{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:25:37Z","timestamp":1792027537326,"version":"4.4.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Neonatal sepsis continues to be a leading cause of death and disability in newborns worldwide. Early identification is difficult due to vague and overlapping clinical signs. Reliance on a single biomarker often yields suboptimal sensitivity or specificity. This study aimed to assess the added clinical value of combining serum interleukin-6 (IL-6), procalcitonin (PCT), and serum amyloid A (SAA) for the early recognition and severity grading of neonatal sepsis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 140 neonates admitted to the neonatal intensive care unit (NICU) between January 2022 and December 2023 were enrolled. Based on clinical criteria and blood culture results, they were assigned to three groups: confirmed sepsis (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f60), suspected sepsis (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f40), and non-infective control (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f40). Among sepsis patients, 24 were classified as severe and 36 as mild\/moderate according to predefined severity criteria. Serum concentrations of IL-6, PCT, and SAA were measured at admission (prior to antibiotic therapy). Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves, and associations with disease severity were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum levels of IL-6, PCT, and SAA were markedly higher in the confirmed sepsis group than in the suspected sepsis and control groups (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). Levels were also significantly elevated in severe sepsis compared with mild\/moderate cases (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01 for each marker). For diagnosing confirmed sepsis, the area under the ROC curve (AUC) was 0.908 for IL-6, 0.932 for PCT, 0.913 for SAA, and 0.985 for the combined panel (IL-6\u202f+\u202fPCT\u202f+\u202fSAA). The combined approach achieved a sensitivity of 93.3% and specificity of 92.5%, outperforming any single biomarker. Furthermore, all three markers showed positive correlations with severity scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Optimal cut-off values for diagnosing sepsis were IL-6\u202f&amp;gt;\u202f52.8\u202fpg.\/mL, PCT\u202f&amp;gt;\u202f2.15\u202fng\/mL, and SAA\u202f&amp;gt;\u202f28.6\u202fmg\/L.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Simultaneous measurement of serum IL-6, PCT, and SAA substantially enhances early diagnostic accuracy for neonatal sepsis and helps differentiate disease severity. This panel can serve as a rapid, reliable, and minimally invasive adjunct to blood culture in the NICU setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1891357","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:10:20Z","timestamp":1785237020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical utility of combined serum IL-6, PCT, and SAA assays for early diagnosis and severity stratification of neonatal sepsis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yu","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neonatology, Affiliated Huai\u2019an Hospital of Xuzhou Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Affiliated Huai\u2019an Hospital of Xuzhou Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Affiliated Huai\u2019an Hospital of Xuzhou Medical University","place":["Huai\u2019an, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/s41390-021-01696-z","article-title":"Diagnosis of neonatal sepsis: the past, present and future","volume":"91","author":"Celik","year":"2022","journal-title":"Pediatr Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"318","DOI":"10.31729\/jnma.7324","article-title":"Progress in diagnosis and treatment of neonatal sepsis: a review article","volume":"60","author":"Yadav","year":"2022","journal-title":"JNMA J Nepal Med 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caused by neonatal asphyxia","volume":"52","author":"Liu","year":"2023","journal-title":"Iran J Public Health"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.ijbiomac.2021.12.045","article-title":"Molecular imprinting based electrochemical biosensor for identification of serum amyloid a (SAA), a neonatal sepsis biomarker","volume":"195","author":"Balayan","year":"2022","journal-title":"Int J Biol Macromol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e0314702","DOI":"10.1371\/journal.pone.0314702","article-title":"Diagnosis of neonatal and adult sepsis using a serum amyloid a lateral flow test","volume":"20","author":"Nowak","year":"2025","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.7754\/Clin.Lab.2022.220737","article-title":"Application of PCT, IL-6, CRP, and WBC for diagnosing neonatal sepsis","volume":"69","author":"An","year":"2023","journal-title":"Clin 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