Detectable A Disintegrin and Metalloproteinase With Thrombospondin Motifs-1 in Serum Is Associated With Adverse Outcome in Pediatric Sepsis.

ImportanceA Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 is hypothesized to play a role in the pathogenesis of invasive infection, but studies in sepsis are lacking.ObjectivesTo study A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 protein level in pediatric sepsis and to study the association with outcome.DesignData from two prospective cohort studies.Setting and participantsCohort 1 is from a single-center study involving children admitted to PICU with meningococcal sepsis (samples obtained at three time points). Cohort 2 includes patients from a multicenter study involving children admitted to the hospital with invasive bacterial infections of differing etiologies (samples obtained within 48 hr after hospital admission).Main outcomes and measuresPrimary outcome measure was mortality. Secondary outcome measures were PICU-free days at day 28 and hospital length of stay.ResultsIn cohort 1 (n = 59), nonsurvivors more frequently had A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels above the detection limit than survivors at admission to PICU (8/11 [73%] and 6/23 [26%], respectively; p = 0.02) and at t = 24 hours (2/3 [67%] and 3/37 [8%], respectively; p = 0.04). In cohort 2 (n = 240), A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels in patients within 48 hours after hospital admission were more frequently above the detection limit than in healthy controls (110/240 [46%] and 14/64 [22%], respectively; p = 0.001). Nonsurvivors more often had detectable A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 levels than survivors (16/21 [76%] and 94/219 [43%], respectively; p = 0.003), which was mostly attributable to patients with Neisseria meningitidis.Conclusions and relevanceIn children with bacterial infection, detection of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 within 48 hours after hospital admission is associated with death, particularly in meningococcal sepsis. Future studies should confirm the prognostic value of A Disintegrin and Metalloproteinase with Thrombospondin Motifs-1 and should study pathophysiologic mechanisms