable. Matrix metalloproteinase 7 (MMP-7) is a highly specific and sensitive marker for BA in serum and DBS and has been proposed as an appropriate screening parameter. We aimed to evaluate MMP-7 levels in DBS from patients with BA to assess its potential for NBS. STUDY DESIGN: Original DBS NBS cards of infants with BA (n=49) were retrospectively obtained from screening laboratories. Additional DBS and blood samples were collected at Kasai portoenterostomy (n=5). To assess MMP-7 stability, a fresh DBS sample was stored at different intervals before freezing. Healthy newborns served as controls (n=24). MMP-7 was measured by ELISA and correlated with BA type, outcome, fibrosis score, and bilirubin levels. Diagnostic performance was assessed by ROC analysis in both the study cohort and a modeled real-world prevalence setting. RESULTS: Patients with BA showed significantly higher MMP-7 levels than controls (BA 22.80 ng/mL±12.28, HC 13.82 ng/mL±2.97, p<0.001). Exploratory stability assessment suggested a time-dependent decrease in MMP-7 concentrations during room temperature storage, which appeared moderate within the initial days. MMP-7 levels at birth did not correlate with clinical parameters at Kasai portoenterostomy. ROC analysis demonstrated good test performance within our study cohort; however, extrapolation to real-world prevalence yielded insufficient screening performance. CONCLUSIONS: MMP-7 is elevated in BA patients' DBS at birth, but current performance characteristics are insufficient for reliable NBS. Larger studies and multiparametric approaches may be needed to improve screening feasibility.