{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:44:34Z","timestamp":1792525474935,"version":"4.5.0"},"reference-count":19,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophil extracellular traps (NETs) contribute to innate immunity in sepsis, but their diagnostic value in neonates is unclear. We evaluated whether circulating NET-associated biomarkers discriminate septic from non-infected neonates. In this prospective observational study 96 neonates (\u226534 weeks gestational age) with clinical suspicion of infection were enrolled (36 sepsis, 60 controls). Serum cell-free DNA (cfDNA), myeloperoxidase\u2013DNA complexes (MPO-DNA), neutrophil elastase\u2013DNA complexes (NE-DNA), and citrullinated histone H3 (H3cit) were measured alongside CRP and IL-6 at days 1, 3, and 5. Diagnostic performance was assessed by receiver operating characteristic (ROC) analysis with bootstrap confidence intervals. CRP (AUC 0.75, 95% CI 0.66\u20130.85) and IL-6 (AUC 0.73, 95% CI 0.61\u20130.83) showed the best diagnostic performance. cfDNA demonstrated moderate discrimination (AUC 0.72, 95% CI 0.60\u20130.84) but was only transiently elevated at day 1. MPO-DNA (AUC 0.47), NE-DNA (AUC 0.44), and H3cit (AUC 0.47) performed no better than chance. Within the sepsis group, MPO-DNA and NE-DNA at day 3 strongly correlated with the immature-to-total neutrophil ratio (\u03c1 = 0.76 and 0.72), suggesting these markers reflect neutrophil degranulation rather than NET formation. NET-associated biomarkers do not improve diagnostic accuracy for neonatal sepsis beyond CRP and IL-6. These findings support the concept that neonatal innate immune responses differ fundamentally from adult patterns.<\/jats:p>","DOI":"10.3390\/ijms27104500","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4500","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating DNA and Neutrophil-Derived Biomarkers in Neonatal Sepsis"],"prefix":"10.3390","volume":"27","author":[{"given":"Ana Maria","family":"Behrami","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg, 20246 Hamburg, Germany"},{"name":"Department of Pediatrics, Friedrich-Ebert-Krankenhaus, 24534 Neum\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2922-9370","authenticated-orcid":false,"given":"Jasmin","family":"Knopf","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany"},{"name":"Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"},{"name":"Mannheim Center for Inflammation Medicine (MaCIM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4972-9866","authenticated-orcid":false,"given":"Michael","family":"Boettcher","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, University Medical Center Mannheim, Heidelberg University, 68167 Mannheim, Germany"},{"name":"Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"},{"name":"Mannheim Center for Inflammation Medicine (MaCIM), Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6699-0989","authenticated-orcid":false,"given":"Chinedu Ulrich","family":"Ebenebe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg, 20246 Hamburg, Germany"},{"name":"Department of Pediatrics, St. Marienkrankenhaus, 67067 Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Stiel, C.U., Ebenebe, C.U., Trochimiuk, M., Pagarols Raluy, L., Vincent, D., Singer, D., Reinshagen, K., and Boettcher, M. 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