The application of pre-discharge delta total bilirubin to predict the need for post-discharge phototherapy in healthy neonates 35 weeks’ gestation or later

The application of pre-discharge delta total bilirubin to predict the need for post-discharge phototherapy in healthy neonates 35 weeks’ gestation or later | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The application of pre-discharge delta total bilirubin to predict the need for post-discharge phototherapy in healthy neonates 35 weeks’ gestation or later Thawinee Maneesilasan, Mallika Pomrop This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6240272/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 14 Nov, 2025 Read the published version in BMC Pediatrics → Version 1 posted 11 You are reading this latest preprint version Abstract Background The American Academy of Pediatrics recommended the use of pre-discharge delta total bilirubin (DeltaTB) to determine appropriate follow-up timing. Objectives To determine the incidence of post-discharge phototherapy after using the predischarge DeltaTB and to evaluate the effectiveness of DeltaTB to predict post-discharge phototherapy needs. Methods This is a prospective cohort study conducted at Chiang Mai University Hospital. The pre-discharge DeltaTB, defined as the difference between the bilirubin level and the phototherapy threshold at the time of measurement. Based on pre-discharge DeltaTB (mg/dL), patients were categorized into 3 risk groups: high-risk ( 7). Post-discharge phototherapy, pre-discharge TB, and number of follow-up were compared between the risk groups. DeltaTB levels in different age intervals were analyzed using ROC curve analysis to determine the cutoff in each interval. Results Out of 150 neonates, 31 (20.6%) required post-discharge phototherapy, with 9 neonates were classified as requiring subthreshold phototherapy. There were 17.3%, 53.3% and 19.3% of 150 neonates categorized as high, moderate, and low risk by pre-discharge DeltaTB, respectively. The high-risk group, had the highest incidence of post-discharge phototherapy, mean pre-discharge bilirubin level and number of follow-up visits and were significantly different from other groups ( P-value < 0.001). The optimal timing for measuring pre-discharge bilirubin was aged 49–72 hours (AUC of 0.851). Conclusion According to the new guideline, 20.6% required post-discharge phototherapy without any cases of severe hyperbilirubinemia. The pre-discharge DeltaTB was effective to differentiate the risk of need post-discharge phototherapy. The incidence of post-discharge phototherapy was significantly higher in high-risk group compared to others. neonatal jaundice post-discharge phototherapy new phototherapy guideline 2022 pre-discharge delta total bilirubin Figures Figure 1 Figure 2 Figure 3 Introduction Neonatal jaundice is one of the most common conditions in neonates ( 1 – 7 ). affecting around 60% of term neonates and 80% of preterm neonates during their first week of life ( 1 , 2 , 8 ). Pathological jaundice can progress to severe hyperbilirubinemia, which may lead to acute and chronic bilirubin encephalopathy, an irreversible complication ( 4 ). Risk factors for neonatal jaundice can be categorized into maternal and neonatal factors. Maternal factors include Asian race, advanced maternal age, blood group incompatibility, lower gestational age, a family history suggesting hereditary red blood cell diseases, and gestational diabetes mellitus (GDM). Neonatal factors include male gender, low birth weight, scalp hematomas or bruising related to birth trauma, and exclusive breastfeeding with suboptimal intake ( 1 , 2 , 7 , 9 – 12 ). Most neonates develop jaundice within the first week of life ( 1 , 6 ), with bilirubin levels typically peaking at approximately 72–120 hours of age ( 6 , 8 ). In Thailand, healthy neonates are typically discharged at 2–3 days after birth. This is usually before their serum bilirubin reach to the peak levels. Therefore, neonatal jaundice is the leading cause of readmission in healthy neonates ( 1 ). Delayed or inappropriate follow-up to newborn jaundice increases the risk of severe hyperbilirubinemia and delays timely treatment. These are possibly leading to severe neurological complications, including acute bilirubin encephalopathy, kernicterus, long-term developmental impairments, and sensorineural hearing loss ( 13 – 16 ). Proper time for post-discharge follow-up of neonatal jaundice is important to prevent these serious consequences. The American Academy of Pediatrics (AAP) 2009 guidelines had been used extensively to guide the management of neonatal hyperbilirubinemia in late preterm and term infants based on Bhutani nomogram which was based on bilirubin level, risk factors for severe hyperbilirubinemia and postnatal age ( 3 ). Based on this guideline, the incidence of readmission in healthy neonates due to neonatal jaundice in Thailand is ranged from 3.8–24%. Most of these cases were infants who initially had no significant risk factors for severe jaundice ( 17 – 19 ). In 2021, Kuzniewicz et al. compared different models for predicting the need for phototherapy after discharge. They found that using Δ-TSB (the difference between pre-discharge bilirubin level and the phototherapy threshold) was more accurate than the Bhutani Nomogram and may be easier to use in clinical practice ( 20 ). AAP released new guidelines for managing neonatal jaundice in 2022, which use the difference between pre-discharge total bilirubin and the new phototherapy threshold (Delta TB), and with neurotoxicity risk factors to determine the follow up time ( 5 ). Since its implementation, no study has evaluated the effectiveness of this recommendation in Thailand. To preventing complications and delay treatment of severe hyperbilirubinemia during post-discharge follow-up, this study also aims to evaluate the utility the use of DeltaTB to guide follow-up timing as a predictive tool of the need of post-discharge phototherapy. Method This prospective cohort study was conducted at Chiang Mai University Hospital from August 2023 to December 2024. The study was approved by the Research Ethics Committee of the Faculty of Medicine at Chiang Mai University (Study code: PED-2566-0283). Neonates eligible for enrollment were inborn and healthy, with a gestational age of ≥ 35 weeks and a birth weight of ≥ 2000 grams, and who had never received phototherapy before discharge. The exclusion criteria included newborns with direct hyperbilirubinemia or newborns requiring intensive care. This study collected maternal and neonatal demographic data, and perinatal history from electronic medical record. Maternal data included age, gravidity, parity, gestational age (GA), blood group, underlying conditions, and antenatal care (ANC) laboratory results such as serology, thalassemia screening, and gestational diabetes mellitus (GDM) status. Perinatal history included the mode of delivery and any resuscitation during delivery. Neonatal data included sex, birth weight, length, head circumference, discharge date, body weight before discharge and at follow-up time, scalp hematoma (e.g., cephalohematoma or subgaleal hematoma), and feeding type (e.g., exclusive breastfeeding, formula, or both). Jaundice screening and follow up after discharge At our institution, all healthy neonates are screened for jaundice by testing total serum bilirubin (TSB), direct bilirubin (DB) and hematocrit (Hct) at the age 48–72 hours. They are typically discharged after 48 hours of life and have at least one post-discharge follow-up visit. To streamline clinical practice, we categorized neonates into three risk groups based on their pre-discharge DeltaTB levels, with follow-up timing determined according to the 2022 AAP guidelines ( 5 ) High risk group : neonates with a DeltaTB of 7 mg/dL, follow-up at 3–5 days after discharge. During the follow-up visit, medical history, vital signs, weight and physical examination findings were recorded. Blood sampling for TSB, DB and Hct was obtained. If the TSB level meets the phototherapy threshold according to the AAP 2022 guidelines, the neonate will be admitted for phototherapy and has the jaundice work up which includes complete blood count (CBC), reticulocyte count (RC), serum albumin, glucose-6-phosphate dehydrogenase (G6PD) level, blood group, indirect and direct antiglobulin test (IAT and DAT). The outpatient department discharge criteria for neonatal jaundice are either DeltaTB of > 7 mg/dL or appropriate weight gain. They are generally scheduled for subsequent follow-up visits until meeting the discharge criteria. Sample size calculation The sample size was calculated assuming a 95% confidence level and 5% margin of error. Based on the study by Tantiprabha W, et al. ( 17 ), which reported a 9.5% incidence rate of post-discharge phototherapy, the required sample size for this study was 132 neonates. Statistical analysis Statistical analyses were conducted using IBM SPSS Statistics 25 (SPSS, Armonk, NY, USA). Continuous variables were described using the mean and standard deviation, depending on their distribution. Categorical data were analyzed using the Chi-square test. One-way ANOVA (Bonferroni) was used to compare the means outcomes between the three risk groups. DeltaTB levels in different age intervals were analyzed using ROC curve analysis to determine the cutoff in each interval. To evaluate the diagnostic performance of DeltaTB at different age intervals in predicting post-discharge phototherapy, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and the area under the ROC curve (AUC) based on the optimal cutoff values. Definition Significant hyperbilirubinemia: A TSB level that is at or above the threshold for treatment, which varies based on the infant's age in hours, risk factors, and gestational age Subthreshold phototherapy: Phototherapy when TSB levels were 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold ( 21 ) Severe hyperbilirubinemia: TSB level above 25 mg/dL or within 2 mg/dL of exchange transfusion threshold ( 15 ) Results Out of 150 neonates, 31 (20.6%) required post-discharge phototherapy. Of these, 22 neonates had significant hyperbilirubinemia, while 9 neonates received subthreshold phototherapy without severe hyperbilirubinemia as shown in Fig. 1 . The mean age onset of phototherapy was 115.87 ± 28.57 hours. There were no neonates with severe hyperbilirubinemia. The mean GA was 38.25 ± 1.1 weeks, and the mean birth weight was 3,008 ± 389.8 grams. The most common cause jaundice in neonates who required post-discharge phototherapy was inconclusive jaundice (45%) followed by breast non-feeding (23%), scalp hematoma (13%), breastmilk jaundice (7%), ABO incompatibility (6%), G6PD deficiency (3%), and hemoglobin H disease (3%). Per our institutional protocol, all neonates required pre-discharge TSB and at least one post-discharge TSB at the follow-up visit. Among 150 neonates, 122 (81.3%) adhered to the follow-up protocol before discharge. The adherence decreased with subsequent follow-up appointments as shown in Fig. 2 . The mean number of follow-up duration was 2.31 ± 1.34 times (range 1–7 times). Table 1 shows demographic data comparing the post-discharge phototherapy and no phototherapy groups. Maternal factors, including advanced maternal age, nulliparity, gestation diabetes, maternal blood group O and positive thalassemia screening, were not significantly associated with post-discharge phototherapy. Similarly, perinatal factors including assisted vaginal delivery and resuscitation were also not significantly different. Scalp hematoma was more common in the phototherapy group (12.9% vs. 4.2%, P = 0.088) but not statistically significant. Pre-and post-discharge percentage of weight loss from the birth weight was higher in the phototherapy group, only post-discharge percentage of weight loss (-4.18% vs. -2.19%, P = 0.041) was statistically significant. Other neonatal factors, including male sex, small for gestational age, and exclusive breast feeding were not significantly different. Table 1 Demographic data Baseline characteristics No Phototherapy (N = 119) Phototherapy (N = 31) P -value Maternal factors • Advanced Maternal age, n (%) 39 (32.7%) 6 (19.3%) 0.188 • Preterm, n (%) 7 (5.9%) 3 (9.7%) 0.432 • Nulliparity, n (%) 61 (51.3%) 18 (58.1%) 0.549 • Gestational diabetes mellitus, n (%) 36 (30.3%) 8 (26.7%) 0.815 • Maternal Blood group O, n (%) 46 (38.7%) 10 (32.3%) 0.830 • Positive thalassemia screening, n (%) 1 (0.9%) 2 (6.7%) 0.112 Perinatal factors • Assisted Vaginal Delivery, n (%) 8 (6.7%) 1 (3.2%) 0.686 • Resuscitation, n (%) 9 (7.6%) 2 (6.5%) 1.000 Neonatal factors • Male 55 (46.2%) 16 (51.6%) 0.687 • SGA 13 (10.9%) 3 (9.7%) 1.00 • Scalp hematoma 5 (4.2%) 4 (12.9%) 0.088 • Exclusive breast feeding 78 (65.5%) 23 (74.2%) 0.399 • Pre-discharge %weight loss, Mean (SD) -1.32 (0.33) -2.87% (0.9) 0.053 • Post-discharge %weight loss at first follow-up, Mean (SD) -2.19% (0.44) -4.18% (0.81) 0.041 Based on their pre-discharge DeltaTB, 150 newborns were divided into three risk categories. There were 41 neonates (17.3%) in the high-risk group, 80 neonates (53.3%) in the moderate-risk group, and 29 neonates (19.3%) in the low-risk group. Figure 3 shows significant differences in outcomes across risk groups. Post-discharge phototherapy incidence was highest in the high-risk group (22 cases, 53.6%), significantly higher than in the moderate-risk (7 cases, 8.7%) and low-risk groups (2 cases,6.9%), with P < 0.001. Mean pre-discharge TB levels were also significantly higher in the high-risk group (15.07 ± 1.65 mg/dL) compared to the moderate-risk (12.53 ± 2.70 mg/dL) and low-risk groups (8.3 ± 4.57 mg/dL), with P < 0.001. Follow-up times were significantly higher in the high-risk group (2.95 ± 1.67 times) compared to moderate-risk (2.32 ± 1.12 times) with P = 0.029 and low-risk groups (1.38 ± 0.72 times) with P = 0.002. The optimal time for pre-discharge bilirubin screening was 49–72 hours, with the highest area under the curve (AUC) at 0.851. At the cutoff level of 3.5 mg/dL at 49–72 hours of life, sensitivity and specificity were 80% and 82% respectively. With different time intervals, the cutoff levels of DeltaTB for predicting post-discharge phototherapy were different. Table 2 demonstrates that the cutoff DeltaTB was higher with early pre-discharge bilirubin screening than for later screening. Table 2 Predictive ability and cutoff of DeltaTB at different time intervals Age (hours of life) Area Under Curve (AUC) Cutoff DeltaTB (mg/dL) Sensitivity Specificity Positive predictive value (PPV) Negative predictive value (NPV) 48 0.783 3.7 77% 76% 46.7% 92% 49–72 0.851 3.5 80% 82% 55.5% 93% 73–96 0.836 2.5 80% 77% 69% 60% Discussion In this study, the incidence of post-discharge phototherapy was 20.6%, higher than previous studies conducted in Thailand, which ranged from 3.8–9.5% ( 17 – 19 ). However, in the study by Kankaew et al. ( 22 ) conducted at Ramathibodi Hospital, the incidence was 24%, nearly the same in this study. Notably, the previous studies used the AAP 2009 phototherapy guidelines, and some included subthreshold phototherapy during birth admissions, while this study uses the AAP 2022 phototherapy guidelines, and our institution did not have guidelines for subthreshold phototherapy during birth admission. Also, the research by Wickremasinghe et al. ( 21 ) showed that neonates who got subthreshold phototherapy during birth admission had a lower chance of being readmitted for post-discharge phototherapy without adverse outcomes. The study by Sarathy L et al. showed that the overall readmission rate for phototherapy remained stable after the new AAP 2022 guidelines (0.9% vs 0.8%). However, among readmitted jaundice neonates, those exceeding the phototherapy threshold increased from 11–22.1%, and those receiving subthreshold phototherapy (exceed more than 2 mg/dL below the threshold) rose from 33–50.5% ( 23 ). These findings suggest that while the overall rate of post-discharge phototherapy has remained stable, the characteristics of affected neonates have changed, with a higher reach of the phototherapy threshold and an increase in subthreshold phototherapy cases. This differs from our study, which observed a rising trend in the incidence of post-discharge phototherapy following the implementation of the new guidelines, along with an increase in subthreshold phototherapy cases. The higher rate of post-discharge phototherapy in this current study compared to previous studies could be due to the new phototherapy threshold changes based on the gestational age of neonates, and our hospital did not use subthreshold phototherapy guidelines. It may cause neonates who have low DeltaTB values, especially those who are in high-risk groups, to be discharged and have close follow-up within 1–2 days. At follow-up time after discharge, their bilirubin levels met the threshold for phototherapy. In previous studies, the main causes of post-discharge phototherapy were inconclusive jaundice and breast non-feeding jaundice ( 17 – 19 ), which is consistent with our findings, where inconclusive jaundice was the leading cause, followed by breast non-feeding jaundice. The significant risk factor for post-discharge phototherapy in our study was post-discharge % weight loss greater than 4.18% at first follow up. This finding was consistent with other studies, such as the one by Booranavanich et al. at Vajira Hospital ( 18 ), which reported that weight loss greater than 3.31% was associated with post-discharge phototherapy. Similarly, the study by Prachukthum et al. at Thammasat Hospital ( 19 ) show that weight loss of greater than 6% on the second day of life was a risk factor for post-discharge phototherapy. These results suggest that the higher percentage of weight loss in the early days of life is a significant factor influencing the need for post-discharge phototherapy. This study found that the mean age onset of post-discharge phototherapy was 115 hours, or Day of Life (DOL) 4 to 5. This finding was similar to the study by Prachukthum et al. at Thammasat Hospital ( 19 ), where the onset of post-discharge phototherapy occurred around DOL 6. These results are consistent with the natural progression of neonatal jaundice, as total bilirubin levels typically rise and peak approximately on DOL 3 to 5 (72–120 hours of age) ( 6 , 8 ). In this study, DeltaTB levels were categorized into three risk groups: high risk (DeltaTB 7). It was found that the incidence of post-discharge phototherapy was highest in the high-risk group as expected. However, even within the low-risk group, there remained a possibility of requiring post-discharge phototherapy. This highlights the importance of follow-up after discharge, as it is crucial for early detection and appropriate intervention, regardless of the initial risk classification. The optimal time to screen pre-discharge total bilirubin is between 49–72 hours, as this provides the best prediction for the likelihood of post-discharge phototherapy. A cut-off value of 3.5 is identified as the threshold for predicting the need for post-discharge phototherapy with sensitivity at 80% and specificity at 82%. Additionally, it was observed that the younger the infant's age at the time of pre-discharge total bilirubin screening, the higher the cutoff value tends to be. This suggests that age at screening plays a role in determining the appropriate DeltaTB threshold for predicting the need for post-discharge phototherapy. The strength of this study is that it was a prospective cohort study in which all neonates were followed at least once to check their TSB levels. The limitations of this study include the small sample size and approximately 80% adherence to the follow-up protocol. This reduced adherence may be due to this guideline used by various levels of healthcare providers, which could result in inconsistent protocol compliance and varied management practices. It would be beneficial to provide better training, streamline the protocol, and monitor across all levels of healthcare providers to improve adherence. Subthreshold phototherapy during newborn admission should be used in high-risk groups, as it may reduce the post-discharge phototherapy rate. Furthermore, future research should involve multi-center cohort studies for validation and focus on clinical implications, such as the cost-effectiveness of pre-discharge subthreshold phototherapy. Conclusion After applying the AAP 2022 neonatal hyperbilirubinemia guidelines at our institution, we found an incidence of post-discharge phototherapy of 20.6%, which significantly increased compared to other studies that used the AAP 2009 guidelines. The high-risk group neonates with a DeltaTB < 3.5 mg/dL were at the highest risk of requiring post-discharge phototherapy. However, post-discharge phototherapy was still observed in the low-risk group. Therefore, at least one post-discharge follow-up is needed for all neonates. Pre-discharge total bilirubin screening should be performed between 49–72 hours of life, as this is the optimal time for predicting the need for post-discharge phototherapy. Declarations Human Ethics and Consent to Participate declarations This study was approved by the Research Ethics Committee of the Faculty of Medicine at Chiang Mai University (Study code: PED-2566-0283). Written informed consent was obtained from the parents or legal guardians of all participants before their enrollment in the study. Consent for publication Not applicable. Clinical Trial Number Not applicable. Data availability The author confirms that there is no research data available outside the submitted manuscript file. Competing interests The authors declare that they have no competing interests. Funding This study received no funding. Authors' contributions All the authors have made substantial contributions to the intellectual content of the paper. Maneesilasan T. contributed to the concept and design of the study, acquisition and analysis of the data, and the draft of the manuscript. Pomrop M. contributed to the concept and design of the study, analysis, and interpretation of the data and critically revised the manuscript. All authors approved the final manuscript as submitted. Acknowledgements The authors would like to express their sincere gratitude to Kosarat S. and Prempraphan P. for their valuable support, guidance, and suggestions in improving this study. References Mitra S, Rennie J. Neonatal jaundice: aetiology, diagnosis and treatment. Br J Hosp Med (Lond). 2017;78(12):699-704. Okulu E. Neonatal jaundice: Recommendations for follow-up and treatment. Global Pediatrics. 2024;7:100131. 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Pediatrics. 2024;153(4). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 14 Nov, 2025 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 30 Jul, 2025 Reviews received at journal 27 Apr, 2025 Reviews received at journal 24 Apr, 2025 Reviewers agreed at journal 19 Apr, 2025 Reviewers agreed at journal 19 Apr, 2025 Reviewers agreed at journal 17 Apr, 2025 Reviewers invited by journal 17 Apr, 2025 Editor assigned by journal 09 Apr, 2025 Editor invited by journal 24 Mar, 2025 Submission checks completed at journal 22 Mar, 2025 First submitted to journal 22 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6240272","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":447600073,"identity":"2d5c5f18-edcc-489b-9d0a-a28fff067572","order_by":0,"name":"Thawinee Maneesilasan","email":"","orcid":"","institution":"Chiang Mai University","correspondingAuthor":false,"prefix":"","firstName":"Thawinee","middleName":"","lastName":"Maneesilasan","suffix":""},{"id":447600074,"identity":"69d57576-89b7-4751-8277-b660c74a4912","order_by":1,"name":"Mallika Pomrop","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYBACgwPMjQcSDgBZ7A0wMR78WiwPMDZAtPAcgAqxEdBiD9LCAFItkUCkFrPjBxsOPDhjx2Au+fjpZh4GO3kG+d4D+LWcSQQ67EYyg+XsNLPbPAzJhg1sfAn4tRwAafnAzGBwO4cNqIU5AegwA7xaDM4/BGmpZzC4eQakpZ4ILTfADjsMZPCAtBwmRgvIljPHeSx70sxuzjE4btjGlkPIYckHH/44Vi1nzn742Y03FdXy/Mxn8GuBAahjgCQbUeqhikfBKBgFo2AUYAcAs8NLNI/QiqwAAAAASUVORK5CYII=","orcid":"","institution":"Chiang Mai University","correspondingAuthor":true,"prefix":"","firstName":"Mallika","middleName":"","lastName":"Pomrop","suffix":""}],"badges":[],"createdAt":"2025-03-17 02:38:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6240272/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6240272/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-025-06238-8","type":"published","date":"2025-11-14T15:57:44+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82117918,"identity":"7c87b173-d134-43ed-ac1a-e8e1f2a6136c","added_by":"auto","created_at":"2025-05-07 03:04:31","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":144083,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence of post discharge phototherapy\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6240272/v1/38dc9633a3eecc84a95c4dbd.png"},{"id":82117917,"identity":"9aa9d61d-5e34-4394-8a48-aab49f3f46a6","added_by":"auto","created_at":"2025-05-07 03:04:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":30256,"visible":true,"origin":"","legend":"\u003cp\u003eNumber to follow up times and adherence to protocol\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6240272/v1/17c454199afa79ba14b2b96c.png"},{"id":82117932,"identity":"75789887-7f96-4d9b-9b94-e94c150941cf","added_by":"auto","created_at":"2025-05-07 03:04:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":20617,"visible":true,"origin":"","legend":"\u003cp\u003eComparison incidence post-discharge phototherapy, mean post discharge TB and follow up times between risk group\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6240272/v1/ac582ae27aad1ae0e946af01.png"},{"id":96105024,"identity":"c3f2e60c-4d8b-4dbe-945e-416293924845","added_by":"auto","created_at":"2025-11-17 16:07:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":842576,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6240272/v1/80fd26aa-5af2-49a1-99ea-4e687fd3e2c4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The application of pre-discharge delta total bilirubin to predict the need for post-discharge phototherapy in healthy neonates 35 weeks’ gestation or later","fulltext":[{"header":"Introduction","content":"\u003cp\u003eNeonatal jaundice is one of the most common conditions in neonates (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). affecting around 60% of term neonates and 80% of preterm neonates during their first week of life (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Pathological jaundice can progress to severe hyperbilirubinemia, which may lead to acute and chronic bilirubin encephalopathy, an irreversible complication (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Risk factors for neonatal jaundice can be categorized into maternal and neonatal factors. Maternal factors include Asian race, advanced maternal age, blood group incompatibility, lower gestational age, a family history suggesting hereditary red blood cell diseases, and gestational diabetes mellitus (GDM). Neonatal factors include male gender, low birth weight, scalp hematomas or bruising related to birth trauma, and exclusive breastfeeding with suboptimal intake (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMost neonates develop jaundice within the first week of life (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), with bilirubin levels typically peaking at approximately 72\u0026ndash;120 hours of age (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In Thailand, healthy neonates are typically discharged at 2\u0026ndash;3 days after birth. This is usually before their serum bilirubin reach to the peak levels. Therefore, neonatal jaundice is the leading cause of readmission in healthy neonates (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDelayed or inappropriate follow-up to newborn jaundice increases the risk of severe hyperbilirubinemia and delays timely treatment. These are possibly leading to severe neurological complications, including acute bilirubin encephalopathy, kernicterus, long-term developmental impairments, and sensorineural hearing loss (\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Proper time for post-discharge follow-up of neonatal jaundice is important to prevent these serious consequences.\u003c/p\u003e \u003cp\u003eThe American Academy of Pediatrics (AAP) 2009 guidelines had been used extensively to guide the management of neonatal hyperbilirubinemia in late preterm and term infants based on Bhutani nomogram which was based on bilirubin level, risk factors for severe hyperbilirubinemia and postnatal age (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Based on this guideline, the incidence of readmission in healthy neonates due to neonatal jaundice in Thailand is ranged from 3.8\u0026ndash;24%. Most of these cases were infants who initially had no significant risk factors for severe jaundice (\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn 2021, Kuzniewicz et al. compared different models for predicting the need for phototherapy after discharge. They found that using Δ-TSB (the difference between pre-discharge bilirubin level and the phototherapy threshold) was more accurate than the Bhutani Nomogram and may be easier to use in clinical practice (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). AAP released new guidelines for managing neonatal jaundice in 2022, which use the difference between pre-discharge total bilirubin and the new phototherapy threshold (Delta TB), and with neurotoxicity risk factors to determine the follow up time (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Since its implementation, no study has evaluated the effectiveness of this recommendation in Thailand. To preventing complications and delay treatment of severe hyperbilirubinemia during post-discharge follow-up, this study also aims to evaluate the utility the use of DeltaTB to guide follow-up timing as a predictive tool of the need of post-discharge phototherapy.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003eThis prospective cohort study was conducted at Chiang Mai University Hospital from August 2023 to December 2024. The study was approved by the Research Ethics Committee of the Faculty of Medicine at Chiang Mai University (Study code: PED-2566-0283). Neonates eligible for enrollment were inborn and healthy, with a gestational age of \u0026ge;\u0026thinsp;35 weeks and a birth weight of \u0026ge;\u0026thinsp;2000 grams, and who had never received phototherapy before discharge. The exclusion criteria included newborns with direct hyperbilirubinemia or newborns requiring intensive care.\u003c/p\u003e \u003cp\u003eThis study collected maternal and neonatal demographic data, and perinatal history from electronic medical record. Maternal data included age, gravidity, parity, gestational age (GA), blood group, underlying conditions, and antenatal care (ANC) laboratory results such as serology, thalassemia screening, and gestational diabetes mellitus (GDM) status. Perinatal history included the mode of delivery and any resuscitation during delivery. Neonatal data included sex, birth weight, length, head circumference, discharge date, body weight before discharge and at follow-up time, scalp hematoma (e.g., cephalohematoma or subgaleal hematoma), and feeding type (e.g., exclusive breastfeeding, formula, or both).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eJaundice screening and follow up after discharge\u003c/h2\u003e \u003cp\u003eAt our institution, all healthy neonates are screened for jaundice by testing total serum bilirubin (TSB), direct bilirubin (DB) and hematocrit (Hct) at the age 48\u0026ndash;72 hours. They are typically discharged after 48 hours of life and have at least one post-discharge follow-up visit. To streamline clinical practice, we categorized neonates into three risk groups based on their pre-discharge DeltaTB levels, with follow-up timing determined according to the 2022 AAP guidelines (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eHigh risk group\u003c/b\u003e: neonates with a DeltaTB of \u0026lt;\u0026thinsp;3.5 mg/dL, follow-up at 1 day after discharge.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eModerate risk group\u003c/b\u003e: neonates with a DeltaTB 3.5\u0026ndash;6.9 mg/dL, follow-up at 2 days after discharge.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eLow risk group\u003c/b\u003e: neonates with a DeltaTB value of \u0026gt;\u0026thinsp;7 mg/dL, follow-up at 3\u0026ndash;5 days after discharge.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eDuring the follow-up visit, medical history, vital signs, weight and physical examination findings were recorded. Blood sampling for TSB, DB and Hct was obtained. If the TSB level meets the phototherapy threshold according to the AAP 2022 guidelines, the neonate will be admitted for phototherapy and has the jaundice work up which includes complete blood count (CBC), reticulocyte count (RC), serum albumin, glucose-6-phosphate dehydrogenase (G6PD) level, blood group, indirect and direct antiglobulin test (IAT and DAT). The outpatient department discharge criteria for neonatal jaundice are either DeltaTB of \u0026gt;\u0026thinsp;7 mg/dL or appropriate weight gain. They are generally scheduled for subsequent follow-up visits until meeting the discharge criteria.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003eThe sample size was calculated assuming a 95% confidence level and 5% margin of error. Based on the study by Tantiprabha W, et al. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), which reported a 9.5% incidence rate of post-discharge phototherapy, the required sample size for this study was 132 neonates.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted using IBM SPSS Statistics 25 (SPSS, Armonk, NY, USA). Continuous variables were described using the mean and standard deviation, depending on their distribution. Categorical data were analyzed using the Chi-square test. One-way ANOVA (Bonferroni) was used to compare the means outcomes between the three risk groups. DeltaTB levels in different age intervals were analyzed using ROC curve analysis to determine the cutoff in each interval.\u003c/p\u003e \u003cp\u003eTo evaluate the diagnostic performance of DeltaTB at different age intervals in predicting post-discharge phototherapy, we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and the area under the ROC curve (AUC) based on the optimal cutoff values.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinition\u003c/h3\u003e\n\u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSignificant hyperbilirubinemia: A TSB level that is at or above the threshold for treatment, which varies based on the infant's age in hours, risk factors, and gestational age\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSubthreshold phototherapy: Phototherapy when TSB levels were 0.1 to 3.0 mg/dL below the appropriate AAP phototherapy threshold (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eSevere hyperbilirubinemia: TSB level above 25 mg/dL or within 2 mg/dL of exchange transfusion threshold (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOut of 150 neonates, 31 (20.6%) required post-discharge phototherapy. Of these, 22 neonates had significant hyperbilirubinemia, while 9 neonates received subthreshold phototherapy without severe hyperbilirubinemia as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean age onset of phototherapy was 115.87\u0026thinsp;\u0026plusmn;\u0026thinsp;28.57 hours. There were no neonates with severe hyperbilirubinemia. The mean GA was 38.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 weeks, and the mean birth weight was 3,008\u0026thinsp;\u0026plusmn;\u0026thinsp;389.8 grams.\u003c/p\u003e \u003cp\u003eThe most common cause jaundice in neonates who required post-discharge phototherapy was inconclusive jaundice (45%) followed by breast non-feeding (23%), scalp hematoma (13%), breastmilk jaundice (7%), ABO incompatibility (6%), G6PD deficiency (3%), and hemoglobin H disease (3%). Per our institutional protocol, all neonates required pre-discharge TSB and at least one post-discharge TSB at the follow-up visit. Among 150 neonates, 122 (81.3%) adhered to the follow-up protocol before discharge. The adherence decreased with subsequent follow-up appointments as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The mean number of follow-up duration was 2.31\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34 times (range 1\u0026ndash;7 times).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows demographic data comparing the post-discharge phototherapy and no phototherapy groups. Maternal factors, including advanced maternal age, nulliparity, gestation diabetes, maternal blood group O and positive thalassemia screening, were not significantly associated with post-discharge phototherapy. Similarly, perinatal factors including assisted vaginal delivery and resuscitation were also not significantly different. Scalp hematoma was more common in the phototherapy group (12.9% vs. 4.2%, P\u0026thinsp;=\u0026thinsp;0.088) but not statistically significant. Pre-and post-discharge percentage of weight loss from the birth weight was higher in the phototherapy group, only post-discharge percentage of weight loss (-4.18% vs. -2.19%, P\u0026thinsp;=\u0026thinsp;0.041) was statistically significant. Other neonatal factors, including male sex, small for gestational age, and exclusive breast feeding were not significantly different.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Phototherapy\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;119)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePhototherapy\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal factors\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Advanced Maternal age, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39 (32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (19.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Preterm, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (5.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.432\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Nulliparity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61 (51.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (58.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Gestational diabetes mellitus, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36 (30.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (26.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.815\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Maternal Blood group O, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46 (38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.830\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Positive thalassemia screening, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.112\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePerinatal factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Assisted Vaginal Delivery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8 (6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.686\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Resuscitation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeonatal factors\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Male\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e55 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (51.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.687\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; SGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (10.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (9.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Scalp hematoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Exclusive breast feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e78 (65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23 (74.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.399\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Pre-discharge %weight loss, Mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-1.32 (0.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-2.87% (0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026bull; Post-discharge %weight loss at first follow-up, Mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.19% (0.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e-4.18% (0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eBased on their pre-discharge DeltaTB, 150 newborns were divided into three risk categories. There were 41 neonates (17.3%) in the high-risk group, 80 neonates (53.3%) in the moderate-risk group, and 29 neonates (19.3%) in the low-risk group. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows significant differences in outcomes across risk groups. Post-discharge phototherapy incidence was highest in the high-risk group (22 cases, 53.6%), significantly higher than in the moderate-risk (7 cases, 8.7%) and low-risk groups (2 cases,6.9%), with P\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Mean pre-discharge TB levels were also significantly higher in the high-risk group (15.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.65 mg/dL) compared to the moderate-risk (12.53\u0026thinsp;\u0026plusmn;\u0026thinsp;2.70 mg/dL) and low-risk groups (8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.57 mg/dL), with P\u0026thinsp;\u0026lt;\u0026thinsp;0.001. Follow-up times were significantly higher in the high-risk group (2.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67 times) compared to moderate-risk (2.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12 times) with P\u0026thinsp;=\u0026thinsp;0.029 and low-risk groups (1.38\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72 times) with P\u0026thinsp;=\u0026thinsp;0.002. The optimal time for pre-discharge bilirubin screening was 49\u0026ndash;72 hours, with the highest area under the curve (AUC) at 0.851. At the cutoff level of 3.5 mg/dL at 49\u0026ndash;72 hours of life, sensitivity and specificity were 80% and 82% respectively. With different time intervals, the cutoff levels of DeltaTB for predicting post-discharge phototherapy were different. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e demonstrates that the cutoff DeltaTB was higher with early pre-discharge bilirubin screening than for later screening.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePredictive ability and cutoff of DeltaTB at different time intervals\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003cp\u003e(hours of life)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eArea Under Curve (AUC)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCutoff DeltaTB\u003c/p\u003e \u003cp\u003e(mg/dL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePositive predictive value (PPV)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNegative predictive value (NPV)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e76%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e92%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e49\u0026ndash;72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e82%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e55.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e93%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e73\u0026ndash;96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.836\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e77%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e69%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the incidence of post-discharge phototherapy was 20.6%, higher than previous studies conducted in Thailand, which ranged from 3.8\u0026ndash;9.5% (\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). However, in the study by Kankaew et al. (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) conducted at Ramathibodi Hospital, the incidence was 24%, nearly the same in this study. Notably, the previous studies used the AAP 2009 phototherapy guidelines, and some included subthreshold phototherapy during birth admissions, while this study uses the AAP 2022 phototherapy guidelines, and our institution did not have guidelines for subthreshold phototherapy during birth admission. Also, the research by Wickremasinghe et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) showed that neonates who got subthreshold phototherapy during birth admission had a lower chance of being readmitted for post-discharge phototherapy without adverse outcomes. The study by Sarathy L et al. showed that the overall readmission rate for phototherapy remained stable after the new AAP 2022 guidelines (0.9% vs 0.8%). However, among readmitted jaundice neonates, those exceeding the phototherapy threshold increased from 11\u0026ndash;22.1%, and those receiving subthreshold phototherapy (exceed more than 2 mg/dL below the threshold) rose from 33\u0026ndash;50.5% (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). These findings suggest that while the overall rate of post-discharge phototherapy has remained stable, the characteristics of affected neonates have changed, with a higher reach of the phototherapy threshold and an increase in subthreshold phototherapy cases. This differs from our study, which observed a rising trend in the incidence of post-discharge phototherapy following the implementation of the new guidelines, along with an increase in subthreshold phototherapy cases. The higher rate of post-discharge phototherapy in this current study compared to previous studies could be due to the new phototherapy threshold changes based on the gestational age of neonates, and our hospital did not use subthreshold phototherapy guidelines. It may cause neonates who have low DeltaTB values, especially those who are in high-risk groups, to be discharged and have close follow-up within 1\u0026ndash;2 days. At follow-up time after discharge, their bilirubin levels met the threshold for phototherapy.\u003c/p\u003e \u003cp\u003eIn previous studies, the main causes of post-discharge phototherapy were inconclusive jaundice and breast non-feeding jaundice (\u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), which is consistent with our findings, where inconclusive jaundice was the leading cause, followed by breast non-feeding jaundice.\u003c/p\u003e \u003cp\u003eThe significant risk factor for post-discharge phototherapy in our study was post-discharge % weight loss greater than 4.18% at first follow up. This finding was consistent with other studies, such as the one by Booranavanich et al. at Vajira Hospital (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), which reported that weight loss greater than 3.31% was associated with post-discharge phototherapy. Similarly, the study by Prachukthum et al. at Thammasat Hospital (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) show that weight loss of greater than 6% on the second day of life was a risk factor for post-discharge phototherapy. These results suggest that the higher percentage of weight loss in the early days of life is a significant factor influencing the need for post-discharge phototherapy.\u003c/p\u003e \u003cp\u003eThis study found that the mean age onset of post-discharge phototherapy was 115 hours, or Day of Life (DOL) 4 to 5. This finding was similar to the study by Prachukthum et al. at Thammasat Hospital (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), where the onset of post-discharge phototherapy occurred around DOL 6. These results are consistent with the natural progression of neonatal jaundice, as total bilirubin levels typically rise and peak approximately on DOL 3 to 5 (72\u0026ndash;120 hours of age) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn this study, DeltaTB levels were categorized into three risk groups: high risk (DeltaTB\u0026thinsp;\u0026lt;\u0026thinsp;3.5), moderate risk (DeltaTB 3.5\u0026ndash;6.9), and low risk (DeltaTB\u0026thinsp;\u0026gt;\u0026thinsp;7). It was found that the incidence of post-discharge phototherapy was highest in the high-risk group as expected. However, even within the low-risk group, there remained a possibility of requiring post-discharge phototherapy. This highlights the importance of follow-up after discharge, as it is crucial for early detection and appropriate intervention, regardless of the initial risk classification.\u003c/p\u003e \u003cp\u003eThe optimal time to screen pre-discharge total bilirubin is between 49\u0026ndash;72 hours, as this provides the best prediction for the likelihood of post-discharge phototherapy. A cut-off value of 3.5 is identified as the threshold for predicting the need for post-discharge phototherapy with sensitivity at 80% and specificity at 82%. Additionally, it was observed that the younger the infant's age at the time of pre-discharge total bilirubin screening, the higher the cutoff value tends to be. This suggests that age at screening plays a role in determining the appropriate DeltaTB threshold for predicting the need for post-discharge phototherapy.\u003c/p\u003e \u003cp\u003eThe strength of this study is that it was a prospective cohort study in which all neonates were followed at least once to check their TSB levels. The limitations of this study include the small sample size and approximately 80% adherence to the follow-up protocol. This reduced adherence may be due to this guideline used by various levels of healthcare providers, which could result in inconsistent protocol compliance and varied management practices. It would be beneficial to provide better training, streamline the protocol, and monitor across all levels of healthcare providers to improve adherence. Subthreshold phototherapy during newborn admission should be used in high-risk groups, as it may reduce the post-discharge phototherapy rate. Furthermore, future research should involve multi-center cohort studies for validation and focus on clinical implications, such as the cost-effectiveness of pre-discharge subthreshold phototherapy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e After applying the AAP 2022 neonatal hyperbilirubinemia guidelines at our institution, we found an incidence of post-discharge phototherapy of 20.6%, which significantly increased compared to other studies that used the AAP 2009 guidelines. The high-risk group neonates with a DeltaTB\u0026thinsp;\u0026lt;\u0026thinsp;3.5 mg/dL were at the highest risk of requiring post-discharge phototherapy. However, post-discharge phototherapy was still observed in the low-risk group. Therefore, at least one post-discharge follow-up is needed for all neonates. Pre-discharge total bilirubin screening should be performed between 49\u0026ndash;72 hours of life, as this is the optimal time for predicting the need for post-discharge phototherapy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Research Ethics Committee of the Faculty of Medicine at Chiang Mai University (Study code: PED-2566-0283). Written informed consent was obtained from the parents or legal guardians of all participants before their enrollment in the study.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author confirms that there is no research data available outside the submitted manuscript file.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no funding.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll the authors have made substantial contributions to the intellectual content of the paper. Maneesilasan T. contributed to the concept and design of the study, acquisition and analysis of the data, and the draft of the manuscript. Pomrop M. contributed to the concept and design of the study, analysis, and interpretation of the data and critically revised the manuscript. All authors approved the final manuscript as submitted.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to express their sincere gratitude to Kosarat S. and Prempraphan P. for their valuable support, guidance, and suggestions in improving this study.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMitra S, Rennie J. Neonatal jaundice: aetiology, diagnosis and treatment. Br J Hosp Med (Lond). 2017;78(12):699-704.\u003c/li\u003e\n\u003cli\u003eOkulu E. Neonatal jaundice: Recommendations for follow-up and treatment. Global Pediatrics. 2024;7:100131.\u003c/li\u003e\n\u003cli\u003eMaisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF. Hyperbilirubinemia in the newborn infant \u0026gt; or =35 weeks\u0026apos; gestation: an update with clarifications. Pediatrics. 2009;124(4):1193-8.\u003c/li\u003e\n\u003cli\u003eKhan DS, Mirza A, Bhatti A, Shabbir A, Tariq B, Rizvi A. Effectiveness of Transcutaneous Bilirubin Measurement in High-Risk Neonates and to Evaluate Validity of Transcutaneous Bilirubin With Total Serum Bilirubin Levels in Both Low and High-Risk Neonates at a Tertiary Care Center in a Developing Country. Cureus. 2021;13(3):e13685.\u003c/li\u003e\n\u003cli\u003eKemper AR, Newman TB, Slaughter JL, Maisels MJ, Watchko JF, Downs SM, et al. Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics. 2022;150(3).\u003c/li\u003e\n\u003cli\u003eBlumovich A, Mangel L, Yochpaz S, Mandel D, Marom R. Risk factors for readmission for phototherapy due to jaundice in healthy newborns: a retrospective, observational study. BMC Pediatrics. 2020;20(1):248.\u003c/li\u003e\n\u003cli\u003eHansen TWR. Narrative review of the epidemiology of neonatal jaundice. Pediatric Medicine. 2021;4.\u003c/li\u003e\n\u003cli\u003eRajan N, Kumar Kommu PP, Krishnan L, Mani M. Significant Hyperbilirubinemia in Near-term and Term Newborns: A Case\u0026ndash;Control Study. Journal of Clinical Neonatology. 2017;6(4).\u003c/li\u003e\n\u003cli\u003eBattersby C, Michaelides S, Upton M, Rennie JM. Term admissions to neonatal units in England: a role for transitional care? A retrospective cohort study. BMJ Open. 2017;7(5):e016050.\u003c/li\u003e\n\u003cli\u003eYu ZB, Han SP, Chen C. Bilirubin nomograms for identification of neonatal hyperbilirubinemia in healthy term and late-preterm infants: a systematic review and meta-analysis. World J Pediatr. 2014;10(3):211-8.\u003c/li\u003e\n\u003cli\u003eThielemans L, Peerawaranun P, Mukaka M, Paw MK, Wiladphaingern J, Landier J, et al. High levels of pathological jaundice in the first 24 hours and neonatal hyperbilirubinaemia in an epidemiological cohort study on the Thailand-Myanmar border. PLoS One. 2021;16(10):e0258127.\u003c/li\u003e\n\u003cli\u003eTikmani SS, Warraich HJ, Abbasi F, Rizvi A, Darmstadt GL, Zaidi AK. Incidence of neonatal hyperbilirubinemia: a population-based prospective study in Pakistan. Trop Med Int Health. 2010;15(5):502-7.\u003c/li\u003e\n\u003cli\u003eMaisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med. 2008;358(9):920-8.\u003c/li\u003e\n\u003cli\u003eWatchko JF. Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in newborns. Neuromolecular Med. 2006;8(4):513-29.\u003c/li\u003e\n\u003cli\u003eAmerican Academy of Pediatrics Subcommittee on H. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004;114(1):297-316.\u003c/li\u003e\n\u003cli\u003eBhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin North Am. 2004;51(4):843-61, vii.\u003c/li\u003e\n\u003cli\u003eTantiprabha W, Tiyaprasertkul W. Transcutaneous bilirubin nomogram for the first 144\u0026thinsp;hours in Thai neonates. J Matern Fetal Neonatal Med. 2020;33(10):1688-94.\u003c/li\u003e\n\u003cli\u003eBooranavanich K, Chakthranont N. Incidence and Risks of Readmission due to Neonatal Jaundice. Vajira Medical Journal : Journal of Urban Medicine. 2022;66(4):237-44.\u003c/li\u003e\n\u003cli\u003ePrachukthum S, Tanprasertkul C, Intarakhao S. Predictive Factors for Term Infants with Neonatal Hyperbilirubinemia Requiring Readmission for Phototherapy. Asian Medical Journal and Alternative Medicine. 2021;21(1):14-20.\u003c/li\u003e\n\u003cli\u003eKuzniewicz MW, Park J, Niki H, Walsh EM, McCulloch CE, Newman TB. Predicting the Need for Phototherapy After Discharge. Pediatrics. 2021;147(5).\u003c/li\u003e\n\u003cli\u003eWickremasinghe AC, Kuzniewicz MW, McCulloch CE, Newman TB. Efficacy of Subthreshold Newborn Phototherapy During the Birth Hospitalization in Preventing Readmission for Phototherapy. JAMA Pediatr. 2018;172(4):378-85.\u003c/li\u003e\n\u003cli\u003eKankaew S, Daramas T, Patoomwan A. Frequency of Breastfeeding, Bilirubin Levels, and Re-admission for Jaundice in Neonates. The Bangkok Medical Journal. 2019;15(2):180.\u003c/li\u003e\n\u003cli\u003eSarathy L, Chou JH, Romano-Clarke G, Darci KA, Lerou PH. Bilirubin Measurement and Phototherapy Use After the AAP 2022 Newborn Hyperbilirubinemia Guideline. Pediatrics. 2024;153(4).\u003cstrong\u003e\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"neonatal jaundice, post-discharge phototherapy, new phototherapy guideline 2022, pre-discharge delta total bilirubin","lastPublishedDoi":"10.21203/rs.3.rs-6240272/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6240272/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe American Academy of Pediatrics recommended the use of pre-discharge delta total bilirubin (DeltaTB) to determine appropriate follow-up timing.\u003c/p\u003e\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo determine the incidence of post-discharge phototherapy after using the predischarge DeltaTB and to evaluate the effectiveness of DeltaTB to predict post-discharge phototherapy needs.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis is a prospective cohort study conducted at Chiang Mai University Hospital. The pre-discharge DeltaTB, defined as the difference between the bilirubin level and the phototherapy threshold at the time of measurement. Based on pre-discharge DeltaTB (mg/dL), patients were categorized into 3 risk groups: high-risk (\u0026lt;\u0026thinsp;3.5), moderate risk (3.5\u0026ndash;6.9) and high risk (\u0026gt;\u0026thinsp;7). Post-discharge phototherapy, pre-discharge TB, and number of follow-up were compared between the risk groups. DeltaTB levels in different age intervals were analyzed using ROC curve analysis to determine the cutoff in each interval.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOut of 150 neonates, 31 (20.6%) required post-discharge phototherapy, with 9 neonates were classified as requiring subthreshold phototherapy. There were 17.3%, 53.3% and 19.3% of 150 neonates categorized as high, moderate, and low risk by pre-discharge DeltaTB, respectively. The high-risk group, had the highest incidence of post-discharge phototherapy, mean pre-discharge bilirubin level and number of follow-up visits and were significantly different from other groups (\u003cem\u003eP-value\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The optimal timing for measuring pre-discharge bilirubin was aged 49\u0026ndash;72 hours (AUC of 0.851).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e According to the new guideline, 20.6% required post-discharge phototherapy without any cases of severe hyperbilirubinemia. The pre-discharge DeltaTB was effective to differentiate the risk of need post-discharge phototherapy. The incidence of post-discharge phototherapy was significantly higher in high-risk group compared to others.\u003c/p\u003e","manuscriptTitle":"The application of pre-discharge delta total bilirubin to predict the need for post-discharge phototherapy in healthy neonates 35 weeks’ gestation or later","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 03:04:27","doi":"10.21203/rs.3.rs-6240272/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-30T14:03:27+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-27T18:59:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-24T04:25:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"71398068957587076368866598587731580681","date":"2025-04-19T09:05:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"37844368066023351461338816042709067187","date":"2025-04-19T08:57:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124730741052367441497101490206939415840","date":"2025-04-17T06:38:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-17T05:44:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-09T16:53:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-24T07:41:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-22T09:24:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2025-03-22T09:23:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2afd0fef-5779-4929-a271-a5f86fa13dcc","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-17T16:01:12+00:00","versionOfRecord":{"articleIdentity":"rs-6240272","link":"https://doi.org/10.1186/s12887-025-06238-8","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2025-11-14 15:57:44","publishedOnDateReadable":"November 14th, 2025"},"versionCreatedAt":"2025-05-07 03:04:27","video":"","vorDoi":"10.1186/s12887-025-06238-8","vorDoiUrl":"https://doi.org/10.1186/s12887-025-06238-8","workflowStages":[]},"version":"v1","identity":"rs-6240272","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6240272","identity":"rs-6240272","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}