Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India

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Abstract

Background: Neonatal jaundice is one of the most prevalent conditions during first week of life causing morbidity and even mortality in few, especially in low – middle income countries. Although visual inspection for jaundice has been a time tested method, serum bilirubin is the gold standard investigation of choice. Due to this, newborns receive many heel or vein pricks for testing, hence the transcutaneous bilirubinometer can be a helpful non-invasive tool for diagnosing jaundice requiring phototherapy. Methods This prospective study was carried out in a tertiary care hospital in Mangalore, Karnataka to compare a non invasive method of detecting bilirubin levels and serum bilirubin levels. Performance of a transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine venous serum bilirubin testing before phototherapy during neonatal care in the first two weeks of life. Results were derived by analysing the correlation coefficient between two methods and direct agreement was analysed using Bland Altman analysis. Results Total of 271 neonates (>35 weeks) were included in the study. Transcutaneous bilirubinometry and serum bilirubin values were done on all of them in the first week of life. Correlation analysis showed significant relationship with a Pearson correlation coefficient of 0.629. Values of transcutaneous bilirubinometer showed excellent agreement with venous serum bilirubin concentration in Bland Altman analysis. Conclusions The transcutaneous bilirubinometer is a reliable tool to screen neonates and identify those needing phototherapy there by reducing invasive blood sampling.
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Although visual inspection for jaundice has been a time tested method, serum bilirubin is the gold standard investigation of choice. Due to this, newborns receive many heel or vein pricks for testing, hence the transcutaneous bilirubinometer can be a helpful non-invasive tool for diagnosing jaundice requiring phototherapy. Methods This prospective study was carried out in a tertiary care hospital in Mangalore, Karnataka to compare a non invasive method of detecting bilirubin levels and serum bilirubin levels. Performance of a transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine venous serum bilirubin testing before phototherapy during neonatal care in the first two weeks of life. Results were derived by analysing the correlation coefficient between two methods and direct agreement was analysed using Bland Altman analysis. Results Total of 271 neonates (>35 weeks) were included in the study. Transcutaneous bilirubinometry and serum bilirubin values were done on all of them in the first week of life. Correlation analysis showed significant relationship with a Pearson correlation coefficient of 0.629. Values of transcutaneous bilirubinometer showed excellent agreement with venous serum bilirubin concentration in Bland Altman analysis. Conclusions The transcutaneous bilirubinometer is a reliable tool to screen neonates and identify those needing phototherapy there by reducing invasive blood sampling. " } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/14-403", "name": "Correlation of transcutaneous and serum bilirubin levels in late preterm..." } } ] } Home Browse Correlation of transcutaneous and serum bilirubin levels in late preterm... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Chandranaik D, Zakir S, Kamath L et al. Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.12688/f1000research.162608.3 ) 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 Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] Doreswamy Chandranaik https://orcid.org/0000-0002-5837-0982 1 , Shahla Zakir 1 , Laxmi Kamath https://orcid.org/0000-0002-2379-155X 1 , Nutan Kamath 1 , Suchetha S Rao https://orcid.org/0000-0002-5232-9727 1 Doreswamy Chandranaik https://orcid.org/0000-0002-5837-0982 1 , Shahla Zakir 1 , [...] Laxmi Kamath https://orcid.org/0000-0002-2379-155X 1 , Nutan Kamath 1 , Suchetha S Rao https://orcid.org/0000-0002-5232-9727 1 PUBLISHED 19 Nov 2025 Author details Author details 1 Department of Paediatrics, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India Doreswamy Chandranaik Roles: Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation Shahla Zakir Roles: Investigation, Project Administration Laxmi Kamath Roles: Data Curation, Formal Analysis, Methodology, Project Administration, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Nutan Kamath Roles: Supervision, Validation Suchetha S Rao Roles: Supervision, Validation OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Health Services gateway. This article is included in the Manipal Academy of Higher Education gateway. Abstract Background Neonatal jaundice is one of the most prevalent conditions during first week of life causing morbidity and even mortality in few, especially in low – middle income countries. Although visual inspection for jaundice has been a time tested method, serum bilirubin is the gold standard investigation of choice. Due to this, newborns receive many heel or vein pricks for testing, hence the transcutaneous bilirubinometer can be a helpful non-invasive tool for diagnosing jaundice requiring phototherapy. Methods This prospective study was carried out in a tertiary care hospital in Mangalore, Karnataka to compare a non invasive method of detecting bilirubin levels and serum bilirubin levels. Performance of a transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine venous serum bilirubin testing before phototherapy during neonatal care in the first two weeks of life. Results were derived by analysing the correlation coefficient between two methods and direct agreement was analysed using Bland Altman analysis. Results Total of 271 neonates (>35 weeks) were included in the study. Transcutaneous bilirubinometry and serum bilirubin values were done on all of them in the first week of life. Correlation analysis showed significant relationship with a Pearson correlation coefficient of 0.629. Values of transcutaneous bilirubinometer showed excellent agreement with venous serum bilirubin concentration in Bland Altman analysis. Conclusions The transcutaneous bilirubinometer is a reliable tool to screen neonates and identify those needing phototherapy there by reducing invasive blood sampling. READ ALL READ LESS Keywords Transcutaneous bilirubinometer; bilirubin; correlation analysis; phototherapy; Bland Altman analysis; noninvasive; Neonatal jaundice Corresponding Author(s) Laxmi Kamath ( [email protected] ) Close Corresponding author: Laxmi Kamath Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Chandranaik D 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: Chandranaik D, Zakir S, Kamath L et al. Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.12688/f1000research.162608.3 ) First published: 07 Apr 2025, 14 :403 ( https://doi.org/10.12688/f1000research.162608.1 ) Latest published: 19 Nov 2025, 14 :403 ( https://doi.org/10.12688/f1000research.162608.3 ) Revised Amendments from Version 2 The revised manuscript (version 3) reflects substantial improvements made in response to peer reviewer feedback. There are few changes in the statistical analysis and new table and figures are added wherein the Pearson's corelation coefficient is calculated between transcutaneous bilirubin (TCB) and total serum bilirubin (TSB) for the entire cohort and separately for two gestational group late preterm (35–36 weeks) and term (≥ 37 weeks) to assess consistency across maturities. The difference between TCB and TSB has been plotted against gestational age and hours of life for better understanding. Additionally, the Discussion now includes a detailed review of literature of other studies using different devices and the device in our study. We have also strengthened the manuscript by incorporating additional references to support our findings and ensure alignment with current literature. These revisions aim to enhance the clarity, relevance, and scientific rigor of the study, making it more informative for clinicians and researchers working in similar healthcare settings. The revised manuscript (version 3) reflects substantial improvements made in response to peer reviewer feedback. There are few changes in the statistical analysis and new table and figures are added wherein the Pearson's corelation coefficient is calculated between transcutaneous bilirubin (TCB) and total serum bilirubin (TSB) for the entire cohort and separately for two gestational group late preterm (35–36 weeks) and term (≥ 37 weeks) to assess consistency across maturities. The difference between TCB and TSB has been plotted against gestational age and hours of life for better understanding. Additionally, the Discussion now includes a detailed review of literature of other studies using different devices and the device in our study. We have also strengthened the manuscript by incorporating additional references to support our findings and ensure alignment with current literature. These revisions aim to enhance the clarity, relevance, and scientific rigor of the study, making it more informative for clinicians and researchers working in similar healthcare settings. See the authors' detailed response to the review by Sanjoy Kumer Dey READ REVIEWER RESPONSES Introduction Neonatal hyperbilirubinemia is a prevalent condition in newborns, marked by the appearance of jaundice within the first week after birth. It affects approximately 60% of term neonates and up to 80% of preterm neonates. This condition occurs due to the accumulation of unconjugated bilirubin, a lipid-soluble pigment, in the skin and mucous membranes, leading to a yellowish discolouration. 1 Neonatal hyperbilirubinemia, while generally benign, is commonly seen postnatally in newborns. However, premature neonates and certain high-risk groups are more susceptible to severe forms, which, if not managed, can progress to complications like kernicterus. 2 Neonatal jaundice is clinically identified by a yellowish discolouration of the sclera, skin, and mucous membranes resulting from increased bilirubin levels in the bloodstream. The condition is categorised into two types: Unconjugated Hyperbilirubinemia and Conjugated Hyperbilirubinemia. 3 Phototherapy and exchange transfusion are the primary interventions for the prevention and management of bilirubin encephalopathy. The primary methods for assessing bilirubin levels in newborns include visual inspection, measurement of total serum bilirubin, and transcutaneous bilirubinometry. Visual assessment is simple using Kramer’s rule but has notable limitations, as it is highly subjective; factors such as the physician’s experience, the baby’s skin colour, clothing, and lighting conditions can all influence the accuracy of visual estimation. Total serum bilirubin (TSB) measurement continues to be the gold standard for accurate assessment for monitoring bilirubin levels before and after phototherapy in both term and preterm neonates. However, obtaining blood samples via heel stick or venipuncture is not only painful and time-intensive but also elevates the risk of local and systemic infections, particularly in preterm neonates. Transcutaneous bilirubin (TCB) assessment uses a handheld electronic device to measure bilirubin levels non-invasively on the skin’s surface, providing a painless and convenient method for screening jaundice in term and near-term neonates. The device, Transcutaneous Jaundice Detector (Drager Model MBJ20), utilises optical spectroscopy by emitting light into the skin and analysing the reflected wavelengths to estimate total serum bilirubin levels. It is increasingly accepted in clinical settings due to its simplicity and effectiveness. The National Institute for Health and Care Excellence (NICE) guidelines advise against using transcutaneous bilirubin (TCB) measurements within the first day of life or for neonates born before 35 weeks of gestation. Additionally, despite these limitations, TCB is a non-invasive screening method used to determine the need for phototherapy, and use of TCB can reduce infection risks. 4 In contrast, total serum bilirubin (TSB) measurement involves drawing a blood sample. The blood sample report is plotted on a nomogram, which is hour-specific to assess the neonatal hyperbilirubinemia risk. 2 Although TCB is an established screening method worldwide, its reliability may vary depending on ethnicity, skin pigmentation, hydration status and health system context. 5 , 6 In India, available studies are relatively few 7 , 8 and most are from limited sample sizes. This highlights a research gap, as findings from Western and East Asian populations 9 – 13 cannot always be extrapolated to Indian neonates. Moreover, darker skin pigmentation may affect optical bilirubin detection, 5 underlining the need for region-specific validation. Against this backdrop, our study provides novel data by evaluating TcB in late preterm and term neonates in South India, with a larger sample size and additional analysis of correlation with hours of life and gestational age. This strengthens the evidence base for TcB adoption in resource-limited neonatal units especially southern India. Methods This prospective study was carried out at a tertiary care NICU in a tier 2 city of south India following approval from the Institutional Ethics Committee, Kasturba medical college, Mangalore (Reg No. ECR/541/Inst/KA/2014/RR-20) with approval No IEC KMC MLR 08/2024/543 approved on 21/08/2024. The study is done as per STROBE guidelines for cross-sectional observational study. We adhered to all ethical parameters as per Declaration of Helsinki. The primary objective was to examine the correlation between transcutaneous bilirubin (TCB) and total serum bilirubin (TSB) levels in neonates with jaundice who required phototherapy. The study included 271 neonates admitted to the NICU between August 2024 and December 2024. Both term and preterm neonates (>35 weeks) with clinical jaundice were included, while neonates with major congenital anomalies, skin conditions affecting the forehead or sternum, or those who had already received phototherapy or undergone exchange transfusions were excluded. For each neonate, demographic details, antenatal history, maternal complications, feeding patterns, and clinical examination findings were documented using a structured pro forma. Bilirubin levels were assessed using two methods: 1. Transcutaneous Bilirubin (TCB): Measurements were taken using a Transcutaneous Jaundice Detector (Model MBJ20). Three readings were taken over the mid-sternum or forehead by the duty doctor, and their average was recorded in mg/dL. 2. Total Serum Bilirubin (TSB): Venous blood samples were collected, and TSB levels were measured using standard laboratory methods. Each neonate underwent both TCB and TSB measurements within 15 minutes of each other and the paired values were analysed for correlation. Phototherapy was initiated for most neonates based on visual assessment, while a few were started on phototherapy later, guided by their TSB values. Data was systematically recorded in an Excel sheet. Sample size To detect a mean difference of 0.23 mg/dL between TSB and TCB measurements with a statistical power of 80% and a significance level of p = 0.05, the required sample size was calculated as 271. This value considers the variability in measurements (σ=1.75) and the critical value for a 95% confidence interval (Zα/2=1.96} = 1.96). A design effect of 1.17 was incorporated to account for potential clustering or variability across different population subgroups. This adjustment ensures the study is adequately powered to detect clinically significant differences while maintaining the robustness of the results. This calculation aligns with findings from a previous study, which reported a mean TSB of 8.54 mg/dL and highlighted a standard deviation of 1.75 mg/dL in the average difference between TSB and TCB measurements, with negligible variation by gestational age or ethnicity. These findings provide a reliable basis for estimating the sample size required to achieve statistical validity in detecting the specified mean difference. 14 Statistical analysis Categorical variables were expressed as frequencies and percentages (%), while continuous variables were summarised as means ± standard deviations (SD) and medians with interquartile ranges (25th–75th percentiles). Pearson correlation coefficients were computed between TCB and TSB levels. Additional correlations were analysed separately for hours of life and gestational age to explore potential confounders. To visualise the stability of transcutaneous readings, the difference Δ = (TCB − TSB) was plotted against hours of life. Pearson correlation coefficients were calculated between transcutaneous bilirubin (TCB) and total serum bilirubin (TSB) for the entire cohort and separately for two gestational groups-late preterm (35–36 weeks) and term (≥37 weeks) to assess consistency across maturities. The difference Δ = (TCB − TSB) was plotted against gestational age to evaluate whether measurement bias varied with gestational age. A p < 0.05 was considered statistically significant. Bland-Altman analysis was performed to assess the agreement limits between TCB and TSB. Data entry was completed using Microsoft Excel, and statistical analyses were carried out using SPSS software (version 29). Results A total of 271 neonates requiring phototherapy were included in the study to assess the correlation between transcutaneous bilirubin (TCB) and serum bilirubin (TSB) levels. Among the subjects, 140 (51.66%) were male neonates, and 131 (48.34%) were female neonates. Table 1 provides a summary of the baseline characteristics of the study participants. Table 1. Description of Baseline characteristics. Baseline Characteristics Value (n=271) Mean gestational age (weeks) 38.34 ± 1.43 Mean hours of life at phototherapy (hours) 54.29 ± 27.2 Mean birth weight (kilograms) 2.91 ± 0.44 Male: Female 140:131 (1.06:1) NVD (normal vaginal delivery) 49.07% (133) LSCS (lower segment cesarean section) 50.9% (138) Table 2 outlines the descriptive statistics for transcutaneous bilirubin (TCB) and serum bilirubin (TSB) levels ( Figure 1 ). Table 2. Descriptive statistics of transcutaneous bilirubin and Serum Bilirubin. Variable Mean ± SD Median (25th–75th percentile) Range Transcutaneous bilirubin (mg/dL) 13.2 ± 3.14 13 (11.1–15.85) 2–19 Serum bilirubin (mg/dL) 11.4 ± 2.97 11.3 (9.5–13.5) 2.04–18.7 Figure 1. Box-and-whisker plot showing the median values of TCB and TSB. There was a significant positive correlation between TCB and TSB levels, with a Pearson correlation coefficient of 0.629 ( Table 3 , Figure 2 ). This correlation was statistically significant, with a p-value of <0.0001. Table 3. Correlation of Transcutaneous bilirubin with serum bilirubin: Pearson correlation coefficient. Variables Serum bilirubin (mg/dL) Transcutaneous bilirubin (mg/dL) Pearson Correlation coefficient: 0.629 P value: <0.0001 Figure 2. Correlation of transcutaneous bilirubin (mg/dL) with serum bilirubin (mg/dL). The correlation of TCB and TSB levels with gestational age is summarised in Table 4 . Table 4. Correlation of transcutaneous bilirubin and serum bilirubin with gestational age. Group Gestational range n Mean GA (weeks) r (TCB vs TSB) p value Late preterm 35 – 36 + 6 weeks 42 35.8 ± 0.4 0.612 <0.001 Term ≥ 37 weeks 229 38.6 ± 0.8 0.633 <0.001 Pearson correlation coefficients were calculated between transcutaneous bilirubin (TCB) and total serum bilirubin (TSB) for the entire cohort and separately for two gestational group late preterm (35–36 weeks) and term (≥37 weeks) to assess consistency across maturities. The difference Δ = (TCB − TSB) was plotted against gestational age ( Figure 3 ) to evaluate whether measurement bias varied with gestational age. Figure 3. Correlation of gestational age with difference of transcutaneous bilirubin and ttotal serum bilirubin (mg/dL). The difference between correlation coefficients was statistically nonsignificant (z = 0.19, p > 0.8), indicating that gestational maturity did not significantly alter the relationship between TCB and TSB. We also compared the difference Δ = (TCB − TSB) across gestational ages. The bias remained consistent (+1.81 mg/dL on average) throughout 35–40 weeks, with no visible trend (r = −0.03, p > 0.05). The mean difference (Δ = TCB − TSB) was +1.84 mg/dL in late-preterm infants (35–36 weeks) and +1.79 mg/dL in term infants (≥37 weeks), showing no significant difference between the two groups (p > 0.05). The difference Δ = (TCB − TSB) plotted against hours of life showed that the mean bias of +1.81 mg/dL remained stable throughout the first five days of life (r = 0.08, p > 0.05). This indicates that transcutaneous bilirubin measurements maintained consistent agreement with serum values across the early neonatal period ( Figure 4 ). Figure 4. Correlation of hours of life with difference of transcutaneous bilirubin and total serum bilirubin. The Bland-Altman plot ( Figure 5 ) demonstrates good agreement between TCB and TSB levels, with a mean difference of 1.81 mg/dL between the two values. Figure 5. Bland Altman plot shows good agreement between TCB and TSB with a mean difference of 1.81 mg/dl between the two values. Discussion The use of TCB measurement is increasingly favoured in hospital postnatal wards and neonatal intensive care units (NICUs) due to its ability to provide early detection, prompt intervention, and timely treatment, ultimately reducing neonatal morbidity and mortality associated with neonatal jaundice. However, its widespread adoption remains limited, particularly in developing countries, due to cost concerns and limited data supporting its use. TCB offers a non-invasive, rapid alternative to TSB tests, reducing the need for painful blood draws. This study evaluated whether TCB measurements reliably correlate with TSB levels. Our study found a strong positive correlation between TCB levels and TSB levels. A previous multicentric study by Taylor et al. shows that a correlation of 0.78 was observed, similar to the positive correlation found in our study. The mean difference between TCB and TSB was noted as 0.84 mg/dL, 15 while our findings also showed a close approximation between these two measurements. Surana et al. (2017) reported a strong correlation (r = 0.836) among 160 neonates of varying gestational ages, similar to our findings. 7 In the study by Arasar Seeralar et al., involving 267 neonates, there was a significant correlation between TCB and TSB levels, which aligns closely with our findings. 8 Majid Mansouri et al. 14 have also shown that TCB measurement is a reliable estimate of TSB levels in neonates. These studies support the use of TCB as an effective, non-invasive method for monitoring jaundice in newborns. The strong positive correlation between TCB and TSB levels with hours of life observed in this study is consistent with findings by Rahmawati D et al., a study conducted at Dr Soetomo General Hospital among neonates. 9 A high correlation between TCB and TSB has also been shown among infants of Asian descent, such as Indonesian, 10 Chinese, 11 Japanese, 12 and Myanmar. 13 Plotting Δ (TCB − TSB) against hours of life showed no systematic trend, confirming stable performance of the device during the first five days of life. A few isolated outliers may represent infants with undiagnosed pathological jaundice or dehydration. Stratified analysis revealed that the agreement between TCB and TSB did not differ significantly between late-preterm and term neonates. The absence of systematic change in Δ (TCB − TSB) across 35–40 weeks suggests that gestational maturity does not materially affect the optical accuracy of transcutaneous bilirubinometry. Hence, TCB measurement can be reliably used for screening neonatal hyperbilirubinemia in infants ≥35 weeks in our population. The Bland-Altman analysis in this study demonstrated a mean bias of +1.81 mg/dl, indicating that TcB values tended to be slightly higher than the corresponding TSB values. The 95% limits of agreement ranged from −3.36 mg/dl to +6.97 mg/dl, suggesting that, for most paired measurements, TcB values could be as much as 3.36 mg/dl lower or 6.97 mg/dl higher than TSB. Most data points fell within approximately 5.16 mg/dl of the mean bias, consistent with the calculated limits of agreement. Although the overall mean difference was small, the relatively wide limits indicate that individual discrepancies between TcB and TSB may be clinically significant, particularly at higher bilirubin levels. Previous studies have demonstrated that a mean bias within ±2 mg/dL is considered acceptable for TCB-based screening, as confirmatory serum estimation is routinely performed when readings approach phototherapy thresholds. 1 , 2 , 8 Our observed mean bias of +1.81 mg/dL therefore falls well within this accepted range. Occasionally wider discrepancies between TCB and TSB measurements can be attributed to physiological and optical factors such as skin pigmentation, hydration status, and subcutaneous tissue thickness that influence light reflectance and absorption. Hence, the intended role of TCB is primarily as a screening and triage device , not a diagnostic substitute. A small positive bias is clinically desirable, as it promotes early identification and timely referral of neonates at risk for hyperbilirubinemia. 5 , 8 , 10 When we reviewed literature for other studies with different instruments we found that in a study done by Rubaltelli et al in Japan studied and compared two instruments viz BiliCheck and Minolta Airshields JM 102 with total serum bilirubin at different sites. The correlation coefficients ranged from 0.71 to 0.81, indicating good agreement between TCB and TSB levels. However like in our study they also had few outliers more in Minolta Airshields device. BiliCheck measures TcB by isolating bilirubin absorption from other factors such as hemoglobin and melanin using spectral subtraction. This allows TcB readings that are largely independent of race, gestational age, or birth weight, a finding supported by previous studies. 16 In another study done in Australia by Khajehei et al. JM-105 and MBJ-20 TcB measurements correlated strongly with each other and with serum bilirubin with correlation coefficient of 0.81, slightly overestimating SBR but providing reliable, high-sensitivity readings at lower levels and high-specificity readings at higher levels. In this study they found that chances of overestimating was equally high in both devices as they had relatively high rate of false positives. This interpretation was confirmed in the mean differences and limits of agreement plot which had outliers like in our study. This difference could be due to melanin content or exposed areas having continuous exposure to room light or natural light, which again explained why sternum area was more reliable than forehead. We had checked forehead and sternum area in our study. The few outliers in our study could be due to dark color of the skin in few babies, undiagnosed pathological jaundice, also hydration status of babies could contribute to overestimation in TCB. 17 In another study done by Madubuike et al used the MBJ-20 device to examine neonatal jaundice in 88 Nigerian neonates with gestational ages of 28 to 36 weeks. TcB measurements showed a strong positive linear relationship with TSB, with correlation coefficients of 0.904 for forehead readings and 0.917 for sternum readings, indicating excellent agreement across both sites. They also showed that compared with the forehead measurements, the sternum measurement using the MBJ-20 had greater correlation with the TSB in both preterm and term neonates and is a useful bilirubinometer for estimating TSB levels in neonates. The Bland altman plot analysis in this study although majority of the measurements fell within a 95% confidence interval, signifying strong agreement between the standard laboratory method and the MBJ20 transcutaneous bilirubinometer, also highlighted that the level of imprecision was great with an overestimation of bilirubin value like in our study. Clinical implication of such results is that TCB cannot replace TSB measurements in evaluation of severe jaundice and can only be used as surrogate marker. 18 The rate of cesarean deliveries in our cohort was relatively high compared to reports from Western populations. Our institution serves as a regional perinatal referral center, receiving mothers with complications such as preeclampsia, gestational diabetes, intrauterine growth restriction, and preterm labor, all of which contribute to an increased likelihood of operative delivery. Also, if we see the current obstetric trends in many tertiary-care centers in South India, cesarean delivery rates often range from 35–45%, particularly in referral hospitals that manage high-risk pregnancies. 19 Therefore, the higher cesarean rate observed in this study reflects the high risk obstetric population rather than a bias in sampling. Nevertheless, this should be considered when interpreting the generalizability of our findings to lower-risk or community settings thereby mandating more such studies from different cohorts of our country. In resource-limited settings where the prevalence of prematurity is high, it often leads to prolonged NICU stays and phlebotomy-induced blood loss. Given the challenges of access to advanced laboratory techniques, TCB measurement is a more efficient and less invasive screening tool than visual assessment alone. It is quick, painless, and reliable for early identification of hyperbilirubinemia, reducing the reliance on invasive TSB tests. Regular TCB assessments can effectively guide early intervention, thereby improving neonatal outcomes. The accuracy of TcB is known to be influenced by skin pigmentation, with several studies noting variations across different ethnic populations. 15 , 20 South Indians predominantly belong to the Dravidian ethnic group and typically have darker skin tones compared to North Indian or Caucasian populations. Skin hydration is also another factor which can influence TcB measurements, although this has not yet been extensively studied and validated in literature. 21 Our center is in a coastal region where neonatal dehydration is relatively common. Accordingly, we included invasive serum bilirubin measurement as the reference standard for comparison, prioritizing patient safety and keeping in line with our institutional protocol. While this may appear to increase invasive blood sampling, it provided robust paired data for correlation and Bland–Altman analysis, which is one of the best parameters for external validation. 22 Future multicentric studies in Indian settings should focus on validating TcB at recommended cut-offs, which would allow safe reduction of unnecessary blood sampling. Another limitation is the single-center design, which may limit generalizability, though our results provide important baseline evidence for South India. Conclusions TCB estimation is a valuable non-invasive screening method for detecting neonatal hyperbilirubinemia. Its simplicity, rapid results, and ability to minimise painful blood sampling make it an excellent tool for monitoring jaundice in neonates, especially in settings with limited resources. This method can aid in timely identification and management, thus reducing morbidity associated with severe hyperbilirubinemia. Ethics and consent This prospective study was carried out at a tertiary care NICU in a tier 2 city of south India following approval from the Institutional Ethics Committee, Kasturba medical college, Mangalore (Reg No. ECR/541/Inst/KA/2014/RR-20) with approval No IEC KMC MLR 08/2024/543 approved on 21/08/2024. The study is done as per STROBE guidelines for cross-sectional observational study. We adhered to all ethical parameters as per Declaraion of Helsinki. Written informed consent was taken from parents of newborns (mother or father). Data availability Figshare: CORRELATION OF TRANSCUTANEOUS AND SERUM BILIRUBIN LEVELS IN LATE PRETERM AND TERM NEONATES AT A TERTIARY CARE CENTER IN SOUTH INDIA. https://doi.org/10.6084/m9.figshare.28514285.v3 . 23 The project contains the following underlying data: 1. TCB EXCEL sheet. xlsx 2. consent form of TCB study.docx Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). Acknowledgments We are thankful to the department faculty and our patients. Without their support, this study would not have been possible. References 1. Kantroo S, Shakuntal G, Gode V: Correlation between transcutaneous bilirubin levels and total serum bilirubin levels in the postnatal period in a tertiary care center. Int J Contemp Pediatr. 2023; 10 : 272–274. Publisher Full Text 2. Sharma AK, Dhawan K, Makkar M, et al. : A correlation study between transcutaneous bilirubin and total serum bilirubin levels among neonates. Asian J Pharm Clin Res. 2022; 10 (3): 272–274. Publisher Full Text 3. Jegathesan T, Campbell DM, Ray JG, et al. : Transcutaneous versus total serum bilirubin measurements in preterm infants. Neonatology. 2021; 118 (4): 443–453. PubMed Abstract | Publisher Full Text 4. Raba AA, O’Sullivan A, Miletin J: Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study. BMJ Paediatr Open. 2020; 4 (1): e000681. PubMed Abstract | Publisher Full Text | Free Full Text 5. Dam-Vervloet AJ, Morsink CF, Krommendijk ME, et al. : Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation. Pediatr Res. 2025 Apr; 97 (5):1706–1710. PubMed Abstract | Publisher Full Text | Free Full Text 6. van Erk MD , Dam-Vervloet AJ, de Boer FA , et al. : How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation. Pediatr Res. 2019 Oct; 86 (4):471–477. PubMed Abstract | Publisher Full Text | Free Full Text 7. Surana AU, Patel S, Prasad R, et al. : Comparison of transcutaneous bilirubin with serum bilirubin measurements in neonates at a tertiary care center in the western part of India. Int J Contemp Pediatr. 2017; 4 : 1445–1449. Publisher Full Text 8. Arasar Seeralar AT, Ganesh J, Suganya M, et al. : Correlation between transcutaneous and serum bilirubin measurements in neonates in a tertiary neonatal care center. Int J Contemp Med Res. 2016; 10 (8): 272–274. Publisher Full Text 9. Rahmawati D, Sampurna MTA, Etika R, et al. : Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates. F1000Res. 2020; 9 : 300. PubMed Abstract | Publisher Full Text | Free Full Text 10. Rohsiswatmo R, Oswari H, Amandito R, et al. : Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr. 2018; 18 : 315. PubMed Abstract | Publisher Full Text | Free Full Text 11. Ho EY, Lee SY, Chow CB, et al. : BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice in the Chinese population. Hong Kong Med J. 2006; 12 (2): 99–102. Accessed August 20, 2024. PubMed Abstract Reference Source 12. Yamana K, Morioka I, Kurokawa D, et al. : Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns. Pediatr Int. 2017; 59 : 1058–1063. PubMed Abstract | Publisher Full Text 13. Yasuda S, Suzuki H, Htun Y, et al. : Hour-specific nomogram for transcutaneous bilirubin in newborns in Myanmar. Pediatr Int. 2020; 62 : 1049–1053. PubMed Abstract | Publisher Full Text 14. Mansouri M, Mahmoodnejad A, Taghizadeh Sarvestani R, et al. : A comparison between transcutaneous bilirubin and total serum bilirubin measurements in term neonates. J Pediatr Perspect. 2015; 3 (3.1): 633–641. Publisher Full Text 15. Taylor JA, Burgos AE, Flaherman V, et al. : Discrepancies between transcutaneous and serum bilirubin measurements. Pediatrics. 2015; 135 (2): 224–231. PubMed Abstract | Publisher Full Text | Free Full Text 16. Rubaltelli FF, Gourley GR, Loskamp N, et al. : Transcutaneous bilirubin measurement: a multicenter evaluation of a new device. Pediatrics. 2001 Jun 1; 107 (6): 1264–1271. Publisher Full Text 17. Khajehei M, Chua SC, Gidaszewski B, et al. : Comparing JM-105 and MBJ-20 transcutaneous bilirubinometers according to the area tested in ethnically diverse late-preterm and term neonates. J Perinat Neonatal Nurs. 2021 Jul 1; 35 (3): E30–E37. Publisher Full Text 18. Madubuike C, Ugochukwu EF, Ezeanosike O, et al. : Evaluation of MBJ20 ® Transcutaneous Bilirubinometer in the assessement of severity of neonatal jaundice. Int J Neonatal Screen. 2016 Oct 19; 2 (4): 8. Publisher Full Text 19. Singh M, Singh A, Gupta J: Exploring Cesarean Section Delivery Patterns in South India: A Bayesian Multilevel and Geospatial analysis of Population-Based Cross-Sectional Data. BMC Public Health. 2024 Sep 16; 24 (1): 2514. Publisher Full Text 20. Maya-Enero S, Candel-Pau J, Garcia-Garcia J, et al. : Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own. Eur J Pediatr. 2021 Feb; 180 (2):607–616. PubMed Abstract | Publisher Full Text 21. Ercan Ş, Özgün G: The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population. Clin Biochem. 2018 May; 55 (55):69–74. Publisher Full Text 22. Krobath DM, Naumova EN, Cuevas AG, et al. : Use of Bland-Altman Analysis to Examine the Racial and Ethnic Representativeness of Study Populations in Community-Based Pediatric Health Research. JAMA Netw Open. 2023 May 1; 6 (5):e2312920. PubMed Abstract | Publisher Full Text | Free Full Text 23. Kamath L, Chandranaik D: TCB EXCEL sheet. and consent form. Dataset. figshare. 2025. Publisher Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 07 Apr 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Paediatrics, Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Manipal, India Doreswamy Chandranaik Roles: Formal Analysis, Investigation, Methodology, Project Administration, Supervision, Writing – Original Draft Preparation Shahla Zakir Roles: Investigation, Project Administration Laxmi Kamath Roles: Data Curation, Formal Analysis, Methodology, Project Administration, Supervision, Validation, Writing – Original Draft Preparation, Writing – Review & Editing Nutan Kamath Roles: Supervision, Validation Suchetha S Rao Roles: Supervision, Validation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (3) version 3 Revised Published: 19 Nov 2025, 14:403 https://doi.org/10.12688/f1000research.162608.3 version 2 Revised Published: 02 Sep 2025, 14:403 https://doi.org/10.12688/f1000research.162608.2 version 1 Published: 07 Apr 2025, 14:403 https://doi.org/10.12688/f1000research.162608.1 Copyright © 2025 Chandranaik D 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 Chandranaik D, Zakir S, Kamath L et al. Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.12688/f1000research.162608.3 ) 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 3 VERSION 3 PUBLISHED 19 Nov 2025 Revised Views 0 Cite How to cite this report: Shapiro A. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.191336.r434251 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v3#referee-response-434251 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 28 Dec 2025 Alyssa Shapiro , The George Washington University, Washington, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.191336.r434251 The authors have made significant changes to the manuscript which I think make the results easy to interpret and the discussion very well written. I have a few minor additional comments, but I would say that once these are addressed, ... Continue reading READ ALL The authors have made significant changes to the manuscript which I think make the results easy to interpret and the discussion very well written. I have a few minor additional comments, but I would say that once these are addressed, then this manuscript is ready for indexing. Abstract – The Abstract lists the brand of TCB device as Drager JM-105; could you please change this to Drager MBJ20 to reflect what is written in the body? Introduction – Where you say “Additionally, despite these limitations,” I might instead just say “Despite these limitations,” Introduction- The intent of my previous comment on the Introduction was to rearrange the content in order to improve flow. You start with Jaundice in general, then talk about Visual Inspection and TSB, and then next go into detail about TCB, and where your study addresses a research gap with TCB. With that in mind, this second short paragraph about TSB could either be moved or deleted: “In contrast, total serum bilirubin (TSB) measurement involves drawing a blood sample… hyperbilirubinemia risk.” Were all TCB and TSB pairs completed before phototherapy treatment was initiated? The Methods section states the criteria for starting phototherapy, but not the timing. Is possible that phototherapy treatment itself, started before TSB and/or TCB, could have an effects on the bilirubin readings by both methods. I personally disagree with this statement: “A small positive bias is clinically desirable, as it promotes early identification and timely referral of neonates at risk of hyperbilirubinemia.” I might instead make the following statement as my own opinion, “It is helpful for South Indian clinicians to be aware that the that the Drager MBJ20 TCB has a small positive bias in South Indian populations, because this gives clinicians helpful information to interpret TCB results accordingly when making decisions about individual patients.” However, I leave it up to the authors to leave their writing as is, or modify it if they would like, as I think the readers have the information needed to come to their own conclusions. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Bioengineering, Jaundice 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Shapiro A. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.191336.r434251 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v3#referee-response-434251 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 2 VERSION 2 PUBLISHED 02 Sep 2025 Revised Views 0 Cite How to cite this report: Shapiro A. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.187250.r420926 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v2#referee-response-420926 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 11 Oct 2025 Alyssa Shapiro , The George Washington University, Washington, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.187250.r420926 This article evaluated the accuracy of the Drager model MBJ20 transcutaneous bilirubin (TCB) compared to standard total serum bilirubin measurement in South India. This is an important research question, as TCB measurement provides a low-cost, noninvasive alternative to blood sampling, ... Continue reading READ ALL This article evaluated the accuracy of the Drager model MBJ20 transcutaneous bilirubin (TCB) compared to standard total serum bilirubin measurement in South India. This is an important research question, as TCB measurement provides a low-cost, noninvasive alternative to blood sampling, and South India - like many LMICs - are underrepresented in many research studies including those evaluating TCB accuracy. TCB performance is known to be population-dependent and can especially vary in darker skin tones. The authors mention that there are darker skin tones in South Indian populations along with frequent dehydration, both of which can affect TCB performance. The research methods presented here are well done. Below are some suggestions that can further improve the manuscript. Major suggestions: In the Statistical Analysis section, what is meant by “accounting for hours of life and gestational age”? I believe that Figure 3 and Table 4 address hours of life, correct? I was confused by Figure 3, because the TCB increase in the first five days of life is known to vary greatly among individual newborns due to gestational age and risk factors. For example, if a newborn has pathological jaundice (for example, due to hemolytic anemia) rather than physiological jaundice, the rate of bilirubin increase is much higher. I think that if you are looking to show the utility of the TCB throughout the first five days of life, one possibility could be to show “TCB-TSB” on the Y axis, compared to “Hours of life” on the X axis. Likewise, in Table 4, I found it confusing to do a direct correlation of TCB to gestational age. I would recommend instead doing 1) Pearson correlation coefficient of TCB and TSB, for two groups, one of term newborns and one of preterm newborns, then compare those two correlation coefficients, or 2) Compare “TCB – TSB” vs gestational age (perhaps a graph like Figure 2), and show that this difference does not change drastically for different gestational ages. I see that your Result is that there is a mean bias of +1.81 mg/dL, and the 95% limits of agreement are -3.36 – 6.97. Your Conclusion is that the there is good agreement between TCB and TSB levels. I personally disagree with your Conclusion; or rather, to me it’s a bit concerning that there is this mean bias and also that many individual data points show a huge difference between TCB and TSB (for example, TCB of around 16 when TSB is around 5). However, your results do align quite well with other studies that evaluate TCB vs. TSB, so I’m not doubting the accuracy of your results, only your interpretation of them. I would suggest adding some text in the Discussion along those lines. Or rather, could you please further elaborate about why you conclude that the agreement is good? Related to the previous statement, I would suggest commenting further on how your results compare to other studies evaluating both TCB in general, as well as the Drager model MBJ20 in particular. References 7-15 are a good start; what were their Pearson’s values? Which brand of TCB device did they use? Did they also have some measurements with such a large difference between TSB and TCB? Can you include some other references that specifically evaluate the MBJ20? Could you please comment on why some individual measurements may have such a discrepancy (for example, TCB around 16 when TSB is around 5)? Did these newborns have particular pre-existing conditions? Were they preterm newborns? Do you have some theories as to why you found a positive overestimation (+1.81 mg/dL) in your study? Do you think it’s related to the darker skin tones of your population? If so, could you comment further on this in the Discussion? Minor suggestions: Could you please briefly clarify that all measurements were taken before phototherapy began? Also, how was it determined that neonates required phototherapy? (Via visual inspection?) Most data points fell within +/- 1.96 times the SD of the difference between TSB and TcB values --- I would remove this statement, as by definition, 95% data points on a Bland-Altman plot will fall within +/- 1.96 SD. I would instead modify this statement to say something like, ‘Most data points fell within 5.16 mg/dL of the mean bias’. Could you be more specific about how much time had passed between TCB and TSB measurements? You say ‘at the same time’; could you instead say something like ‘within 30 minutes of each other,’ ‘within 15 minutes of each other,’ etc? The C-section rate is quite high. Could you please comment on whether this is an expected finding? Perhaps this is normal in south India, but American authors might be surprised and curious about this. If this reflect that this hospital sees a higher-risk population than the general population, that might affect the generalizability of your findings (which you have already commented on in the Discussion). Minor suggestions to improve the English writing: (Overall the English & writing were good): Abstract: One of the most prevalent condition --> one of the most prevalent conditions Due to this newborn receive many heel or vein pricks for testing, hence transcutaneous bilirubinometer can --> Due to this, newborns receive many heel or vein pricks for testing, hence the transcutaneous bilirubinometer can Introduction: “The primary methods for assessing bilirubin levels in newborns include visual inspection, transcutaneous bilirubinometry, and measurement of total serum bilirubin. Visual assessment is simple using Kramer’s rule but has notable limitations, as it is highly subjective; factors such as the physician's experience, the baby's skin colour, clothing, and lighting conditions can all influence the accuracy of visual estimation. Transcutaneous bilirubinometry provides a non-invasive alternative, whereas total serum bilirubin measurement continues to be the gold standard for accurate assessment. Requiring a blood sample for confirmation, especially in high-risk cases. Transcutaneous bilirubin (TCB) assessment uses a handheld electronic device to measure bilirubin levels non-invasively on the skin's surface, providing a painless and convenient method for screening jaundice in term and near-term neonates. It is increasingly accepted in clinical settings due to its simplicity and effectiveness. The device, Transcutaneous Jaundice Detector (Drager Model MBJ20). utilises optical spectroscopy by emitting light into the skin and analysing the reflected wavelengths to estimate total serum bilirubin levels. This method offers a reliable alternative for early jaundice detection without requiring blood draws. 4 ” --> “The primary methods for assessing bilirubin levels in newborns include visual inspection, measurement of total serum bilirubin, and transcutaneous bilirubinometry. Visual assessment is simple using Kramer’s rule but has notable limitations, as it is highly subjective; factors such as the physician's experience, the baby's skin colour, clothing, and lighting conditions can all influence the accuracy of visual estimation. Total serum bilirubin (TSB) measurement continues to be the gold standard for accurate assessment for monitoring bilirubin levels before and after phototherapy in both term and preterm neonates. However, obtaining blood samples via heel stick or venipuncture is not only painful and time-intensive but also elevates the risk of local and systemic infections, particularly in preterm neonates. Transcutaneous bilirubin (TCB) assessment uses a handheld electronic device to measure bilirubin levels non-invasively on the skin's surface, providing a painless and convenient method for screening jaundice in term and near-term neonates. The device, Transcutaneous Jaundice Detector (Drager Model MBJ20). utilises optical spectroscopy by emitting light into the skin and analysing the reflected wavelengths to estimate total serum bilirubin levels. It is increasingly accepted in clinical settings due to its simplicity and effectiveness. The National Institute for Health and Care Excellence (NICE) guidelines advise against using transcutaneous bilirubin (TCB) measurements within the first day of life or for neonates born before 35 weeks of gestation. Additionally, Despite these limitations, TCB is a non-invasive screening method used to determine the need for phototherapy, and use of TCB can reduce infection risks. ^This is one quick possibility of rearranging the Introduction to reduce repetitive sentences and incomplete sentences, as well as to keep all the TSB info together and TCB info together. Sample Size: A design effect 1.17 --> A design effect of 1.17 Discussion: A previous multicentric study by James A. et al. shows a correlation of 0.78 was observed, similar to the positive correlation found in our study. --> A previous multicentric study by Taylor et al. shows that a correlation of 0.78 was observed, similar to the positive correlation found in our study. Which is one of the best parameter for external validation --> Which is one of the best parameters for external validation 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? Yes 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: Bioengineering, Jaundice 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 Shapiro A. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.187250.r420926 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v2#referee-response-420926 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: Kumer Dey S. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.187250.r411195 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v2#referee-response-411195 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 19 Sep 2025 Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Approved VIEWS 0 https://doi.org/10.5256/f1000research.187250.r411195 Thanks for allowing me to review again. I’ve ... Continue reading READ ALL Thanks for allowing me to review again. I’ve gone through it it seems all comments have been addressed Competing Interests: No competing interests were disclosed. Reviewer Expertise: neonatal health 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Kumer Dey S. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.187250.r411195 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v2#referee-response-411195 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 07 Apr 2025 Views 0 Cite How to cite this report: Kumer Dey S. Reviewer Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.178836.r395736 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v1#referee-response-395736 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 22 Aug 2025 Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.178836.r395736 It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information ... Continue reading READ ALL It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article. From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically. 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? 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: neonatal health 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: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.178836.r395736 ) The direct URL for this report is: https://f1000research.com/articles/14-403/v1#referee-response-395736 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 10 Sep 2025 laxmi kamath , Pediatrics, Kasturba medical college Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal,576104, India, India 10 Sep 2025 Author Response Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. ... Continue reading Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. Comment 1: “It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article.” Response: We agree with the reviewer. While TcB is indeed an established screening tool, its performance may vary by ethnicity, skin pigmentation, hydration status and healthcare context. Data from India remain relatively limited, with only a few published studies¹-², often with smaller sample sizes. By contrast, most validation studies have been conducted in Western or East Asian populations³⁻⁷, which cannot always be extrapolated to the Indian subcontinent. To address this, we have added a new paragraph in the Introduction (Version 2) highlighting the research gap and rationale. The novelty of our work lies in: Providing one of the larger single-center datasets from South India (n=271) evaluating TcB against TSB. Assessing TcB correlation not only with TSB but also with hours of life and gestational age, which adds clinically relevant insight. Generating population-specific evidence in darker-skinned neonates, thereby strengthening the case for wider adoption of TcB in Indian neonatal practice. Comment 2: “From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically.” Response: We acknowledge this important ethical concern. International guidelines suggest using TcB thresholds to decide when TSB is required⁸⁻⁹. However, at the time of our study TcB was not validated in our population and was not part of routine NICU practice. The accuracy of TcB is known to be influenced by skin pigmentation, with several studies noting variations across different ethnic populations. 10,11 Since South Indians predominantly belong to the Dravidian ethnic group and typically have darker skin tones compared to North Indian or Caucasian populations, we aimed to evaluate the reliability of TcB in this group. Skin hydration is also another factor which can influence TcB measurements, although this has not yet been extensively studied and validated in the literature. 12,13 Our center is in a coastal region where neonatal dehydration is relatively common. Accordingly, we included invasive serum bilirubin measurement as the reference standard for comparison, prioritizing patient safety and keeping in line with our institutional protocol. This allowed us to generate paired TcB–TSB data for direct correlation and Bland–Altman analysis, which is one of the best parameter for external validation. 14 We agree that a future step would be to validate TcB specifically at recommended cut-offs in Indian neonates, which would reduce unnecessary blood sampling. To clarify this, we have added a new paragraph in the Discussion (Version 2) explicitly addressing this ethical aspect and acknowledging the limitation. The findings from our study may offer valuable insights for pediatricians and neonatologists working in similar coastal environments and resource-limited settings. Comment 3: “Is the work clearly and accurately presented and does it cite the current literature? – Partly.” Response: We have now strengthened the Introduction and Discussion with additional references already cited in our paper¹⁻⁷ to better contextualized our findings and support the novelty. This addresses the reviewer’s concern and ensures alignment with existing literature. References: Surana AU, Patel S, Prasad R, et al. Comparison of transcutaneous bilirubin with serum bilirubin measurements in neonates at a tertiary care center in the western part of India. Int J Contemp Pediatr . 2017;4:1445–3283. Arasar Seeralar AT, Ganesh J, Suganya M, et al. Correlation between transcutaneous and serum bilirubin measurements in neonates in a tertiary neonatal care center. Int J Contemp Med Res . 2016;10(8):272–274. Rahmawati D, Sampurna MTA, Etika R, et al. Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates. F1000Res . 2020;9:300. Rohsiswatmo R, Oswari H, Amandito R, et al. Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr . 2018;18:315. Ho EY, Lee SY, Chow CB, et al. BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice in the Chinese population. Hong Kong Med J . 2006;12(2):99–102. Yamana K, Morioka I, Kurokawa D, et al. Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns. Pediatr Int . 2017;59:1058–1063. Yasuda S, Suzuki H, Htun Y, et al. Hour-specific nomogram for transcutaneous bilirubin in newborns in Myanmar. Pediatr Int . 2020;62:1049–1053. Sharma AK, Dhawan K, Makkar M, et al. A correlation study between transcutaneous bilirubin and total serum bilirubin levels among neonates. Asian J Pharm Clin Res . 2022;10(3):272–274. Raba AA, O'Sullivan A, Miletin J. Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study. BMJ Paediatr Open . 2020;4(1):e000681. Dam-Vervloet AJ, Morsink CF, Krommendijk ME, Nijholt IM, van Straaten HL, Poot L, Bosschaart N. Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation. Pediatric Research. 2025 Apr;97(5):1706-10. Maya-Enero S, Candel-Pau J, Garcia-Garcia J, Duran-Jordà X, López-Vílchez MÁ. Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own. European Journal of Pediatrics. 2021 Feb;180(2):607-16. van Erk MD, Dam-Vervloet AJ, de Boer FA, Boomsma MF, Straaten HV, Bosschaart N. How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation. Pediatric research. 2019 Oct;86(4):471-7. Ercan Ş, Özgün G. The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population. Clinical biochemistry. 2018 May 1;55:69-74. Krobath DM, Naumova EN, Cuevas AG, Sacheck JM, Wilson NL, Economos CD. Use of Bland-Altman Analysis to Examine the Racial and Ethnic Representativeness of Study Populations in Community-Based Pediatric Health Research. JAMA network open. 2023 May 1;6(5):e2312920-. Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. Comment 1: “It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article.” Response: We agree with the reviewer. While TcB is indeed an established screening tool, its performance may vary by ethnicity, skin pigmentation, hydration status and healthcare context. Data from India remain relatively limited, with only a few published studies¹-², often with smaller sample sizes. By contrast, most validation studies have been conducted in Western or East Asian populations³⁻⁷, which cannot always be extrapolated to the Indian subcontinent. To address this, we have added a new paragraph in the Introduction (Version 2) highlighting the research gap and rationale. The novelty of our work lies in: Providing one of the larger single-center datasets from South India (n=271) evaluating TcB against TSB. Assessing TcB correlation not only with TSB but also with hours of life and gestational age, which adds clinically relevant insight. Generating population-specific evidence in darker-skinned neonates, thereby strengthening the case for wider adoption of TcB in Indian neonatal practice. Comment 2: “From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically.” Response: We acknowledge this important ethical concern. International guidelines suggest using TcB thresholds to decide when TSB is required⁸⁻⁹. However, at the time of our study TcB was not validated in our population and was not part of routine NICU practice. The accuracy of TcB is known to be influenced by skin pigmentation, with several studies noting variations across different ethnic populations. 10,11 Since South Indians predominantly belong to the Dravidian ethnic group and typically have darker skin tones compared to North Indian or Caucasian populations, we aimed to evaluate the reliability of TcB in this group. Skin hydration is also another factor which can influence TcB measurements, although this has not yet been extensively studied and validated in the literature. 12,13 Our center is in a coastal region where neonatal dehydration is relatively common. Accordingly, we included invasive serum bilirubin measurement as the reference standard for comparison, prioritizing patient safety and keeping in line with our institutional protocol. This allowed us to generate paired TcB–TSB data for direct correlation and Bland–Altman analysis, which is one of the best parameter for external validation. 14 We agree that a future step would be to validate TcB specifically at recommended cut-offs in Indian neonates, which would reduce unnecessary blood sampling. To clarify this, we have added a new paragraph in the Discussion (Version 2) explicitly addressing this ethical aspect and acknowledging the limitation. The findings from our study may offer valuable insights for pediatricians and neonatologists working in similar coastal environments and resource-limited settings. Comment 3: “Is the work clearly and accurately presented and does it cite the current literature? – Partly.” Response: We have now strengthened the Introduction and Discussion with additional references already cited in our paper¹⁻⁷ to better contextualized our findings and support the novelty. This addresses the reviewer’s concern and ensures alignment with existing literature. References: Surana AU, Patel S, Prasad R, et al. Comparison of transcutaneous bilirubin with serum bilirubin measurements in neonates at a tertiary care center in the western part of India. Int J Contemp Pediatr . 2017;4:1445–3283. Arasar Seeralar AT, Ganesh J, Suganya M, et al. Correlation between transcutaneous and serum bilirubin measurements in neonates in a tertiary neonatal care center. Int J Contemp Med Res . 2016;10(8):272–274. Rahmawati D, Sampurna MTA, Etika R, et al. Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates. F1000Res . 2020;9:300. Rohsiswatmo R, Oswari H, Amandito R, et al. Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr . 2018;18:315. Ho EY, Lee SY, Chow CB, et al. BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice in the Chinese population. Hong Kong Med J . 2006;12(2):99–102. Yamana K, Morioka I, Kurokawa D, et al. Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns. Pediatr Int . 2017;59:1058–1063. Yasuda S, Suzuki H, Htun Y, et al. Hour-specific nomogram for transcutaneous bilirubin in newborns in Myanmar. Pediatr Int . 2020;62:1049–1053. Sharma AK, Dhawan K, Makkar M, et al. A correlation study between transcutaneous bilirubin and total serum bilirubin levels among neonates. Asian J Pharm Clin Res . 2022;10(3):272–274. Raba AA, O'Sullivan A, Miletin J. Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study. BMJ Paediatr Open . 2020;4(1):e000681. Dam-Vervloet AJ, Morsink CF, Krommendijk ME, Nijholt IM, van Straaten HL, Poot L, Bosschaart N. Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation. Pediatric Research. 2025 Apr;97(5):1706-10. Maya-Enero S, Candel-Pau J, Garcia-Garcia J, Duran-Jordà X, López-Vílchez MÁ. Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own. European Journal of Pediatrics. 2021 Feb;180(2):607-16. van Erk MD, Dam-Vervloet AJ, de Boer FA, Boomsma MF, Straaten HV, Bosschaart N. How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation. Pediatric research. 2019 Oct;86(4):471-7. Ercan Ş, Özgün G. The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population. Clinical biochemistry. 2018 May 1;55:69-74. Krobath DM, Naumova EN, Cuevas AG, Sacheck JM, Wilson NL, Economos CD. Use of Bland-Altman Analysis to Examine the Racial and Ethnic Representativeness of Study Populations in Community-Based Pediatric Health Research. JAMA network open. 2023 May 1;6(5):e2312920-. Competing Interests: nil Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 10 Sep 2025 laxmi kamath , Pediatrics, Kasturba medical college Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal,576104, India, India 10 Sep 2025 Author Response Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. ... Continue reading Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. Comment 1: “It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article.” Response: We agree with the reviewer. While TcB is indeed an established screening tool, its performance may vary by ethnicity, skin pigmentation, hydration status and healthcare context. Data from India remain relatively limited, with only a few published studies¹-², often with smaller sample sizes. By contrast, most validation studies have been conducted in Western or East Asian populations³⁻⁷, which cannot always be extrapolated to the Indian subcontinent. To address this, we have added a new paragraph in the Introduction (Version 2) highlighting the research gap and rationale. The novelty of our work lies in: Providing one of the larger single-center datasets from South India (n=271) evaluating TcB against TSB. Assessing TcB correlation not only with TSB but also with hours of life and gestational age, which adds clinically relevant insight. Generating population-specific evidence in darker-skinned neonates, thereby strengthening the case for wider adoption of TcB in Indian neonatal practice. Comment 2: “From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically.” Response: We acknowledge this important ethical concern. International guidelines suggest using TcB thresholds to decide when TSB is required⁸⁻⁹. However, at the time of our study TcB was not validated in our population and was not part of routine NICU practice. The accuracy of TcB is known to be influenced by skin pigmentation, with several studies noting variations across different ethnic populations. 10,11 Since South Indians predominantly belong to the Dravidian ethnic group and typically have darker skin tones compared to North Indian or Caucasian populations, we aimed to evaluate the reliability of TcB in this group. Skin hydration is also another factor which can influence TcB measurements, although this has not yet been extensively studied and validated in the literature. 12,13 Our center is in a coastal region where neonatal dehydration is relatively common. Accordingly, we included invasive serum bilirubin measurement as the reference standard for comparison, prioritizing patient safety and keeping in line with our institutional protocol. This allowed us to generate paired TcB–TSB data for direct correlation and Bland–Altman analysis, which is one of the best parameter for external validation. 14 We agree that a future step would be to validate TcB specifically at recommended cut-offs in Indian neonates, which would reduce unnecessary blood sampling. To clarify this, we have added a new paragraph in the Discussion (Version 2) explicitly addressing this ethical aspect and acknowledging the limitation. The findings from our study may offer valuable insights for pediatricians and neonatologists working in similar coastal environments and resource-limited settings. Comment 3: “Is the work clearly and accurately presented and does it cite the current literature? – Partly.” Response: We have now strengthened the Introduction and Discussion with additional references already cited in our paper¹⁻⁷ to better contextualized our findings and support the novelty. This addresses the reviewer’s concern and ensures alignment with existing literature. References: Surana AU, Patel S, Prasad R, et al. Comparison of transcutaneous bilirubin with serum bilirubin measurements in neonates at a tertiary care center in the western part of India. Int J Contemp Pediatr . 2017;4:1445–3283. Arasar Seeralar AT, Ganesh J, Suganya M, et al. Correlation between transcutaneous and serum bilirubin measurements in neonates in a tertiary neonatal care center. Int J Contemp Med Res . 2016;10(8):272–274. Rahmawati D, Sampurna MTA, Etika R, et al. Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates. F1000Res . 2020;9:300. Rohsiswatmo R, Oswari H, Amandito R, et al. Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr . 2018;18:315. Ho EY, Lee SY, Chow CB, et al. BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice in the Chinese population. Hong Kong Med J . 2006;12(2):99–102. Yamana K, Morioka I, Kurokawa D, et al. Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns. Pediatr Int . 2017;59:1058–1063. Yasuda S, Suzuki H, Htun Y, et al. Hour-specific nomogram for transcutaneous bilirubin in newborns in Myanmar. Pediatr Int . 2020;62:1049–1053. Sharma AK, Dhawan K, Makkar M, et al. A correlation study between transcutaneous bilirubin and total serum bilirubin levels among neonates. Asian J Pharm Clin Res . 2022;10(3):272–274. Raba AA, O'Sullivan A, Miletin J. Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study. BMJ Paediatr Open . 2020;4(1):e000681. Dam-Vervloet AJ, Morsink CF, Krommendijk ME, Nijholt IM, van Straaten HL, Poot L, Bosschaart N. Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation. Pediatric Research. 2025 Apr;97(5):1706-10. Maya-Enero S, Candel-Pau J, Garcia-Garcia J, Duran-Jordà X, López-Vílchez MÁ. Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own. European Journal of Pediatrics. 2021 Feb;180(2):607-16. van Erk MD, Dam-Vervloet AJ, de Boer FA, Boomsma MF, Straaten HV, Bosschaart N. How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation. Pediatric research. 2019 Oct;86(4):471-7. Ercan Ş, Özgün G. The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population. Clinical biochemistry. 2018 May 1;55:69-74. Krobath DM, Naumova EN, Cuevas AG, Sacheck JM, Wilson NL, Economos CD. Use of Bland-Altman Analysis to Examine the Racial and Ethnic Representativeness of Study Populations in Community-Based Pediatric Health Research. JAMA network open. 2023 May 1;6(5):e2312920-. Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. Comment 1: “It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article.” Response: We agree with the reviewer. While TcB is indeed an established screening tool, its performance may vary by ethnicity, skin pigmentation, hydration status and healthcare context. Data from India remain relatively limited, with only a few published studies¹-², often with smaller sample sizes. By contrast, most validation studies have been conducted in Western or East Asian populations³⁻⁷, which cannot always be extrapolated to the Indian subcontinent. To address this, we have added a new paragraph in the Introduction (Version 2) highlighting the research gap and rationale. The novelty of our work lies in: Providing one of the larger single-center datasets from South India (n=271) evaluating TcB against TSB. Assessing TcB correlation not only with TSB but also with hours of life and gestational age, which adds clinically relevant insight. Generating population-specific evidence in darker-skinned neonates, thereby strengthening the case for wider adoption of TcB in Indian neonatal practice. Comment 2: “From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically.” Response: We acknowledge this important ethical concern. International guidelines suggest using TcB thresholds to decide when TSB is required⁸⁻⁹. However, at the time of our study TcB was not validated in our population and was not part of routine NICU practice. The accuracy of TcB is known to be influenced by skin pigmentation, with several studies noting variations across different ethnic populations. 10,11 Since South Indians predominantly belong to the Dravidian ethnic group and typically have darker skin tones compared to North Indian or Caucasian populations, we aimed to evaluate the reliability of TcB in this group. Skin hydration is also another factor which can influence TcB measurements, although this has not yet been extensively studied and validated in the literature. 12,13 Our center is in a coastal region where neonatal dehydration is relatively common. Accordingly, we included invasive serum bilirubin measurement as the reference standard for comparison, prioritizing patient safety and keeping in line with our institutional protocol. This allowed us to generate paired TcB–TSB data for direct correlation and Bland–Altman analysis, which is one of the best parameter for external validation. 14 We agree that a future step would be to validate TcB specifically at recommended cut-offs in Indian neonates, which would reduce unnecessary blood sampling. To clarify this, we have added a new paragraph in the Discussion (Version 2) explicitly addressing this ethical aspect and acknowledging the limitation. The findings from our study may offer valuable insights for pediatricians and neonatologists working in similar coastal environments and resource-limited settings. Comment 3: “Is the work clearly and accurately presented and does it cite the current literature? – Partly.” Response: We have now strengthened the Introduction and Discussion with additional references already cited in our paper¹⁻⁷ to better contextualized our findings and support the novelty. This addresses the reviewer’s concern and ensures alignment with existing literature. References: Surana AU, Patel S, Prasad R, et al. Comparison of transcutaneous bilirubin with serum bilirubin measurements in neonates at a tertiary care center in the western part of India. Int J Contemp Pediatr . 2017;4:1445–3283. Arasar Seeralar AT, Ganesh J, Suganya M, et al. Correlation between transcutaneous and serum bilirubin measurements in neonates in a tertiary neonatal care center. Int J Contemp Med Res . 2016;10(8):272–274. Rahmawati D, Sampurna MTA, Etika R, et al. Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates. F1000Res . 2020;9:300. Rohsiswatmo R, Oswari H, Amandito R, et al. Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr . 2018;18:315. Ho EY, Lee SY, Chow CB, et al. BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice in the Chinese population. Hong Kong Med J . 2006;12(2):99–102. Yamana K, Morioka I, Kurokawa D, et al. Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns. Pediatr Int . 2017;59:1058–1063. Yasuda S, Suzuki H, Htun Y, et al. Hour-specific nomogram for transcutaneous bilirubin in newborns in Myanmar. Pediatr Int . 2020;62:1049–1053. Sharma AK, Dhawan K, Makkar M, et al. A correlation study between transcutaneous bilirubin and total serum bilirubin levels among neonates. Asian J Pharm Clin Res . 2022;10(3):272–274. Raba AA, O'Sullivan A, Miletin J. Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study. BMJ Paediatr Open . 2020;4(1):e000681. Dam-Vervloet AJ, Morsink CF, Krommendijk ME, Nijholt IM, van Straaten HL, Poot L, Bosschaart N. Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation. Pediatric Research. 2025 Apr;97(5):1706-10. Maya-Enero S, Candel-Pau J, Garcia-Garcia J, Duran-Jordà X, López-Vílchez MÁ. Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own. European Journal of Pediatrics. 2021 Feb;180(2):607-16. van Erk MD, Dam-Vervloet AJ, de Boer FA, Boomsma MF, Straaten HV, Bosschaart N. How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation. Pediatric research. 2019 Oct;86(4):471-7. Ercan Ş, Özgün G. The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population. Clinical biochemistry. 2018 May 1;55:69-74. Krobath DM, Naumova EN, Cuevas AG, Sacheck JM, Wilson NL, Economos CD. Use of Bland-Altman Analysis to Examine the Racial and Ethnic Representativeness of Study Populations in Community-Based Pediatric Health Research. JAMA network open. 2023 May 1;6(5):e2312920-. Competing Interests: nil Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 07 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 Version 3 (revision) 19 Nov 25 read Version 2 (revision) 02 Sep 25 read read Version 1 07 Apr 25 read Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh Alyssa Shapiro , The George Washington University, Washington, USA 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 Shapiro A. 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. 28 Dec 2025 | for Version 3 Alyssa Shapiro , The George Washington University, Washington, USA 0 Views copyright © 2026 Shapiro A. 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 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 The authors have made significant changes to the manuscript which I think make the results easy to interpret and the discussion very well written. I have a few minor additional comments, but I would say that once these are addressed, then this manuscript is ready for indexing. Abstract – The Abstract lists the brand of TCB device as Drager JM-105; could you please change this to Drager MBJ20 to reflect what is written in the body? Introduction – Where you say “Additionally, despite these limitations,” I might instead just say “Despite these limitations,” Introduction- The intent of my previous comment on the Introduction was to rearrange the content in order to improve flow. You start with Jaundice in general, then talk about Visual Inspection and TSB, and then next go into detail about TCB, and where your study addresses a research gap with TCB. With that in mind, this second short paragraph about TSB could either be moved or deleted: “In contrast, total serum bilirubin (TSB) measurement involves drawing a blood sample… hyperbilirubinemia risk.” Were all TCB and TSB pairs completed before phototherapy treatment was initiated? The Methods section states the criteria for starting phototherapy, but not the timing. Is possible that phototherapy treatment itself, started before TSB and/or TCB, could have an effects on the bilirubin readings by both methods. I personally disagree with this statement: “A small positive bias is clinically desirable, as it promotes early identification and timely referral of neonates at risk of hyperbilirubinemia.” I might instead make the following statement as my own opinion, “It is helpful for South Indian clinicians to be aware that the that the Drager MBJ20 TCB has a small positive bias in South Indian populations, because this gives clinicians helpful information to interpret TCB results accordingly when making decisions about individual patients.” However, I leave it up to the authors to leave their writing as is, or modify it if they would like, as I think the readers have the information needed to come to their own conclusions. Competing Interests No competing interests were disclosed. Reviewer Expertise Bioengineering, Jaundice 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. reply Respond to this report Responses (0) Shapiro A. Peer Review Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.191336.r434251) 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/14-403/v3#referee-response-434251 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Shapiro A. 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. 11 Oct 2025 | for Version 2 Alyssa Shapiro , The George Washington University, Washington, USA 0 Views copyright © 2025 Shapiro A. 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 article evaluated the accuracy of the Drager model MBJ20 transcutaneous bilirubin (TCB) compared to standard total serum bilirubin measurement in South India. This is an important research question, as TCB measurement provides a low-cost, noninvasive alternative to blood sampling, and South India - like many LMICs - are underrepresented in many research studies including those evaluating TCB accuracy. TCB performance is known to be population-dependent and can especially vary in darker skin tones. The authors mention that there are darker skin tones in South Indian populations along with frequent dehydration, both of which can affect TCB performance. The research methods presented here are well done. Below are some suggestions that can further improve the manuscript. Major suggestions: In the Statistical Analysis section, what is meant by “accounting for hours of life and gestational age”? I believe that Figure 3 and Table 4 address hours of life, correct? I was confused by Figure 3, because the TCB increase in the first five days of life is known to vary greatly among individual newborns due to gestational age and risk factors. For example, if a newborn has pathological jaundice (for example, due to hemolytic anemia) rather than physiological jaundice, the rate of bilirubin increase is much higher. I think that if you are looking to show the utility of the TCB throughout the first five days of life, one possibility could be to show “TCB-TSB” on the Y axis, compared to “Hours of life” on the X axis. Likewise, in Table 4, I found it confusing to do a direct correlation of TCB to gestational age. I would recommend instead doing 1) Pearson correlation coefficient of TCB and TSB, for two groups, one of term newborns and one of preterm newborns, then compare those two correlation coefficients, or 2) Compare “TCB – TSB” vs gestational age (perhaps a graph like Figure 2), and show that this difference does not change drastically for different gestational ages. I see that your Result is that there is a mean bias of +1.81 mg/dL, and the 95% limits of agreement are -3.36 – 6.97. Your Conclusion is that the there is good agreement between TCB and TSB levels. I personally disagree with your Conclusion; or rather, to me it’s a bit concerning that there is this mean bias and also that many individual data points show a huge difference between TCB and TSB (for example, TCB of around 16 when TSB is around 5). However, your results do align quite well with other studies that evaluate TCB vs. TSB, so I’m not doubting the accuracy of your results, only your interpretation of them. I would suggest adding some text in the Discussion along those lines. Or rather, could you please further elaborate about why you conclude that the agreement is good? Related to the previous statement, I would suggest commenting further on how your results compare to other studies evaluating both TCB in general, as well as the Drager model MBJ20 in particular. References 7-15 are a good start; what were their Pearson’s values? Which brand of TCB device did they use? Did they also have some measurements with such a large difference between TSB and TCB? Can you include some other references that specifically evaluate the MBJ20? Could you please comment on why some individual measurements may have such a discrepancy (for example, TCB around 16 when TSB is around 5)? Did these newborns have particular pre-existing conditions? Were they preterm newborns? Do you have some theories as to why you found a positive overestimation (+1.81 mg/dL) in your study? Do you think it’s related to the darker skin tones of your population? If so, could you comment further on this in the Discussion? Minor suggestions: Could you please briefly clarify that all measurements were taken before phototherapy began? Also, how was it determined that neonates required phototherapy? (Via visual inspection?) Most data points fell within +/- 1.96 times the SD of the difference between TSB and TcB values --- I would remove this statement, as by definition, 95% data points on a Bland-Altman plot will fall within +/- 1.96 SD. I would instead modify this statement to say something like, ‘Most data points fell within 5.16 mg/dL of the mean bias’. Could you be more specific about how much time had passed between TCB and TSB measurements? You say ‘at the same time’; could you instead say something like ‘within 30 minutes of each other,’ ‘within 15 minutes of each other,’ etc? The C-section rate is quite high. Could you please comment on whether this is an expected finding? Perhaps this is normal in south India, but American authors might be surprised and curious about this. If this reflect that this hospital sees a higher-risk population than the general population, that might affect the generalizability of your findings (which you have already commented on in the Discussion). Minor suggestions to improve the English writing: (Overall the English & writing were good): Abstract: One of the most prevalent condition --> one of the most prevalent conditions Due to this newborn receive many heel or vein pricks for testing, hence transcutaneous bilirubinometer can --> Due to this, newborns receive many heel or vein pricks for testing, hence the transcutaneous bilirubinometer can Introduction: “The primary methods for assessing bilirubin levels in newborns include visual inspection, transcutaneous bilirubinometry, and measurement of total serum bilirubin. Visual assessment is simple using Kramer’s rule but has notable limitations, as it is highly subjective; factors such as the physician's experience, the baby's skin colour, clothing, and lighting conditions can all influence the accuracy of visual estimation. Transcutaneous bilirubinometry provides a non-invasive alternative, whereas total serum bilirubin measurement continues to be the gold standard for accurate assessment. Requiring a blood sample for confirmation, especially in high-risk cases. Transcutaneous bilirubin (TCB) assessment uses a handheld electronic device to measure bilirubin levels non-invasively on the skin's surface, providing a painless and convenient method for screening jaundice in term and near-term neonates. It is increasingly accepted in clinical settings due to its simplicity and effectiveness. The device, Transcutaneous Jaundice Detector (Drager Model MBJ20). utilises optical spectroscopy by emitting light into the skin and analysing the reflected wavelengths to estimate total serum bilirubin levels. This method offers a reliable alternative for early jaundice detection without requiring blood draws. 4 ” --> “The primary methods for assessing bilirubin levels in newborns include visual inspection, measurement of total serum bilirubin, and transcutaneous bilirubinometry. Visual assessment is simple using Kramer’s rule but has notable limitations, as it is highly subjective; factors such as the physician's experience, the baby's skin colour, clothing, and lighting conditions can all influence the accuracy of visual estimation. Total serum bilirubin (TSB) measurement continues to be the gold standard for accurate assessment for monitoring bilirubin levels before and after phototherapy in both term and preterm neonates. However, obtaining blood samples via heel stick or venipuncture is not only painful and time-intensive but also elevates the risk of local and systemic infections, particularly in preterm neonates. Transcutaneous bilirubin (TCB) assessment uses a handheld electronic device to measure bilirubin levels non-invasively on the skin's surface, providing a painless and convenient method for screening jaundice in term and near-term neonates. The device, Transcutaneous Jaundice Detector (Drager Model MBJ20). utilises optical spectroscopy by emitting light into the skin and analysing the reflected wavelengths to estimate total serum bilirubin levels. It is increasingly accepted in clinical settings due to its simplicity and effectiveness. The National Institute for Health and Care Excellence (NICE) guidelines advise against using transcutaneous bilirubin (TCB) measurements within the first day of life or for neonates born before 35 weeks of gestation. Additionally, Despite these limitations, TCB is a non-invasive screening method used to determine the need for phototherapy, and use of TCB can reduce infection risks. ^This is one quick possibility of rearranging the Introduction to reduce repetitive sentences and incomplete sentences, as well as to keep all the TSB info together and TCB info together. Sample Size: A design effect 1.17 --> A design effect of 1.17 Discussion: A previous multicentric study by James A. et al. shows a correlation of 0.78 was observed, similar to the positive correlation found in our study. --> A previous multicentric study by Taylor et al. shows that a correlation of 0.78 was observed, similar to the positive correlation found in our study. Which is one of the best parameter for external validation --> Which is one of the best parameters for external validation 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? Yes 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 Bioengineering, Jaundice 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) Shapiro A. Peer Review Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.187250.r420926) 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/14-403/v2#referee-response-420926 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. 19 Sep 2025 | for Version 2 Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, 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 (0) 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 Thanks for allowing me to review again. I’ve gone through it it seems all comments have been addressed Competing Interests No competing interests were disclosed. Reviewer Expertise neonatal health 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. reply Respond to this report Responses (0) Kumer Dey S. Peer Review Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.187250.r411195) 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/14-403/v2#referee-response-411195 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. 22 Aug 2025 | for Version 1 Sanjoy Kumer Dey , Bangabandhu Sheikh Mujib Medical University, Dhaka, 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 It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article. From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically. 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? 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 neonatal health 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 10 Sep 2025 laxmi kamath, Pediatrics, Kasturba medical college Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal,576104, India, India Author Response to Reviewer Comments We sincerely thank the reviewer for the thoughtful and constructive feedback. Below we provide a point-by-point response, and have revised the manuscript (Version 2) accordingly. Comment 1: “It is already established method to detect Neonatal Jaundice by doing TcB. In introduction author could search more literatures to find the research gap. Rationale of the study is not clearly mentioned. It needs to be clear what new information is generated and novelty of the study which seems missing in this article.” Response: We agree with the reviewer. While TcB is indeed an established screening tool, its performance may vary by ethnicity, skin pigmentation, hydration status and healthcare context. Data from India remain relatively limited, with only a few published studies¹-², often with smaller sample sizes. By contrast, most validation studies have been conducted in Western or East Asian populations³⁻⁷, which cannot always be extrapolated to the Indian subcontinent. To address this, we have added a new paragraph in the Introduction (Version 2) highlighting the research gap and rationale. The novelty of our work lies in: Providing one of the larger single-center datasets from South India (n=271) evaluating TcB against TSB. Assessing TcB correlation not only with TSB but also with hours of life and gestational age, which adds clinically relevant insight. Generating population-specific evidence in darker-skinned neonates, thereby strengthening the case for wider adoption of TcB in Indian neonatal practice. Comment 2: “From ethical point of view as it is established that there are some cut off values determined by TcB upon which TSB is recommended to send to avoid unnecessary blood sampling but here it is being observed that all babies having jaundice detected by TcB undergone blood sampling. Alternatively they could compare TcB value where TSB is recommended to prove it to be sound ethically.” Response: We acknowledge this important ethical concern. International guidelines suggest using TcB thresholds to decide when TSB is required⁸⁻⁹. However, at the time of our study TcB was not validated in our population and was not part of routine NICU practice. The accuracy of TcB is known to be influenced by skin pigmentation, with several studies noting variations across different ethnic populations. 10,11 Since South Indians predominantly belong to the Dravidian ethnic group and typically have darker skin tones compared to North Indian or Caucasian populations, we aimed to evaluate the reliability of TcB in this group. Skin hydration is also another factor which can influence TcB measurements, although this has not yet been extensively studied and validated in the literature. 12,13 Our center is in a coastal region where neonatal dehydration is relatively common. Accordingly, we included invasive serum bilirubin measurement as the reference standard for comparison, prioritizing patient safety and keeping in line with our institutional protocol. This allowed us to generate paired TcB–TSB data for direct correlation and Bland–Altman analysis, which is one of the best parameter for external validation. 14 We agree that a future step would be to validate TcB specifically at recommended cut-offs in Indian neonates, which would reduce unnecessary blood sampling. To clarify this, we have added a new paragraph in the Discussion (Version 2) explicitly addressing this ethical aspect and acknowledging the limitation. The findings from our study may offer valuable insights for pediatricians and neonatologists working in similar coastal environments and resource-limited settings. Comment 3: “Is the work clearly and accurately presented and does it cite the current literature? – Partly.” Response: We have now strengthened the Introduction and Discussion with additional references already cited in our paper¹⁻⁷ to better contextualized our findings and support the novelty. This addresses the reviewer’s concern and ensures alignment with existing literature. References: Surana AU, Patel S, Prasad R, et al. Comparison of transcutaneous bilirubin with serum bilirubin measurements in neonates at a tertiary care center in the western part of India. Int J Contemp Pediatr . 2017;4:1445–3283. Arasar Seeralar AT, Ganesh J, Suganya M, et al. Correlation between transcutaneous and serum bilirubin measurements in neonates in a tertiary neonatal care center. Int J Contemp Med Res . 2016;10(8):272–274. Rahmawati D, Sampurna MTA, Etika R, et al. Transcutaneous bilirubin level to predict hyperbilirubinemia in preterm neonates. F1000Res . 2020;9:300. Rohsiswatmo R, Oswari H, Amandito R, et al. Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr . 2018;18:315. Ho EY, Lee SY, Chow CB, et al. BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice in the Chinese population. Hong Kong Med J . 2006;12(2):99–102. Yamana K, Morioka I, Kurokawa D, et al. Evaluation of BiliCare transcutaneous bilirubin device in Japanese newborns. Pediatr Int . 2017;59:1058–1063. Yasuda S, Suzuki H, Htun Y, et al. Hour-specific nomogram for transcutaneous bilirubin in newborns in Myanmar. Pediatr Int . 2020;62:1049–1053. Sharma AK, Dhawan K, Makkar M, et al. A correlation study between transcutaneous bilirubin and total serum bilirubin levels among neonates. Asian J Pharm Clin Res . 2022;10(3):272–274. Raba AA, O'Sullivan A, Miletin J. Transcutaneous bilirubinometry during and after phototherapy in preterm infants: a prospective observational study. BMJ Paediatr Open . 2020;4(1):e000681. Dam-Vervloet AJ, Morsink CF, Krommendijk ME, Nijholt IM, van Straaten HL, Poot L, Bosschaart N. Skin color influences transcutaneous bilirubin measurements: a systematic in vitro evaluation. Pediatric Research. 2025 Apr;97(5):1706-10. Maya-Enero S, Candel-Pau J, Garcia-Garcia J, Duran-Jordà X, López-Vílchez MÁ. Reliability of transcutaneous bilirubin determination based on skin color determined by a neonatal skin color scale of our own. European Journal of Pediatrics. 2021 Feb;180(2):607-16. van Erk MD, Dam-Vervloet AJ, de Boer FA, Boomsma MF, Straaten HV, Bosschaart N. How skin anatomy influences transcutaneous bilirubin determinations: an in vitro evaluation. Pediatric research. 2019 Oct;86(4):471-7. Ercan Ş, Özgün G. The accuracy of transcutaneous bilirubinometer measurements to identify the hyperbilirubinemia in outpatient newborn population. Clinical biochemistry. 2018 May 1;55:69-74. Krobath DM, Naumova EN, Cuevas AG, Sacheck JM, Wilson NL, Economos CD. Use of Bland-Altman Analysis to Examine the Racial and Ethnic Representativeness of Study Populations in Community-Based Pediatric Health Research. JAMA network open. 2023 May 1;6(5):e2312920-. View more View less Competing Interests nil reply Respond Report a concern Kumer Dey S. Peer Review Report For: Correlation of transcutaneous and serum bilirubin levels in late preterm and term neonates at a tertiary care center in south India [version 3; peer review: 2 approved] . F1000Research 2025, 14 :403 ( https://doi.org/10.5256/f1000research.178836.r395736) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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