Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore

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This study will assist in determining whether SIMs can be used to predict neonatal sepsis at the bedside and as an early sensitive predictor of sepsis in preterms. Methods A case-control study was done, where the Systemic Inflammatory Indices of the two groups of preterms – one control group without sepsis and one case group with sepsis–were compared to assess their value in predicting Neonatal Sepsis. Data from 138 preterm neonates were used in the present study. Systemic Inflammatory Indices were calculated from the collected data using the following formulae: 1) Systemic Immune Inflammatory Index (SII)=[platelet/lymphocyte]∗Neutrophil 2) Systemic Inflammation Response Index (SIRI)=[monocyte/lymphocyte]∗Neutrophil 3) PanImmune Inflammation Value (PIV)=Platelet∗[monocyte/lymphocyte]∗Neutrophil 4) Neutrophil to Lymphocyte Ratio (NLR) 5) Platelet to Lymphocyte Ratio (PLR) 6) 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 and optimal cut-off value of 219500. It had a sensitivity of 75.4 and specificity of 65.2. PIV had an AUC of 0.665, 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. With sensitivity and specificity of 66.7 and 62.3 respectively, SII had an AUC of 0.65. Conclusion There was substantial 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. 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F1000Research 2026, 14 :390 ( https://doi.org/10.12688/f1000research.162331.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Revised Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] Smrithi GM https://orcid.org/0009-0001-4653-3801 1 , Gayathri Renganathan https://orcid.org/0009-0009-0116-6858 2 , Smitha D'sa 2 Smrithi GM https://orcid.org/0009-0001-4653-3801 1 , Gayathri Renganathan https://orcid.org/0009-0009-0116-6858 2 , Smitha D'sa 2 PUBLISHED 23 Feb 2026 Author details Author details 1 Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 2 Department of Pediatrics, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India Smrithi GM Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Gayathri Renganathan Roles: Conceptualization, Formal Analysis, Methodology, Project Administration, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Smitha D'sa Roles: Data Curation, Formal Analysis, Supervision, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Manipal Academy of Higher Education gateway. Abstract Background The utility of Systemic Inflammatory Markers (SIMs) as accurate indicators of neonatal sepsis in the Indian population has not been shown in any current research. This study will assist in determining whether SIMs can be used to predict neonatal sepsis at the bedside and as an early sensitive predictor of sepsis in preterms. Methods A case-control study was done, where the Systemic Inflammatory Indices of the two groups of preterms – one control group without sepsis and one case group with sepsis–were compared to assess their value in predicting Neonatal Sepsis. Data from 138 preterm neonates were used in the present study. Systemic Inflammatory Indices were calculated from the collected data using the following formulae: 1) Systemic Immune Inflammatory Index (SII)=[platelet/lymphocyte]∗Neutrophil 2) Systemic Inflammation Response Index (SIRI)=[monocyte/lymphocyte]∗Neutrophil 3) PanImmune Inflammation Value (PIV)=Platelet∗[monocyte/lymphocyte]∗Neutrophil 4) Neutrophil to Lymphocyte Ratio (NLR) 5) Platelet to Lymphocyte Ratio (PLR) 6) 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 and optimal cut-off value of 219500. It had a sensitivity of 75.4 and specificity of 65.2. PIV had an AUC of 0.665, 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. With sensitivity and specificity of 66.7 and 62.3 respectively, SII had an AUC of 0.65. Conclusion There was substantial 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. READ ALL READ LESS Keywords Neonatal Sepsis, Prevention, Preterm, Inflammatory markers, Early diagnosis Corresponding Author(s) Gayathri Renganathan ( [email protected] ) Close Corresponding author: Gayathri Renganathan Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2026 GM S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: GM S, Renganathan G and D'sa S. Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.12688/f1000research.162331.2 ) First published: 03 Apr 2025, 14 :390 ( https://doi.org/10.12688/f1000research.162331.1 ) Latest published: 23 Feb 2026, 14 :390 ( https://doi.org/10.12688/f1000research.162331.2 ) Revised Amendments from Version 1 Thank you for your constructive feedback. We have revised the manuscript accordingly. The abstract has been modified as suggested, and the manuscript has been aligned with the STROBE checklist. The summary of evidence has been refined for clarity and conciseness. The methodology section has been strengthened with clarification of the sample size calculation, culture methods, matching process, and inclusion of a study flow diagram. The results have been rewritten to avoid overinterpretation, emphasizing associations rather than predictions, and the discussion has been revised accordingly. The results tables have also been updated to improve clarity. Thank you for your constructive feedback. We have revised the manuscript accordingly. The abstract has been modified as suggested, and the manuscript has been aligned with the STROBE checklist. The summary of evidence has been refined for clarity and conciseness. The methodology section has been strengthened with clarification of the sample size calculation, culture methods, matching process, and inclusion of a study flow diagram. The results have been rewritten to avoid overinterpretation, emphasizing associations rather than predictions, and the discussion has been revised accordingly. The results tables have also been updated to improve clarity. See the authors' detailed response to the review by Dr Shashidhar A See the authors' detailed response to the review by Sanjoy Kumer Dey See the authors' detailed response to the review by K. Shreedhara Avabratha READ REVIEWER RESPONSES Introduction Dysregulation of the host response to any systemic bacterial, viral, or fungal infection within day 28 of the life of both term and preterm newborns can result in neonatal sepsis, a potentially fatal and life-threatening illness. 1 It is categorized based on onset - early-onset sepsis (EOS), diagnosed at or before 72 hours of life (some define as 7 days), and late-onset sepsis (LOS), diagnosed after 72 hours. 2 Neonatal sepsis accounts for approximately 8% of all neonatal fatalities. Particularly in low- and middle-income nations, it is the primary cause of neonatal morbidity and mortality. 3 The approximate statistic for EOS is 2,496 in 100,000 live births, that is 2.6 times greater than the incidence of LOS, which is 946 per 100 live births, per a systematic review & meta-analysis. 4 The highest rate of clinical sepsis (17,000per 1,000,000 live births) has been reported in India. 5 The fatality rate due to sepsis in Indian newborns ranges from 25% to 65%. 6 Blood culture remains the gold standard for diagnosis, 7 but results take 48–72 hours, and lack of distinct early clinical signs make timely diagnosis difficult. 8 , 9 Therefore, a sensitive and simple bedside diagnostic tool is required for early detection of newborn sepsis. According to studies, newborn sepsis can be accurately predicted by the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and Systemic Immune Inflammatory Index (SII). 10 Other indices like Monocyte-to-Lymphocyte Ratio (MLR), Systemic Inflammation Response Index (SIRI), and Pan Immune Inflammation Value (PIV) have been demonstrated to be higher in EOS. 11 We aimed to determine whether the SII, SIRI,MLR, NLR, PIV, and PLR are valuable markers for the early diagnosis of neonatal sepsis in preterms in the Indian population. Summary of evidence According to Zhu et al., PLR, SII, and NLR are all accurate indicators of newborn sepsis, with SII having the best predictive value. 10 SIRI was found by Cakir et al. to be a good indicator for identifying early-onset sepsis in very low birth weight preterm infants, especially when paired with additional markers. 11 The prognostic significance of NLR and SII for newborn sepsis in babies with congenital heart disease was shown by Aydogan et al. 12 Güngör et al. found SII to be a predictor of urinary tract infections in neonates, 13 while Runqiang Liang et al. highlighted its role in diagnosing serious bacterial infections. 14 In premature infants, elevated SII levels were also linked to respiratory distress syndrome. 15 Increased SII, SIRI, PIV, and NLR values were observed in infants with hypoxic–ischemic encephalopathy. 16 Higher SIRI and SII levels were linked to a higher risk of secondary infections in preterm newborns, according to Chen et al. 17 The utility of SII, NLR, SIRI and PLR in predicting outcomes in inflammatory diseases was confirmed by a review by Muzaffer Islam et al. 18 Tanacan et al identified SII as a potential biomarker for adverse neonatal outcomes in PPROM. 19 Mangalesh et al. reported NLR, SII, and PLR as independent predictors of sepsis-related mortality, with SII contributing to SOFA score increments. 20 Day-one WBC and platelet counts were revealed to be helpful warning signs for mortality in newborn sepsis by Xianghui Liang et al. 21 Cruz et al. observed that total leukocyte parameters by themselves were not accurate enough to detect invasive bacterial infections. 22 On the other hand, TLC, ANC, and thrombocyte count showed good diagnostic efficacy for newborn sepsis in a study by Minichil Worku et al. 23 Thrombocytopenia was consistently associated with increased mortality in neonatal sepsis, particularly in gram-negative infections, as reported by Isabelle M C Ree et al and Vizcarra-Jimenez et al. 24 , 25 Ashour et al and Can et al found that NLR and PLR showed significant diagnostic utility and were positively associated with early-onset sepsis. 26 , 27 Vardar et al revealed that preterm neonates with late-onset sepsis were shown to have higher SII levels. 28 Mubaraki et al. reported strong associations between neonatal sepsis and leukopenia, thrombocytopenia, and anemia, while Li et al. found a significant association with increased NLR. 29 , 30 Need for study No recent study has demonstrated the utility of Systemic Inflammatory Markers (SIMs) as reliable predictors of Neonatal Sepsis in the Indian population. This study will help determine whether SIMs can be used as an early sensitive predictor of sepsis in preterms and will be useful in predicting neonatal sepsis at the bedside. This will also help reduce neonatal morbidity and mortality. Methods The Neonatal Intensive Care Unit (NICU), Government Lady Goschen Hospital, Mangalore, was the site of this prospective case–control study. The case group consisted of neonatal sepsis preterm infants, and the control group consisted of preterm infants without sepsis. The study duration was six months. The sample size was calculated using OpenEpi version 3.01. Effect estimates for inflammatory indices were derived from a previously published study by Zhu et al., 10 which evaluated NLR, PLR, and SII as diagnostic markers of neonatal sepsis. Sample size calculations were performed separately for three inflammatory indices, and the largest calculated sample size was selected to ensure adequate statistical power. Based on this approach, a total of 138 preterm neonates (69 cases and 69 controls) were included in the study. The inclusion criteria for selection were preterm neonates admitted to NICU. Term neonates admitted to the NICU, healthy newborns in postnatal wards, and those unwilling to participate in the study were excluded from the study. Infants born preterm are born before 37 weeks of gestation. They were further categorized as extremely preterm (<28 weeks), very preterm (28-31 weeks), late (34-36 weeks), and moderately preterm (32-33 weeks). 31 The “gold standard” to confirm neonatal sepsis is still the conventional culture methods. If microbial growth is observed in blood cultures or other sterile body fluids, sepsis is considered culture-proven. 32 Preterms will be divided into a case group consisting of 69 preterms with sepsis and a control group consisting of 69 preterms without sepsis based on their blood culture reports sent according to the NICU protocol. Preterms with positive blood cultures will be in the case group, and preterms with negative blood culture reports and no other clinical signs of sepsis will be selected for the control group ( Figure 1 ). 33 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. Figure 1. Flow diagram showing selection of cases and controls among preterm neonates admitted to the NICU. Samples will be collected from the neonate after 24 h of life as per the routine newborn screening protocol. Data were obtained from neonatal health records. Blood cultures were performed using the BACTEC system following NICU protocol. From the collected data, the SII, SIRI, PIV, NLR, MLR, and PLR were calculated using the following formulae: 1) Systemic Immune Inflammatory Index ( SII ) = [ platelet / lymphocyte ] ∗ Neutrophil 34 2) Systemic Inflammation Response Index ( SIRI ) = [ monocyte / lymphocyte ] ∗ Neutrophil 35 3) Pan Immune Inflammation Value ( PIV ) = Platelet ∗ [ monocyte / lymphocyte ] ∗ Neutrophil 36 4) Neutrophil to Lymphocyte Ratio ( NLR ) 10 5) Platelet to Lymphocyte Ratio ( PLR ) 10 6) Monocyte to Lymphocyte Ratio ( MLR ) 11 The selected indices (SII, SIRI, PIV, NLR, MLR, PLR) are well-established markers of systemic inflammation and immune status. For instance, SII integrates platelet, neutrophil, and lymphocyte counts, reflecting the balance between inflammation and immune response. 10 , 11 , 18 These indices have been previously validated as prognostic or diagnostic markers in sepsis and neonatal inflammatory conditions. 32 , 34 Therefore, they were chosen to comprehensively evaluate the inflammatory status in preterm neonates with sepsis. IBM SPSS (Statistical Package for Social Sciences) Statistics for Windows Version 29.0. Armonk, NY:IBM Corp. used to analyse the data. Descriptive statistics were presented as standard deviations and means. An independent sample t-test was used to compare the scores of the case and control arms. Statistical significance was defined as a p-value of less than 0.05. To assess the predictive ability of the diagnostic markers, ROC (Receiver Operating Characteristic) analysis was performed. Additionally, the optimum cut-off value was determined using the Youden Index. Results A total of 138 preterm neonates were included in this study, out of which, 50% of patients belonged to the sepsis group. Table 1 shows the clinical characteristics of the neonates. Of the 69 infants in the control group, 49.3% were male. The babies were categorized as late preterm (52.2%), moderate preterm (18.8%), very preterm (27.5%), and extremely preterm (1.4%). The majority of babies were delivered via normal vaginal delivery (60.9%). There were 38 babies with low birth weight (LBW), 29 with very low birth weight (VLBW), one with extremely low birth weight (ELBW) baby and 1 baby of normal birth weight. 31.9 Of the babies, 31.9% were found to be small for gestational age (SGA) and 68.1% were found to be appropriate for gestational age (AGA). Table 1. Maternal and neonatal characteristics of the study population. 37 Characteristic Sepsis group (n = 69) n (%) Control group (n = 69) n (%) Maternal age (years) 26.46 ± 5.41 28.06 ± 4.86 Sex of neonate Male 35 (50.7) 34 (49.3) Female 34 (49.3) 35 (50.7) Gestational age category Late preterm (34–36 weeks) 23 (33.3) 36 (52.2) Moderate preterm (32–33 weeks) 16 (23.2) 13 (18.8) Very preterm (28–31 weeks) 29 (42.0) 19 (27.5) Extremely preterm (<28 weeks) 1 (1.4) 1 (1.4) Mode of delivery Vaginal delivery 39 (56.5) 42 (60.9) Lower segment cesarean section (LSCS) 30 (43.5) 27 (39.1) Birth weight category Low birth weight (LBW) 14 (20.3) 38 (55.1) Very low birth weight (VLBW) 54 (78.3) 29 (42.0) Extremely low birth weight (ELBW) 1 (1.4) 1 (1.4) Normal birth weight (NBW) 0 (0.0) 1 (1.4) Growth status Small for gestational age (SGA) 14 (20.3) 22 (31.9) Appropriate for gestational age (AGA) 55 (79.7) 47 (68.1) 50.7 Of the patients in the sepsis group, 50.7% were male. Preterm sepsis was categorized as late preterm (33.3%), moderate preterm (23.3%), very preterm (42%), and extremely preterm (1.4%). None of the infants with sepsis had a normal birth weight. The majority of babies were delivered via normal vaginal delivery (56.5%). There were 14 LBW infants, 54 VLBW infants, and 1 ELBW infant. 20.3 Of the infants, 20.3% were small for gestational age (SGA) and 79.7% were appropriate for gestational age (AGA). Table 2 shows laboratory parameters of the neonates. Compared to the control group, preterm babies of sepsis group had lower WBC, lower monocyte, lower neutrophil, lower platelet and lymphocyte counts. Values of platelet counts (P < 0.001), SII (P = 0.002), PIV (P < 0.001) and PLR (P < 0.001) were found to be statistically significant. Values of total count (P = 0.116), monocyte (P = 0.197), neutrophil (P = 0.692), lymphocyte (P = 0.434), SIRI (P = 0.942), NLR (P = 0.58) and MLR (P = 0.871) were not statistically significant. Table 2. Laboratory parameters and inflammatory indices in preterm neonates with and without sepsis. 37 Parameter Control (n = 69) Median (IQR) Case (n = 69) Median (IQR) P value Total leukocyte count (cells/μL) 11,500 (8,275–16,390) 9,670 (6,600–16,710) 0.116 Monocytes (%) 8.0 (5.5–10.0) 6.0 (4.5–10.0) 0.197 Neutrophils (%) 59.0 (49.5–66.5) 56.0 (45.0–70.0) 0.692 Platelet count (cells/μL) 248,000 (197,500–303,000) 164,000 (66,500–229,000) <0.001 Lymphocytes (%) 28.0 (21.0–36.0) 25.0 (17.0–36.5) 0.434 SII (Systemic Immune-Inflammatory Index) 92,233.7 (92,233.7–92,233.7) 92,233.7 (92,233.7–92,233.7) 0.002 SIRI (Systemic Inflammation Response Index) 16.0 (8.9–25.6) 14.9 (4.9–32.4) 0.942 PIV (Pan-Immune Inflammation Value) 9,223.4 (9,223.4–9,223.4) 9,223.4 (9,223.4–9,223.4) <0.001 NLR (Neutrophil-to-Lymphocyte Ratio) 2.1 (1.4–3.2) 2.2 (1.2–3.9) 0.580 PLR (Platelet-to-Lymphocyte Ratio) 8,833.3 (4,809.0–9,223.4) 4,939.4 (2,577.7–9,223.4) <0.001 MLR (Monocyte-to-Lymphocyte Ratio) 0.30 (0.20–0.40) 0.30 (0.10–0.50) 0.871 To evaluate the predictive power of SII, platelet count, PIV, and PLR for neonatal sepsis, the area under the curve (AUC) values were calculated from the receiver operating characteristic (ROC) curves. The cutoff points were determined using the Youden Index. The ROC curves for the predictive ability of SII, platelet count, PIV, and PLR are shown in Figure 2 . Tables 3 and 4 show the ROC analysis and optimal cutoff values. Of the four variables, platelet count had the highest AUC value (0.715), with an ideal cut-off concentrations of 219500, and sensitivity and specificity of 75.4 and 65.2 respectively. The AUC value for PLR was 0.668, the sensitivity and specificity were 72.5 and 58%, respectively, and the ideal cut-off value was 7923.19. The AUC value and cut-off value for PIV were 0.665 and 2187333.33, respectively, with a sensitivity of 60.9 and specificity of 68.1. The AUC value was lowest for SII (0.65), with an ideal cut-off values of 37656.79, and sensitivity and specificity of 66.7 and 62.3%, respectively. Figure 2. ROC curve analysis. 37 Table 3. ROC analysis to assess predictive ability of diagnostic markers to predict neonatal sepsis. 37 Parameter AUC p value 95% CI Lower Bound 95% CI Upper Bound SII (Systemic Immune-Inflammatory Index) 0.65 0.002 0.558 0.743 Platelet count (cells/μL) 0.715 <0.001 0.628 0.802 PIV (Pan-Immune Inflammation Value) 0.665 0.001 0.574 0.755 PLR (Platelet-to-Lymphocyte Ratio) 0.668 0.001 0.577 0.758 Table 4. Optimal cutoff determined using ROC analysis. 37 Parameter Cut-off Sensitivity (%) Specificity (%) SII (Systemic Immune-Inflammatory Index) 37,656.79 66.7 62.3 Platelet count (cells/μL) 219,500 75.4 65.2 PIV (Pan-Immune Inflammation Value) 2,187,333.33 60.9 68.1 PLR (Platelet-to-Lymphocyte Ratio) 7,923.19 72.5 58.0 Critical reflection Of the 138 preterm babies included in the study, the majority were late preterm, 23 belonged to the sepsis group, and 36 belonged to the control group. Most of the babies in both the sepsis (56.5%) and control (60.9%) groups were delivered by normal vaginal delivery. The majority of babies in the sepsis group had very low birth weight (78.3%) and the majority in the control group had low birth weight (55.1%). Platelet count, SII, PIV, and PLR were found to be significant predictors of neonatal sepsis. Platelet count had the highest predictive value, with an AUC value of 0.715 and optimal cut-off value of 219500. It had a sensitivity of 75.4 and specificity of 65.2. Discussion Early detection of neonatal sepsis remains challenging due to nonspecific clinical signs and the time required for blood culture results. PLR, SII, and platelet count all showed differences between neonates with and without sepsis in our study, with platelet count exhibiting the strongest correlation. These findings are consistent with other research indicating that platelet-related indices may be useful in evaluating newborn sepsis. Day-one WBC and platelet counts could serve as early markers of sepsis, according to Xianghui Liang et al. and Minichil Worku et al. 21 , 23 According to Isabelle M. C. Ree et al. and Vizcarra-Jimenez et al., 24 , 25 thrombocytopenia has also been linked to higher mortality in neonatal sepsis, especially in gram-negative infections. Previous research has also assessed inflammatory indices such SII, NLR, PLR, and SIRI. According to Zhu et al., newborn sepsis may be reflected by PLR, SII, and NLR, with SII exhibiting a comparatively larger predictive value. 10 Similarly SII, PLR, and NLR may also be useful in diagnosing sepsis-related outcomes, according to Mangalesh et al. and Islam et al. 18 , 20 Higher SIRI and SII levels were linked to a higher risk of secondary infections in preterm newborns, according to Chen et al. 17 However, SIRI did not significantly differ in our study, suggesting that its effectiveness may differ depending on the population. The potential application of SII in particular newborn diseases is supported by additional research. While Güngör et al and Runqiang Liang et al 13 , 14 emphasized SII in urinary tract infections and serious bacterial infections respectively, Aydogan et al. reported that NLR and SII may be linked to outcomes in infants with congenital heart disease. 12 Preterm newborns with late-onset sepsis have increased SII levels, according to Vardar et al. 28 Furthermore, links between neonatal sepsis and hematologic abnormalities such as leukopenia, thrombocytopenia, anemia, and increased NLR were found by Mubaraki et al. and Li et al. 29 , 30 These results imply that a variety of hematologic and inflammatory indices may be useful in predicting newborn sepsis, although the relative effectiveness of these indices may differ depending on the situation. It is important to note several limitations. The results of our study may not be generalizable to other groups because it was limited to a single tertiary care facility. The found associations may be influenced by variables like gestational age, birth weight, comorbidities, and laboratory techniques. Multivariate analysis and larger sample size will be required to establish independent predictive efficacy. To define uniform thresholds for clinical use and to further investigate the potential utility of these markers, larger multicenter trials are required. Overall, our findings suggest that SII and PLR, as well as platelet count and thrombocyte-related indices, may have potential utility for predicting newborn sepsis. These findings support earlier research while emphasizing the need for careful interpretation and additional validation in larger groups. Limitations This study was performed only among preterm infants in the NICU, and studies involving term infants admitted to the NICU and culture negative sepsis cases may be required. Further multicenter studies with larger patient populations and multivariate analysis will be required. Conclusion There was substantial 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. This will aid in early sepsis diagnosis and management and, in turn, reduce neonatal morbidity and mortality associated with sepsis. Ethical approval statement On 17/10/24, ethical clearance was granted by The Institutional Ethics Committee at Kasturba Medical College in Mangalore (Protocol No: IECKMCMLR10/2024/606). The MS of the Government Lady Goschen Hospital has given us permission to conduct this study. Consent statement As this was a laboratory record–based observational study utilizing 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. Data availability statement Figshare: Data – Excel Sheet (Neonatal sepsis research data Excel) https://doi.org/10.6084/m9.figshare.28395161.v1 . 37 The project contains the following underlying data: • Sepsis Data 2 Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgment The Medical Superintendent, Government Lady Goschen Hospital, Mangalore. Dr. Suchetha S Rao, Professor and Head of Department, Department of Pediatrics, KMC Mangalore. References 1. Vincent JL: Sepsis and infection: two words that should not be confused. Front. Med (Lausanne). 2023; 10 : 1156732. PubMed Abstract | Publisher Full Text | Free Full Text 2. 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Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 03 Apr 2025 ADD YOUR COMMENT Comment Author details Author details 1 Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 2 Department of Pediatrics, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India Smrithi GM Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Gayathri Renganathan Roles: Conceptualization, Formal Analysis, Methodology, Project Administration, Supervision, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Smitha D'sa Roles: Data Curation, Formal Analysis, Supervision, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 23 Feb 2026, 14:390 https://doi.org/10.12688/f1000research.162331.2 version 1 Published: 03 Apr 2025, 14:390 https://doi.org/10.12688/f1000research.162331.1 Copyright © 2026 GM S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article GM S, Renganathan G and D'sa S. Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.12688/f1000research.162331.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 23 Feb 2026 Revised Views 0 Cite How to cite this report: Shanbhag DS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r468909 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-468909 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 03 Apr 2026 Dr. Sweta Shanbhag , Father Muller Medical College, Mangalore, Karnataka, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.196572.r468909 This is a clinically relevant and a well-structured study. I appreciate the authors for incorporating most of the changes and suggestions by previous reviewers. However there are a few more areas where you can improve the precision, tone and statistical ... Continue reading READ ALL This is a clinically relevant and a well-structured study. I appreciate the authors for incorporating most of the changes and suggestions by previous reviewers. However there are a few more areas where you can improve the precision, tone and statistical presentation to make it more impactful for a high-tier journal like this one. ABSTRACT: 1. Authors are switching between systemic inflammatory markers and systemic inflammatory indices. I recommend you stick to systemic inflammatory indices, as this specifically refers to the ratios that you are calculating. 2. "Has not been shown in any current research" is a bit of a bold statement. It would be safer to say "Remains underexplored in Indian population" or something on similar lines. 3. Prospective/Retrospective not mentioned in methods section in abstract. 4. Since you have used Culture proven sepsis as the case group, the same needs to be clearly mentioned in abstract. 5. Instead of listing out all the formulae, phrase it in a better way like "Six indices were evaluated namely __________________________" (That should be enough for an abstract). Details about the indices can be listed out later on in the manuscript. 6. results section in abstract - apart from AUC, Sensitivity and specificity mention 95% C.I. and p value too. 7. Platelet count should be followed by units (cells/cu mm) 8. Conclusion of abstract - "Substantial is an vague term, rather use acceptable or moderate which are preferred terminologies for your range of AUC. 9.No mention of SIRI, MLR in results despite being part of the methodology. Even if they are not statistically significant, to be mentioned in brief. MAIN TEXT: 1. Introduction - No recent study is again a bold claim, use words like "due to paucity of data in the Indian context" or something like that. 2. Use the terminology systemic inflammatory indices throughout 3.Exclusion criteria is very brief - add on pre terms with major congenital anomalies and those whose mothers received intra partum antibiotics (if you have actually excluded these babies) - as these are major confounders for haematological indices. 4. In Table 2 SII values in both groups are exactly the same, looks like a copy paste error or a miscalculation. Considering you have a p value of 0.002, the medians should have been different in both the groups. Please double check. 5. Check PIV, SII values in Table 2 again - they are quite high - ensure the units and decimal placements are consistent through out. 6. AUC of 0.7 is acceptable or moderate and not excellent to be a standalone tool. Expand upon this point in the discussion section, that these tests can be used as adjunctive tools in addition to clinical judgement and culture, but not as a replacement. 7. NLR is a standard index in most adult studies, while here you didn't get any significance. Add on a sentence in the discussion section explaining why - one of the probable reasons could also be due to the unique neonatal haematological response or immature neutrophil pool in pre terms. 8. Mention all the various maternal and neonatal factors that can influence haematological indices, which were not controlled for in this study and add this in your limitations. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Paediatric Infectious diseases, General Paediatrics, Neonatology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Shanbhag DS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r468909 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-468909 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Utamayasa IKA and Nastiti P. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r468911 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-468911 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 01 Apr 2026 I Ketut Alit Utamayasa , Children’s Health Sciences, Airlangga University Department of Children’s Health Sciences (Ringgold ID: 592763), East Java, Indonesia Prima Nastiti , Department of Pediatrics, Airlangga University (Ringgold ID: 148005), Surabaya, East Java, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.196572.r468911 This manuscript addresses an important and clinically relevant topic, namely the utility of systemic inflammatory indices in the early identification of neonatal sepsis in preterm infants. The study includes a reasonable sample size and applies commonly used indices (SII, SIRI, ... Continue reading READ ALL This manuscript addresses an important and clinically relevant topic, namely the utility of systemic inflammatory indices in the early identification of neonatal sepsis in preterm infants. The study includes a reasonable sample size and applies commonly used indices (SII, SIRI, PIV, NLR, PLR, MLR) along with ROC analysis to evaluate diagnostic performance. The topic is particularly relevant in low-resource settings where rapid and accessible biomarkers are needed. However, several important methodological and interpretative issues need to be addressed. First, the manuscript repeatedly refers to these indices as “predictors” of neonatal sepsis. Given the case–control 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. Second, no 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. Third, the 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. Fourth, clarification 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. Fifth, the 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 emphasized more clearly. Additionally, some 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. Minor revisions include shortening and refining the Introduction, improving clarity and consistency of terminology, and further polishing of language. In conclusion, the study contributes useful exploratory data, but revisions are needed to improve methodological clarity, correct interpretation of results, and strengthen clinical applicability. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pediatric cardiology, neonatology congenital heart disease We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Utamayasa IKA and Nastiti P. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r468911 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-468911 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Avabratha KS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r461444 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-461444 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 05 Mar 2026 K. Shreedhara Avabratha , Father muller medical college, Mangalore, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.196572.r461444 1.Do not see much improvement from earlier version 2. Introduction need to be crisp. Summary of evidence and need for study give a feel of dissertation presentation. 3. Which preterm neonates are excluded from the selected group?. Exclusion criteria ... Continue reading READ ALL 1.Do not see much improvement from earlier version 2. Introduction need to be crisp. Summary of evidence and need for study give a feel of dissertation presentation. 3. Which preterm neonates are excluded from the selected group?. Exclusion criteria need to be clear. 4. Is it routine practice to send blood culture for all preterms ? even for no clinical sepsis preterms . 5. Tense -will be to be corrected. 6.Conclusions are very general. It should be from the present study Competing Interests: No competing interests were disclosed. Reviewer Expertise: General pediatrics, neonatology, pediatric hem oncology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Avabratha KS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r461444 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-461444 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 03 Apr 2025 Views 0 Cite How to cite this report: Avabratha KS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r442649 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-442649 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 16 Jan 2026 K. Shreedhara Avabratha , Father muller medical college, Mangalore, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.178518.r442649 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation ... Continue reading READ ALL 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: General pediatrics, neonatology, pediatric hem oncology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Avabratha KS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r442649 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-442649 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 23 Feb 2026 Smrithi null , Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 23 Feb 2026 Author Response We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed ... Continue reading We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed each point as follows: Reviewer Report : 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Author Response : 1. Clarify when lab tests were collected? Prior to confirmation of sepsis or after blood culture positivity? Response: We thank the reviewer for this important question. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. The values used in this study were routinely collected laboratory data prior to confirmation of sepsis. 2. What about culture-negative clinical sepsis? Response: We sincerely appreciate this insightful comment. In the present study, only culture-proven sepsis cases were included to ensure microbiological confirmation and diagnostic accuracy. Culture-negative clinical sepsis was therefore excluded, which we acknowledge as a limitation of the study. 3. Retrospective or prospective case-control study? Response: The study was conducted as a prospective case–control study. 4. Sample size calculation lacks details. Response: We thank the reviewer for highlighting this point. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024). The largest calculated sample size was selected to ensure adequate statistical power. 5. No multivariate analysis performed. Response: The study was designed as an exploratory analysis using routinely collected laboratory data. Multivariable logistic regression was not performed due to the limited sample size and absence of comprehensive covariate information. A statement acknowledging that multivariable analysis may be explored in future studies has been added to the Discussion. 6. Revise tables for clarity. Response: All tables have been revised for clarity, with clear headings, units, and footnotes to enhance readability and comprehension. 7. Improve discussion part about clinical implications. Response: The Discussion section has been revised and strengthened to better highlight the clinical implications of the study findings. 8. Introduction has become too long. Response: The Introduction has been condensed for improved readability while retaining all essential points and references. 9. Use correct tense e.g., “will be” etc. Response: All relevant sections have been carefully revised for correct tense. 10. Page numbers in reference 10 missing. Response: The reference list has been updated to include the correct page numbers for reference 10. We hope that the revisions made have satisfactorily addressed all concerns and have improved the clarity and readability of the manuscript. Thank you very much for your valuable feedback in improving the standard of study and taking the time to address the areas of improvement in our article. We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed each point as follows: Reviewer Report : 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Author Response : 1. Clarify when lab tests were collected? Prior to confirmation of sepsis or after blood culture positivity? Response: We thank the reviewer for this important question. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. The values used in this study were routinely collected laboratory data prior to confirmation of sepsis. 2. What about culture-negative clinical sepsis? Response: We sincerely appreciate this insightful comment. In the present study, only culture-proven sepsis cases were included to ensure microbiological confirmation and diagnostic accuracy. Culture-negative clinical sepsis was therefore excluded, which we acknowledge as a limitation of the study. 3. Retrospective or prospective case-control study? Response: The study was conducted as a prospective case–control study. 4. Sample size calculation lacks details. Response: We thank the reviewer for highlighting this point. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024). The largest calculated sample size was selected to ensure adequate statistical power. 5. No multivariate analysis performed. Response: The study was designed as an exploratory analysis using routinely collected laboratory data. Multivariable logistic regression was not performed due to the limited sample size and absence of comprehensive covariate information. A statement acknowledging that multivariable analysis may be explored in future studies has been added to the Discussion. 6. Revise tables for clarity. Response: All tables have been revised for clarity, with clear headings, units, and footnotes to enhance readability and comprehension. 7. Improve discussion part about clinical implications. Response: The Discussion section has been revised and strengthened to better highlight the clinical implications of the study findings. 8. Introduction has become too long. Response: The Introduction has been condensed for improved readability while retaining all essential points and references. 9. Use correct tense e.g., “will be” etc. Response: All relevant sections have been carefully revised for correct tense. 10. Page numbers in reference 10 missing. Response: The reference list has been updated to include the correct page numbers for reference 10. We hope that the revisions made have satisfactorily addressed all concerns and have improved the clarity and readability of the manuscript. Thank you very much for your valuable feedback in improving the standard of study and taking the time to address the areas of improvement in our article. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 23 Feb 2026 Smrithi null , Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 23 Feb 2026 Author Response We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed ... Continue reading We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed each point as follows: Reviewer Report : 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Author Response : 1. Clarify when lab tests were collected? Prior to confirmation of sepsis or after blood culture positivity? Response: We thank the reviewer for this important question. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. The values used in this study were routinely collected laboratory data prior to confirmation of sepsis. 2. What about culture-negative clinical sepsis? Response: We sincerely appreciate this insightful comment. In the present study, only culture-proven sepsis cases were included to ensure microbiological confirmation and diagnostic accuracy. Culture-negative clinical sepsis was therefore excluded, which we acknowledge as a limitation of the study. 3. Retrospective or prospective case-control study? Response: The study was conducted as a prospective case–control study. 4. Sample size calculation lacks details. Response: We thank the reviewer for highlighting this point. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024). The largest calculated sample size was selected to ensure adequate statistical power. 5. No multivariate analysis performed. Response: The study was designed as an exploratory analysis using routinely collected laboratory data. Multivariable logistic regression was not performed due to the limited sample size and absence of comprehensive covariate information. A statement acknowledging that multivariable analysis may be explored in future studies has been added to the Discussion. 6. Revise tables for clarity. Response: All tables have been revised for clarity, with clear headings, units, and footnotes to enhance readability and comprehension. 7. Improve discussion part about clinical implications. Response: The Discussion section has been revised and strengthened to better highlight the clinical implications of the study findings. 8. Introduction has become too long. Response: The Introduction has been condensed for improved readability while retaining all essential points and references. 9. Use correct tense e.g., “will be” etc. Response: All relevant sections have been carefully revised for correct tense. 10. Page numbers in reference 10 missing. Response: The reference list has been updated to include the correct page numbers for reference 10. We hope that the revisions made have satisfactorily addressed all concerns and have improved the clarity and readability of the manuscript. Thank you very much for your valuable feedback in improving the standard of study and taking the time to address the areas of improvement in our article. We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed each point as follows: Reviewer Report : 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Author Response : 1. Clarify when lab tests were collected? Prior to confirmation of sepsis or after blood culture positivity? Response: We thank the reviewer for this important question. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. The values used in this study were routinely collected laboratory data prior to confirmation of sepsis. 2. What about culture-negative clinical sepsis? Response: We sincerely appreciate this insightful comment. In the present study, only culture-proven sepsis cases were included to ensure microbiological confirmation and diagnostic accuracy. Culture-negative clinical sepsis was therefore excluded, which we acknowledge as a limitation of the study. 3. Retrospective or prospective case-control study? Response: The study was conducted as a prospective case–control study. 4. Sample size calculation lacks details. Response: We thank the reviewer for highlighting this point. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024). The largest calculated sample size was selected to ensure adequate statistical power. 5. No multivariate analysis performed. Response: The study was designed as an exploratory analysis using routinely collected laboratory data. Multivariable logistic regression was not performed due to the limited sample size and absence of comprehensive covariate information. A statement acknowledging that multivariable analysis may be explored in future studies has been added to the Discussion. 6. Revise tables for clarity. Response: All tables have been revised for clarity, with clear headings, units, and footnotes to enhance readability and comprehension. 7. Improve discussion part about clinical implications. Response: The Discussion section has been revised and strengthened to better highlight the clinical implications of the study findings. 8. Introduction has become too long. Response: The Introduction has been condensed for improved readability while retaining all essential points and references. 9. Use correct tense e.g., “will be” etc. Response: All relevant sections have been carefully revised for correct tense. 10. Page numbers in reference 10 missing. Response: The reference list has been updated to include the correct page numbers for reference 10. We hope that the revisions made have satisfactorily addressed all concerns and have improved the clarity and readability of the manuscript. Thank you very much for your valuable feedback in improving the standard of study and taking the time to address the areas of improvement in our article. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: A DS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r429880 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-429880 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Dec 2025 Dr Shashidhar A , St John's Medical College Hospital, Bengaluru, Karnataka, India Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.178518.r429880 Abstract 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- should be only based on the ... Continue reading READ ALL Abstract 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- should be only based on the results. Use Mesh terms Main 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 Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Neonatology, spesis I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT A DS. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r429880 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-429880 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 23 Feb 2026 Smrithi null , Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 23 Feb 2026 Author Response We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. We greatly appreciate the suggestions, which have helped us improve the ... Continue reading We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. 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. Reviewer report: “Abstract - 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—should be only based on the results. Use MeSH terms.” Author response: 1. Background should clarify the need for the study. Can delete the rest. Response: The Abstract has been revised to clarify the study’s rationale, and unnecessary portions have been removed. 2. Study design to be stated. Give formulae for the indices in methods. Response: The study design has been explicitly stated as a case–control study. The formulae for all inflammatory indices are now included in the Methods. 3. Data should be in results. Response: Significant study data have been appropriately included in the Results section. 4. Avoid overconcluding—should be only based on the results. Response: The conclusion has been revised to ensure that statements are strictly supported by study results. 5. Use MeSH terms. Response: Relevant MeSH terms have been applied to the manuscript keywords. Reviewer report: “Main 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.” Author response: 1. Use STROBE checklist for reporting this observational study throughout. 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. 2. Summary of evidence is too long; should be made crisp and moved to discussion. Response: The summary of evidence has been condensed, with relevant details now included in the Discussion section. 3. Physiological basis of choosing these indices to be quoted. Response: The physiological rationale for selection of the inflammatory indices has now been incorporated in the Methods section. 4. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines 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. 5. How were controls chosen given that the yield of culture may be less? 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 [33] . Consecutive eligible preterm neonates meeting these criteria during the study period were included. 6. What method of culture was done and when? 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. 7. Was any matching done? 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. 8. Consent would be required as the controls are being sampled, data collected and planned for publication. Response: As this was a laboratory record–based 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. 9. Study flow is missing. 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. 10. Unclear when the tests were done and in case of multiple values which one were chosen. 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. 11. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression. 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. We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. 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. Reviewer report: “Abstract - 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—should be only based on the results. Use MeSH terms.” Author response: 1. Background should clarify the need for the study. Can delete the rest. Response: The Abstract has been revised to clarify the study’s rationale, and unnecessary portions have been removed. 2. Study design to be stated. Give formulae for the indices in methods. Response: The study design has been explicitly stated as a case–control study. The formulae for all inflammatory indices are now included in the Methods. 3. Data should be in results. Response: Significant study data have been appropriately included in the Results section. 4. Avoid overconcluding—should be only based on the results. Response: The conclusion has been revised to ensure that statements are strictly supported by study results. 5. Use MeSH terms. Response: Relevant MeSH terms have been applied to the manuscript keywords. Reviewer report: “Main 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.” Author response: 1. Use STROBE checklist for reporting this observational study throughout. 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. 2. Summary of evidence is too long; should be made crisp and moved to discussion. Response: The summary of evidence has been condensed, with relevant details now included in the Discussion section. 3. Physiological basis of choosing these indices to be quoted. Response: The physiological rationale for selection of the inflammatory indices has now been incorporated in the Methods section. 4. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines 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. 5. How were controls chosen given that the yield of culture may be less? 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 [33] . Consecutive eligible preterm neonates meeting these criteria during the study period were included. 6. What method of culture was done and when? 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. 7. Was any matching done? 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. 8. Consent would be required as the controls are being sampled, data collected and planned for publication. Response: As this was a laboratory record–based 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. 9. Study flow is missing. 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. 10. Unclear when the tests were done and in case of multiple values which one were chosen. 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. 11. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression. 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. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 23 Feb 2026 Smrithi null , Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 23 Feb 2026 Author Response We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. We greatly appreciate the suggestions, which have helped us improve the ... Continue reading We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. 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. Reviewer report: “Abstract - 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—should be only based on the results. Use MeSH terms.” Author response: 1. Background should clarify the need for the study. Can delete the rest. Response: The Abstract has been revised to clarify the study’s rationale, and unnecessary portions have been removed. 2. Study design to be stated. Give formulae for the indices in methods. Response: The study design has been explicitly stated as a case–control study. The formulae for all inflammatory indices are now included in the Methods. 3. Data should be in results. Response: Significant study data have been appropriately included in the Results section. 4. Avoid overconcluding—should be only based on the results. Response: The conclusion has been revised to ensure that statements are strictly supported by study results. 5. Use MeSH terms. Response: Relevant MeSH terms have been applied to the manuscript keywords. Reviewer report: “Main 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.” Author response: 1. Use STROBE checklist for reporting this observational study throughout. 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. 2. Summary of evidence is too long; should be made crisp and moved to discussion. Response: The summary of evidence has been condensed, with relevant details now included in the Discussion section. 3. Physiological basis of choosing these indices to be quoted. Response: The physiological rationale for selection of the inflammatory indices has now been incorporated in the Methods section. 4. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines 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. 5. How were controls chosen given that the yield of culture may be less? 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 [33] . Consecutive eligible preterm neonates meeting these criteria during the study period were included. 6. What method of culture was done and when? 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. 7. Was any matching done? 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. 8. Consent would be required as the controls are being sampled, data collected and planned for publication. Response: As this was a laboratory record–based 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. 9. Study flow is missing. 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. 10. Unclear when the tests were done and in case of multiple values which one were chosen. 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. 11. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression. 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. We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. 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. Reviewer report: “Abstract - 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—should be only based on the results. Use MeSH terms.” Author response: 1. Background should clarify the need for the study. Can delete the rest. Response: The Abstract has been revised to clarify the study’s rationale, and unnecessary portions have been removed. 2. Study design to be stated. Give formulae for the indices in methods. Response: The study design has been explicitly stated as a case–control study. The formulae for all inflammatory indices are now included in the Methods. 3. Data should be in results. Response: Significant study data have been appropriately included in the Results section. 4. Avoid overconcluding—should be only based on the results. Response: The conclusion has been revised to ensure that statements are strictly supported by study results. 5. Use MeSH terms. Response: Relevant MeSH terms have been applied to the manuscript keywords. Reviewer report: “Main 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.” Author response: 1. Use STROBE checklist for reporting this observational study throughout. 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. 2. Summary of evidence is too long; should be made crisp and moved to discussion. Response: The summary of evidence has been condensed, with relevant details now included in the Discussion section. 3. Physiological basis of choosing these indices to be quoted. Response: The physiological rationale for selection of the inflammatory indices has now been incorporated in the Methods section. 4. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines 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. 5. How were controls chosen given that the yield of culture may be less? 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 [33] . Consecutive eligible preterm neonates meeting these criteria during the study period were included. 6. What method of culture was done and when? 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. 7. Was any matching done? 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. 8. Consent would be required as the controls are being sampled, data collected and planned for publication. Response: As this was a laboratory record–based 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. 9. Study flow is missing. 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. 10. Unclear when the tests were done and in case of multiple values which one were chosen. 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. 11. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression. 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. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Kumer Dey S. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r426933 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-426933 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Dec 2025 Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, Dhaka Division, Bangladesh Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.178518.r426933 Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention ... Continue reading READ ALL Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Neonatal sepsis, IUGR, Neeborn screening, Birth Defect, Online learning I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kumer Dey S. Reviewer Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r426933 ) The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-426933 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 23 Feb 2026 Smrithi null , Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 23 Feb 2026 Author Response We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved ... Continue reading We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved our study's scientific rigor, clarity and organization. Each comment is addressed below. Reviewer Report : Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Author Response : 1. Sample size calculation needs to be detailed for better understanding. Response: We thank the reviewer for this suggestion. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024), with the largest calculated sample size chosen for the study. 2. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and controls (culture negative). Response: We appreciate this recommendation. A study flow diagram has now been added (Figure 1) to illustrate the total number of preterm neonates enrolled, exclusions, and the final allocation into cases (culture positive) and controls (culture negative). In addition, a textual description of the participant flow has been included in the Methods section for clarity. 3. Better to mention where and how investigations were done and who had followed up the babies. Response: Blood cultures were performed using BACTEC system following NICU protocol. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. Culture positivity defined sepsis cases. As this was a laboratory record–based observational study, no additional clinical follow-up of the neonates was performed; the study utilized only routinely collected laboratory data. 4. Data to be made available. Response: We have included all the relevant data and the underlying findings under the Data Availability Section. We sincerely thank the reviewer once again for their time and valuable 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. We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved our study's scientific rigor, clarity and organization. Each comment is addressed below. Reviewer Report : Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Author Response : 1. Sample size calculation needs to be detailed for better understanding. Response: We thank the reviewer for this suggestion. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024), with the largest calculated sample size chosen for the study. 2. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and controls (culture negative). Response: We appreciate this recommendation. A study flow diagram has now been added (Figure 1) to illustrate the total number of preterm neonates enrolled, exclusions, and the final allocation into cases (culture positive) and controls (culture negative). In addition, a textual description of the participant flow has been included in the Methods section for clarity. 3. Better to mention where and how investigations were done and who had followed up the babies. Response: Blood cultures were performed using BACTEC system following NICU protocol. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. Culture positivity defined sepsis cases. As this was a laboratory record–based observational study, no additional clinical follow-up of the neonates was performed; the study utilized only routinely collected laboratory data. 4. Data to be made available. Response: We have included all the relevant data and the underlying findings under the Data Availability Section. We sincerely thank the reviewer once again for their time and valuable 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. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 23 Feb 2026 Smrithi null , Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India 23 Feb 2026 Author Response We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved ... Continue reading We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved our study's scientific rigor, clarity and organization. Each comment is addressed below. Reviewer Report : Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Author Response : 1. Sample size calculation needs to be detailed for better understanding. Response: We thank the reviewer for this suggestion. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024), with the largest calculated sample size chosen for the study. 2. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and controls (culture negative). Response: We appreciate this recommendation. A study flow diagram has now been added (Figure 1) to illustrate the total number of preterm neonates enrolled, exclusions, and the final allocation into cases (culture positive) and controls (culture negative). In addition, a textual description of the participant flow has been included in the Methods section for clarity. 3. Better to mention where and how investigations were done and who had followed up the babies. Response: Blood cultures were performed using BACTEC system following NICU protocol. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. Culture positivity defined sepsis cases. As this was a laboratory record–based observational study, no additional clinical follow-up of the neonates was performed; the study utilized only routinely collected laboratory data. 4. Data to be made available. Response: We have included all the relevant data and the underlying findings under the Data Availability Section. We sincerely thank the reviewer once again for their time and valuable 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. We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved our study's scientific rigor, clarity and organization. Each comment is addressed below. Reviewer Report : Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Author Response : 1. Sample size calculation needs to be detailed for better understanding. Response: We thank the reviewer for this suggestion. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024), with the largest calculated sample size chosen for the study. 2. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and controls (culture negative). Response: We appreciate this recommendation. A study flow diagram has now been added (Figure 1) to illustrate the total number of preterm neonates enrolled, exclusions, and the final allocation into cases (culture positive) and controls (culture negative). In addition, a textual description of the participant flow has been included in the Methods section for clarity. 3. Better to mention where and how investigations were done and who had followed up the babies. Response: Blood cultures were performed using BACTEC system following NICU protocol. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. Culture positivity defined sepsis cases. As this was a laboratory record–based observational study, no additional clinical follow-up of the neonates was performed; the study utilized only routinely collected laboratory data. 4. Data to be made available. Response: We have included all the relevant data and the underlying findings under the Data Availability Section. We sincerely thank the reviewer once again for their time and valuable 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. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 03 Apr 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 4 5 Version 2 (revision) 23 Feb 26 read read read Version 1 03 Apr 25 read read read Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Dr Shashidhar A , St John's Medical College Hospital, Bengaluru, India K. Shreedhara Avabratha , Father muller medical college, Mangalore, India I Ketut Alit Utamayasa , Airlangga University Department of Children’s Health Sciences (Ringgold ID: 592763), East Java, Indonesia Prima Nastiti , Airlangga University (Ringgold ID: 148005), Surabaya, Indonesia Dr. Sweta Shanbhag , Father Muller Medical College, Mangalore, India Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Shanbhag D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 03 Apr 2026 | for Version 2 Dr. Sweta Shanbhag , Father Muller Medical College, Mangalore, Karnataka, India 0 Views copyright © 2026 Shanbhag D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This is a clinically relevant and a well-structured study. I appreciate the authors for incorporating most of the changes and suggestions by previous reviewers. However there are a few more areas where you can improve the precision, tone and statistical presentation to make it more impactful for a high-tier journal like this one. ABSTRACT: 1. Authors are switching between systemic inflammatory markers and systemic inflammatory indices. I recommend you stick to systemic inflammatory indices, as this specifically refers to the ratios that you are calculating. 2. "Has not been shown in any current research" is a bit of a bold statement. It would be safer to say "Remains underexplored in Indian population" or something on similar lines. 3. Prospective/Retrospective not mentioned in methods section in abstract. 4. Since you have used Culture proven sepsis as the case group, the same needs to be clearly mentioned in abstract. 5. Instead of listing out all the formulae, phrase it in a better way like "Six indices were evaluated namely __________________________" (That should be enough for an abstract). Details about the indices can be listed out later on in the manuscript. 6. results section in abstract - apart from AUC, Sensitivity and specificity mention 95% C.I. and p value too. 7. Platelet count should be followed by units (cells/cu mm) 8. Conclusion of abstract - "Substantial is an vague term, rather use acceptable or moderate which are preferred terminologies for your range of AUC. 9.No mention of SIRI, MLR in results despite being part of the methodology. Even if they are not statistically significant, to be mentioned in brief. MAIN TEXT: 1. Introduction - No recent study is again a bold claim, use words like "due to paucity of data in the Indian context" or something like that. 2. Use the terminology systemic inflammatory indices throughout 3.Exclusion criteria is very brief - add on pre terms with major congenital anomalies and those whose mothers received intra partum antibiotics (if you have actually excluded these babies) - as these are major confounders for haematological indices. 4. In Table 2 SII values in both groups are exactly the same, looks like a copy paste error or a miscalculation. Considering you have a p value of 0.002, the medians should have been different in both the groups. Please double check. 5. Check PIV, SII values in Table 2 again - they are quite high - ensure the units and decimal placements are consistent through out. 6. AUC of 0.7 is acceptable or moderate and not excellent to be a standalone tool. Expand upon this point in the discussion section, that these tests can be used as adjunctive tools in addition to clinical judgement and culture, but not as a replacement. 7. NLR is a standard index in most adult studies, while here you didn't get any significance. Add on a sentence in the discussion section explaining why - one of the probable reasons could also be due to the unique neonatal haematological response or immature neutrophil pool in pre terms. 8. Mention all the various maternal and neonatal factors that can influence haematological indices, which were not controlled for in this study and add this in your limitations. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Paediatric Infectious diseases, General Paediatrics, Neonatology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Shanbhag DS. Peer Review Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r468909) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-468909 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Utamayasa I et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 01 Apr 2026 | for Version 2 I Ketut Alit Utamayasa , Children’s Health Sciences, Airlangga University Department of Children’s Health Sciences (Ringgold ID: 592763), East Java, Indonesia Prima Nastiti , Department of Pediatrics, Airlangga University (Ringgold ID: 148005), Surabaya, East Java, Indonesia 0 Views copyright © 2026 Utamayasa I et al. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions This manuscript addresses an important and clinically relevant topic, namely the utility of systemic inflammatory indices in the early identification of neonatal sepsis in preterm infants. The study includes a reasonable sample size and applies commonly used indices (SII, SIRI, PIV, NLR, PLR, MLR) along with ROC analysis to evaluate diagnostic performance. The topic is particularly relevant in low-resource settings where rapid and accessible biomarkers are needed. However, several important methodological and interpretative issues need to be addressed. First, the manuscript repeatedly refers to these indices as “predictors” of neonatal sepsis. Given the case–control 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. Second, no 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. Third, the 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. Fourth, clarification 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. Fifth, the 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 emphasized more clearly. Additionally, some 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. Minor revisions include shortening and refining the Introduction, improving clarity and consistency of terminology, and further polishing of language. In conclusion, the study contributes useful exploratory data, but revisions are needed to improve methodological clarity, correct interpretation of results, and strengthen clinical applicability. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Pediatric cardiology, neonatology congenital heart disease We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however we have significant reservations, as outlined above. reply Respond to this report Responses (0) Utamayasa IKA and Nastiti P. Peer Review Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r468911) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-468911 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Avabratha K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 05 Mar 2026 | for Version 2 K. Shreedhara Avabratha , Father muller medical college, Mangalore, India 0 Views copyright © 2026 Avabratha K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1.Do not see much improvement from earlier version 2. Introduction need to be crisp. Summary of evidence and need for study give a feel of dissertation presentation. 3. Which preterm neonates are excluded from the selected group?. Exclusion criteria need to be clear. 4. Is it routine practice to send blood culture for all preterms ? even for no clinical sepsis preterms . 5. Tense -will be to be corrected. 6.Conclusions are very general. It should be from the present study Competing Interests No competing interests were disclosed. Reviewer Expertise General pediatrics, neonatology, pediatric hem oncology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Avabratha KS. Peer Review Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.196572.r461444) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-390/v2#referee-response-461444 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2026 Avabratha K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 16 Jan 2026 | for Version 1 K. Shreedhara Avabratha , Father muller medical college, Mangalore, India 0 Views copyright © 2026 Avabratha K. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise General pediatrics, neonatology, pediatric hem oncology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 23 Feb 2026 Smrithi null, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India We sincerely thank Dr Shreedhara Avabratha for taking the time to carefully evaluate our manuscript and for providing constructive and valuable comments. We greatly appreciate the insights and have addressed each point as follows: Reviewer Report : 1. Clarify when lab tests were collected ? Prior to confirmation of sepsis or after blood culture positivity? 2. What about culture negative clinical sepsis ? 3.Retrospective or prospective case control study ? 4. Sample size calculation lacks details. 5. No multivariate analysis performed . 6. Revise tables for clarity. 7.Improve discussion part about clinical implications. 8.Introduction has become too long. 9. Use Correct tense e.g will be etc ... 10.Page numbers in ref 10 missing Author Response : 1. Clarify when lab tests were collected? Prior to confirmation of sepsis or after blood culture positivity? Response: We thank the reviewer for this important question. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. The values used in this study were routinely collected laboratory data prior to confirmation of sepsis. 2. What about culture-negative clinical sepsis? Response: We sincerely appreciate this insightful comment. In the present study, only culture-proven sepsis cases were included to ensure microbiological confirmation and diagnostic accuracy. Culture-negative clinical sepsis was therefore excluded, which we acknowledge as a limitation of the study. 3. Retrospective or prospective case-control study? Response: The study was conducted as a prospective case–control study. 4. Sample size calculation lacks details. Response: We thank the reviewer for highlighting this point. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024). The largest calculated sample size was selected to ensure adequate statistical power. 5. No multivariate analysis performed. Response: The study was designed as an exploratory analysis using routinely collected laboratory data. Multivariable logistic regression was not performed due to the limited sample size and absence of comprehensive covariate information. A statement acknowledging that multivariable analysis may be explored in future studies has been added to the Discussion. 6. Revise tables for clarity. Response: All tables have been revised for clarity, with clear headings, units, and footnotes to enhance readability and comprehension. 7. Improve discussion part about clinical implications. Response: The Discussion section has been revised and strengthened to better highlight the clinical implications of the study findings. 8. Introduction has become too long. Response: The Introduction has been condensed for improved readability while retaining all essential points and references. 9. Use correct tense e.g., “will be” etc. Response: All relevant sections have been carefully revised for correct tense. 10. Page numbers in reference 10 missing. Response: The reference list has been updated to include the correct page numbers for reference 10. We hope that the revisions made have satisfactorily addressed all concerns and have improved the clarity and readability of the manuscript. Thank you very much for your valuable feedback in improving the standard of study and taking the time to address the areas of improvement in our article. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Avabratha KS. Peer Review Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r442649) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-442649 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 A D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Dec 2025 | for Version 1 Dr Shashidhar A , St John's Medical College Hospital, Bengaluru, Karnataka, India 0 Views copyright © 2025 A D. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Abstract 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- should be only based on the results. Use Mesh terms Main 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 Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Neonatology, spesis I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 23 Feb 2026 Smrithi null, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India We sincerely thank Dr. Shashidhar for taking the time to review our manuscript and provide detailed and constructive feedback. 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. Reviewer report: “Abstract - 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—should be only based on the results. Use MeSH terms.” Author response: 1. Background should clarify the need for the study. Can delete the rest. Response: The Abstract has been revised to clarify the study’s rationale, and unnecessary portions have been removed. 2. Study design to be stated. Give formulae for the indices in methods. Response: The study design has been explicitly stated as a case–control study. The formulae for all inflammatory indices are now included in the Methods. 3. Data should be in results. Response: Significant study data have been appropriately included in the Results section. 4. Avoid overconcluding—should be only based on the results. Response: The conclusion has been revised to ensure that statements are strictly supported by study results. 5. Use MeSH terms. Response: Relevant MeSH terms have been applied to the manuscript keywords. Reviewer report: “Main 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.” Author response: 1. Use STROBE checklist for reporting this observational study throughout. 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. 2. Summary of evidence is too long; should be made crisp and moved to discussion. Response: The summary of evidence has been condensed, with relevant details now included in the Discussion section. 3. Physiological basis of choosing these indices to be quoted. Response: The physiological rationale for selection of the inflammatory indices has now been incorporated in the Methods section. 4. Rationale for sample size should be mentioned. Structure of methods section to be revamped as per author guidelines 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. 5. How were controls chosen given that the yield of culture may be less? 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 [33] . Consecutive eligible preterm neonates meeting these criteria during the study period were included. 6. What method of culture was done and when? 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. 7. Was any matching done? 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. 8. Consent would be required as the controls are being sampled, data collected and planned for publication. Response: As this was a laboratory record–based 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. 9. Study flow is missing. 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. 10. Unclear when the tests were done and in case of multiple values which one were chosen. 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. 11. Results seem to show an association more than prediction. May need additional analysis like multivariate and logistic regression. 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. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern A DS. Peer Review Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r429880) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-429880 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Kumer Dey S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Dec 2025 | for Version 1 Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, Dhaka Division, Bangladesh 0 Views copyright © 2025 Kumer Dey S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? Partly If applicable, is the statistical analysis and its interpretation appropriate? I cannot comment. A qualified statistician is required. Are all the source data underlying the results available to ensure full reproducibility? No Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Neonatal sepsis, IUGR, Neeborn screening, Birth Defect, Online learning I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 23 Feb 2026 Smrithi null, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India We would like to express our gratitude to Dr. Sanjoy Kumer Dey for reviewing our article and offering helpful criticism. We are very grateful for the advice, which has improved our study's scientific rigor, clarity and organization. Each comment is addressed below. Reviewer Report : Sample size calculation needs to be detailed for better understanding. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and control (culture negative). Better to mention where and how investigations were done and who had followed up the babies. Data to be made available. Author Response : 1. Sample size calculation needs to be detailed for better understanding. Response: We thank the reviewer for this suggestion. The sample size calculation has now been described in detail in the Methods section, including the software used (OpenEpi Version 3.01), the variables considered, and the reference study by Zhu et al. (2024), with the largest calculated sample size chosen for the study. 2. A flow chart could explain the total number of preterm newborns enrolled (population), cases (culture positive) and controls (culture negative). Response: We appreciate this recommendation. A study flow diagram has now been added (Figure 1) to illustrate the total number of preterm neonates enrolled, exclusions, and the final allocation into cases (culture positive) and controls (culture negative). In addition, a textual description of the participant flow has been included in the Methods section for clarity. 3. Better to mention where and how investigations were done and who had followed up the babies. Response: Blood cultures were performed using BACTEC system following NICU protocol. Samples were collected aseptically after 24 hours of life and processed according to standard microbiological procedures. Culture positivity defined sepsis cases. As this was a laboratory record–based observational study, no additional clinical follow-up of the neonates was performed; the study utilized only routinely collected laboratory data. 4. Data to be made available. Response: We have included all the relevant data and the underlying findings under the Data Availability Section. We sincerely thank the reviewer once again for their time and valuable 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. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Kumer Dey S. Peer Review Report For: Accuracy of Systemic Inflammatory Indices in identifying Neonatal Sepsis in preterms in a tertiary care hospital in Mangalore [version 2; peer review: 4 approved with reservations, 1 not approved] . F1000Research 2026, 14 :390 ( https://doi.org/10.5256/f1000research.178518.r426933) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-390/v1#referee-response-426933 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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