Proadrenomedullin and neonatal sepsis: a systematic review and meta-analysis of diagnostic accuracy

The association of proadrenomedullin and neonatal sepsis has been examined in numerous studies. The object of our meta-analysis is to evaluate differences in proadrenomedullin among neonates with sepsis and health neonates. We systematically searched the following databases: MEDLINE, Clinicaltrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, and WHO (International Clinical Trials Register Platform) using a structured algorithm. Statistical analysis was conducted using Revman 5.3 and R software. Included studies in the meta-analysis were assessed using the Newcastle-Ottawa scale. Proadrenomedullin levels were found significantly higher in neonates with sepsis than healthy neonates with an SMD equal with 3.07 [95% CI 1.71, 4.42 (p < 10^-5, I² = 98%)]. The optimal cutoff point of pro-ADM was calculated at 17.559 with a sensitivity of 0.879 (0.458; 0.984) and a specificity of 0.994 (0.820; 1.000), and an AUC of 0.905. Subgroup analysis, leave-one-out meta-analysis, and meta-regression were performed in an effort to lower inter-study heterogeneity. Sensitivity analysis was conducted by excluding high risk of bias studies and those contributing to the overall heterogeneity shown by the Baujat plot. Publication bias was assessed using a funnel plot and the trim-and-fill method. Certainty assessment was evaluated using the GRADE score.Conclusion: The findings of our meta-analysis suggest that proadrenomedullin is elevated in neonates with sepsis. However, future prospective cohort studies need to be conducted in order to assess its diagnostic accuracy. What is Known: • Proadrenomedullin has been found increased in adult patients with infectious diseases such as community acquired pneumonia. • Proadrenomedullin plays a major role in the pathophysiology of sepsis in adults. What is New: • Proadrenomedullin is increased in neonates with sepsis. • Future cohort studies need to be conducted in order to elucidate the value of proadrenomedullin in a safer way.