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Extreme levels of bilirubin in newborn is a major cause of lifelong neurodevelopmental impairment, which places a financial burden on healthcare resources and caregivers. To determine the incidence, aetiology and short-term outcomes of extreme hyperbilirubinaemia in term infants born in a resource-limited setting. This is a retrospective observational study looking at term neonates with a birth weight ≥2500 g, born in the Western health subdistrict of Cape Town, South Africa, between 1 January 2019 and 31 December 2020, who were exposed to a serum bilirubin level of ≥430 µmol/L in the first week of life and received care in the public health system. Extreme hyperbilirubinaemia occurred in 59 term infants. The incidence was 74 cases per 100 000 (<0.01%) live births equating to 1 case in every 1345 live births. The cause of hyperbilirubinaemia was identified in 51 of the cases (86%), the most common being ABO incompatibility (31/51, 61%), followed by glucose-6-phosphate dehydrogenase deficiency (11/51, 22%). Twelve infants (20 %) underwent an exchange transfusion. Six infants were encephalopathic. Forty-seven infants (80%) were readmitted after initial post-natal discharge, with a mean age of readmission of 113 h old (SD 31 h). The incidence of extreme hyperbilirubinaemia in the Western health subdistrict of Cape Town is higher than in high-income settings. Further work should focus on training of healthcare workers and education of caregivers, for the early detection of significant hyperbilirubinaemia to prevent neurological complications caused by bilirubin toxicity.

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OBJECTIVE: To summarize the principles and application of phototherapy consistent with the current 2022 American Academy of Pediatrics "Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation." METHODS: Relevant literature was reviewed regarding phototherapy devices in the United States, specifically those that incorporate blue to blue-green light-emitting diode, fluorescent, halogen, or fiberoptic light sources, and their currently marketed indications. RESULTS: The efficacy of phototherapy devices varies widely because of nonstandardized use of light sources and configurations and irradiance meters. In summary, the most effective and safest devices have the following characteristics: (1) incorporation of narrow band blue-to-green light-emitting diode lamps (∼460-490 nm wavelength range; 478 nm optimal) that would best overlap the bilirubin absorption spectrum; (2) emission of irradiance of at least 30 µW/cm2/nm (in term infants); and (3) illumination of the exposed maximal body surface area of an infant (35% to 80%). Furthermore, accurate irradiance measurements should be performed using the appropriate irradiance meter calibrated for the wavelength range delivered by the phototherapy device. CONCLUSIONS: With proper administration of effective phototherapy to an infant without concurrent hemolysis, total serum or plasma bilirubin concentrations will decrease within the first 4 to 6 hours of initiation safely and effectively.

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This study aimed to assess the magnitude of hematological toxicity and associated factors in newborns with hyperbilirubinemia. A cross-sectional study was conducted from April to December 2023. A total of 247 newborns were included. The data were collected using questionnaires and a data extraction sheet. Four 4 ml of blood was collected. A Sysmex KX-21 analyzer was used for blood analysis, and a Mindray BS-240 analyzer was used for bilirubin measurement. The data were entered into Epi-data and analyzed by SPSS. The logistic regression was used. The P value was set at 0.05. Before phototherapy, the hematological toxicities, such as anemia, leucopenia, and thrombocytopenia, were 45.7%, 22.2%, and 6.1%, respectively, whereas after phototherapy, anemia and thrombocytopenia, significantly increased, but the leucopenia, significantly decreased. The risk of developing anemia increased, 3.5, 2.7, and 2.1-fold among newborns with bilirubin > 18 mg/dl, with Rh blood group incompatibility, and treated with intensive phototherapy, respectively. Both low birth weight and intensive phototherapy increased the incidence of thrombocytopenia by 2 and 3.4-fold, respectively. Hematological toxicity was found to be a severe public health issue in newborns. Thus, strict follow-up and early detection of toxicity by considering aggravation factors are necessary.

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Measurement of total bilirubin (TBil) concentration in serum is the gold standard approach for diagnosing neonatal unconjugated hyperbilirubinemia. It is of utmost importance that the measured TBil concentration is sufficiently accurate to prevent under treatment, unnecessary escalation of care, or overtreatment. However, it is widely recognized that TBil measurements urgently require improvement in neonatal clinical chemistry. External quality assessment (EQA) programs for TBil assess for differences between laboratories and provide supporting evidence of significant differences between various methods, manufacturers and measurement platforms. At the same time, many countries have adopted or only slightly adapted the neonatal hyperbilirubinemia management guidelines from the USA or UK, often without addressing differences in the methodology of TBil measurements. In this report, we provide an overview of the components of bilirubin that are measured by laboratory platforms, the availability of current reference measurement procedures and reference materials, and the role of EQA surveys in this context. Furthermore, the current status of agreement in neonatal bilirubin against clinical decision thresholds is reviewed. We advocate for enhancements in accuracy and comparability of neonatal TBil measurements, propose a path forward to accomplish this, and reflect on the position of the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Working Group Neonatal Bilirubin (WG-NB) in this matter.

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Background: Exchange transfusion (ET) is an effective treatment for acute bilirubin encephalopathy and extreme neonatal hyperbilirubinemia (ENH). It can reduce mortality and morbidity. This study aimed to investigate the trends and risk factors of ENH requiring ET in hospitalized neonates in Iran. Methods: A retrospective analysis of medical records of neonates who underwent ET due to ENH was conducted from 2011 to 2021, in Shiraz, Iran. Clinical records were used to gather demographic and laboratory data. The quantitative data were expressed as mean±SD, and qualitative data was presented as frequency and percentage. P<0.05 was considered statistically significant. Results: During the study, 377 ETs were performed for 329 patients. The annual rate of ET decreased by 71.2% during the study period. The most common risk factor of ENH was glucose-6-phosphate dehydrogenase (G6PD) deficiency (35%), followed by prematurity (13.06%), ABO hemolytic disease (7.6%), sepsis (6.4%), Rh hemolytic disease (6.08%), and minor blood group incompatibility (3.34%). In 28.52% of the cases, the cause of ENH was not identified. 17 (5.1%) neonates had acute bilirubin encephalopathy, of whom 6 (35.29%) had G6PD deficiency, 6 (35.29%) had ABO incompatibility, and 2 (11.76%) had Rh incompatibility. Conclusion: Although the rate of ET occurrence has decreased, it seems necessary to consider different risk factors and appropriate guidelines for early identification and management of neonates at risk of ENH should be developed. The findings of the study highlighted the important risk factors of ENH in southern Iran, allowing for the development of appropriate prevention strategies.

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OBJECTIVE: We aimed to evaluate the effect of hyperbilirubinemia and phototherapy on total apoptotic, platelet-derived, endothelial-derived, and tissue factor (TF)-positive apoptotic microparticle (MP) levels in neonates with nonhemolytic pathologic hyperbilirubinemia. METHODS: Thirty-three term neonates with nonhemolytic pathologic hyperbilirubinemia and 25 healthy term neonates were included. MP levels were analyzed by flow cytometry using peripheral blood samples only once for the neonates in the control group and twice for the neonates in the study group (before and after phototherapy). Annexin V-positive MPs were defined as apoptotic MPs. Platelet-derived MPs were defined as those containing CD31. MPs containing CD144 were defined as endothelial-derived MPs, and MPs expressing TF were identified as those containing CD142. RESULTS: The rates of total apoptotic and endothelial-derived apoptotic MPs were significantly higher in the study group than the control group before phototherapy (P = 0.012 and P = 0.003, respectively) and after phototherapy (P = 0.046 and P = 0.001, respectively). Total apoptotic, platelet-derived, endothelial-derived, and TF-positive apoptotic MPs did not show any significant differences before and after phototherapy in the study group (P = 0.908, P = 0.823, P = 0.748, and P = 0.437, respectively). CONCLUSIONS: Our study demonstrated that total apoptotic and endothelial-derived apoptotic MPs are increased in cases of nonhemolytic pathologic hyperbilirubinemia. We showed that phototherapy does not have a significant effect on apoptotic MP levels. Further studies are needed to evaluate the risk of elevated apoptotic MPs on the development of thromboembolism in neonates with nonhemolytic pathologic hyperbilirubinemia.

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High neonatal bilirubin is a common phenomenon responding to phototherapy. We report a case of a newborn with a highly elevated bilirubin of 37.3 mg/dL due to ABO incompatibility between the mother (Group O) and the newborn (Group A) requiring whole blood exchange, a procedure performed rarely to treat newborn hyperbilirubinemia. The newborn (38.8 weeks of gestation) initially showed a total bilirubin of 8.4 mg/dL and was discharged after being stabilized by phototherapy. However, the baby returned to the hospital with highly elevated bilirubin and was admitted to the Neonatal Intensive Care Unit (NICU). Emergent reconstituted whole blood exchanger therapy was initiated due to refractoriness to phototherapy and IVIG. Markedly elevated anti-A titer was found in the mother's blood (1:512) and cord blood (1:128). The baby was stabilized and eventually discharged with a serum bilirubin of 13.8 mg/dL. This case demonstrates the possible predictive value of mother/cord blood anti-A titers in severe newborn hyperbilirubinemia, which may prevent premature discharge and trigger early initiation of lifesaving therapy.

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To evaluate the risk of epilepsy in children who received neonatal phototherapy. A cohort of live singletons born at a Danish hospital (2002-2016) with a gestational age ≥ 35 weeks. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of epilepsy in children treated with neonatal phototherapy compared to children not treated with neonatal phototherapy in the general population, and in a subpopulation of children who had serum bilirubin measurement. Adjusted HRs (aHR) were computed using multivariable and propensity score matching models to take maternal and neonatal factors into consideration. Children were followed from day 29 after birth to diagnosis of epilepsy, death, emigration, or December 31, 2016. Among 65,365 children, 958 (1.5%) received neonatal phototherapy. Seven children (incidence rates (IRs): 10.8 /10,000 person-years) who received neonatal phototherapy and 354 children (IR: 7.7) who did not receive neonatal phototherapy were diagnosed with epilepsy. Neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 0.95, 95% CI: 0.43-2.09) and propensity score matched (aHR 0.94, 95% CI: 0.39-2.28) models. In the subpopulation of 9,378 children with bilirubin measurement, 928 (9.9%) received neonatal phototherapy. In the analysis of the subpopulation in which bilirubin level and age at the time of bilirubin measurement were further taking into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy using the multivariable (aHR 1.26, 95% CI: 0.54-2.97) and propensity score matched (aHR 1.24, 95% CI: 0.47-3.25) models,Conclusions: Neonatal phototherapy was not associated with an increased risk of epilepsy after taking maternal and neonatal factors into consideration. What is known: • A few studies have suggested that neonatal phototherapy for hyperbilirubinemia may increase the risk of childhood epilepsy. • Whether the observed associations contribute to hyperbilirubinemia, phototherapy, or underlying factors requires further investigation. What is new: • This study revealed no increased risk of epilepsy in children treated with neonatal phototherapy compared to children not treated with phototherapy after taking maternal and neonatal factors into consideration. • After further taking bilirubin level and age at the time of bilirubin measurement into consideration, neonatal phototherapy was not associated with an increased risk of epilepsy.

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Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g.    Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP.    Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.

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Neonatal hyperbilirubinemia is one of the most common conditions managed by pediatricians. Although many infants are affected, most will experience complete resolution without complication. Acute bilirubin encephalopathy and kernicterus are rare yet debilitating sequelae of severe hyperbilirubinemia that can be avoided through careful monitoring and treatment with phototherapy. Appropriate management of neonatal hyperbilirubinemia must balance the risks of these severe conditions with the effects of overtreatment. Released in 2022, the American Academy of Pediatrics revised the clinical practice guideline for the management of hyperbilirubinemia, which aims to provide that balance through updates to the previous guideline. This article will provide the reader with (1) an evidence-based harm and benefit analysis of the guideline, (2) an overview of key changes and clarifications made in the new guideline, and (3) a practical summary of guideline updates. [Pediatr Ann. 2024;53(6):e208-e216.].

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OBJECTIVE: To investigate the effects of tub bathing on the skin and bilirubin levels of newborns receiving tunnel and light-emitting diode phototherapy. METHODS: In this randomized controlled trial, hospitalized newborns diagnosed with hyperbilirubinemia treated with a tunnel or light-emitting diode device were randomly assigned to either the experimental (bath) or control (no bath) groups using a computer program. The skin integrity moisture balance of all groups was recorded using the Newborn Skin Condition Score at 6, 12, and 24 hours after phototherapy, and their total serum bilirubin measurements were evaluated. RESULTS: A statistically significant difference was observed in the babies' total serum bilirubin levels; this decrease was the highest in the experimental groups. Further, the skin integrity-moisture balance was higher in the experimental groups than in the control groups; it was highest in the tunnel-experimental group and lowest in the tunnel control group. CONCLUSIONS: These results show that bathing is effective in reducing total bilirubin levels. This study adds to the evidence on skin integrity and moisture balance in newborns who were bathed during phototherapy.

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OBJECTIVE: This study aimed to increase the adoption of revised newborn hyperbilirubinemia guidelines by building a clinical decision support (CDS) tool into templated notes. METHODS: We created a rule-based CDS tool that correctly populates the phototherapy threshold from more than 2,700 possible values directly into the note and guides clinicians to an appropriate follow-up plan consistent with the new recommendations. We manually reviewed notes before and after CDS tool implementation to evaluate new guidelines adherence, and surveys were used to assess clinicians' perceptions. RESULTS: Postintervention documentation showed a decrease in old risk stratification methods (48 to 0.4%, p < 0.01) and an increase in new phototherapy threshold usage (39 to 95%, p < 0.01) and inclusion of follow-up guidance (28 to 79%, p < 0.01). Survey responses on workflow efficiency and satisfaction did not significantly change after CDS tool implementation. CONCLUSION: Our study details an innovative CDS tool that contributed to increased adoption of newly revised guidelines after the addition of this tool to templated notes.

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AIM: To examine the association between Midwifery Continuity of Care (MCoC) and exclusive breastfeeding at hospital discharge and neonatal hyperbilirubinemia. METHODS: A matched cohort design was employed using data from the Swedish Pregnancy Register. The study included 12,096 women who gave birth at a university hospital in Stockholm, Sweden from January 2019 to August 2021. Women and newborns cared for in a MCoC model were compared with a propensity-score matched set receiving standard care. Risk ratios (RR) were determined with 95 % confidence intervals (CI) based on the matched cohort through modified Poisson regressions with robust standard error. A mediation analysis assessed the direct and indirect effects of MCoC on exclusive breastfeeding at hospital discharge and neonatal hyperbilirubinemia and to what extent the association was mediated by preterm birth. FINDING: Findings showed that MCoC was associated with a higher chance of exclusive breastfeeding rate (RR: 1.06, 95 % CI: 1.01-1.12) and lower risk of neonatal hyperbilirubinemia (RR: 0.51, 95 % CI: 0.32-0.82) compared with standard care. Mediation analysis demonstrated that lower preterm birth accounted for approximately 28 % of total effect on the reduced risk of neonatal hyperbilirubinemia. DISCUSSION/CONCLUSION: This matched cohort study provided preliminary evidence that MCoC models could be an intervention for improving exclusive breastfeeding rates at hospital discharge and reducing the risk of neonatal hyperbilirubinemia.

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BACKGROUND: The incidence of neonatal hyperbilirubinemia in Europe and the United States is estimated to be 3.2 and 4.4 per 10,000 live births, respectively. Abdominal massage for hyperbilirubinemia is considered a safe complementary treatment for infants that may increase number of defecations and decrease bilirubin levels. PURPOSE: This study was designed as a randomized controlled trial to determine the effect of abdominal massage on bilirubin levels in term infants receiving phototherapy. METHODS: The sample consisted of 43 term newborns (intervention group: 23; control group: 20) who received phototherapy in a university hospital between June 2019 and February 2021. Information and observation forms were used for data collection. The intervention group received 6 abdominal massages over 2 days, performed 3 times a day, 6 hours apart, and lasting 5 minutes each. RESULTS: Transcutaneous bilirubin levels and heart rate were significantly lower in the intervention group than in the control group at 48 hours (P = .015 and P = .033, respectively). Number of defecations was higher in the intervention group at 24 hours (P = .007) but there was no significant difference at 48 hours. The decrease in serum bilirubin between 24 and 48 hours was significantly greater in the intervention group (P = .005). IMPLICATION FOR PRACTICE AND RESEARCH: Abdominal massage was effective in reducing bilirubin levels and may increase the number of defecations. Providing massage training to the parents of infants who are discharged early could be a protective approach to prevent the rise in bilirubin levels.

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BACKGROUND: The American Academy of Pediatrics and the Canadian Paediatric Society both advise that all newborns should undergo bilirubin screening before leaving the hospital, and this has become the standard practice in both countries. However, the US Preventive Task Force has found no strong evidence to suggest that this practice of universal screening for bilirubin reduces the occurrence of significant outcomes such as bilirubin-induced neurologic dysfunction or kernicterus. OBJECTIVES: To evaluate the effectiveness of transcutaneous screening compared to visual inspection for hyperbilirubinemia to prevent the readmission of newborns (infants greater than 35 weeks' gestation) for phototherapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, ICTRP, and ISRCTN in June 2023. We also searched conference proceedings, and the reference lists of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, or prospective cohort studies with control arm that evaluated the use of transcutaneous bilirubin (TcB) screening for hyperbilirubinemia in newborns before hospital discharge. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) and 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to evaluate the certainty of evidence. MAIN RESULTS: We identified one RCT that met our inclusion criteria. The study included 1858 African newborns at 35 weeks' gestation or greater who were receiving routine care at a well-baby nursery, and were randomly recruited prior to discharge to undergo TcB screening. The study had good methodologic quality. TcB screening versus visual assessment of hyperbilirubinemia in newborns: - probably reduces readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - may have little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - probably increases the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - may have little or no effect on the rate of acute bilirubin encephalopathy (RR 0.33, 95% CI 0.01 to 8.18; low-certainty evidence). The study did not evaluate or report cost of care. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that TcB screening probably reduces hospital readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening may have little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening probably increases the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening may have little or no effect on the rate of acute bilirubin encephalopathy compared to visual inspection. Given that we have only identified one RCT, further studies are necessary to determine whether TcB screening can help to reduce readmission and complications related to neonatal hyperbilirubinemia. In settings with limited newborn follow-up after hospital discharge, identifying newborns at risk of severe hyperbilirubinemia before hospital discharge will be important to plan targeted follow-up of these infants.

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OBJECTIVES: Pediatric direct admissions (DA) have multiple benefits including reduced emergency department (ED) volumes, greater patient and provider satisfaction, and decreased costs without compromising patient safety. We sought to compare resource utilization and outcomes between patients with a primary diagnosis of neonatal hyperbilirubinemia directly admitted with those admitted from the ED. METHODS: Single-center, retrospective study at a large, academic, free-standing children's hospital (2017-2021). Patients were between 24 hours and 14 days old with a gestational age of ≥35 weeks, admitted with a primary diagnosis of neonatal hyperbilirubinemia. Outcomes included length of stay (LOS), time to clinical care, resource utilization, NICU transfer, and 7-day readmission for phototherapy. RESULTS: A total of 1098 patients were included, with 276 (25.1%) ED admissions and 822 (74.9%) DAs. DAs experienced a shorter median time to bilirubin level collection (1.9 vs 2.1 hours, P = .003), received less intravenous fluids (8.9% vs 51.4%, P < .001), had less bilirubin levels collected (median of 3.0 vs 4.0, P < .001), received phototherapy sooner (median of 0.8 vs 4.2 hours, P < .001), and had a shorter LOS (median of 21 vs 23 hours, P = .002). One patient who was directly admitted required transfer to the NICU. No differences were observed in the 7-day readmission rates for phototherapy. CONCLUSIONS: Directly admitting patients for the management of neonatal hyperbilirubinemia is a preferred alternative to ED admission as our study demonstrated that DAs had a shorter time to clinical care, shorter LOS, and less unnecessary resource utilization with no difference in 7-day readmissions for phototherapy.

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Persistent challenges in addressing severe neonatal hyperbilirubinaemia in resource-constrained settings have led to ongoing and often unacceptable rates of morbidity, disability and mortality. These challenges stem from limitations such as inadequate, inefficient or financially inaccessible diagnostic and therapeutic options. However, over the past decade, noteworthy innovations have emerged to address some of these hurdles, and these innovations are increasingly poised for broader implementation. This review provides a concise summary of these novel, economically viable diagnostic solutions, encompassing point-of-care assays and smartphone applications, as well as treatment modalities, notably more effective phototherapy and filtered sunlight. These advancements hold promise and have the potential to meaningfully reduce the burden of neonatal hyperbilirubinaemia, signifying a promising shift in the landscape of neonatal healthcare.

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