Neonatal Unconjugated Hyperbilirubinemia Research Articles

An Overview of Neonatal Unconjugated Hyperbilirubinemia and It’s Management

Neonatal hyperbilirubinemia is the most common clinical condition in the newborn requiring hospital readmission. About 60% of term and 80% of preterm infants develop jaundice during 1st week of life. Unconjugated hyperbilirubinemia occurs mostly due to increased hemolysis, decreased hepatic clearance, enterohepatic circulation, immaturity, blood group incompatibility and infections. Evaluation of neonatal jaundice is done based on history, age of onset of jaundice and physical examination findings which is necessary for proper management. Otherwise significant hyperbilirubinemia may endanger life of the baby and may lead to acute and subsequently chronic bilirubin encephalopathy. There are many diagnostic tools those help to detect jaundice such as Kramer’s rule, transcutaneous bilirubinometer, Bilichecker apps and smartphone apps. Besides these BIND score added a new dimension in diagnosis of acute bilirubin encephalopathy which can be confirmed by measuring bilirubin – albumin ratio in blood. Management of unconjugated hyperbilirubinemia includes: Phototherepy, Exchange transfusion are two major effective therapeutic modalities available today. Additional options include Pharmacotherapy in the form of phenobarbital and intravenous immunoglobulin. Each therapy has its pros and cons. Even there is dilemma in many therapeutic conditions like role of prophylactic phototherapy in preterm neonates, role of sunlight etc. As pediatricians have to deal cases with unconjugated hyperbilirubinemia frequently, so an updated knowledge is required. From this concern we reviewed issues on neonatal unconjugated hyperbilirubinemia and compiled for better understanding of the condition.Bangladesh J Child Health 2018; VOL 42 (1) :30-37

Different causes of prolonged unconjugated Jaundice in the newborns

Background: Prolonged unconjugated hyperbilirubinemia is a type of neonatal jaundice, which occurs in infants with high bilirubin levels (>10 mg/dl) persisting beyond 14-21 days. Prolonged unconjugated hyperbilirubinemia is a common problem among newborns, and the prevalence rate has been estimated at 2-15%. According to the literature, breastfeeding is a major cause of prolonged jaundice, and about 40% of infants who are exclusively breastfed are diagnosed with this disorder. Among other pathological causes associated with prolonged hyperbilirubinemia are urinary tract infection (UTI), congenital hypothyroidism and hemolysis. So, this study was done to know the different causes of unconjugated jaundice in newborn.Methods: This Hospital based prospective descriptive study was carried out at outpatients and inpatients in the Department of pediatrics, SMS medical college Jaipur. Total 100 cases were taken and these neonates were evaluated to know different causes of unconjugated hyperbilirubenemia.Results: Most common cause of persistent jaundice in both term and preterm babies is breast milk jaundice (66%), other causes include isoimmunization (10%), cephalhematoma (7%), hypothyroidism (7%), sepsis (4%) and ABO incompatibility (3%). Etiology of persistent jaundice was not significantly different in term and preterm babies.Conclusions: Although breast milk jaundice is considered as a major cause of prolonged unconjugated hyperbilirubinemia in neonates, identification of other etiological factors, such as UTI, congenital hypothyroidism and hemolysis is also of paramount importance. Early diagnosis and treatment of these disorder could effectively prevent further complication in neonates.

A Prospective Study on Exchange Transfusion in Neonatal Unconjugated Hyperbilirubinemia – in a Tertiary Care Hospital, Nepal

An exchange transfusion involves replacing patient's blood with donor blood in order to remove abnormal blood components and circulating toxins while maintaining adequate circulating blood volume. To observe the incidence, causes of jaundice requiring Exchange and any adverse event of exchange transfusion in newborns with unconjugated hyperbilirubinemia. Prospective study undertaken at Neonatal Intensive Care Unit (NICU) of Manipal Teaching Hospital, Pokhara, Nepal from March 2014 to April 2015. For both mothers and neonates blood group and Rh typing and for all newborns pre and post exchange complete blood count with peripheral smear, serum bilirubin, hemoglobin, calcium, potassium, random blood sugar, C-reactive protein and blood culture and where ever required Direct Coombs test, reticulocyte count, G6PD activity and thyroid function test were done. The incidence, indications, positive outcome, complications and mortality were noted. Out of 481 cases of unconjugated hyperbilirubinemia 29 (6%) required exchange transfusion. 55.2% Pathological Jaundice [13.8% ABO incompatibility, sepsis and hypothyroidism was commonest causes] and 44.8% exaggerated physiological jaundice [27.6% with no underlying pathology, 10.3% preterms 3.4% cephalhematoma] required exchange transfusion. Post transfusion, bilirubin level decreased significantly (p < 0.001). The commonest adverse events noted were anemia (89.7% / p < 0.018), hyperglycemia(51.7% / p < 0.001), hypocalcaemia (48.3% / p < 0.001)), sepsis(10.3%), hypernatremia (13.8%), hyperkalaemia, bradycardia, apnea and feed intolerance (6.9%). None of them had kernicterus and there was no mortalities. Exchange transfusion is an effective procedure to decrease bilirubin levels but is associated with many complications. Hypothyroidism was one of the commonest cause of jaundice requiring Exchange transfusion.

Neuroprotective Effect of Erythropoietin on Phenylhydrazine-Induced Hemolytic Hyperbilirubinemia in Neonatal Rats.

Neonatal unconjugated hyperbilirubinemia might cause severe bilirubin neurotoxicity in especially hemolytic conditions. The study aimed to elucidate the potential neuroprotective effects of erythropoietin (EPO) in hemolysis-induced hyperbilirubinemia. In newborn rats, hyperbilirubinemia secondary to hemolysis was induced by injecting with phenylhydrazine hydrochloride (PHZ) and rats were injected with either vehicle or EPO. At 54th hour of the PHZ injection, rats were decapitated. Serum levels of TNF-α, IL-1β, IL-10, brain-derived neurotrophic factor (BDNF) and S100-B and brain malondialdehyde, glutathione levels and myeloperoxidase activities were measured. TUNEL staining and NF-κB expression were evaluated. As compared to control pups, in vehicle-treated PHZ group, TNF-α and IL-1β levels, malondialdehyde level and myeloperoxidase activity were increased with concomitant decreases in IL-10 and glutathione. All EPO regimens reversed PHZ-induced alterations in IL-10, TNF-α, malondialdehyde and glutathione levels. Three-day-treatment abolished increases in myeloperoxidase activity and IL-1β levels, while BDNF and S100-B were elevated. Increased TUNEL (+) cells and NF-κB expressions in the brain of PHZ group were reduced in the 3-day-treated group. EPO exerted anti-inflammatory effects on PHZ-induced neural damage in newborn rats, while the neuroprotection was more obvious when the treatments were repeated successively. The results suggest that EPO treatment may have a therapeutic potential in supporting neuroplasticity in the hyperbilirubinemic neonates.

Etiology and clinical profile of neonates with pathological unconjugated hyperbilirubinemia with special reference to Rhesus (Rh) D, C, and E incompatibilities: A tertiary care center experience

ObjectiveTo assess etiology, clinical profile, and outcome of pathological neonatal unconjugated hyperbilirubinemia, including various Rhesus (Rh) blood group incompatibilities. MethodsThis was a prospective observational study of 200 neonates, with unconjugated hyperbilirubinemia requiring phototherapy and/or exchange transfusion, presented at tertiary care neonatal unit during August 2011 to July 2012. Detailed history, physical examination, and laboratory work-up were performed. In case, if major blood group incompatibility was found negative, the blood was further processed for G-6PD status, hereditary spherocytosis, and for non-Rh D incompatibility by testing non-Rh D antigens status in mother–infant pair. ResultABO incompatibility (64 cases, 32%), Rh D incompatibility (28 cases, 14%), and sepsis (42 cases, 21%) were major causes of neonatal unconjugated hyperbilirubinemia, while the etiology could not be ascertained in 31 (15.5%) cases. Rh C and Rh E incompatibilities were observed in 28 (14%) and 6 (3%) cases, respectively among those neonates who did not exhibit major blood group incompatibility (ABO and Rh D). Rh C incompatibility was less severe than Rh D, and Rh E was least. ConclusionsBlood group incompatibilities (ABO and Rh D) and sepsis are important causes of unconjugated hyperbilirubinemia in neonates requiring treatment. Though less common, non-Rh D incompatibility can contribute to severe neonatal hyperbilirubinemia, and needs to be investigated.

Analysis of uridine diphosphate glucuronosyl transferase 1A1 gene mutations in neonates with unconjugated hyperbilirubinemia.

This study was carried out to analyze uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) gene mutations in neonates with unconjugated hyperbilirubinemia, from two different ethnic groups. Polymerase chain reaction and gene sequencing were used to analyze the differences in genotypes and allele frequencies of different gene mutations among the ethnic groups; this was followed by checking their correlation with the serum bilirubin level and the occurrence of unconjugated hyperbilirubinemia in neonates. Our results reveal that the UGT1A1 mutant genotype, 211G>A, is distributed differently in the case vs control groups, as well as in the Zhuang vs Han ethnic groups. Moreover, this difference is statistically significant (P < 0.05); the total serum bilirubin (TSB) and unconjugated bilirubin (UCB) levels in patients carrying the single homozygous mutation, 211G>A, were markedly higher than that in patients without the mutation (P < 0.05). Furthermore, the TSB and UCB levels were significantly different between patients carrying single or compound 211G>A heterozygous mutation, (TA)6/7, and 1941C>G/2042C>G heterozygous mutation, and patients without mutation (P > 0.05). Our findings suggest that the 211G>A mutation in the first exon may be a risk factor for unconjugated hyperbilirubinemia in Zhuang and Han neonates. The serum bilirubin levels seem to be affected by the homozygosity or heterozygosity of the UGT1A1 gene mutation; 211G>A homozygous mutation is an important factor that causes a rise in bilirubin in neonates with unconjugated hyperbilirubinemia.

Histological Findings in the Kernicterus-Associated Vulnerable Brain Regions are Linked to Neurodegeneration, Alterations in Astrocyte and Pericyte Distribution, and Vascular Modifications

Kernicterus is a severe manifestation of neonatal unconjugated hyperbilirubinemia. We investigated the neuro-glia-vascular alterations in autopsy material from three infants with kernicterus. Histological and immunohistochemical studies were performed in the cerebellum, hippocampus and basal ganglia, the most vulnerable brain regions to bilirubin-induced neurotoxicity. The data obtained were compared with the relatively spared temporal cortex, as well as with three aged-matched controls with no hyperbilirubinaemia. Our data showed a reduction of the external germinal layer thickness e kernicterus cases cerebellum, indicating that bilirubin compromises the neural progenitor cells. Results also showed that neuronal dysfunction, including neuronal death and reduced neuronal bodies, was prevalent in the cerebellum, hippocampus and basal ganglia. The hippocampus was the region presenting the greatest neuronal loss and vacuolation, also showing astrogliosis and loss of pericyte vascular coverage. A marked decrease in the basement membrane collagen IV immunoreactivity was observed in the cerebellum, a region presenting increased vessel density, particularly in the cerebellar cortex. Moreover, based on the enhanced caveolin-1 expression observed in the cerebellum and hippocampus we hypothesize that a transcellular hyperpermeability may have been involved in cases of kernicterus. The temporal cortex did not show signs of endothelial dysfunction and was the one with the lowest microvessel density and the highest basement membrane thickness, features that may account to the limited bilirubin passage across the blood-brain barrier into the brain and to the low propensity of the temporal cortex to kernicterus. Conclusion: The results obtained in three post-mortem brain samples of children with kernicterus and comorbid factors indicate that neuronal impairment and astrocytosis occur in parallel with microvascular alterations commonly associated with blood-brain barrier impairment.

Etiologies of Prolonged Unconjugated Hyperbilirubinemia in Neonates Admitted to Neonatal Wards

Background: Jaundice is a common condition among neonates. Prolonged unconjugated hyperbilirubinemia occurs when jaundice persists beyond two weeks in term neonates and three weeks in preterm neonates. This study aimed to determine the etiologies of prolonged unconjugated hyperbilirubinemia in infants admitted to the neonatal ward of Besat Hospital in Hamadan, Iran. Methods: This study was conducted on all infants diagnosed with prolonged unconjugated hyperbilirubinemia during 2007-2012 in the neonatal ward of Besat Hospital in Hamadan, Iran. Demographic characteristics of infants, physical examination and laboratory findings were collected and analyzed to determine the etiologies of neonatal hyperbilirubinemia. Results: In total, 100 infants diagnosed with neonatal hyperbilirubinemia were enrolled in this study, including 49 male and 51 female neonates with mean age of 20±1 days and mean bilirubin level of 17.5±4.0 mg/dL. Main causes of hyperbilirubinemia were urinary tract infection, ABO incompatibility, hypothyroidism and glucose-6-phosphate dehydrogenase deficiency in 14%, 5%, 6% and 5% of neonates, respectively. Moreover, unknown etiologies, such as breastfeeding, were detected in 70% of the studied infants. Conclusion: According to the results of this study, determining the main causes of prolonged unconjugated hyperbilirubinemia in neonates is of paramount importance. In the majority of cases, neonatal hyperbilirubinemia is associated with physiological factors, such as breastfeeding.

Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia.

Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required.

Phototherapy: A Simple and Safe Treatment for Neonatal Jaundice

Phototherapy: A simple and safe treatment for Neonatal Jaundice. Jaundice is a common finding in premature and full term newborns. Phototherapy has been widely used in the management of Neonatal unconjugated Hyperbilirubinemia for over five decades. Phototherapy devices include Fluorescent, Halogen, Fiberoptic or Light-Emitting Diode light sources. Safety issues and possible complications of phototherapy are discussed. It is a non invasive, safe and easily available therapy worldwide. This review will focus on the use of phototherapy in newborn nurseries.

Efficacy of zinc sulfate in reducing unconjugated hyperbilirubinemia in neonates

Hyperbilirubinemia is a common disease and unconjugated hyperbilirubinemia has been seen mainly in neonates. Severe form of unconjugated hyperbilirubinemia may cause kernicterus and even death. Conventional treatment for severe unconjugated hyperbilirubinemia consists of phototherapy and exchange transfusion that have several known disadvantages; specially exchange transfusion is associated with a significant morbidity and even mortality. These harmful effects indicate the need to develop alternative pharmacological treatment strategies for unconjugated hyperbilirubinemia. One of these pharmacological agents is zinc salts. Zinc has been shown to lower the bilirubin levels by inhibition of the enterohepatic cycling of unconjugated bilirubin. Oral zinc has been shown to reduce serum unconjugated bilirubin in animals, adolescents and low birth weight neonates. However, studies in healthy term neonates given oral zinc showed no reduction in hyperbilirubinemia based on daily measurement. In order to improve the accuracy, hyperbilirubinemia may be determined based on measurements every hour. More studies are needed to know the effect of zinc in neonatal jaundice.

Hereditary hyperbilirubinemia: An original study of four cases with review of literature.

Crigler Najjar Syndrome (CNS) a congenital non hemolytic hyperbilirubinemia is very rare with an incidence of around 1 in 1,000,000 births associated with a complete hepatic deficit of bilirubin glucoronosyltransferase activity. Herein we present a study of four cases: three siblings from the same family and one independent case. All the three siblings of the same family had history of persistent neonatal unconjugated hyperbilirubinemia, out of which the eldest female sibling died of seizures with severe hyperbilirubinemia giving a high suspiscion of kernicterus. Second eldest and the youngest son had congenital unconjugated hyperbilirubinemia. The third born male child was normal. The independent case had history of

Current Resources for Evidence‐Based Practice January/February 2013

Current Resources for Evidence‐Based Practice January/February 2013

Identification of a novel mutation in UDP-glucuronosyltransferase (UGT1A1) gene in a child with neonatal unconjugated hyperbilirubinemia

Genetic alterations of the UGT1A1 gene result in Crigler–Najjar (CNS) and Gilbert's (GS)-Syndromes, two autosomal recessive conditions characterized by non-hemolytic unconjugated hyperbilirubinemia. While GS is characterized by mild hyperbilirubinemia, CNS is classified as follows: type I (CNS-I), often associated with irreversible neurological damage due to total deficiency of the UGT1A1 enzyme activity, and type II (CNS-II) where a minimal level of UGT1A1 enzyme activity is maintained. In this context, differential diagnosis of CNS forms needs to be supported by clinical molecular laboratory, in order to correlate biochemical findings to specific genetic mutations.Our paper describes in detail the peculiar clinical feature found in a child with severe neonatal unconjugated hyperbilirubinemia, where DNA analysis showed a new compound heterozygosis determined by two mutations, a known (c.508_510delTTC) and a novel mutation (c.1099C>T) giving a genotype compatible with clinical picture of CNS-II.This novel genotype extends the spectrum of known UGT1A1 mutations, which, in our opinion, could be higher than that currently reported in the literature. Finally, genetic analysis may also be helpful for patients' management.

The Use of Intensive Phototherapy in Severe Neonatal Hyperbilirubinemia

Phototherapy has been the therapy of choice for the newborn with indirect hyperbilirubinemia. Intensive phototherapy requires a spectral irradiance of 30 microw/ cm2/nm, delivered over as much of the body surface as possible and is nowadays recommended for cases of neonatal hyperbilirubinemia with elevated total serum bilirubin (TSB) levels according to the guidelines. This study was conducted on neonates presenting to the out-born Neonatal Intensive Care Unit (NICU) of Cairo University Hospital with severe and extreme neonatal unconjugated hyperbilirubinemia during a 6 month period from August 2011 to January 2012. A total of 212 neonates presented with TSB > or = 20 mg/dl and were admitted for intensive phototherapy. The mean TSB on admission for all the cases was 26.8 +/- 6.2 mg/dl, ranging from 20 to 44 mg/dl. The mean duration of intensive phototherapy use was 14 hr. The mean rate of TSB declined during stay in the bilisphere was 1.019 mg/dl/hr. Exchange blood transfusion was indicated in 13 cases with extreme hyperbilirubinemia. 31 cases (14.62%) had rebound hyperbilirubinemia after phototherapy removal.

Clofibrate for unconjugated hyperbilirubinemia in neonates: A systematic review

To evaluate the effect of clofibrate for unconjugated hyperbilirubinemia in neonates. A systematic review with meta-analysis of randomized controlled trials or quasi-randomized controlled trials was conducted to evaluate the clofibrate treatment in neonates with unconjugated hyperbilirubinemia. We followed the guidelines from the Cochrane review group and the PRISMA statement. Of 148 studies identified, a total of 13 studies on 867 infants were included. A single oral administration of clofibrate was associated with decreased need of phototherapy (RR:.38, 95% CI: 0.21 to 0.68), shortened duration of phototherapy (mean duration: 23.88 h, 95% CI: 33.03 to -14.72 h) and reduced peak total serum bilirubin (mean duration: -1.62 mg/dL, 95% CI: 2.13 to -1.11 mg/dL). These effects were especially obvious in term infants and infants without hemolytic diseases. Data regarding mortality or kernicterus were not available from included studies. Clofibrate may have short-term benefits for the infants with hyperbilirubinaemia, especially for population of term infants and infants without hemolytic diseases. Large RCTs with long-term followup are required to verify the safety of clofibrate and assess its long-term effects.

The study of relationship between glucose-6-phosphate dehydrogenase deficiency and hyperbifiliru-binemia

Glucose-6-phosphate dehydrogenase deficiency is a common monogenic inheritance disorder, with extensive distribution around the world and very high gene frequency. Acute hemolysis may lead to rapidly rising of serum total bilirubin concentrations and may eventually result in bilirubin encephalopathy. The hyperbilirubinemia is the result of abnormal bilirubin metabolism due to complex interactions between G-6-phosphate dehydrogenase deficiency and the genetic co-expression. Neonatal unconjugated hyperbilirubinemia is one of the most common conditions encountered by the practicing pediatricians. Key words: Glucose-6-phosphate dehydrogenase deficiency; Hyperbilirubinemia; Neonatal; Bilirubin; Hemolysis; G ene

Crigler Najjar syndrome type 2

Background: Crigler Najjar syndrome (CNS) is an extremely rare disorder of bilirubin metabolism that follows an autosomal recessive pattern of inheritance. CNS is elicited by a lack or deficiency of the enzyme uridine diphosphate glucuronyl transferase (UDGT). Two distinct forms have been described type 1 and type 2. Type 1 CNS is associated with neonatal unconjugated hyperbilirubinemia and kernicterus, which results in very high levels of unconjugated hyperbilirubinemia (up to 50 mg/dL) at birth. Type 2 CNS presents with serum bilirubin levels up to 20 mg/dL and markedly depressed activity of hepatic UDGT are characteristic of type 2 CNS. Objective: To rule out other causes for unconjugated hyperbilirubinemia, and arrive at a definitive diagnosis of Crigler Najjar syndrome type 2. Methods: Clinical examination of the baby and laboratory investigations like hemoglobin, complete blood count, thyroid profile, liver function tests and ultrasound were carried out. Results: Except for unconjugated hyperbilirubinemia, all other reports were within the normal range. Conclusion: Laboratory investigations and the response of the baby to phototherapy and phenobarbitone with decrease in the serum unconjugated bilirubin levels lead to a diagnosis of Crigler Najjar syndrome type 2. Hepatic glucuronyl transferase activity in a liver specimen, obtained by a closed biopsy and in vitro expression of mutant DNA from patient fibroblast, would have been helpful for definitive diagnosis.

Unconjugated Hyperbilirubinemia and Early Childhood Caries in a Diverse Group of Neonates

We evaluated if the development of early childhood caries is associated with the severity of unconjugated hyperbilirubinemia during the first 2 weeks after birth. We performed a retrospective case-control study of children less than 6 years of age seen for comprehensive dental examination by pediatric dentists years following a hospital stay in the neonatal intensive care unit. Exclusion criteria included genetic disorders, cleft palate, direct hyperbilirubinemia, and missing information on jaundice. Children with early childhood caries were compared with those without dental caries for a panel of perinatal and neonatal clinical variables. Seventy-six children met study criteria. Of 76 children, 42 children had early childhood caries, while 34 children had healthy primary dentitions. Among clinical variables, only race and peak total serum bilirubin concentration differed significantly between the two groups on bivariate analysis. On logistic regression, peak total serum bilirubin concentration was significantly associated with early childhood caries (adjusted odds ratio 1.17, 95% confidence interval 1.04 to 1.32). Neonatal unconjugated hyperbilirubinemia may be associated with early childhood caries in children.

Neonatal jaundice in a Special Care Baby Unit (SCBU) in Port Harcourt, Nigeria: a prospective study

Objectives: To determine the incidence, related factors, management and outcome of neonatal jaundice among inborn and outborn babies seen at the University of Port Harcourt Teaching Hospital. Methods: A 6-month prospective study spanning from 1st July to 31st December 2002 of all neonates with significant jaundice admitted into the Special Care Baby Unit of the University of Port Harcourt Teaching Hospital was carried out. Data from the mothers and babies were entered into a specially designed questionnaire and statistical analysis was carried out by χ2, Fisher\'s exact probability and Student\'s t tests. Results: The overall incidence of neonatal jaundice was 21.4%; 27.8% in outborn and 16.4% in inborn babies. Septicaemia was the major associated factor in outborn, while preterm delivery was the main factor in inborn babies, the jaundice being more severe in outborn babies. The best predictor of kernicterus was the peak serum unconjugated bilirubin concentration (two-tailed unpaired t=2.49, df=5, p=0.015). The overall case-fatality rate was 34.1%, being 60% and 40% among outborn and inborn babies respectively. Conclusion: Septicaemia and preterm delivery were found to be the main associated factors in severe unconjugated hyperbilirubinaemia and was more severe in outborn babies, the dominant reason was considerable delay in presenting to hospital. There was therefore need for prompt recognition and treatment of septicaemia and efforts should be focused at the community level to encourage mothers to present early in hospital as soon as jaundice is noticed. Keywords : Neonatal unconjugated hyperbilirubinaemia, Associated factors, Kernicterus, Outcome PHMJ Vol. 2 (2) 2008: pp. 110-117