Plasma miR-1290 Is a Novel and Specific Biomarker for Early Diagnosis of Necrotizing Enterocolitis—Biomarker Discovery with Prospective Cohort Evaluation

• Published in: The Journal of pediatrics 2019-02, Vol.205, p.83-90.e10
• Main Authors: Ng, Pak Cheung, Chan, Kathy Yuen Yee, Yuen, Terence Ping, Sit, Tony, Lam, Hugh Simon, Leung, Kam Tong, Wong, Raymond Pui On, Chan, Lawrence Chi Ngong, Pang, Yennie Lap Ian, Cheung, Hon Ming, Chu, Winnie Chiu Wing, Li, Karen
• Format: Article
• Language: English
• Subjects: biomarkers; miR-1290; NEC; Sepsis
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2018.09.031

To discover specific circulating microRNA (miRNA) biomarkers for the early differentiation of necrotizing enterocolitis (NEC) from neonatal sepsis and inflammatory conditions. The study comprised 3 distinct phases: differential microarray analysis to compare plasma miRNA expression profiles of NEC vs sepsis and non-NEC/nonsepsis cases, a case-control study to quantify dysregulated miRNAs as potential specific biomarkers of NEC, and a prospective cohort study to assess the diagnostic usefulness of the best miRNA biomarker(s). A distinct miRNA expression profile was observed in the NEC compared with the sepsis and non-NEC/nonsepsis groups. miR-1290, miR-1246, and miR-375 were discovered to be specific biomarkers of NEC in the case-control study. In the cohort study (n = 301), plasma miR-1290 (day 0; >220 copies/µL) provided the greatest diagnostic usefulness for identifying both mild medical and severe surgical NEC cases. Of 20 infants with miR-1290 >650 copies/µL, 15 were diagnosed with NEC. Incorporating C-reactive protein (day 1; >15.8 mg/L) for cases with intermediate levels (220-650 copies/µL) in a 2-stage algorithm further optimized the diagnostic profile with a sensitivity of 0.83, a specificity of 0.96, a positive predictive value of 0.75, and a negative predictive value of 0.98. Importantly, 7 of 36 infants with NEC (19.4%) could be diagnosed 7.8-32.2 hours earlier (median, 13.3 hours) using miR-1290. Plasma miR-1290 is a novel and specific biomarker that can effectively differentiate NEC cases from neonatal sepsis. miR-1290 facilitates neonatologists to confidently and timely reach a decision for early transfer of sick infants with NEC from community-based hospitals to tertiary surgical centers.