Treatment Of Hyperbilirubinemia Research Articles

Supporting risk management through cyberspace: An adaptive network model simulating AI coach effects by inducing adherence to guidelines in neonatal medical protocols

In this article, it is shown how second-order adaptive agent-based network models can be used to support a medical team in healthcare institutions to adhere to specific Neonatal Hypoglycemia and Neonatal Hyperbilirubinemia treatment guidelines through the integration of an Artificial Intelligence (AI) Virtual Coach. The proposed AI Coach is designed to provide timely interventions and correct deviations when lapses in the health care practitioner’s internal mental model occur. Through simulating three different scenarios, the internal dynamics of these mental models, adaptive changes of these mental models (learning and forgetting), and the interaction between health care practitioners and the world is shown when: (1) There is perfect adherence to guidelines, (2) There is imperfect adherence to guidelines and (3) There is both perfect and imperfect adherence to guidelines alongside interventions of the AI Coach in the latter case.

Splanchnic and cerebral oxygenation during cyclic phototherapy in preterm infants with hyperbilirubinemia

Cyclic phototherapy (cPT) can achieve a reduction in total serum bilirubin comparable to that achieved with standard continuous PT in preterm infants. Our aim was to assess the effect of cPT on splanchnic (rSO2S) and cerebral (rSO2C) oxygenation measured by near-infrared spectroscopy (NIRS). We prospectively studied 16 infants with a gestational age of 25–34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebro-splanchnic oxygenation ratio (CSOR) were recorded before, during, and after cPT discontinuation. We found that rSO2S, FOES, and CSOR did not change during the study period. The overall duration of single or multiple courses of PT was 6.5 (6.0–13.5) h, but by cycling PT, the actual exposure was 3.0 (1.5–4.9) h. Twelve patients (75%) required 15 min/h cPT, and four (25%) required prolonging cPT to 30 min/h. None of the patients developed enteral feeding intolerance.Conclusions: cPT treatment of hyperbilirubinemia in preterm infants does not affect splanchnic oxygenation or intestinal oxygen blood extraction, likely due to the short exposure to PT light, and it could contribute to decreasing the risk of feeding intolerance.What is Known:• The assumption that phototherapy (PT) is innocuous with no serious adverse effects has been questioned.• Cyclic phototherapy (cPT) can achieve a reduction in total serum bilirubin comparable to that achieved with standard continuous PT in preterm infants.What is New:• Splanchnic and cerebral oxygenation measured by near-infrared spectroscopy did not change during KMC.• cPT can contribute to decrease the risk of feeding intolerance likely due to the short exposure to PT light.

Innovative Solutions in Neonatal Care: The Design and Implementation of a Multifunctional Incubator with Integrated Phototherapy for Enhanced Treatment of Hyperbilirubinemia in Newborns

Innovative Solutions in Neonatal Care: The Design and Implementation of a Multifunctional Incubator with Integrated Phototherapy for Enhanced Treatment of Hyperbilirubinemia in Newborns

Managing neonatal hyperbilirubinemia: An updated guideline.

More than 80% of newborn infants experience jaundice as a result of elevated bilirubin during the first few weeks after birth. In most cases, hyperbilirubinemia is physiologic, but persistent and extreme elevations can lead to serious long-term complications, such as kernicterus. To avoid these complications and help clinicians in the successful assessment, evaluation, and treatment of hyperbilirubinemia, the American Academy of Pediatrics updated its clinical practice guideline for neonatal hyperbilirubinemia. This article reviews the guideline and highlights significant updates, such as an elevation in the threshold for phototherapy and exchange transfusion, inclusion of gestational age, and removal of racially based norms.

Fabrication and characterization of chitin/collagen aerogels crosslinked by KH560 for bilirubin adsorption

Hemoperfusion is regarded as the most effective treatment for hyperbilirubinemia. The adsorbent play crucial important role for bilirubin removal. An ideal adsorbent should possess good biocompatibility as well as high bilirubin adsorption capacity. In this study, two natural polymers composed of chitin and collagen plus KH560 that served as a crosslinking agent were selected to fabricate chitin/collagen composite aerogels (CKC), and potentially used as efficient bilirubin adsorption. The fabricated CKC aerogels exhibited homogeneous, dense and nanoscale 3D-porous nanofibrous structures. And the CKC aerogels showed high adsorption capacity (209.62 ± 2.28 mg/g) for free bilirubin within 4 h. More important, dynamic adsorption experiment illustrated the adsorption capacity reached to 265.22 ± 4.77 mg/g, larger than that of static adsorption. The further tests manifested the CKC aerogels had excellent blood compatibility and no toxicity in vivo. This novel naturally-based aerogels were an economical, biocompatible and efficient adsorbent for the bilirubin removal, potentially providing new ideas for development of new adsorbents.

Theory-Driven Tailoring of the Microenvironment of Quaternary Ammonium Binding Sites on Electrospun Nanofibers for Efficient Bilirubin Removal in Hemoperfusion.

Efficient adsorbents for excess bilirubin removal are extremely important for the treatment of hyperbilirubinemia. However, traditional adsorbents, such as activated carbons and ion-exchange resins, still suffer from dissatisfactory adsorption performance and poor blood compatibility. Herein, we adopted a rational design strategy guided by density functional theory (DFT) calculations to prepare blood-compatible quaternary ammonium group grafted electrospun polyacrylonitrile nanofiber adsorbents. The calculation analysis and adsorption experiments were used to investigate the structure-function relationship between group types and bilirubin adsorption, both indicating that quaternary ammonium groups with suitable configurations played a crucial role in bilirubin binding. The obtained nanofiber adsorbents showed the bilirubin removal efficiency above 90% even at a coexisting BSA concentration of 50 g L-1. The maximum adsorption capacities were 818.9 mg g-1 in free bilirubin solution and 163.7 mg g-1 in albumin bound bilirubin solution. The nanofiber adsorbents also showed considerable bilirubin removal in dynamic adsorption to reduce the bilirubin concentration to a normal level, which was better than commercial activated carbons. Our study demonstrates the high feasibility of a theory-driven design method for the development of grafted electrospun nanofibers, which have good potential as bilirubin adsorbents in hemoperfusion applications.

Docosahexaenoic Acid Supplementation for Neonatal Hyperbilirubinemia: A Double-Blind, Randomized Clinical Trial.

Docosahexaenoic acid (DHA) is an essential component for brain development during fetal and early postnatal life. Hyperbilirubinemia is characterized by abnormally high levels of bilirubin in the bloodstream, frequently leading to jaundice in newborns. In severe instances, this condition can progress to neurological damage or kernicterus, a form of brain damage. Initial cell-based experiments conducted by our research team revealed that DHA significantly enhances the survival rate of nerve cells treated with bilirubin and diminishes the oxidative stress indicated by reduced peroxide activity caused by unconjugated bilirubin (UCB). Further investigations through animal studies demonstrated that DHA effectively mitigates bilirubin-induced brain injury in neonatal rats. However, the potential of DHA to decrease the incidence of bilirubin-induced brain damage in clinical settings has not been previously explored or reported. Infants with neonatal hyperbilirubinemia (n = 30 per group) participated in a double-blind, randomized, placebo-controlled parallel study. They received either 100 mg/d DHA or placebo syrup immediately when they were diagnosed. The study found that the bilirubin level at 48 hours of treatment, serum neuron-specific enolase (NSE) levels, mean phototherapy duration, and abnormal rate of cranial magnetic resonance imaging (MRI) were lower in the DHA group than those in the control group (P < .05). These results suggested that DHA is effective as an adjuvant treatment for hyperbilirubinemia in children. It can reduce the incidence of neonatal hyperbilirubinemia brain injury and plays a certain protective role. Clinical study on protective effect of DHA on neonatal bilirubin injury is registered at Chinese Clinical Trial Registry as ChiCTR2300070250.

Research collaboration and knowledge development in Africa: the case of neonatal conditions

The literature has discussed the positive/negative effects of research collaboration (RC). However, no study looks at the effect of RC especially international research collaboration (IRC) on key developments in a research area. Using Main Path Analysis (MPA), I examined the literature on neonatal conditions (NC) produced by African scientists between 2000 and 2019. I found the (1) estimates of deaths of children under five years and their causes, with a focus on neonates and stillbirths, (2) usefulness of tools to collect data on NC-related variables, (3) identification of interventions to reduce deaths, and (4) treatment of hyperbilirubinemia in African neonates as the most important developments in NC in Africa. The high presence of articles with RC, in the MPA, especially those involving IRC between one or more scientists from a single African country and scientists from several non-African countries (60% of the studies) highlights the positive effect of RC on key developments of an area. About 40% of the articles refer the Saving Newborns Lives programme, the Child Health Epidemiology Reference Group (CHERG) or the departments of the World Health Organization (WHO).

The effect of kangaroo mother care of newborns with indirect hyperbilirubinemia on breastfeeding

BackgroundPhototherapy used in the treatment of hyperbilirubinemia may have a negative effect on breastfeeding. AimThe aim of the study was to assess the effect of kangaroo mother care (KMC) applied to newborns with indirect hyperbilirubinemia on breastfeeding. MethodsThis was a non-randomized experimental study with a control group. The study was conducted with 54 neonates (30 control group, 24 experimental group) who met the inclusion criteria. Under the researcher's supervision, the experimental group received KMC twice during hospitalization, with each session lasting for 1 h, during which phototherapy was temporarily interrupted. ResultsThe KMC group had a significantly higher number of breastfeeding episodes, pre-discharge LATCH score, defecation, and a significantly shorter duration of phototherapy compared to those in the control group (p < 0.05). ConclusionKMC applied to newborns with indirect hyperbilirubinemia was found to increase breastfeeding, the LATCH score, and defecations, and decrease the phototherapy duration.

Collagen-modified chitosan microsphere as a novel hemoperfusion adsorbent for efficient removal of bilirubin from human plasma

Hemoperfusion is one of the most effective treatments for the removal of bilirubin from the blood. Chitosan (CS) has been widely investigated as a hemoperfusion adsorbent to remove bilirubin due to its biocompatibility and biodegradability. However, the limited adsorption capacity of CS for free bilirubin or albumin-rich bilirubin solution, and the strong adsorption for albumin, limit its extensive use. The goal of this work is to improve specific bilirubin adsorption of CS while reducing its adsorption for albumin. In this study, collagen (Col) was chosen as a ligand and grafted onto the surface of CS microspheres to form CS-Col microspheres and therefore to improve their adsorption performance for bilirubin. The maximum adsorption capacity of the CS-Col microspheres for bilirubin increases from 24.2 to 76.9 mg/g. The enhancement factor is higher than that of other CS-based adsorbents. Moreover, the adsorption of CS-Col microspheres for albumin is effectively reduced to 2.6 %, while maintaining good blood compatibility. Compared to other CS-based bilirubin adsorbents, our CS-Col microspheres have the advantage of specific adsorbing bilirubin against albumin due to introducing collagen. This work provides new directions for designing high-performance bilirubin adsorbents. Our CS-Col microspheres show great promise for the treatment of hyperbilirubinemia.

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.].

Clinical study to determine the predictability of significant rebound hyperbilirubinemia in neonates after phototherapy and conditions likely to be associated with it: Prospective observational study in a teaching hospital in Eastern India.

Neonatal hyperbilirubinemia is defined as yellowish discoloration of the skin, conjunctive, and sclera from the elevated serum or plasma bilirubin in the newborn. The standard of care for the management of neonatal hyperbilirubinemia is phototherapy to prevent long-term neurological sequelae. The aim of this study was to ascertain the predictability of significant rebound hyperbilirubinemia (SRH) in neonates after phototherapy and the factors associated with it. Neonates ≥ 35 weeks of gestation, who received treatment for hyperbilirubinemia and admitted in our hospital from 15th of March 2019 to 15th of September 2020 were enrolled after taking parental consent. SRH was defined as bilirubin levels crossing the treatment threshold within 72 hours of phototherapy termination. Logistic regression analysis was used to identify the predictability of SRH. Out of 400 neonates treated with phototherapy, 10% developed SRH. Prematurity (Gestational age < 37 weeks), low birth weight (Birth weight < 2000 gram), ABO and Rh incompatibility, Glucose-6-phophate dehydrogenase deficiency (G6PD) deficiency, sepsis, and longer duration of primary phototherapy were found to be significantly associated with rebound hyperbilirubinemia. The probability of SRH increases for all American Academy of Paediatrics (AAP) risk categories as the gestational age decreases and total serum bilirubin at the stoppage of phototherapy increases. The presence of risk factors should be taken into account while planning discharge and follow-up of neonates admitted for neonatal hyperbilirubinemia to prevent long-term complication of bilirubin neurotoxicity.

BSA-Grafted porous amino polypyrrole for efficient removal of excess bilirubin in hemoperfusion

Due to the low adsorption capacity, poor adsorption selectivity and poor biocompatibility of bilirubin adsorption materials currently used, it is still a challenge to design an efficient bilirubin removal material for the treatment of hyperbilirubinemia. In this work, BSA-grafted (bovine serum albumin) porous amino polypyrrole was constructed by grafting bovine serum albumin onto porous amino polypyrrole composites. Comparing with porous amino polypyrrole, its removal rate was as high as 90% in 25 mg/L conjugated bilirubin solution, and it has significantly improved the selectivity of adsorption. In addition, it has good blood compatibility and biocompatibility. Superhydrophobic interaction, hydrogen bond and pore filling were the main reasons for bilirubin adsorption. BSA-grafted porous amino polypyrrole has potential application value in whole blood perfusion.

Novel hemoperfusion adsorbents based on collagen for efficient bilirubin removal – A thought from yellow skin of patients with hyperbilirubinemia

Hemoperfusion is a well-developed method for removing bilirubin from patients with hyperbilirubinemia. The performance of adsorbents is crucial during the process. However, most adsorbents used for bilirubin removal are not suitable for clinical applications, because they either have poor adsorption performance or limited biocompatibility. Patients with hyperbilirubinemia usually have distinctive yellow skin, indicating that collagen, a primary component of the skin, may be an effective material for absorbing bilirubin from the blood. Based on this idea, we designed and synthesized collagen (Col) and collagen-polyethyleneimine (Col-PEI) microspheres and employed them as hemoperfusion adsorbents for bilirubin removal. The microspheres have an efficient adsorption rate, higher bilirubin adsorption capacity, and competitive adsorption of bilirubin in the bilirubin/bovine serum albumin (BSA) solution. The maximum adsorption capacities of Col and Col-PEI microspheres for bilirubin are 150.2 mg/g and 258.4 mg/g, respectively, which are higher than those of most traditional polymer microspheres. Additionally, the microspheres exhibit excellent blood compatibility originating from collagen. Our study provides a new collagen-based strategy for the hemoperfusion treatment of hyperbilirubinemia.

A Randomized Trial Comparing NeoLight Skylife and Blanket Phototherapy in Newborn Indirect Hyperbilirubinemia.

This investigation aimed to assess the safety and efficacy of NeoLight's Skylife phototherapy device for the treatment of hyperbilirubinemia. A prospective, two-arm, randomized, unblinded controlled investigation compared total serum bilirubin (TSB) levels at baseline and discharge for a new phototherapy device (Skylife) with an existing phototherapy treatment in newborn infants. The repeated-measures analysis of variance (RM-ANOVA) indicated a significant main effect for the treatment condition, F(1, 54) = 4.041, P = .049. Post hoc findings showed that the Skylife group had significantly lower TSB levels following treatment (n = 28, Mean = 11.36, SD = 1.69) compared with the standard of care group (n = 28, Mean = 12.37, SD = 2.08), t(54) = 2.01, P = .049). The Skylife phototherapy device was as effective as the currently used therapy, with a shift toward a more rapid decline in bilirubin levels. Using this device may potentially decrease the length of therapy and hospitalization.Clinical Trial Registration Comparison of Phototherapy Using Neolight Skylife Versus Standardized Phototherapy for Hyperbilirubinemia in Newborns is registered at clinicaltrials.gov as NCT03599258.

Indirect Neonatal Hyperbilirubinemia and the Role of Fenofibrate as an Adjuvant to Phototherapy.

One of the most prevalent illnesses in neonates that needs care and treatment is neonatal jaundice. Several drugs are used as pharmacological modalities for treating hyperbilirubinemia, like intravenous immunoglobulin, D-penicillamine, metalloporphyrin, phenobarbital, zinc sulfate and clofibrate. Previous studies suggest the usefulness of fenofibrate in the treatment of hyperbilirubinemia. The study aims at assessing the effectiveness of oral fenofibrate in the treatment of indirect neonatal hyperbilirubinemia in full-term neonates. This is a quasi-experimental study that was conducted at Heevi Pediatrics Teaching Hospital in Duhok, which is located in the Kurdistan Region of Iraq. It involved term infants who had jaundice. The neonates who were eligible for the study were randomly assigned to one of two groups: the intervention group or the control group. Both groups were treated with conventional phototherapy. Fenofibrate was administered in a single oral dose of 10 mg/kg to the participants in the intervention group. Throughout the entirety of the treatment, levels of total serum bilirubin were compared and contrasted between the two groups. After 12 h of treatment, a statistically significant difference (p-value = 0.001) was seen in the serum bilirubin levels between the two groups. The difference in serum bilirubin levels became significantly progressively pronounced after 24, 48, and 72 h. The average time of discharge was 63.6 h for the intervention group and 90.9 h for the control group, and this difference was statistically significant (p-value < 0.001). The time it takes to lower high bilirubin levels in neonates may be shortened by combining conventional phototherapy with a single oral dosage of 10 mg/kg fenofibrate. Consequently, these neonates will experience a shorter hospitalization and an accelerated discharge from the hospital.

Bilirubin- and Blue-Green Light-Induced Damage of Human Erythrocytes

Phototherapy is widely used for neonatal hyperbilirubinemia treatment; however, the most important but not completely recognized issue is the determination of the optimal spectral range of light that provides an effective reduction of bilirubin level in the blood of a newborn with minimal adverse side effects. This study demonstrates that the exposure of radiation from LED sources of blue (emission wavelength λ max = 463 nm, FWHM 20 nm) and green (λ max = 517 nm, FWHM 38 nm) spectral regions to the erythrocyte suspension with the same energy dose (D = 14.4 J/cm 2 ) leads to approximately equally effective hemolysis of erythrocytes. It is concluded that the damage of erythrocyte membranes is caused by the excitation of endogenous porphyrin and flavin photosensitizers contained in the cells in low concentrations, but characterized by high efficiency of singlet oxygen generation. When bilirubin is added to the erythrocyte suspension, a spontaneous (dark) erythrocyte hemolysis intensifies, but the light-induced hemolysis slows down (compared to cells containing no bilirubin). Under the same conditions, the leakage of potassium ions from light-exposed erythrocytes is accelerating, with the light of green spectral region has a more pronounced effect, despite more intense absorption of blue light by bilirubin localized in cells.

Preparation of chitin/MXene/poly(L-arginine) composite aerogel spheres for specific adsorption of bilirubin

Currently, hemoperfusion is clinically the most rapid and effective treatment for removing toxins from the blood. The core of hemoperfusion is the sorbent inside the hemoperfusion device. Due to the complex composition of the blood, adsorbents tend to adsorb substances such as proteins in the blood (non-specific adsorption) while adsorbing toxins. Hyperbilirubinemia is caused by excessive levels of bilirubin in the human blood, causing irreversible damage to the patient's brain and nervous system, and even leading to death. High adsorption and high biocompatibility adsorbents with specific bilirubin adsorption are urgently needed to treat hyperbilirubinemia. Herein, poly(L-arginine) (PLA) which can specifically adsorb bilirubin, was introduced into chitin/MXene (Ch/MX) composite aerogel spheres. Ch/MX/PLA prepared by supercritical CO2 technology had higher mechanical properties than Ch/MX and can withstand 50,000 times its own weight. The in vitro simulated hemoperfusion test showed that the adsorption capacity of Ch/MX/PLA was as high as 596.31 mg/g, which was 15.38 % higher than that of Ch/MX. Binary and ternary competitive adsorption tests showed that Ch/MX/PLA also had good adsorption capacity in the presence of a variety of interfering molecules. In addition, hemolysis rate testing and CCK-8 testing confirmed that Ch/MX/PLA had better biocompatibility and hemocompatibility. Ch/MX/PLA can meet the required properties of clinical hemoperfusion sorbents and has the ability to produce mass production. It has good application potential in the clinical treatment of hyperbilirubinemia.

Community health worker-led household screening and management of neonatal hyperbilirubinemia in rural Bangladesh: a cluster randomized control trial protocol

Background: Extreme hyperbilirubinemia leading to neurologic disability and death is disproportionately high in low to middle income countries (LMIC) such as Bangladesh, and is largely preventable through timely treatment. Of the estimated 50% of newborns born in LMICs born at home, few receive screening or treatment for hyperbilirubinemia, leading to 6 million newborns per year who need phototherapy treatment for hyperbilirubinemia but are untreated. Household screening and treatment for neonatal hyperbilirubinemia with phototherapy administered by a trained community health worker (CHW) may increase indicated treatment for neonatal hyperbilirubinemia in comparison to the existing care system in Bangladesh. Methods: 530 Bangladeshi women in their 2nd or 3rd trimester of pregnancy from the rural community of Sakhipur, Bangladesh will be recruited for a cluster randomized trial and randomized to the intervention arm — home screening and treatment for neonatal hyperbilirubinemia — or the comparison arm to receive usual care. In the intervention arm, CHWs will provide mothers with two prenatal visits, visit newborns by 2 days of age and then daily for 3 days to measure transcutaneous bilirubin (TcB) and monitor clinical danger signs. Newborns without danger signs but with a TcB above the treatment threshold &lt;15 mg/dL will be treated with light-emitting diode (LED) phototherapy at home. Newborns with danger signs or TcB &gt;15 mg/dL will be referred to a hospital for treatment. Treatment rates for neonatal hyperbilirubinemia in each arm will be compared. Conclusion: This study will evaluate the effectiveness of CHW-led home phototherapy to increase neonatal hyperbilirubinemia treatment rates in rural Bangladesh. LMICs are expanding access to postnatal care by using CHWs, and our work will give CHWs a curative treatment option for neonatal hyperbilirubinemia. Similar projects in other LMICs can be pursued to dramatically extend healthcare access to vulnerable newborns with hyperbilirubinemia.

Amino-rich nanofiber membrane with favorable hemocompatibility for highly efficient removal of bilirubin from plasma

Bilirubin is a serious toxin in the blood of liver failure patients, and the development of bilirubin adsorbent with high removal efficiency, excellent hemocompatibility is crucial to improve the efficacy of hemoperfusion therapy. Herein, PAN/PEI nanofiber membrane (NFM) with amino-rich and smooth surface structure was prepared through a more facile co-blended electrospun method. During simulated adsorption experiments in vitro, PAN/PEI NFMs exhibited a high adsorption capacity of 142.79 mg g−1 for free bilirubin at clinical bilirubin concentration (100 mg L-1) in patients with liver failure. In addition, the bilirubin removal efficiency in static adsorption exceeded 96% when the PAN/PEI NFMs addition was greater than 120 mg. In particular, PAN/PEI NFMs displayed excellent hemocompatibility, presented a low hemolysis rate (0.4%), favorable anti-adhesion properties for hemocyte and plasma protein, and had no significant effect on coagulation. The development of this facile method promotes the feasibility of nanofibrous membranes for the treatment of hyperbilirubinemia with significant implications for improving therapeutic efficacy.