Management Of Hyperbilirubinemia Research Articles

Phototherapy to Prevent Severe Neonatal Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation: Technical Report.

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." 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. 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. 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.

Bilirubin measurements in neonates: uniform neonatal treatment can only be achieved by improved standardization.

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 therole 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.

Management of Neonatal Hyperbilirubinemia: Shedding Light on the American Academy of Pediatrics 2022 Clinical Practice Guideline Revision.

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.].

Prophylactic efficacy of aqueous extract of unripe pawpaw (Carica papaya) fruit on hematological and biochemical parameters in induced hyperbilirubinemia Wistar rats

This research offers a comprehensive examination of hyperbilirubinaemia, characterized by elevated levels of bilirubin in the bloodstream leading to jaundice. It presents a prevalent challenge during the neonatal phase, as bilirubin can accumulate in various body parts resulting in potential neurotoxicity. The discussion encompasses factors influencing bilirubin production, conjugation, and elimination in the organism, along with an overview of the causes and symptoms of hyperbilirubinaemia. The study delves into the potential advantages of utilizing Carica papaya, a tropical fruit, for the prevention of hyperbilirubinaemia. Traditional medical approaches for managing this condition are linked to numerous adverse effects, hence the necessity to develop more affordable, easily accessible, and efficacious drugs with minimal or no side effects. Blood samples were procured and subjected to full blood cell count analysis via an automated hematologic analyzer, while serum samples were utilized for quantifying liver enzymes and bilirubin employing a spectrophotometric technique. Additionally, the weight of visceral organs was determined using a Mettler weighing balance. The outcomes of an experimental study conducted on rodents revealed that pretreatment with Carica papaya extract notably decreased bilirubin and liver enzyme levels in the subjects. This highlights the potential role of Carica papaya in the preventive management of hyperbilirubinaemia, underscoring the imperative for further investigation in this domain. In essence, this research serves as a valuable repository of knowledge for healthcare practitioners and researchers keen on addressing hyperbilirubinaemia.

Ontario Midwifery Clients' Experiences with the Management of Hyperbilirubinemia

Hyperbilirubinemia is the most common reason for the hospitalization of a newborn within the first week of life. Very little is known, however, about the impact this diagnosis and subsequent management has on parents, particularly within the midwifery context. The Clinical Knowledge Translation department at the Association of Ontario Midwives conducted a multimethod qualitative research study in 2017 to better understand the experiences of midwifery clients whose newborns have been diagnosed with and required management of severe hyperbilirubinemia. Three focus-group discussions and one in-depth, in-person interview were conducted with midwifery clients in Ontario. Findings were analyzed using NVivo software, resulting in the extraction of key themes. Clients discussed how the transition from midwifery-led care to care being led by other health care providers in the hospital impacted them in the postpartum period. Clients also observed changes in the continuity of care provided by their midwives during management of hyperbilirubinemia, and discussed both the positive and negative impacts these changes had on their broader experience of the early postpartum period. These findings have informed the development of a series of knowledge translation tools that support midwives in providing optimal care to clients whose infants require phototherapy. This article has been peer reviewed.

Evaluating the Phototherapy Practice and Adherence to Guideline in Managing Neonatal Hyperbilirubinemia in an Indonesian Tertiary Referral Hospital

A guideline for the management of hyperbilirubinemia in infants has recently been established in Indonesia, but physician acceptance and adherence to these standards are unknown. The objective of this study was to assess the current state of phototherapy practice and to determine if this was in-line with the Indonesian Hyperbilirubinemia Guideline. The study was done in the neonatal care units of Dr. Soetomo Hospital in Surabaya, Indonesia. We evaluated all babies on phototherapy between September 2019 and September 2020. The conformity to core elements in the national guideline was assessed on hyperbilirubinemia management for 89 infants, two-third of these being preterm and low birth weight. One-third of infants were commenced on phototherapy just based on transcutaneous bilirubin measurement. A significant proportion of infants had phototherapy ceased without bilirubin level assessment or confirmation that jaundice had significantly resolved. Almost all (95.9%) of the phototherapy sessions did not conform to guidelines, with the most common being inadequate exposure of the body surface area to light. In spite of a guideline adapted to be pragmatic and applicable to the local setting, healthcare practitioners were not sufficiently aligned, thus an urgent reassessment of the implementation and adoption of the current hyperbilirubinemia guideline is required.

Hypocalcaemia- The detrimental effect of phototherapy.

Background: Jaundice is the single most common abnormal physical finding in the first week of life. Jaundice is observed during the 1st week of life in approximately 60% of term infants and 80% of preterm infants. The most common used methods of treating hyperbilirubinemia are phototherapy, exchange transfusion and pharmacological therapy. Potential but lesser known complication of phototherapy is hypocalcaemia. Our objective is to study the effect of phototherapy used for the management of hyperbilirubinemia and its consequent effect on calcium homeostasis.
 
 Methodology: This study was conducted on total 180 neonates admitted to Neonatal intensive care unit of a tertiary care center of ‘Steel city of Central India’. All study participants are included in two groups. One group included 45 preterm neonates (gestational age >32 week but <37 week) and other group included 45 full term neonates (gestational age >37 week). In addition, 45 neonates served in each group as control. All had hyperbilirubinemia. The controls were fully matched with the study group. All the neonates included in the study group required management with phototherapy. The neonates in the control group were managed without phototherapy. Total Serum bilirubin levels and serum calcium levels were checked before and after phototherapy.
 
 Result: The mean total serum calcium showed a statistically significant fall after exposure to phototherapy in the study group. The commonest complication observed after phototherapy was loose stools and rashes in preterm and full term neonates.
 
 Conclusion: In neonates with hyperbilirubinemia serum calcium level significantly decreases due to phototherapy. Preterm new-borns suffer more from hypocalcaemia than full term new-borns after receiving phototherapy.

Updated Clinical Practice Guidelines for Management of Hyperbilirubinemia in Infants Born at 35 Weeks or More Gestation.

Given the prevalence of jaundice in newborns, and the consequences of untreated hyperbilirubinemia, the long-awaited revised clinical practice guidelines for hyperbilirubinemia were finally released in August 2022 by the American Academy of Pediatrics as an update to the 2004 guidelines on the same topic. As new evidence and data become available, it is important for pediatricians and neonatologists to re-assess their clinical decision-making over time to ensure that patients are receiving the best care possible. With improvements in medical equipment and medical technology, and growing concerns about the overtreatment of hyperbilirubinemia, the newest clinical practice guidelines attempt to tackle the prevention, risk assessment, monitoring, and treatment of hyperbilirubinemia with these things in mind. [Pediatr Ann. 2023;52(12):e436-e439.].

Know Your Guidelines Series: Key Recommendations for the Hospitalist from the 2022 AAP Clinical Practice Guideline on the Management of Hyperbilirubinemia.

Know Your Guidelines Series: Key Recommendations for the Hospitalist from the 2022 AAP Clinical Practice Guideline on the Management of Hyperbilirubinemia.

A "Gold Standard" Test for Diagnosing and Quantifying Hemolysis in Neonates and Infants.

Identifying "gold standard" diagnostic tests can promote evidence-based neonatology practice. Hemolysis is a pathological shortening of the erythrocyte lifespan, differing from erythrocyte senescence in responsible mechanisms and clinical implications. Diagnosing hemolysis goes beyond a binary (yes vs. no) determination. It is characterized according to magnitude, and as acute vs. chronic, and genetically based vs. not. For neonates with significant hyperbilirubinemia or anemia, detecting hemolysis and quantifying its magnitude provides diagnostic clarity. The 2022 American Academy of Pediatrics (AAP) Clinical Practice Guideline on management of hyperbilirubinemia in the newborn states that hemolysis is a risk factor for developing significant hyperbilirubinemia and neurotoxicity. The guideline recommends identifying hemolysis from any cause, but specific guidance is not provided. A spectrum of laboratory tests has been endorsed as diagnostic methods for hemolysis. Herein we examine these laboratory tests and recommend one as the "gold standard" for diagnosing and quantifying hemolysis in neonates and infants.

Gut–liver axis and the impact of probiotics on neonatal jaundice symptoms: a review

Neonatal jaundice, which can affect up to 60% of term and 80% of preterm babies, can have a serious detrimental effect on their health. The effects of microbiota on neonatal bilirubin are poorly understood, which creates a critical knowledge gap about how they affect the neonate's blood bilirubin levels and how the gut delicately balances close contact with the host. Prebiotics and probiotics have a significant impact on the management of hyperbilirubinemia, but their effectiveness is still being debated. To offer a compelling novel therapeutic approach for newborn hyperbilirubinemia, a thorough understanding of the process is required.

#6768 TIO2/TI3C2 NANOCOMPOSITES FOR BILIRUBIN CLEARANCE FROM BLOOD

Abstract Background and Aims The artificial liver treatment based on blood purification is an important and commonly used treatment for liver failure. Aggressive management of hyperbilirubinemia is one of the key steps to reduce mortality in patients with liver failure. Herein, targeting bilirubin in nano-sized, we synthesized a TiO2/Ti3C2 nanocomposite from Ti3C2 MXenes via hydrothermal oxidation for bilirubin clearance from whole blood. Method Firstly, Ti3C2 MXene was prepared by hydrofluoric acid etching method reported in our previous work [1]. Then, it was transferred into Teflon-lined stainless-steel autoclaves (2 mg/ml, 30 ml) and was undergone the hydrothermal process at 180 °C for 6 h and 12 h. TiO2/Ti3C2 nanocomposites were obtained after lyophilization. Hemocompatibility evaluation assays include hemolysis ratio test, complement activation (human complement fragment 5a (C5a)), contact activation (Thrombin–anti-thrombin (TAT) complex) and platelet activation (platelet factor 4 (PF 4)) were systemically conducted in vitro to evaluate the feasibility of the novel nanocomposites (0.5 mg/ml) in contact with blood. We evaluated the bilirubin adsorption capacity of original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) at the concentration of 0.5 mg/ml, respectively, in bilirubin solution (250 mg/l, 10 ml) for 2 h at 37 °C in an air bath away from light. The sphere-forming properties of TiO2/Ti3C2 with polyethersulfone (PES), a commonly used blood purification material, were first verified using a liquid-liquid inversion method. Results TiO2/Ti3C2 (6 h and 12 h) showed better hemocompatibility than the original Ti3C2 (0 h) (Figure 1). The bilirubin adsorption capacities by the original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) were 354.11 mg/g, 492.83 mg/g and 492.52 mg/g, respectively. From the original Ti3C2 (0 h) to TiO2/Ti3C2 (6 h), the clearance rate of bilirubin improved from 70.82% to 98.57%. Therefore, we chose TiO2/Ti3C2 (6 h) to verify the sphere-forming properties of TiO2/Ti3C2 with PES. TiO2/Ti3C2-PES spheres were constructed successfully by a liquid-liquid inversion method. More 3D porous structure on the surface and uniform distribution of TiO2/Ti3C2 (Ti element) in the substrate were observed via a scanning electron microscope (SEM) images and energy dispersive spectroscopy (EDS) mapping images (Figure 2). Conclusion The TiO2/Ti3C2 nanocomposite showed excellent bilirubin clearance capability, superior hemocompatibility, and the great application potential in the form of spheres for hemoperfusion, which may provide a promising choice in the performance enhancement of artificial liver characterized by bilirubin clearance. Importantly, the above properties are adjustable by the heating temperature and the time period, other application forms and strategies of the TiO2/Ti3C2 nanocomposite to target bilirubin in nano-sized are worth being explored and expected.

Determination of intensity and spread of light to the surrounding in conventional phototherapy and comparison with novel converging photo unit — an observational study

BackgroundBlue light phototherapy used extensively in the management of hyperbilirubinemia has many side effects like dry eyes, blurring, headache, and altered circadian rhythm. Healthcare providers working around the phototherapy are unduly exposed to these side effects. Altered circadian rhythm results in disruption in the sleep-wake cycle affecting healthcare providers particularly working during the night shift. The constant glare of the blue light interrupts in clinical observation of the baby on phototherapy. With the intent of providing effective phototherapy with minimal exposure of blue light to healthcare providers, a light source called the photo unit was designed and developed.The objective of this study was to estimate the intensity and spread of blue light to the surrounding in conventional phototherapy and to compare the same with newly developed converging photo unit.ResultsThe therapeutic range of irradiance was noted up to 22 inch in diameter with conventional phototherapy compared to only 7 inch with our photo unit. The light spread with a conventional phototherapy unit was seen beyond 50 inch in all directions whereas was confined to 19-inch diameter with photo unit.ConclusionPhoto unit developed by the authors has minimal divergence of light to the surrounding, thereby mitigating the side effects of blue light exposure to the people working in the vicinity. Multiple of these photo units can be used to make a phototherapy device.

Interpretation of the 2022 American Academy of Pediatrics guidelines for the management of hyperbilirubinemia in newborn infants

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

Long-Awaited AAP Hyperbilirubinemia Guidelines Have Arrived.

Long-Awaited AAP Hyperbilirubinemia Guidelines Have Arrived.

Intensive phototherapy as the initial management of severe hyperbilirubinemia in neonates

Hyperbilirubinemia is one of the most common clinical phenomena found in newborns, which is about 60% of term infants and 80% of preterm infants in the first week of life. Severe hyperbilirubinemia can cause encephalopathy and permanent neurodevelopmental damage with an incidence that varies between 4% - 60.3% and mortality rate of 13% to 56.8% worldwide. Phototherapy and exchange transfusion are therapeutic modalities for infants with severe hyperbilirubinemia. Intensive phototherapy has fewer side effects and can reduce the need for exchange transfusion. This treatment is rarely needed if intensive phototherapy is effective, current guidelines for the management of hyperbilirubinemia focus on the use of intensive phototherapy as initial treatment. This literature review aims to discuss intensive phototherapy as the initial management of severe hyperbilirubinemia in neonates.

Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study.

BackgroundNeonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET).MethodsThis retrospective cohort study was conducted at the Central Women’s Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer’s rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth.ResultsGroups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8–67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively).ConclusionThe management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.

Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation

Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation

Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.

Severe hyperbilirubinemia is associated with kernicterus. Informed guidance on hyperbilirubinemia management, including preventive treatment thresholds, is essential to safely minimize neurodevelopmental risk. To update the evidence base necessary to develop the 2022 American Academy of Pediatrics clinical practice guideline for management of hyperbilirubinemia in the newborn infant ≥35 weeks' gestation. PubMed. English language randomized controlled trials and observational studies. Excluded: case reports or series, nonsystematic reviews, and investigations focused on <35-weeks' gestation infants. Topics addressed in the previous clinical practice guideline (2004) and follow-up commentary (2009) were updated with new evidence published through March 2022. Evidence reviews were conducted for previously unaddressed topics (phototherapy-associated adverse effects and effectiveness of intravenous immune globulin [IVIG] to prevent exchange transfusion). New evidence indicates that neurotoxicity does not occur until bilirubin concentrations are well above the 2004 exchange transfusion thresholds. Systematic review of phototherapy-associated adverse effects found limited and/or inconsistent evidence of late adverse effects, including cancer and epilepsy. IVIG has unclear benefit for preventing exchange transfusion in infants with isoimmune hemolytic disease, with a possible risk of harm due to necrotizing enterocolitis. The search was limited to 1 database and English language studies. Accumulated evidence justified narrowly raising phototherapy treatment thresholds in the updated clinical practice guideline. Limited evidence for effectiveness with some evidence of risk of harm support the revised recommendations to limit IVIG use.

Evaluation of a mobile application tool (BiliNorm) to improve care for newborns with hyperbilirubinemia in Indonesia.

Severe hyperbilirubinemia is more frequent in low- and middle-income countries such as Indonesia than in high-income countries. One of the contributing factors might be the lack of adherence to existing guidelines on the diagnosis and treatment of hyperbilirubinemia. We developed a new national guideline for hyperbilirubinemia management in Indonesia. To help healthcare workers use this guideline, a web-based decision support tool application may improve both the adherence to the guideline and the care for infants with hyperbilirubinemia. We developed a web-based application (BiliNorm) to be used on a smartphone that displays the bilirubin level of the patient on the nomogram and advises about the treatment that should be started. Healthcare workers of two teaching hospitals in East Java, Indonesia, were trained on the use of BiliNorm. At 6 months after the introduction, a questionnaire was sent to those who worked with the application enquiring about their experiences. An observational study was conducted in two time epochs. A chart review of infants with hyperbilirubinemia in the two hospitals was sent. The appropriateness of hyperbilirubinemia management during a 6-month period before BiliNorm introduction was compared to that during a 7-month period after its introduction. A total of 43 participants filled in the questionnaire, the majority (72%) of them indicated that BiliNorm was well received and easy to use. Moreover, 84% indicated that BiliNorm was helpful for the decision to start phototherapy. Chart review of 255 infants before BiliNorm introduction and that of 181 infants after its introduction indicated that significantly more infants had received treatment according to the guideline (38% vs 51%, p = 0.006). Few infants received phototherapy, but bilirubin level was not measured (14% vs 7%, p = 0.024). There was no difference in the proportion of infants who were over- and under-treated (34% vs 32% and 14% vs 10%, respectively). The web-based decision tool BiliNorm appears to be a valuable application. It is easy to use for healthcare workers and helps them adhere to the guideline. It improves the care for infants with hyperbilirubinemia and may help reduce the incidence of severe hyperbilirubinemia in Indonesia.