MicroRNAs and Necrotizing Enterocolitis

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Necrotizing enterocolitis (NEC) is defined as an inflammatory condition of the gastrointestinal system which mainly affects premature infants and is associated with a high mortality rate. The cause of NEC is multi-factorial (likely a combination of infectious, vascular, and intestinal permeability issues), and early diagnosis would be helpful in order to start therapy and to prevent disease progression. MicroRNAs (miRNAs or small, non-coding RNAs) have been shown to be potential markers of intestinal inflammation, and the authors of this study evaluated the miRNA profiles of premature infants to determine if NEC could be diagnosed early in order to provide expeditious treatment.

A miRNA analysis occurred across 4 groups of infants which included premature infants with proven NEC (Bell stage II or higher), infants with sepsis (who had elevated C-reactive protein levels and had received parenteral antibiotics), infants with suspected sepsis but who ended up with other disease processes instead (heart failure, anemia, etc.), and healthy control infants. Microarray analysis for miRNA from plasma specimens was performed at the initial time of proven NEC and sepsis evaluation. Samples for miRNA on healthy control infants were obtained in the first 6 weeks of life. Potential miRNA biomarker for NEC were selected if they were associated with a greater than two-fold elevation in expression and with a significantly statistical difference in expression between NEC and non-NEC cases. Using this criteria, 7 potential miRNA biomarkers were noted, and polymerase chain reaction was done to quantify the amount of expression of these specific miRNAs between the 4 study groups in a case-control manner. Finally, a cohort of consecutive patients with NEC, sepsis, and non-NEC/non-sepsis were evaluated to determine the 3 highest potential miRNA biomarkers.

The case-control study had 50 infants that were compared between the 4 groups, and four of the 7 potential miRNAs had high enough levels of expression for detection (miR-1290, miR-1246, miR-375, and miR-619-5p). Significantly more copies of miR-1290, miR-1246, and miR-375 were found in patients with NEC compared to the other groups, and these same miRNAs decreased significantly between day 0 and day 1 of patients with NEC. Finally, ROC curve analysis showed that plasma miR-1290 at the initial time of NEC presentation provided the most accurate diagnosis regardless of NEC severity (>220 copies / microliter; sensitivity 0.83, specificity 0.92, PPV 0.60, and NPV 0.98). When miR-1290 levels of greater than 650 copies / microliter were considered, the specificity increased to 0.98 with a PPV 0.75, and when this initial miR-1290 level at time of NEC diagnosis was combined with an elevated C-reactive protein level above 15.8 mg/dL one day later, it was determined that this level of miR-1290 had a sensitivity 0.83, a specificity 0.96, PPV 0.75, and NPV 0.98. No significant correlation was noted between miR-1290 and gestational age or postnatal age in any of the infants. The authors conclude that miR-1290 has the potential to be a very good biomarker for detecting NEC early in its development. It remains to be seen how feasible it is to use such as potential biomarker in other hospital systems especially in regards to cost and timing of lab result returns.

Ng P, Chan K, Yuen T, Sit T, Lam H, Leung K, Wong R, Chan L, Pang Y, Cheung H, Chu W, Li K. Plasma miR-1290 is a novel and specific biomarker for early diagnosis of necrotizing enterocolitis – biomarker discover with prospective cohort evaluation. Journal of Pediatrics 2019; 205: 83-90.