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Schematic illustration of bilirubin metabolism. Aging red blood cells are recognized and phagocytosed by mononuclear macrophages in the circulation, which then release hemoglobin. The released hemoglobin is catabolized to produce heme, which is then reduced and oxidized to bilirubin. Bilirubin formed by this process first binds to plasma albumin and is then transported to the liver as a bilirubin-albumin complex. Next, bilirubin is first separated from albumin and then taken up by hepatocytes. Subsequently, it is combined with ligandins (Y and Z proteins) to form a bilirubin-ligand complex, and is then transported to the smooth endoplasmic reticulum of the hepatocyte, where is conjugated with glucuronic acid to form conjugated bilirubin. Conjugated bilirubin is then released into the intestine with bile, hydrolyzed and reduced to generate bilinogen, the majority of which is excreted with the feces, while a small quantity of bilinogen is reabsorbed into the circulation by intestinal mucosal cells. The majority (~90%) of the reabsorbed bilinogen is discharged into the intestinal cavity with bile, forming the enterohepatic circulation of bilinogen, whereas only a small amount (~10%) enters the systemic circulation, passes through the kidneys and is excreted in the urine.
Source publication
Phototherapy is universally recognized as the first option for treating neonatal jaundice due to its unparalleled efficiency and safety in reducing the high serum free bilirubin levels and limiting its neurotoxic effects. However, several studies have suggested that phototherapy may elicit a series of short- and long-term adverse reactions associat...
Contexts in source publication
Context 1
... is reabsorbed into the circulation by intestinal mucosal cells. The majority (~90%) of the reabsorbed bilinogen is discharged into the intestinal cavity with bile, forming the enterohepatic circulation of bilinogen (18), whereas only a small amount (~10%) enters the systemic circulation, passes through the kidneys and is excreted in the urine (Fig. ...
Context 2
... main mechanism through which phototherapy removes unconjugated bilirubin from the body is by isomerization. As the newborn's antioxidant mechanisms are immature and the skin has low antioxidant capacity, blue light directly induces the generation of free oxygen radicals, which may cause DNA damage in the mitochondria and nucleus of the cell (41,103). p53 is a tumor suppressor gene that is mainly involved in maintaining normal cell growth and inhibiting malignant proliferation, and participates in the process of DNA replication and repair (104). If the repair mechanism fails, p53 induces cell apoptosis to prevent malignant transformation (105). ...
Similar publications
Jaundice caused by hyperbilirubinaemia is a common phenomenon during the neonatal period. Population-based studies evaluating assessment, management, and incidence of jaundice and need for phototherapy among otherwise healthy neonates are scarce. We prospectively explored these aspects in a primary care setting via assessing care as usual during th...
Neonatal jaundice contributes to around 16-18% of NICU admissions, next to respiratory problems
and sepsis. The present study was performed with the purpose of establishing the role of the various maternal
factors with hyperbilirubinemia in neonates. Material and method: The cross sectional study was conducted on
200 neonates upto 15 days of lif...
Citations
... It also affects the circadian rhythm of babies and causes dehydration, hypocalcaemia and renal damage. 13 Neonatal jaundice is occurring in varied incidence (about 60%-90%) worldwide. 6 The incidence in North America is about 34%. ...
Introduction
Neonatal jaundice is a common and life-threatening health problem in neonates due to overaccumulation of circulating unconjugated bilirubin. Gut flora has a potential influence on bilirubin metabolism. The infant gut microbiome is commonly copied from the maternal gut. During pregnancy, due to changes in dietary habits, hormones and body weight, maternal gut dysbiosis is common, which can be stabilised by probiotics supplementation. However, whether probiotic supplements can reach the baby through the mother and reduce the incidence of neonatal jaundice has not been studied yet. Therefore, we aim to evaluate the effect of prenatal maternal probiotic supplementation on the incidence of neonatal jaundice.
Methods and analysis
This is a randomised double-blind placebo-controlled clinical trial among 94 pregnant women (47 in each group) in a tertiary hospital in Hong Kong. Voluntary eligible participants will be recruited between 28 and 35 weeks of gestation. Computer-generated randomisation and allocation to either the intervention or control group will be carried out. Participants will take either one sachet of Vivomixx (450 billion colony-forming units per sachet) or a placebo per day until 1 week post partum. Neither the study participants nor researchers will know the randomisation and allocation. The intervention will be initiated at 36 weeks of gestation. Neonatal bilirubin level will be measured to determine the primary outcome (hyperbilirubinaemia) while the metagenomic microbiome profile of breast milk and maternal and infant stool samples as well as pregnancy outcomes will be secondary outcomes. Binary logistic and linear regressions will be carried out to assess the association of the microbiome data with different clinical outcomes.
Ethics and dissemination
Ethics approval is obtained from the Joint CUHK-NTEC Clinical Research Ethics Committee, Hong Kong (CREC Ref: 2023.100-T). Findings will be published in peer-reviewed journals and presented at international conferences.
Trial registration number
NCT06087874 .
... One of the early lines of treatment for jaundice is phototherapy, whereby light is employed to convert bilirubin into photoisomers that can be eliminated through bile and urine (4). If phototherapy does not yield a response, or in cases of severe jaundice, blood exchange transfusion may be considered (5). ...
Background and Objective: Jaundice is common in infants and occurs because of
hyperbilirubinemia, which can lead to brain injury in neonates. Phototherapy, in addition to its serious
side effects, does not seem to be enough in resolving jaundice. This clinical trial aims to compare the
efficacy of orlistat and phototherapy combination therapy with that of phototherapy alone in the
treatment of neonatal jaundice.
Methods: This clinical trial was performed on 120 term neonates with jaundice. Block randomization
was used to allocate the infants to the intervention and control groups. The intervention group
received orlistat (4 mg/kg body weight) for three consecutive oral doses at the first, second and third
day of hospitalization, along with phototherapy. The control group received a placebo and
phototherapy. Total and direct plasma bilirubin levels were measured at baseline (before
intervention) as well as 24 and 72 h after treatment.
Findings: There were no statistically significant differences between the two groups in terms of
infant sex, weight, or age. The mean total and direct bilirubin levels in the experimental group did
not change compared to those in the control group at the end of the trial (10.44±1.35 vs. 10.6±2.8
and 0.4±0.1 vs. 0.5±0.1, respectively).
Conclusion: Orlistat appears to be ineffective in accelerating bilirubin reduction in neonates with
jaundice, at least for the first three days of life
... Our patients were not in the risky premature infant's category and we did not identify any negative effects of phototherapy on Ca metabolism. Anyway, phototherapy-related hypocalcaemia is very rarely clinically evident and resolves spontaneously within 24 h after PT is discontinued [32]. ...
Phototherapy (PT) is a widely used treatment for neonatal jaundice, yet the ideal model of application remains controversial. In this study, the effects of continuous phototherapy (CPT) and intermittent phototherapy (IPT) models were compared in the treatment of neonatal indirect hyperbilirubinemia (IHB) and whether IPT is a superior modality is investigated. Single-centre parallel randomized controlled open label trial. A computer-based table of random numbers was used to allocate treatments. Newborns ≥ 34 weeks’ gestation who received phototherapy in our neonatal intensive care unit (NICU) between July 2022 and April 2023 were included. CPT was applied continuously for 6 h, and IPT was applied as 2 cycles of 1 h on and 2 h off in a 6-h session. Rebound TSB was measured 8 h after phototherapy was stopped in both groups. Phototherapy duration, TSB reduction rate and rebound bilirubin rate were compared between intervention groups. One hundered and four neonates met the inclusion criteria during the study period. CPT and IPT were each used in 52 newborns. Demographic characteristics of the study groups, including sex, mode of delivery, birth weight, admission weight, age at postnatal presentation, diet, discharge weight, and history of PT in siblings, were similar (p > 0.05). The most common cause of IHB in both groups was ABO incompatibility. The median phototherapy time was 12 h (6–15) in the CPT group and 4 h (2–4) in the IPT group (p < 0.001). The mean rate of bilirubin decrease was 1.12 ± 0.73 mg/dl/h in those who underwent IPT and 0.51 ± 0.33 mg/dl/h in those who underwent CPT (p < 0.001). The mean rebound bilirubin rate 8 h after phototherapy was 0.08 ± 0.28 mg/dl/h in the CPT group, and −0.01 ± 0.17 mg/dl/h in the IPT group (p = 0.039). The length of hospital stay was longer in the CPT group (p = 0.032). Skin rash, diarrhoea and increased body temperature were less frequent in the IPT group (p < 0.001).
Conclusions: In this study, IPT was found to be at least as effective as CPT in reducing total serum bilirubin. Even though the duration of PT is shorter in IPT, the slower rate of rebound bilirubin, shorter hospital stays and lower incidence of side effects indicated that intermittent phototherapy is superior to continuous phototherapy. Choosing IPT over CPT is a more rational approach in neonatal jaundice.
ClinicalTrials.gov Identifier: NCT 06386731 (registered retrospectively on 23/04/2024)
What is Known:
• PT is common used in the treatment of neonatal jaundice.
• There is no standard model of application for PT.
What is New:
• The IPT model is as effective as CPT.
• Newborns are discharged faster with IPT.
... A causal association has previously been reported between extreme levels of bilirubin and increased risk of gallstone disease (Stender et al., 2013). Bilirubin (E,E) is one of the water soluble isomers of bilirubin that is converted from unconjugated bilirubin (Z,Z) upon exposure to light (Wang et al., 2021). The identity of X-21796 is unknown. ...
Introduction: Circulating metabolites act as biomarkers of dysregulated metabolism and may inform disease pathophysiology. A portion of the inter-individual variability in circulating metabolites is influenced by common genetic variation. We evaluated whether a genetics-based “virtual” metabolomics approach can identify novel metabolite-disease associations.
Methods: We examined the association between polygenic scores for 724 metabolites with 1,247 clinical phenotypes in the BioVU DNA biobank, comprising 57,735 European ancestry and 15,754 African ancestry participants. We applied Mendelian randomization (MR) to probe significant relationships and validated significant MR associations using independent GWAS of candidate phenotypes.
Results and Discussion: We found significant associations between 336 metabolites and 168 phenotypes in European ancestry and 107 metabolites and 56 phenotypes in African ancestry. Of these metabolite-disease pairs, MR analyses confirmed associations between 73 metabolites and 53 phenotypes in European ancestry. Of 22 metabolitephenotype pairs evaluated for replication in independent GWAS, 16 were significant (false discovery rate p < 0.05). These included associations between bilirubin and X–21796 with cholelithiasis, phosphatidylcholine (16:0/22:5n3,18:1/20:4) and arachidonate with inflammatory bowel disease and Crohn’s disease, and campesterol with coronary artery disease and myocardial infarction. These associations may represent biomarkers or potentially targetable mediators of disease risk.
... 2 Previous studies have focused on the efficacy of phototherapy in reducing bilirubin levels, but a comprehensive understanding of its influence on electrolyte balance is yet to be elucidated. 3 Electrolyte imbalances in neonates can have profound consequences, impacting various physiological processes, including renal function and neuromuscular excitability. 4 This study, conducted at the Neonatology unit in Jawaharlal Nehru Medical College and AVBR Hospital, Sawangi, Wardha, Central India, aims to bridge this knowledge gap. ...
Introduction
This study protocol outlines a comprehensive investigation into the impact of phototherapy on electrolyte levels in newborns with hyperbilirubinemia. With a focus on neonates admitted to the Neonatal Intensive Care Unit (NICU) at Jawaharlal Nehru Medical College and AVBR Hospital, Sawangi, Wardha, Central India, the research aims to contribute valuable insights into the physiological changes associated with this common neonatal condition. The study’s introduction highlights the rationale, significance, and gaps in current knowledge, emphasising the need for a detailed exploration of electrolyte dynamics before and after phototherapy.
Method
The methodology involves a descriptive, interventional cross-sectional design with a calculated sample size of 264 neonates. Standardised protocols for data collection, including serum electrolyte analysis and urine-specific gravity assessment, will be employed. Inclusion and exclusion criteria are clearly defined to ensure a homogenous study population. Statistical analyses, utilising R Studio 4.3.1 will encompass descriptive statistics, comparative analysis, correlation analysis, and multivariate analysis to explore the nuanced relationships between variables. Rigorous ethical considerations and transparency in reporting will guide the data collection process.
Expected Result
Anticipated outcomes include a nuanced understanding of changes in serum electrolyte levels following phototherapy and the correlation of these changes with the treatment duration. The study is poised to shed light on the impact of gestational age and birth weight on electrolyte responses. Through rigorous statistical analysis, the research aims to provide evidence-based insights that can inform neonatal care protocols. The anticipated findings hold the potential to influence clinical practices, enhancing the quality of care provided to newborns with hyperbilirubinemia undergoing phototherapy.
... Currently available allergic rhinitis phototherapy devices on the market feature varying wavelengths and do not specify a time limit for the irradiation process. Exceeding the recommended time can result in dry nasal cavities and a burning sensation, while using phototherapy for a shorter duration may delay the healing process and potentially worsen allergic rhinitis symptoms [12], [13]. ...
The set of timers in using phototherapy is major problem which has to be resolved to get a good performance of rhinitis phototherapy. This research aims to develop a prototype of phototherapy for allergic rhinitis, incorporating a timer based on light energy. The prototype utilizes a laser diode as a visible light source, specifically with a wavelength of 650 nm. The recommended safe and effective dose of light energy ranges from 1 to 10 Joules, which has been converted into minutes. Measurement tests indicate an average wavelength of 652.40 nm for the right laser, with a measurement uncertainty of ±0.11, and 653.23 nm for the left laser, with a measurement uncertainty of ±0.05. The laser diode source has an average voltage of 1.91 volts and an average current of 1.89 milliamperes, with a measurement uncertainty of ±0.00 and ±0.01, respectively. Additionally, the average discrepancy in the timer is 0.082 minutes for the 10-minute setting and 0.082 minutes for the 20-minute setting. These results confirm the effectiveness and suitability of the developed tool for practical use. The proposed method was useful for rhinitis therapy by using light energy.
... When an infant's skin is exposed to light, the non-polar unconjugated bilirubin present in the skin undergoes a process known as photoisomerization. This transformation results in the conversion of bilirubin into water-soluble isomers that can be readily excreted from the body through bile or urine, consequently reducing serum bilirubin levels [13]. The efficacy and speed of this photoisomerization process are significantly influenced by the dose of phototherapy, a metric determined by factors such as the wavelength of the light, its intensity, and the distance between the light source and the infant [3]. ...
... Despite its efficacy, phototherapy is not without potential drawbacks. Excessive bilirubin decomposition induced by phototherapy may stimulate the intestinal wall, leading to unintended consequences [13]. Furthermore, the skin's protective barrier can be compromised during phototherapy, resulting in adverse effects such as burns, retinal damage, thermoregulatory instability, loose stools, dehydration, and skin irritation [20]. ...
... In the short term, adverse effects encompass skin rashes, dehydration, and disruptions in electrolyte balance. The spectrum of long-term adverse effects extends to concerns such as DNA damage, elevated cancer risk, and potential neurodevelopmental delays [13]. Notably, a study has posited an association between phototherapy and the occurrence of late-onset solid tumors, including those affecting the brain and central nervous system [48]. ...
This comprehensive review thoroughly examines the historical evolution, physiological foundations, and contemporary advancements in the application of phototherapy for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia, a common condition resulting from the immature hepatic processes in newborns, poses potential risks, including neurotoxicity, if left untreated. The review traces the historical progression from early recognition of neonatal jaundice to the development of various phototherapy modalities, showcasing the dynamic landscape of neonatal care. Emphasizing the physiological intricacies of bilirubin metabolism in neonates, the study underscores the vulnerability of newborns to hyperbilirubinemia due to delayed hepatic maturation. Phototherapy is a cornerstone in managing hyperbilirubinemia, demonstrating consistent efficacy in reducing unconjugated bilirubin levels. The implications for clinical practice are significant, offering healthcare professionals insights into tailoring treatment strategies based on individual neonatal characteristics and the severity of jaundice. Integrating advanced monitoring and control systems enhances the precision and safety of phototherapy. Recommendations for future research emphasize the need to investigate long-term outcomes, explore adjunctive therapies, and address resource limitations to ensure global access to effective neonatal care. Overall, this review contributes to the ongoing refinement of neonatal care practices, offering a comprehensive understanding of neonatal hyperbilirubinemia and its evolving treatment landscape.
... While phototherapy is broadly safe, and the benefits of preventing acute bilirubin encephalopathy and kernicterus unambiguously outweigh the harms, recent research highlights phototherapy risks. [3][4][5] Phototherapy utilization interferes with infant-mother bonding and breastfeeding, as it requires physical separation of the infant into an isolette or bassinet, which can interfere with breastfeeding. 6 Phototherapy use may also be associated with a slight, yet significant increase in the risk of childhood epilepsy and hematologic malignancies. ...
Introduction
Infants commonly require phototherapy in the nursery to prevent kernicterus, but it can interfere with parent-infant bonding. Minimizing unnecessary phototherapy is important. We noticed frequent delays in initiating and discontinuing phototherapy at our hospital. Our primary aim was to start or stop phototherapy within 3 hours of the intended blood draw time for more than 80% of patients by August 2022. Our secondary aims were to have the bilirubin result available within two hours of the intended draw time and for the result to be actioned upon within 1 hour of becoming available.
Methods
We audited all patients requiring phototherapy, from January 2021 to December 2021 (n = 250). In PDSA cycle 1, we used electronic medical record result alerts. In cycle 2, we educated residents on the importance of acting promptly on results. In cycle 3, we asked residents to message the nurse to alert them to any laboratory draws for that shift. In cycle 4, we implemented a standardized laboratory draw policy.
Results
We increased the percentage of results acted upon within 3 hours from 56% to more than 80%. We also reduced the mean time from blood draw to action from 184 minutes to 134 minutes. The time from intended draw to result availability decreased from 115 minutes to 95 minutes, and the time to action decreased from 67 minutes to 42 minutes.
Conclusions
Combining resident education, electronic medical record result alerts, and policy standardization allowed us to achieve our stated aim and improved care for our neonates.
... The prompt identification of clinically significant hyperbilirubinemia is of paramount importance in averting kernicterus (28). Phototherapy remains the conventional approach to hyperbilirubinemia treatment, although exchange transfusions may be requisite in severe cases (29). While exchange transfusions are infrequent in high-income nations, it's risk persists in low-income and lower-middle-income countries (26). ...
All national and international pediatric guidelines universally prescribe meticulous bilirubin screening for neonates as a critical measure to mitigate the incidence of acute bilirubin encephalopathy (ABE) and Kernicterus. The prevailing gold standard for jaundice detection in neonates necessitates invasive blood collection, followed by subsequent biochemical testing. While the invasive procedure provides dependable bilirubin measurements and continues to be the sole gold standard diagnostic method for assessing bilirubin concentration. There exists a pressing need to innovate non-invasive screening tools that alleviate the sampling stress endured by newborns, mitigate iatrogenic anemia, and expedite the turnaround time for obtaining results. The exploration of non-invasive modalities for bilirubin measurements is gaining momentum, driven by the overarching goal of minimizing the number of pricks inflicted upon neonates, thereby rendering screening a swift, efficient, comfortable, and dependable process. This comprehensive review article delves extensively into the array of non-invasive approaches and digital solutions that have been proposed, implemented, and utilized for neonatal bilirubin screening, with a particular emphasis on their application in low-resource settings. Within this context, the review sheds light on the existing methodologies and their practical applications, with a specific focus on transcutaneous bilirubin meters. Moreover, it underscores the prevailing open challenges in this domain and outlines potential directions for future research endeavors. Notably, the review underscores the imperative need for robust educational programs targeted at both families and healthcare personnel to expedite the process of seeking timely care for neonatal jaundice. Additionally, it underscores the necessity for the development of enhanced screening and diagnostic tools that can offer greater accuracy in clinical practice.
... Mothers of newborns who develop jaundice are more likely to interrupt breastfeeding, even if the interruption is not necessary(18). It should be noted that phototherapy is associated with changes in the circadian rhythm (3,19) which can interfere with breastfeeding performance (20). ...
Background: Prematurity is a risk factor for eating disorders. However, late preterm newborns are generally cared for in a rooming-in unit, with no different management from term newborns. Hyperbilirubinemia is considered physiological, but can be potentially neurotoxic at high levels. Phototherapy is the most widely used treatment, but it can lead to adverse events, such as circadian rhythm changes. Preterm infants are at greater risk of neurotoxicity due to hyperbilirubinemia and feeding difficulties are a risk factor for increased serum bilirubin levels. In view of this, it is necessary to evaluate the breastfeeding performance of late preterm infants in order to provide data that will enable appropriate management in the face of possible difficulties and guarantee that preterm infants undergoing phototherapy will have an effective feed and adequate intake.
Methods: Controlled cross-sectional study. Conducted in a public maternity hospital, the sample was based on convenience and consisted of 60 mother/late preterm newborn dyads, assisted in the Joint Lodging, divided into two groups. One group comprised of 30 mother/newborn dyads in which the newborns had hyperbilirubinemia that required phototherapy (case group) and another group with 30 dyads in which the newborns did not require phototherapy (control group). Data characterizing the sample was obtained through anamnesis and medical/hospital records. Breastfeeding performance was assessed using the Breastfeeding Observation Form proposed by UNICEF. The analyses were carried out using Jamovi (version 2.4.1). The significance level of 5% was adopted for all analyses. The study was approved by the Research Ethics Committee. All participants/guardians signed the Free and Informed Registration Form.
Results: Newborns in the case group had a higher occurrence of "fair" and "poor" scores in all the protocol categories.
Conclusion: The study concluded that late preterm newborns undergoing phototherapy have more difficulties in breastfeeding compared to late preterm newborns who do not require the treatment, and therefore need careful and individualized attention in the management of breastfeeding.
