{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:04:58Z","timestamp":1785323098223,"version":"3.55.0"},"update-to":[{"DOI":"10.12688\/f1000research.162331.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000}},{"DOI":"10.12688\/f1000research.162331.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000}},{"DOI":"10.12688\/f1000research.162331.3","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000}}],"reference-count":36,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns5:p>Background The utility of Systemic Inflammatory Indices as accurate indicators of neonatal sepsis remains underexplored in the Indian population. This study will assist in determining whether these indices can be used to predict neonatal sepsis at the bedside and as an early sensitive predictor of sepsis in preterms. Methods A prospective case-control study was done, where the Systemic Inflammatory Indices of the two groups of preterms \u2013 one control group without sepsis and one case group with culture proven sepsis\u2013were compared to assess their value in predicting Neonatal Sepsis. Data from 138 preterm neonates were used in the present study. Six Systemic Inflammatory Indices were calculated - Systemic Immune Inflammatory Index (SII), Systemic Inflammation Response Index (SIRI), PanImmune Inflammation Value (PIV), Neutrophil to Lymphocyte Ratio (NLR), Platelet to Lymphocyte Ratio (PLR) and Monocyte to Lymphocyte Ratio (MLR). These values from both the case and control groups were compared. Results Platelet count had the highest predictive value, with an AUC value of 0.715(95% CI 0.628-0.802, p&lt;0.001) and optimal cut-off value of 219500 cells\/cu mm. It had a sensitivity of 75.4 and specificity of 65.2. PIV had an AUC of 0.665(95% CI 0.574-0.755, p=0.001), a sensitivity of 60.9, and a specificity of 68.1. For PLR, Sensitivity and specificity were 72.5 and 58, respectively, with an AUC of 0.668(95% CI 0.577-0.758, p=0.001). With sensitivity and specificity of 66.7 and 62.3 respectively, SII had an AUC of 0.65(95% CI 0.558-0.743, p=0.002). SIRI, NLR and MLR did not demonstrate statistically significant differences between the groups(p&gt;0.05). Conclusion There was moderate correlation between the studied hematological indices and positive cultures, suggesting their potential role as inflammatory markers. Larger prospective trials should be conducted to further validate their potential clinical value.<\/ns5:p>","DOI":"10.12688\/f1000research.162331.4","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:39:05Z","timestamp":1785321545000},"page":"390","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Accuracy of Systemic Inflammatory Indices in Identifying Neonatal Sepsis in Preterms in a Tertiary Care Hospital in Mangalore"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4653-3801","authenticated-orcid":false,"given":"Smrithi","family":"GM","sequence":"first","affiliation":[{"name":"Kasturba Medical College Mangalore Manipal Manipal Academy of Higher Education"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0116-6858","authenticated-orcid":false,"given":"Gayathri","family":"Renganathan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kasturba Medical College Mangalore Manipal Manipal Academy of Higher Education"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smitha","family":"D'sa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kasturba Medical College Mangalore Manipal Manipal Academy of Higher Education"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1156732","DOI":"10.3389\/fmed.2023.1156732","article-title":"Sepsis and infection: two words that should not be confused.","volume":"10","author":"J Vincent","year":"2023","journal-title":"Front. Med (Lausanne)."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"135-140","DOI":"10.1097\/MOP.0000000000000315","article-title":"Defining neonatal sepsis.","volume":"28","author":"J Wynn","year":"2016 Apr","journal-title":"Curr. Opin. Pediatr."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"745-752","DOI":"10.1136\/archdischild-2020-320217","article-title":"Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis.","volume":"106","author":"C Fleischmann","year":"2021","journal-title":"Arch. Dis. Child."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"223-230","DOI":"10.1016\/S2213-2600(18)30063-8","article-title":"The global burden of paediatric and neonatal sepsis: a systematic review.","volume":"6","author":"C Fleischmann-Struzek","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"254-258","DOI":"10.4103\/2277-8632.146632","article-title":"Neonatal sepsis: A risk approach.","volume":"3","author":"V Bangi","year":"2014","journal-title":"J Dr NTR University Health Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"574-583","DOI":"10.1038\/pr.2017.134","article-title":"Diagnostics for neonatal sepsis: current approaches and future directions.","volume":"82","author":"P Iroh Tam","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"S69-S74","DOI":"10.1016\/S0378-3782(12)70019-1","article-title":"Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units.","volume":"88","author":"C Hornik","year":"2012","journal-title":"Early Hum. Dev."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"285","DOI":"10.3389\/fped.2018.00285","article-title":"Culture-Negative Early-Onset Neonatal Sepsis \u2013 At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship.","volume":"6","author":"C Klingenberg","year":"2018","journal-title":"Front. Pediatr."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"3000605241270696","DOI":"10.1177\/03000605241270696","article-title":"Assessment of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and systemic immune-inflammatory index, as diagnostic markers for neonatal sepsis.","volume":"52","author":"S Zhu","year":"2024 Aug","journal-title":"J. Int. Med. Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"169-176","DOI":"10.3233\/NPM-230174","article-title":"Evaluation of systemic inflammatory indices in the diagnosis of early onset neonatal sepsis in very low birth weight infants.","volume":"17","author":"U Cakir","year":"2024","journal-title":"J. Neonatal Perinatal Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1826-1832","DOI":"10.1017\/S1047951122001202","article-title":"Role of systemic immune-inflammatory index in early diagnosis of sepsis in newborns with CHD.","volume":"32","author":"S Aydogan","year":"2022 Nov","journal-title":"Cardiol. Young."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"698-702","DOI":"10.1080\/00325481.2022.2091373","article-title":"Utility of the systemic immune-inflammation index to predict serious bacterial infections in infants with fever without a source.","volume":"134","author":"A G\u00fcng\u00f6r","year":"2022","journal-title":"Postgrad. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e137","DOI":"10.1017\/S0950268823001231","article-title":"A diagnostic model based on routine blood examination for serious bacterial infections in neonates-a cross-sectional study.","volume":"151","author":"R Liang","year":"2023 Jul 31","journal-title":"Epidemiol. Infect."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"e1546-e1552","DOI":"10.1055\/a-2051-8544","article-title":"Evaluation of the Effectiveness of Systemic Inflammatory Indices in the Diagnosis of Respiratory Distress Syndrome in Preterm with Gestational Age of \u226432 Weeks.","volume":"41","author":"U Cakir","year":"2024 May","journal-title":"Am. J. Perinatol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"248-254","DOI":"10.1055\/a-1673-1616","article-title":"Diagnostic Role of Systemic Inflammatory Indices in Infants with Moderate-to-Severe Hypoxic Ischemic Encephalopathy.","volume":"41","author":"B Ceran","year":"2024 Feb","journal-title":"Am. J. Perinatol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1512884","DOI":"10.3389\/fcimb.2024.1512884","article-title":"Immunoinflammatory markers SIRI and NAR as predictors of respiratory distress syndrome and secondary infections in premature infants.","volume":"14","author":"X Chen","year":"2024 Dec 13","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"8-19","DOI":"10.4103\/tjem.tjem_198_23","article-title":"Unraveling the clinical significance and prognostic value of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and delta neutrophil index: An extensive literature review.","volume":"24","author":"M Islam","year":"2024 Jan 8","journal-title":"Turk. J. Emerg. Med."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1333-1341","DOI":"10.1111\/jog.14320","article-title":"A cut-off value for systemic immune-inflammation index in the prediction of adverse neonatal outcomes in preterm premature rupture of the membranes.","volume":"46","author":"A Tanacan","year":"2020","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"345-351","DOI":"10.1080\/00325481.2022.2140535","article-title":"The systemic immune-inflammation index in predicting sepsis mortality.","volume":"135","author":"S Mangalesh","year":"2022","journal-title":"Postgrad. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"110780","DOI":"10.1016\/j.intimp.2023.110780","article-title":"Prognostic value of blood inflammatory parameters for predicting mortality in neonates with sepsis.","volume":"123","author":"X Liang","year":"2023 Oct","journal-title":"Int. Immunopharmacol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e172927","DOI":"10.1001\/jamapediatrics.2017.2927","article-title":"Accuracy of Complete Blood Cell Counts to Identify Febrile Infants 60 Days or Younger With Invasive Bacterial Infections.","volume":"171","author":"A Cruz","year":"2017 Nov 6","journal-title":"JAMA Pediatr."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1186\/s12887-022-03471-3","article-title":"Role of complete blood cell count parameters in the diagnosis of neonatal sepsis.","volume":"22","author":"M Worku","year":"2022 Jul 13","journal-title":"BMC Pediatr."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"342","DOI":"10.3390\/tropicalmed7110342","article-title":"Predictors of Death in Patients with Neonatal Sepsis in a Peruvian Hospital.","volume":"7","author":"D Vizcarra-Jim\u00e9nez","year":"2022 Oct 31","journal-title":"Trop. Med. Infect. Dis."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"e0185581","DOI":"10.1371\/journal.pone.0185581","article-title":"Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors.","volume":"12","author":"I Ree","year":"2017 Oct 4","journal-title":"PLoS One."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"252-260","DOI":"10.21608\/svuijm.2021.67088.1124","article-title":"The pattern of systemic inflammatory markers response in neonatal sepsis.","volume":"5","author":"R Ashour","year":"2022","journal-title":"SVU Int. J. Med. Sci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e229-e232","DOI":"10.1097\/MPH.0000000000001059","article-title":"The Value of Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio for Detecting Early-onset Neonatal Sepsis.","volume":"40","author":"E Can","year":"2018 May","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"319-325","DOI":"10.5472\/marumj.1367904","article-title":"Diagnostic utility of the systemic immune-inflammatory index in preterm neonates with late-onset sepsis.","volume":"36","author":"G Vardar","year":"2023","journal-title":"Marmara Med. J."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.3390\/medicina59081425","article-title":"Blood Biomarkers of Neonatal Sepsis with Special Emphasis on the Monocyte Distribution Width Value as an Early Sepsis Index.","volume":"59","author":"M Mubaraki","year":"2023 Aug 4","journal-title":"Medicina (Kaunas)."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"7650713","DOI":"10.1155\/2020\/7650713","article-title":"Association of Neutrophil-Lymphocyte Ratio and the Presence of Neonatal Sepsis.","volume":"2020","author":"T Li","year":"2020 Dec 2","journal-title":"J. Immunol. Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e2023062511","DOI":"10.1542\/peds.2023-062511","article-title":"APP Council on Children With Disabilities, Committee on Fetus and Newborn. Primary Care Framework to Monitor Preterm Infants for Neurodevelopmental Outcomes in Early Childhood.","volume":"152","author":"B Davis","year":"2023","journal-title":"Pediatrics."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"337-350","DOI":"10.1038\/s41390-021-01696-z","article-title":"Diagnosis of neonatal sepsis: the past, present and future.","volume":"91","author":"I Celik","year":"2022 Jan","journal-title":"Pediatr. Res."},{"key":"ref33","article-title":"Neonatal Sepsis STANDARD TREATMENT GUIDELINES 2022 Upendra Kinjawadekar IAP President-Elect 2022 Under the Auspices of the IAP Action Plan 2022.","author":"S Santhanam","year":"2022"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e5886","DOI":"10.1097\/MD.0000000000005886","article-title":"Systemic immune-inflammation index (SII) is a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus.","volume":"96","author":"J Feng","year":"2017 Jan","journal-title":"Medicine (Baltimore)."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1049241","DOI":"10.3389\/fneur.2022.1049241","article-title":"Systemic inflammation response index as a prognostic predictor in patients with acute ischemic stroke: A propensity score matching analysis.","volume":"13","author":"H Dang","year":"2023 Jan 10","journal-title":"Front. Neurol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"830138","DOI":"10.3389\/fonc.2022.830138","article-title":"Pan-Immune-Inflammation Value: A New Prognostic Index in Operative Breast Cancer.","volume":"12","author":"F Lin","year":"2022 Apr 13","journal-title":"Front. 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We greatly appreciate the suggestions, which have helped us improve the clarity, structure, and scientific rigor of our study. Below, we provide point-by-point responses to each comment.  \n<b>Reviewer report:<\/b> \u201cAbstract - Background should clarify the need for the study. Can delete the rest. Study design to be stated. Give formulae for the indices in methods. Data should be in results. Avoid overconcluding\u2014should be only based on the results. Use MeSH terms.\u201d  \n<b>Author response:<\/b>  1.&nbsp;\n<b>Background should clarify the need for the study. Can delete the rest.<\/b> Response: The Abstract has been revised to clarify the study\u2019s rationale, and unnecessary portions have been removed.  \n<b>2. Study design to be stated. Give formulae for the indices in methods.<\/b> Response: The study design has been explicitly stated as a case\u2013control study. The formulae for all inflammatory indices are now included in the Methods.  \n<b>3. Data should be in results.<\/b> Response: Significant study data have been appropriately included in the Results section.  \n<b>4. Avoid overconcluding\u2014should be only based on the results.<\/b> Response: The conclusion has been revised to ensure that statements are strictly supported by study results.  \n<b>5. Use MeSH terms.<\/b> Response: Relevant MeSH terms have been applied to the manuscript keywords.   \n<b>Reviewer report:<\/b> \u201cMain Text - Use STROBE checklist for reporting this observational study throughout. Summary of evidence is too long should be made crisp and moved to discussion. Physiological basis of choosing these indices to be quoted. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines. How were controls chosen given that the yield of culture may be less? What method of culture was done and when? Was any matching done? Consent would be required as the controls are being sampled, data collected and planned for publication. Study flow is missing. Unclear when the tests were done and in case of multiple values which one were chosen. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression.\u201d  \n<b>Author response:<\/b>  \n<b>1. Use STROBE checklist for reporting this observational study throughout.<\/b> Response: We thank the reviewer for this suggestion. The manuscript has been revised to align with the STROBE checklist. We have added a participant flow diagram (STROBE item 13), clarified variables (item 7), and described selection of cases and controls (item 6b). Data collection, timing, and measurement procedures have been clearly described (items 8 and 11). Sample size calculation details have been included (item 10), and Methods section structure has been revised to comply with journal guidelines.  \n<b>2. Summary of evidence is too long; should be made crisp and moved to discussion.<\/b> Response: The summary of evidence has been condensed, with relevant details now included in the Discussion section.  \n<b>3. Physiological basis of choosing these indices to be quoted.<\/b> Response: The physiological rationale for selection of the inflammatory indices has now been incorporated in the Methods section.  \n<b>4. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines<\/b>Response: The Methods section has been revised to provide greater clarity, including the sample size calculation. Sample size was determined using OpenEpi Version 3.01, based on three variables from the reference study by Zhu et al. (2024), with the largest calculated sample size chosen.  \n<b>5. How were controls chosen given that the yield of culture may be less?<\/b> Response: Given the known limitations of blood culture sensitivity in neonatal sepsis, controls were defined based on both microbiological criteria (negative blood culture) and the absence of clinical signs of sepsis\n<sup>[33]<\/sup>. Consecutive eligible preterm neonates meeting these criteria during the study period were included.  \n<b>6. What method of culture was done and when?<\/b> Response: Blood cultures were performed using BACTEC system according to NICU protocol. Samples were collected aseptically after 24 hours of life and processed as per standard microbiological procedures. Culture positivity defined sepsis cases.  \n<b>7. Was any matching done?<\/b>Response: Formal matching was not performed; however, both cases and controls were drawn from the same source population of preterm neonates admitted to the NICU during the same study period, which helps reduce potential selection bias.  \n<b>8. Consent would be required as the controls are being sampled, data collected and planned for publication.<\/b> Response: As this was a laboratory record\u2013based observational study using routinely collected clinical and laboratory data without any additional sampling or intervention, individual informed consent was waived by the Institutional Ethics Committee of Kasturba Medical College, Mangalore. Hence, we have not included the consent.  \n<b>9. Study flow is missing.<\/b> Response: A study flow diagram has now been included (Figure 1) to illustrate participant selection, allocation into cases and controls, and inclusion in the final analysis.  \n<b>10. Unclear when the tests were done and in case of multiple values which one were chosen.<\/b> Response: Blood samples used for calculation of inflammatory indices were obtained from routine laboratory investigations performed after 24 hours of life. Only values available from routine screening records were included in the analysis.  \n<b>11. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression.<\/b> Response: We thank the reviewer for this insightful comment. We agree that the findings primarily demonstrate associations between inflammatory indices and neonatal sepsis. The study was designed as an exploratory analysis using routinely collected laboratory data, and multivariable logistic regression was not performed due to the limited sample size and absence of comprehensive covariate information. The manuscript has been revised to emphasize associations rather than independent prediction, and ROC analysis is described as assessing diagnostic performance. A statement acknowledging that multivariable analysis may be explored in future studies has also been added to the Discussion.  We are grateful for the detailed and constructive suggestions. We believe that the revisions have strengthened the manuscript, and we hope that the changes adequately address all concerns and improve the clarity and overall quality of our study.","URL":"https:\/\/f1000research.com\/articles\/14-390\/v4#referee-comment-15455","order":2,"name":"referee-comment-15455","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.196572.r461444, K. Shreedhara Avabratha, Father muller medical college, Mangalore, 05 Mar 2026, version 2, 4 approved with reservations, 1 not approved","URL":"https:\/\/f1000research.com\/articles\/14-390\/v2#referee-response-461444","order":3,"name":"referee-response-461444","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Smrithi null<\/b>; \n<i>Posted: 21 May 2026<\/i>; We sincerely thank Dr. Avabratha for continued engagement with our manuscript and for the additional comments provided on Version 2. We address each point in detail below. &nbsp; \n<b>REVIEWER COMMENT 1<\/b> Do not see much improvement from earlier version. \n<b>AUTHOR RESPONSE<\/b> We respectfully acknowledge Dr. Avabratha\u2019s concern. We would like to highlight the substantive revisions made in Version 2 in response to the original review: the manuscript was restructured in accordance with the STROBE checklist; a participant flow diagram (Figure 1) was added; sample size calculation details were incorporated in the Methods section; clarification was provided regarding the prospective design, timing of laboratory measurements, and culture methodology; language was corrected throughout; and the Discussion was revised to emphasise associations rather than predictions. We recognise that further improvements remain and have continued to revise the manuscript in response to all reviewer comments received on Version 2. &nbsp; \n<b>REVIEWER COMMENT 2<\/b> Introduction needs to be crisp. Summary of evidence and need for study give a feel of dissertation presentation. \n<b>AUTHOR RESPONSE<\/b> We appreciate this continued feedback. In this revision, we have further condensed the Introduction, Summary of Evidence and Need for study to focus on the core epidemiological burden of neonatal sepsis and the rationale for evaluating systemic inflammatory indices as adjunctive markers. &nbsp; \n<b>REVIEWER COMMENT 3<\/b> Which preterm neonates are excluded from the selected group? Exclusion criteria need to be clear. \n<b>AUTHOR RESPONSE<\/b> We thank Dr. Avabratha for drawing attention to this. We have revised the Methods section to explicitly state the exclusion criteria as follows: term neonates (\u226537 weeks gestation) admitted to the NICU; healthy newborns in postnatal wards; and families unwilling to participate. Additionally, within the preterm population, neonates with incomplete laboratory records and those in whom blood culture was not performed were not included. These criteria have been stated clearly in the revised manuscript to improve transparency and reproducibility. &nbsp; \n<b>REVIEWER COMMENT 4<\/b> Is it routine practice to send blood culture for all preterms, even for those without clinical signs of sepsis? \n<b>AUTHOR RESPONSE<\/b> This is an important question regarding our institutional protocol. At the Government Lady Goschen Hospital NICU, Mangalore, blood culture is performed as part of the routine neonatal screening protocol for all preterm neonates admitted to the NICU, irrespective of the presence of overt clinical signs of sepsis, given the high index of suspicion maintained for this vulnerable population and their often non-specific or absent symptomatology. This is consistent with recommendations for high-risk preterm monitoring in resource-constrained settings. We have added a clarifying statement to the Methods section to make this explicit. &nbsp; \n<b>REVIEWER COMMENT 5<\/b> Tense \u2014 \u2018will be\u2019 to be corrected throughout. \n<b>AUTHOR RESPONSE<\/b> We apologise for the persistence of this error. The entire manuscript has been reviewed again, and all remaining instances of future tense (\u201cwill be,\u201d \u201cwill include,\u201d etc.) in sections describing completed study procedures have been corrected to the appropriate past tense. \n<b>&nbsp; REVIEWER COMMENT 6<\/b> Conclusions are very general. They should be derived from the present study. \n<b>AUTHOR RESPONSE<\/b> We thank Dr. Avabratha for this pointed observation. The Conclusion has been substantially revised to be grounded specifically in the findings of the present study. The revised Conclusion now states that among the indices evaluated, platelet count demonstrated the highest diagnostic utility (AUC 0.715, sensitivity 75.4%, specificity 65.2%), followed by PLR, PIV, and SII, all with moderate performance. It further notes the statistically significant associations between platelet count, SII, PIV, PLR, and positive blood culture in this cohort of preterm neonates, and calls for larger prospective multicentre studies to validate these associations and establish clinically actionable thresholds.","URL":"https:\/\/f1000research.com\/articles\/14-390\/v4#referee-comment-16262","order":4,"name":"referee-comment-16262","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.196572.r468911, I Ketut Alit Utamayasa, Prima Nastiti, Children\u2019s Health Sciences, Airlangga University Department of Children\u2019s Health Sciences (Ringgold ID: 592763), East Java, 01 Apr 2026, version 2, 4 approved with reservations, 1 not approved","URL":"https:\/\/f1000research.com\/articles\/14-390\/v2#referee-response-468911","order":5,"name":"referee-response-468911","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Smrithi null<\/b>; \n<i>Posted: 21 May 2026<\/i>; We sincerely thank Reviewers Utamayasa and Nastiti for their thorough and constructive evaluation of the revised manuscript. Their expert commentary has helped us further strengthen the methodological and interpretive rigour of the work. We address each point below. &nbsp; \n<b>REVIEWER COMMENT 1<\/b> \u201cThe manuscript repeatedly refers to these indices as \u201cpredictors\u201d of neonatal sepsis. Given the case\u2013control design and absence of multivariable analysis, the findings demonstrate associations and diagnostic performance rather than true predictive ability. The terminology should be revised accordingly throughout the manuscript.\u201d \n<b>AUTHOR RESPONSE<\/b> We thank the reviewers for this important methodological observation. We fully agree that the case\u2013control design, in the absence of multivariable analysis, permits demonstration of associations and assessment of diagnostic performance rather than independent predictive efficacy. Accordingly, we have revised all instances of \u201cpredictors\u201d throughout the manuscript to \u201cassociated markers\u201d or \u201cindices with diagnostic utility,\u201d as contextually appropriate. &nbsp; \n<b>REVIEWER COMMENT 2<\/b> \u201cNo multivariate analysis was performed. Potential confounders such as gestational age and birth weight differ between groups and may significantly influence the results. At minimum, this limitation should be more explicitly acknowledged, and if feasible, adjusted analysis should be considered.\u201d \n<b>AUTHOR RESPONSE<\/b> We acknowledge this important limitation. As noted in the manuscript, multivariable logistic regression was not performed due to the limited sample size and the absence of comprehensive covariate data at the time of analysis. We recognise that gestational age and birth weight are potential confounders, and that differences in these parameters between groups \u2014 notably the higher proportion of very low birth weight infants in the sepsis group (78.3% vs. 42.0%) \u2014 may have influenced the inflammatory indices. We have expanded the Limitations section to explicitly acknowledge this, and have added a statement that future studies should incorporate multivariable adjusted analyses to determine the independent diagnostic utility of these markers. &nbsp; \n<b>REVIEWER COMMENT 3<\/b> \u201cThe selection of the control group raises concerns. Controls were defined as culture-negative and without clinical sepsis; however, blood culture has limited sensitivity, and exclusion of culture-negative sepsis may introduce misclassification bias. This limitation should be discussed in more depth.\u201d \n<b>AUTHOR RESPONSE<\/b> This is a well-founded concern and we appreciate the reviewers raising it. It is acknowledged in the neonatal sepsis literature that blood culture, while the current diagnostic gold standard, has a sensitivity of only 50\u201380% in preterm neonates, meaning that some true sepsis cases may yield negative cultures. By restricting the case group to culture-proven sepsis, our study may have excluded a subset of neonates with genuine infection, potentially biasing inflammatory index comparisons toward the null. Conversely, controls defined by negative culture may have included neonates with subclinical or early-stage infection, further contributing to misclassification. We have substantially expanded the discussion of this limitation, including reference to the concept of culture-negative clinical sepsis and its implications for the interpretation of our findings. &nbsp; \n<b>REVIEWER COMMENT 4<\/b> \u201cClarification is needed regarding the timing of laboratory measurements in relation to the onset of clinical suspicion of sepsis. This is essential for assessing the real-world applicability of these indices as early diagnostic markers.\u201d \n<b>AUTHOR RESPONSE<\/b> We thank the reviewers for highlighting this point, which is central to the clinical relevance of our findings. We have clarified in the Methods section that all laboratory values used for calculation of the inflammatory indices were obtained from routine neonatal screening investigations performed after 24 hours of life, prior to confirmation of sepsis by blood culture. These values therefore reflect the inflammatory milieu at the time of clinical suspicion and blood culture collection, rather than post-confirmation. We have added this clarification explicitly in the revised text to assist readers in contextualising the early diagnostic applicability of these markers. &nbsp; \n<b>REVIEWER COMMENT 5<\/b> \u201cThe reported diagnostic performance is only moderate (e.g., platelet AUC ~0.71), and therefore these indices should not be presented as standalone diagnostic tools. Their role as adjunctive markers should be emphasised more clearly.\u201d \n<b>AUTHOR RESPONSE<\/b> We are in complete agreement with this observation. We have revised the Discussion and Conclusion sections to consistently frame these markers as adjunctive or supplementary indicators, intended to complement rather than replace blood culture and existing clinical assessment. We have also removed any language that could be interpreted as overstating their diagnostic utility. &nbsp; \n<b>REVIEWER COMMENT 6<\/b> \u201cSome data in Table 2 appear unusual (e.g., identical median\/IQR values for certain indices across groups), and this should be carefully rechecked for accuracy.\u201d \n<b>AUTHOR RESPONSE<\/b> We thank the reviewers for this careful observation. The identical values displayed in Table 2 for certain indices (specifically SII and PIV) were a formatting artefact that arose from the way medians and interquartile ranges were rounded and tabulated, and do not reflect the underlying data, which do show meaningful distributional differences (as confirmed by the statistically significant p-values). We have revised Table 2. &nbsp; \n<b>REVIEWER COMMENT 7<\/b> \u201cMinor revisions include shortening and refining the Introduction, improving clarity and consistency of terminology, and further polishing of language.\u201d \n<b>AUTHOR RESPONSE<\/b> We have carefully revised the Introduction to improve conciseness, ensuring that background information is focused on the clinical rationale for the study. Terminology has been standardised throughout the manuscript, and the text has been reviewed for language clarity and consistency.","URL":"https:\/\/f1000research.com\/articles\/14-390\/v4#referee-comment-16260","order":6,"name":"referee-comment-16260","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.202236.r492517, Sweta Shanbhag, Father Muller Medical College, Mangalore, Karnataka, 16 Jun 2026, version 3, indexed","URL":"https:\/\/f1000research.com\/articles\/14-390\/v3#referee-response-492517","order":7,"name":"referee-response-492517","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Smrithi null<\/b>; \n<i>Posted: 24 Jul 2026<\/i>; We sincerely thank the reviewer for the careful evaluation of our revised manuscript and for the constructive comments and valuable suggestions. The corresponding revisions have been incorporated into the revised manuscript. Our point-by-point responses are provided below.  \n<b>Comment 1:<\/b>&nbsp;Under&nbsp;\n<i>Need for the Study<\/i>&nbsp;\u2013 2nd line \u2013 &quot;...not been adequately evaluated&quot; \u2013 there is no full stop after the word &quot;evaluated.&quot; \n<b>Response:<\/b>&nbsp;Thank you for pointing this out. A full stop has been added after the word &quot;evaluated.&quot;  \n<b>Comment 2:<\/b>&nbsp;Under the&nbsp;\n<i>Methods<\/i>&nbsp;section \u2013 Case group \u2013 change to &quot;preterm infants with culture-proven sepsis.&quot; The Methods section contains repetitive and redundant text. The 2nd to 4th paragraphs may be condensed to cover the inclusion and exclusion criteria, case and control groups, subgroup classification, sample collection procedure, and flow chart, while retaining the remaining paragraphs. \n<b>Response:<\/b>&nbsp;Thank you for the valuable suggestion. The case group description has been revised to &quot;preterm infants with culture-proven sepsis,&quot; and the Methods section has been condensed by merging the relevant paragraphs to improve clarity and eliminate redundancy while retaining all essential methodological details.  \n<b>Comment 3:<\/b>&nbsp;\n<i>Statistical Analysis<\/i>&nbsp;\u2013 change to &quot;IBM SPSS ... was used to analyze the data.&quot; The verb &quot;was&quot; is missing. \n<b>Response:<\/b>&nbsp;Thank you for identifying this grammatical error. The sentence has been corrected by adding the missing verb &quot;was.&quot;  \n<b>Comment 4:<\/b>&nbsp;In Table 2, the platelet count in the control group is shown as 24,800. This appears to be an error. \n<b>Response:<\/b>&nbsp;Thank you for bringing this to our attention. The value has been verified and corrected in Table 2.  \n<b>Comment 5:<\/b>&nbsp;In the&nbsp;\n<i>Critical Reflection<\/i>&nbsp;section, platelet count is expressed as cells\/cumm. Although technically equivalent to cells\/&micro;L, uniform units should be maintained throughout the manuscript. \n<b>Response:<\/b>&nbsp;Thank you for the suggestion. The unit of platelet count has been revised to maintain uniformity throughout the manuscript.  \n<b>Comment 6:<\/b>&nbsp;There are two separate sections on limitations. Kindly combine them and avoid repetition by presenting all limitations under the separate heading&nbsp;\n<i>Limitations<\/i>. \n<b>Response:<\/b>&nbsp;Thank you for the constructive suggestion. The two sections have been combined into a single&nbsp;\n<b>Limitations <\/b>section.  \n<b>Comment 7:<\/b>&nbsp;Expand &quot;MS&quot; in the Ethical Approval Statement. \n<b>Response:<\/b>&nbsp;Thank you for pointing this out. The abbreviation &quot;MS&quot; has been expanded to \u201cMedical Superintendent\u201d in the Ethical Approval Statement.  \n<b>Comment 8:<\/b>&nbsp;Maintain uniformity in reference formatting (e.g., &quot;Suppl 2,&quot; &quot;S01,&quot; issue numbers in parentheses). Follow the journal guidelines. \n<b>Response:<\/b>&nbsp;Thank you for this observation. All references have been carefully reviewed and revised to ensure consistency with the journal's reference formatting guidelines.","URL":"https:\/\/f1000research.com\/articles\/14-390\/v4#referee-comment-16749","order":8,"name":"referee-comment-16749","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":9,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}