Prospective validation of a biomarker panel to identify pediatric ED patients with abdominal pain who are at low risk for acute appendicitis

Objectives: The objective of the study is to prospectively validate the diagnostic accuracy of a biomarker panel consisting of white blood cell, C-reactive protein, and myeloid-related protein 8/14 levels in identifying pediatric patients with abdominal pain who are at low risk for appendicitis. Methods: This prospective observational study enrolled subjects aged 2 to 20 years presenting to 29 US emergency departments with abdominal pain suggesting possible acute appendicitis. Blood samples were analyzed for white blood cell, C-reactive protein, and myeloid-related protein 8/14 levels from which the composite biomarker panel results were calculated, then correlated with the final diagnosis either positive or negative for acute appendicitis. Results: A total of 2201 patients were enrolled, with 1887 completing all aspects of the study. Prevalence of appendicitis in this cohort was 25.3%. The biomarker panel exhibited a sensitivity of 97.1% (95% confidence interval [CI], 95.1%-98.2%), negative predictive value of 97.4% (95% CI, 95.8%-98.5%), negative likelihood ratio of 0.08 (95% CI, 0.05-0.13), with a specificity of 37.9% (95% CI, 35.4%-40.4%) for appendicitis. The panel correctly identified 534 (37.8%) of 1410 patients who did not have appendicitis with 14 false negatives (2.9%). Overall, 23.7% (132/557) of computed tomographic (CT) scans were done for patients with negative biomarker panel results, including 31.2% (131/420) of patients who had CT but did not have appendicitis. Conclusion: This biomarker panel exhibited high sensitivity and negative predictive value for acute appendicitis in this large prospective cohort. This panel may be useful in identifying pediatric patients who are at low risk for appendicitis and might be followed clinically, potentially reducing the dependence on CT in the evaluation for acute appendicitis.