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Presepsin holds promise as a biomarker for early-onset sepsis (EOS), a systematic review and meta-analysis confirmed.

Across a dozen clinical trials, presepsin had a pooled sensitivity of 0.93 for the primary analysis of culture-proven sepsis (95% CI 0.86-0.96), a pooled specificity of 0.91 (95% CI 0.85-0.95), and a pooled diagnostic odds ratio (DOR) of 131.7 (95% CI 54.9-310.9), reported Chiara Poggi, MD, PhD, of Careggi University Hospital in Florence, Italy, and colleagues.

A secondary analysis using a broader criteria for sepsis produced similar results. The findings suggest presepsin "was a robust biomarker" of EOS and warrant trials to assess its usefulness in guiding early empirical antibiotic treatment, especially for newborns born preterm, the group wrote in .

"EOS diagnosis is a frequent challenge in the neonatal intensive care unit [NICU], as clinical signs are equivocal and the common markers of infection, such as C-reactive protein and procalcitonin, physiologically increase during the first 48 hours of life in response to noninfective stimuli," Poggi and colleagues explained.

As blood culture results take a median 21 hours, up to 96% of infants born extremely preterm are given antibiotics in the NICU, as are 2-15% of those born at term, but "early empirical antibiotics without evidence of positive blood culture are associated with adverse outcomes, such as late-onset sepsis (LOS), necrotizing enterocolitis, death, bronchopulmonary dysplasia, and adverse neurodevelopmental outcomes in preterm newborns," the group noted.

Poggi and colleagues pointed out that prior meta-analyses suggested presepsin to be a "favorable" biomarker for diagnosing neonatal sepsis.

For their analysis, the researchers performed a literature search for studies involving term or preterm infants diagnosed with EOS, which examined presepsin levels (and measured sensitivity/specificity) during workup for suspected cases. Outcomes of interest for both the primary and secondary analysis (either clinical or culture-proven sepsis) were sensitivity, specificity, and DOR.

In all, 12 studies involving 828 newborns (including 460 with EOS and the rest uninfected) met inclusion criteria for the primary analysis. Ten of the studies included a mix of EOS and LOS, four only included infants born at term, two were restricted to preterm infants, and the rest had a mix. Half of the studies were performed in Egypt, while the remaining were conducted in Europe and Asia.

The secondary analysis included 23 studies that met the broader criteria and involved 1,866 newborns (including 1,040 newborns with EOS and the rest uninfected), with seven of the trials involving only newborns with EOS.

Results of the secondary analysis were similar, with a pooled sensitivity of 0.93 (95% CI 0.89-0.96), a pooled specificity of 0.91 (95% CI 0.87-0.94), and a pooled DOR of 141.9 (95% CI 68.6-293.5), though the authors cautioned that "the risk of misdiagnosis remains considerable among studies enrolling clinical sepsis, as noninfectious conditions likely account for a certain proportion of cases, possibly leading to overestimation of presepsin accuracy."

Subgroup analyses showed a higher specificity with presepsin for EOS (versus the mixed groups that included LOS), and the accuracy of presepsin was not associated with differences in gestational age, type of assay (chemiluminescence enzyme immunoassay or enzyme-linked immunosorbent), risk of bias judgment, or study country.

Poggi's team noted several possible limitations, however, including the possibility of publication bias; a high ratio of cases to controls (1:1.25) in the studies meeting criteria, as some studies used a case-control approach; and that none of the studies defined their presepsin cutoffs, instead providing "optimal" calculated values, which could lead to an overestimation of the proposed biomarker's accuracy.

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