Neonatal Unconjugated Hyperbilirubinemia Research Articles

Evaluation of phototherapy effects on platelet numbers and volumes in neonates with unconjugated hyperbilirubinemia in Sulaimani city/Kurdistan region/Iraq

Abstract: BACKGROUND: Unconjugated hyperbilirubinemia is a rather common disease that affects 60% of term and 80% of preterm infants within their 1st week of life. Phototherapy is considered the safest method for the treatment of unconjugated hyperbilirubinemia in neonates, which is the most common problem in the neonatal period. OBJECTIVES: To identify the effect of phototherapy on platelet numbers and volumes, and if the duration of treatment, gestational age, birth weight and other factors have some influences on this effect. PATIENTS, MATERIALS AND METHODS: A prospective cohort study was conducted from November 1, 2023, to April 1, 2024. Seventy-four neonates were enrolled in this study including males and females (1.39:1), with different gestational ages and birth weights. Neonates were selected according to the specific inclusion and exclusion criteria. Thorough history and physical examination performed with several laboratory investigations sent. Total serum bilirubin measured before starting phototherapy, after 24 hours, 48 h, 72 hours, and 4 days later. SPSS program was used to code, enter, and process the gathered data. RESULTS: Platelet number in general decreased with increasing duration of phototherapy regardless of other parameters (P = 0.045). In correlation to the duration of phototherapy and time of jaundice appearance, it was statistically significant for only neonates who required phototherapy for more than 4 days and time of jaundice appearance between 1 and 3 days (P = 0.042). Platelets number decreased with increasing duration of phototherapy especially in low birth weight and very low birth weight neonates, P value 0.028 and 0.047 respectively. There were statistically significant values (P = 0.002 and P = 0.001) in the correlation of decreasing platelet numbers to gestational age and duration of phototherapy, especially more evident with gestational age below 37 weeks (preterm) and in periods after 24 h and 72 h. There were no statistically significant values in platelet volumes in correlation to any of the previous parameters. CONCLUSIONS: Platelets number decreased with phototherapy management, and it is more evident with longer phototherapy duration, low birth weight and early onset, while platelet volume not affected. Hence, it is recommended to avoid unnecessary prolongation of phototherapy.

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.

Forgoing Exchange Transfusion in Neonatal Hyperbilirubinemia: A Single-Center Retrospective Cohort Study.

Unconjugated hyperbilirubinemia is part of the everyday life of the neonatal period as it reflects the adaptation of the metabolism of bilirubin. The neonatal hyperbilirubinemia usually resolves spontaneously, but it can also be the cause of an acute or chronic encephalopathy known as kernicterus. Regardless of the cause, the goal of therapy is to prevent this neurotoxicity while not causing undue harm. Phototherapy and, if it is unsuccessful, exchange transfusion (ECT)remain the primary treatment modalities used to keep the maximal total serum bilirubin (TSB) below pathologic levels. This is a descriptive retrospective cohort study of 69 live neonates hospitalized in the Department of Neonatology and Neonatal Resuscitation of Mohammed VI University Hospital with unconjugated hyperbilirubinemia requiring ECT and treated with intensive phototherapy instead, spanning five years from March 2016 to March 2021. We aim to demonstrate the effectiveness of phototherapy in achieving prolonged reduction of bilirubin levels and the prevention of neurological complications and to compare our results with those in the literature. The use of intensive phototherapy in the treatment of neonatal unconjugated hyperbilirubinemia is very effective in lowering total serum bilirubin when its level is in the range of exchange transfusion, and it has succeeded in preventing the neurological complications of severe hyperbilirubinemia. Through this study, it can be seen that phototherapy is an efficacious, simpler, and less hazardous alternative to exchange transfusion in achieving a sustained reduction of bilirubin levels and preventing neurological complications.

Zinc level alternation after phototherapy in neonates with hyperbilirubinemia

Introduction: One of the old treatment methods for unconjugated hyperbilirubinemia in neonates is blood exchange transfusion, which is expensive, possibly high-risk, and time-consuming. Today phototherapy as a novel method can be a good alternative. Objectives: This study aimed to evaluate the zinc level alternation after phototherapy in neonates with hyperbilirubinemia. Patients and Methods: A descriptive-analytical study was conducted on 85 infants with hyperbilirubinemia who underwent phototherapy referred to the pediatric hospital in Bandar- Abbas, Iran from 2017 to 2018. Healthy infants over two days with idiopathic jaundice with a gestational age greater than 34 weeks and only breast-feed were enrolled. Serum zinc levels were measured before and after phototherapy, and their changes were evaluated. Results: Out of 85 neonates, 42 (49.4%) were male and 43 (50.6%) were female with a mean gestational age of 37.83 ± 0.58 weeks and admission age of 4.15 ± 1.70 days. Zinc level before phototherapy was 84.98 ± 52.06 (μg/dL) and after phototherapy was 234.41 ± 280.98. The difference between serum zinc levels before and after the phototherapy was significant therefore, the zinc level significantly increased after the phototherapy. Conclusion: Results showed that phototherapy increases serum zinc levels, which can cause zinc toxicity. It is wise to measure serum zinc levels before and during phototherapy and seek the appropriate medical care.

Chemoprevention of bilirubin encephalopathy with a nanoceutical agent.

Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-Mn3O4 NP, the nanodrug) to degrade both systemic and neural bilirubin loads. Severe neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine(PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated. Single oral dose (0.25 mg kg-1 bodyweight) of the nanodrug reduced both total serum bilirubin (TSB) and unconjugated bilirubin (UCB) in SNH rodents. Significant (p < 0.0001) UCB and TSB-degradation rates were reported within 4-8 h at 1.84 ± 0.26 and 2.19 ± 0.31 mg dL-1 h-1, respectively. Neural bilirubin load was decreased by 5.6 nmol g-1 (p = 0.0002) along with improved measures of neurobehavior, neuromotor movements, learning, and memory. Histopathological studies confirm that the nanodrug prevented neural cell reduction in Purkinje and substantia nigra regions, eosinophilic neurons, spongiosis, and cell shrinkage in SNH brain parenchyma. Brain oxidative status was maintained in nanodrug-treated SNH cohort. Pharmacokinetic data corroborated the bilirubin degradation rate with plasma nanodrug concentrations. This study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings. None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs), exhibits bilirubin reduction properties in rodents. Chemopreventive properties of this nano-formulation demonstrate an efficacious, efficient agent that appears to be safe in these early studies. Translation of C-Mn3O4 NPs to prospective preclinical and clinical trials in appropriate in vivo models should be explored as a potential novel pharmacotherapy for SNH.

Effect of ursodeoxycholic acid on indirect hyperbilirubinemia (nonhaemolytic and haemolytic) in neonates treated with phototherapy

Background Hyperbilirubinemia is a global problem in neonates. Classic management for indirect neonatal hyperbilirubinemia includes phototherapy and exchange transfusion. Phototherapy shows disadvantages, and exchange transfusion is related to significant morbidity. Aim To assess the added role of ursodeoxycholic acid (UDCA) in reducing unconjugated hyperbilirubinemia in neonates undergoing phototherapy. Patients and methods Our randomized controlled trial was performed on neonates with hyperbilirubinemia who needed phototherapy and were admitted to the neonatal care unit at Tanta University Hospital from May 2017 to March 2019. A total of 120 neonates were randomly divided into four groups: group A (n=30), which included neonates with nonhemolytic indirect hyperbilirubinemia who received UDCA 10 mg/kg/day beside the usual phototherapy; group B (n=30), which included neonates with isoimmune hemolytic indirect hyperbilirubinemia who received UDCA 10 mg/kg/day, besides the usual phototherapy; group C (n=30), which included neonates with nonhemolytic indirect hyperbilirubinemia who received phototherapy only; and group D (n=30), which included neonates with isoimmune hemolytic indirect hyperbilirubinemia who received phototherapy only. The total serum bilirubin (TSB) was determined every 24 h till being less than 10 mg/dl. Results TSB was significantly decreased in group A compared with group C (P&lt;0.05). However, TSB was comparable in groups B and D (P&gt;0.05). Duration of phototherapy was significantly shorter in groups A and B compared with groups C and D (P&lt;0.05). Conclusion UDCA shows a beneficial added role in the treatment of neonatal indirect hyperbilirubinemia, particularly in the nonhemolytic type.

Gilbert or Crigler\u2013Najjar syndrome? Neonatal severe unconjugated hyperbilirubinemia with P364L UGT1A1 homozygosity

BackgroundSeveral mutations of bilirubin uridine diphosphate-glucuronosyltransferase gene (UGT1A1) have been reported in patients with unconjugated hyperbilirubinemia. Few reports are available about the p.Pro364Leu mutation (P364L, c.1091C > T) in homozygous newborns. We describe the clinical, laboratory and therapeutic approach in two Chinese neonates with severe jaundice, homozygous for the P364L mutation.Case presentationTwo Chinese breastfed female infants presented prolonged unconjugated hyperbilirubinemia at the age of 1 month. Total bilirubin was higher than 15 mg/dl (D < 1). An exhaustive etiological work-up to detect possible causes of hyperbilirubinemia (notably hemolytic ones) was negative.The promoter and coding regions of UGT1A1 were amplified by polymerase chain reaction (PCR) from genomic DNA isolated from leukocytes. Both patients resulted homozygous for a variant site within the coding region of the gene in the 4 exon, c.1091C > T, p.Pro364Leu.In front of the persistently high level of unconjugated bilirubin, phototherapy was performed without persistent results. A treatment with phenobarbital was then begun and bilirubin level progressively decreased, with a complete and persistent normalization. The therapy was stopped.ConclusionUGT1A1 enzyme activity associated with the P364L mutation has been described as 35.6% of the wild-type enzyme activity. Photo-therapy and phenobarbital can be useful in front of persistently high level of unconjugated bilirubin.Our cases presented high bilirubin values, overlapping between Gilbert syndrome (GS) and Crigler-Najjar syndrome type II (CNS), but the complete normalization of bilirubin makes GS more likely. Homozygous P364L variant can be associated with severe neonatal unconjugated hyperbilirubinemia in Chinese infants, but jaundice can completely resolve in a few months, contrary to what happens in Crigler-Najjar syndrome type II.

Clinical and Genetic Etiologies of Neonatal Unconjugated Hyperbilirubinemia in the China Neonatal Genomes Project

To investigate the clinical and genetic causes of neonatal unconjugated hyperbilirubinemia. We included 1412 neonates diagnosed with unconjugated hyperbilirubinemia (total serum bilirubin >95 percentile for age), from the China Neonatal Genomes Project between August 2016 and September 2019, in the current study. Clinical data and targeted panel sequencing data on 2742 genes including known unconjugated hyperbilirubinemia genes were analyzed. Among the 1412 neonates with unconjugated hyperbilirubinemia, 37% had severe unconjugated hyperbilirubinemia, with total serum bilirubin levels that met the recommendations for exchange transfusion. Known clinical causes were identified for 68% of patients. The most common clinical cause in the mild unconjugated hyperbilirubinemia group was infection (17%) and in the severe group was combined factors (21%, with infection combined with extravascular hemorrhage the most common). A genetic variant was observed in 55 participants (4%), including 45 patients with variants in genes associated with unconjugated hyperbilirubinemia and 10 patients with variants that were regarded as additional genetic findings. Among the 45 patients identified with unconjugated hyperbilirubinemia-related variants, the genes were mainly associated with enzyme deficiencies, metabolic/biochemical disorders, and red blood cell membrane defects. G6PD and UGT1A1 variants, were detected in 34 of the 45 patients (76%). Known clinical causes, which varied with bilirubin levels, were identified in approximately two-thirds of the patients. Genetic findings were identified in 4% of the patients, including in patients with an identified clinical cause, with G6PD and UGT1A1 being the most common genes in which variants were detected.

Irradiance footprint of phototherapy devices: a comparative study

BackgroundPhototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. The irradiance footprint, i.e., the illuminated area by the PT device with sufficient spectral irradiance, is essential for PT to be effective. Irradiance footprint measurements are not performed in current clinical practice. We describe a user-friendly method to systematically evaluate the high spectral irradiance (HSI) footprint (illuminated area with spectral irradiance of ≥30 μW cm−2 nm−1) of PT devices in clinical practice.Materials and methodsSix commercially available LED-based overhead PT devices were evaluated in overhead configuration with an incubator. Spectral irradiance (µW cm−2 nm−1) and HSI footprint were measured with a radiospectrometer (BiliBlanket Meter II).ResultsThe average measured spectral irradiance ranged between 27 and 52 μW cm−2 nm−1 and HSI footprint ranged between 67 and 1465 cm2, respectively. Three, two, and one PT devices out of six covered the average BSA of an infant born at 22, 26–32, and 40 weeks of gestation, respectively.ConclusionSpectral irradiance of LED-based overhead PT devices is often lower than manufacturer’s specifications, and HSI footprints not always cover the average BSA of a newborn infant. The proposed measurement method will contribute to awareness of the importance of irradiance level as well as footprint measurements in the management of neonatal jaundice.ImpactWhile a sufficient spectral irradiance footprint is essential for PT to be effective, some PT devices have spectral irradiance footprints that are too small to cover the entire body surface area (BSA) of a newborn infant.This study introduces a user-friendly, accessible method to systematically evaluate the spectral irradiance level and footprint of PT devices.This study supports awareness on the role of the spectral irradiance footprint in the efficacy of PT devices. Irradiance footprint can be easily measured during phototherapy with the proposed method.

The Spectrum of Hemolytic Disease of the Newborn: Evaluating the Etiology of Unconjugated Hyperbilirubinemia Among Neonates Pertinent to Immunohematological Workup.

Background and objectiveThe exact burden of hemolytic disease of the newborn (HDN) attributed to neonatal unconjugated hyperbilirubinemia (NUH) in developing nations is still unclear. Still, anti-D is reported to be the most common cause of HDN in India. ABO incompatibility has emerged as a leading cause of exchange transfusion (ET) in many countries. But many centers in our country rely on direct antiglobulin test (DAT) as a screening tool to evaluate immunological causes, whereas advanced immunohematological workup like antibody screening, identification, and elution tests are also required. Early identification of implicated antibodies resulting in HDN can aid in the proper selection of blood units when ET is indicated, and hence also in managing the subsequent pregnancy. This study focused on determining the causes of neonatal hyperbilirubinemia (NH), especially with respect to immunohematological evaluation. This cross-sectional study was conducted on 240 neonates requiring neonatal intensive care unit (NICU) support for NUH at a tertiary care hospital.Materials and methodsDemographic data, along with detailed history pertaining to the cause of hyperbilirubinemia, was collected. Clinical and laboratory evaluation and complete immunohematological work including DAT, heat elution, antibody screening, antibody identification, and Rh Kell phenotyping were performed from neonate blood samples. Data were analyzed using SPSS Statistics version 19 (IBM Corp., Armonk, NY).ResultsPathological jaundice was more common (62.1%) than physiological jaundice (37.9%). The various pathological causes identified were HDN (42.6%), sepsis (12%), cephalohematoma (5.4%), and idiopathic (1.7%). Among HDN cases, ABO incompatibility (39.2%) was the most prevalent cause, followed by Rh HDN and G6PD deficiency (1.7% each). DAT was positive in only 14 cases out of 94 ABO-incompatible cases. Elution revealed antibodies in four DAT-negative neonates with ABO incompatibility and more specificity to the OA setting. DAT was positive with 100% sensitivity in Rh HDN cases (n=4). Elution demonstrated the presence of anti-D (n=2), anti-D + anti-C (n=1) and anti-E (n=1), confirming Rh HDN. DAT strength was found to be significantly associated with hemoglobin (Hb) level (p=0.048). The majority of cases were treated with phototherapy only (94.1%), and 10 cases received both ET and phototherapy. Four neonates' condition improved without any intervention.ConclusionThis study highlighted the shift in the trend from Rh HDN to ABO incompatibility as the cause of hemolytic jaundice in NICU neonates. Elution tests can aid in the diagnosis of DAT-negative ABO-incompatible hemolytic anemia. Early diagnosis, along with timely intervention and appropriate measures, can prevent neonatal morbidity and mortality. Negative DAT does not rule out HDN. Sensitive techniques like elution must be used in the presence of clinical suspicion.

UGT1A1 mutation association with increased bilirubin levels and severity of unconjugated hyperbilirubinemia in ABO incompatible newborns of China

BackgroundNeonatal hyperbilirubinemia causing jaundice is common in East Asian population. Uridine diphosphate glucuronosyltransferase isoenzyme (UGT1A1) glucuronidates bilirubin and converts the toxic form of bilirubin to its nontoxic form.MethodA retrospective study was conducted to review clinical information of ABO hemolysis neonates (ABO HDN) admitted to the Department of Neonatology, referred for neonatal hyperbilirubinemia, in a large general hospital of southern China from 2011 to 2017. Variation status of UGT1A1 was determined by direct sequencing or genotype assays.ResultSixty-nine ABO HDNs were included into the final analysis. UGT1A1 c.211 G > A mutation (UGT1A1*6, p.Arg71Gly, rs4148323) was significantly associated with the increased bilirubin level in ABO HDNs, after adjusted by age, sex and feeding method (P = 0.019 for TBIL, P = 0.02 for IBIL). Moreover, heterozygous and/or homozygous UGT1A1 mutations in the coding sequence region were significantly associated with the increased risk of developing hazardous hyperbilirubinemia (as defined by TSB > 427 umol/L) as compared those with a normal UGT1A1 genotype (ORadj = 9.16, 95%CI 1.99–42.08, P = 0.002) in the study cohort.ConclusionUGT1A1 variant in coding region is actively involved in the pathogenesis of ABO hemolysis related neonatal hyperbilirubinemia. Genetic assessment of UGT1A1 may be useful for clinical diagnosis of neonatal unconjugated hyperbilirubinemia.

Evaluation of using agar combined with phototherapy in management of neonatal unconjugated hyperbilirubinemia

Background:Neonatal hyperbilirubinemia is a common problem in neonates.Phototherapy is an efficient way to decrease the accumulation of bilirubin, although it involves hospitalization, and can force the baby to stop eating due to the breast separation. In certain cases of infant jaundice, the hepatic circulation of bilirubin plays a major role Objectives: The purpose of the study was todetermine the value of oral agar ingestion combined with phototherapy in management of neonatal unconjugated hyperbilirubinemia and to compare it with the use of phototherapy alone in the management. Patients and methods: This was a randomized controlled study conducted at Neonatal intensive care units in Qena university hospital and Qena general hospital. They were divided into: Case group (neonates received oral agar with phototherapy).Control group (neonates received phototherapy alone). The duration of this study was 6 months. Results: The study included 517 neonates,314 neonates (60.74%) treated withphototherapy alone and 203 neonates (39.26%) treated withphototherapy combined with agar .There was a significant decrease in total serum bilirubin (TSB) in both subgroups, but the decrease was more significant in term male babies andin group that received agar with phototherapy than the group received phototherapy alone. Conclusion: Our results show that the administration of oral agar in full-term neonates was safe to decrease total serum bilirubin (TSB) concentrations and to shorten the length of phototherapy in hyperbilirubinemic neonates. As a supplementary treatment for neonates with hyperbilirubinemia, our results indicated that agar may benefit in minimizing the length of hospitalization.

Electrolyte Imbalances in Preterm and Term Hyperbilirubinemic Neonates Following Phototherapy

Neonatal hyperbilirubinemia is the most frequently occurring disorder in neonates. Phototherapy is the most common treatment strategy practiced routinely in the management of neonatal unconjugated hyperbilirubinemia. Reviews on electrolyte variations post phototherapy are highly variable. Therefore our study was aimed to evaluate the effect of phototherapy on calcium, sodium, potassium, magnesium and liver enzymes in physiologically hyperbilirubinemic neonates before and after phototherapy. The study was carried out on 100 (45 preterm, 55 term) hyperbilirubenimic neonates who underwent phototherapy. The overall prevalence of hypocalcemia was found to be 7%, none in preterm, 12.73% in term, 12.12% in males, 13.64% in females, 2.56% in low birthweight and 11.11% in normal birthweight neonates. The incidence of hypomagnesemia was found to be 4.45% in preterm, 7.27% in term, 5.2% in males, 13.64% in females, 5.13% in low birthweight and 7.4% in normal birthweight neonates. We found the incidence of hyponatremia to be 12%, 11.11% in preterm, 12.73 % in term, 12.12% in males, 18.6% in females, 5.13% in low birthweight and 14.8% in normal birthweight neonates. Monitoring of serum calcium and electrolyte levels in neonates undergoing phototherapy will help to identify hypocalcemia and electrolyte imbalances to prevent complications.

"Fenofibrate as an adjuvant to phototherapy in pathological unconjugated hyperbilirubinemia in neonates: a randomized control trial."

Despite widespread phototherapy usage, many new-born infants remain in need of other invasive lines of therapy, such as intravenous immunoglobulins and exchange transfusions. Assessment of the efficacy and the safety of adding fenofibrate to phototherapy for the treatment of pathological jaundice in full-term infants. We conducted a double blinded randomized control study on 180 full-term infants with pathological unconjugated hyperbilirubinemia admitted to the NICU at Mansoura University Children's Hospital. They were randomly assigned to receive either oral fenofibrate 10 mg/kg/day for 1 day or 2 days or placebo in addition to phototherapy. The primary outcome was total serum bilirubin values after 12, 24, 36, 48, and 72 h from intervention. Secondary outcomes were total duration of treatment, need for exchange transfusions and intravenous immunoglobulin, exclusive breast-feeding on discharge, and adverse effects of fenofibrate. This study was registered at www.clinicaltrials.gov (NCT04418180). A total of 180 full-term infants were included, 60 in each group. Infants in group I and II showed significant reduction of bilirubin levels at 36, 48, and 72 h from intervention compared to group III, respectively. Fenofibrate administration was associated with significantly shorter duration of phototherapy, shorter hospital stay, and higher frequency of exclusive breast-feeding compared to phototherapy alone. Fenofibrate as an adjuvant to phototherapy in term neonate with pathological jaundice is well tolerated and associated with significant reduction of serum bilirubin levels, a shorter duration of phototherapy, shorter hospital stay and higher frequency of exclusive breast-feeding, without significant adverse effects in either the single or double dosage.

An insight into neonatal unconjugated hyperbilirubinaemia from the transfusion medicine perspective

Unconjugated hyperbilirubinaemia is a common cause of morbidity and mortality among neonates in Asian and African countries. The aetiology is multifactorial and has wide range of presentation ranging from simple physiological jaundice to severe HDN requiring prompt intervention to prevent long‐term neurological sequelae. Extensive detection of borderline raised bilirubin level in newborn is debatable as it may lead to inappropriately increased phototherapy and unnecessary increased hospital stay. However, those at risk like early presentation of hyperbilirubinaemia within 48 h, prolonged hyperbilirubinaemia, and family history in siblings or having history of HDN must be screened for immune as well as non‐immune causes to prevent the neonate from further severe form of complications. Along with direct antiglobulin test, elution, antibody screening/identification is performed to evaluate the immune causes. Improvement in the molecular technology leads to prompt diagnosis of non‐immune causes which were previously remained as idiopathic. This will aid in the early management like phototherapy or exchange transfusion as per the indication. This review will basically focus on the aetiopathogenesis of neonatal unconjugated hyperbilirubinaemia and approach to immune causes from transfusion medicine prospective.

The Effect of Purgative Manna and Clofibrate on Neonatal Unconjugated Hyperbilirubinemia

Abstract- This study was conducted to determine the effect of purgative Manna and clofibrate on unconjugated hyperbilirubinemia of term neonates. In this randomized clinical trial study, sixty neonates suffering from unconjugated hyperbilirubinemia were evaluated. The neonates were divided into three groups using balanced block randomization. Group A (control group-received only phototherapy), group B (intervention group-received purgative Manna and phototherapy) and group C (intervention group-received clofibrate and phototherapy). After the intervention, the amount of serum bilirubin reduction was compared between groups. There was no significant difference among group A, B, and C in terms of serum bilirubin reduction in 24, 48 and 72 hours after starting the intervention (P&gt;0.05). The hospital stays in the control group was significantly longer than the intervention groups (P&lt;0.05). No side effects were observed related to using purgative Mienna and clofibrate. The present study showed that prescribing of purgative Manna and clofibrate has no effect on reduction of serum bilirubin level in term neonates with unconjugated hyperbilirubinemia. Thus, it seems that the administration of these drugs is not necessary. Further studies in this regard are recommended.

UGT1A1 gene polymorphisms and jaundice in Indonesian neonates

Background Uridine diphospho-glucuronocyltransferase 1A1 (UGT1A1) polymorphisms are a risk factor for unconjugated hyperbilirubinemia in neonates. UGT1A1 polymorphisms decrease bilirubin conjugation, thus causing hyperbilirubinemia. A variety of polymorphisms have been reported, with UGT1A1*60 and UGT1A1*6 especially prominent in the Asian population. Hyperbilirubinemia polymorphism studies are lacking in Indonesian populations.&#x0D; Objective To identify UGT1A1*60 and UGT1A1*6 profiles in Indonesian populations of heterogeneous ethnicity.&#x0D; Methods We enrolled 42 jaundiced neonates who were born from January to April 2017 and treated in the Neonatal Intensive Care Unit of our national referral center, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Genetic mutations *60 of exon 1 and *6 of the promoter region were analyzed by polymerase chain reaction – restriction fragment length polymorphism methods, with DraI and AvaII as restriction enzymes, respectively. Clinical data including total serum bilirubin and racial information were obtained by medical records and interviews with parents.&#x0D; Results There were no homozygous mutations of UGT1A1*6, but 4.8% of subjects were heterozygous. As for UGT1A1*60, 4.8% were heterozygous and 95.2% were homozygous. Racial variations were not observed for UGT1A1*60, while Betawi descendents were found to have many heteroygous forms of UGT1A1*6.&#x0D; Conclusion Polymorphisms of the UGT1A1 gene were found in Indonesian neonates. Some ethnicities also showed increased tendency towards its incidence, such as the heterozygous form of UGT1A1*6.

LED-phototherapy does not induce oxidative DNA damage in hyperbilirubinemic Gunn rats.

Phototherapy (PT) is the standard treatment of neonatal unconjugated hyperbilirubinemia. Fluorescent tube (FT)-emitted PT light is known to induce oxidative DNA damage in neonates. Nowadays, however, FTs have largely been replaced by light-emitting diodes (LEDs) for delivering PT. Until now, it is unknown whether LED-PT causes oxidative DNA damage. We aim to determine whether LED-PT induces oxidative DNA damage in hyperbilirubinemic rats. Adult Gunn rats, with genetically unconjugated hyperbilirubinemia, received LED-PT in the clinically relevant doses of 10 or 30 µW/cm2/nm. Urine was collected at 0, 24, and 48 h of PT. A group of young Gunn rats received intensive LED-PT of 100 µW/cm2/nm for 24 h. Urine was collected every 8 h and analyzed for the levels of oxidative DNA damage marker 8-hydroxy-2'deoxyguanosine (8-OHdG) and creatinine. DNA damage was evaluated by immunohistochemistry (γH2AX) of skin and spleen samples. LED-PT of 10 and 30 µW/cm2/nm did not affect urinary concentrations of 8-OHdG and creatinine or the 8-OHdG/creatinine ratio. Likewise, intensive LED-PT did not affect the 8-OHdG/creatinine ratio or the number of γH2AX-positive cells in the skin or spleen. Our results show that LED-PT does not induce oxidative DNA damage in hyperbilirubinemic Gunn rats either at clinically relevant or intensive dosages.

Comparative study between CFL and LED phototherapy devices for unconjugated hyperbilirubinemia in neonates

Comparative study between CFL and LED phototherapy devices for unconjugated hyperbilirubinemia in neonates

Effect of Purgative Manna on Neonatal Hyperbilirubinemia: A Systematic Review and Meta-analysis.

The aim of this systematic review was to evaluate the effect of purgative manna on the unconjugated hyperbilirubinemia in neonates. Pubmed, Scopus, Chochrane library, Iranmedex and Google scholar were last searched in February 2017. Randomized controlled trials that evaluated the effect of purgative manna on the treatment of neonatal hyperbilirubinemia were included in the review. For meta-analysis, weighted mean difference (WMD) with 95% confidence interval (CI) was used. The outcomes of interests were serum bilirubin levels and length of hospital stay in neonates with jaundice. Seven randomized controlled trials with 812 neonates were eligible to be included in this systematic review. The meta-analysis included six of seven controlled trials. Bilirubin levels were significantly lower at 12 h (WMD: -1.48, 95% CI: -2.31 to -0.65), 24 h (WMD: -2.47, 95% CI: -3.22 to -1.71), 36 h (WMD: -2.83, 95% CI: -4.87 to -0.80), 48 h (WMD: -1.49, 95% CI: -2.36 to -0.63) and 72 h (WMD: -0.68, 95% CI: -1.28 to -0.08) following intervention in purgative manna group. Length of hospital stay was also decreased in purgative manna group (WMD: -0.93, 95% CI: -1.35 to -0.50). Finally, purgative manna administration decreased serum bilirubin level and length of hospital stay in neonates with unconjugated hyperbilirubinemia. More studies are needed to evaluate the efficacy, dosage, and side effects of purgative manna.