neonatal hyperbilirubinemia


Summary: Accumulation of BILIRUBIN, a breakdown product of HEME PROTEINS, in the BLOOD during the first weeks of life. This may lead to NEONATAL JAUNDICE. The excess bilirubin may exist in the unconjugated (indirect) or the conjugated (direct) form. The condition may be self-limiting (PHYSIOLOGICAL NEONATAL JAUNDICE) or pathological with toxic levels of bilirubin.

Top Publications

  1. Watchko J, Lin Z. Exploring the genetic architecture of neonatal hyperbilirubinemia. Semin Fetal Neonatal Med. 2010;15:169-75 pubmed publisher
    The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized...
  2. Varvarigou A, Fouzas S, Skylogianni E, Mantagou L, Bougioukou D, Mantagos S. Transcutaneous bilirubin nomogram for prediction of significant neonatal hyperbilirubinemia. Pediatrics. 2009;124:1052-9 pubmed publisher
    ..5% for values in the low-risk zone of the nomogram. We provide a predictive TcB tool that could allow for a noninvasive, risk-based approach to neonatal hyperbilirubinemia.
  3. Tikmani S, Warraich H, Abbasi F, Rizvi A, Darmstadt G, Zaidi A. Incidence of neonatal hyperbilirubinemia: a population-based prospective study in Pakistan. Trop Med Int Health. 2010;15:502-7 pubmed publisher
    ..WHO guidelines are needed for screening and appropriate management of neonatal jaundice in developing countries. ..
  4. Zecca E, Romagnoli C, De Carolis M, Costa S, Marra R, De Luca D. Does Ibuprofen increase neonatal hyperbilirubinemia?. Pediatrics. 2009;124:480-4 pubmed publisher
    ..The potential role of competition between ibuprofen and bilirubin in the hepatic glucuronidation pathway is discussed. ..
  5. Stevenson D, Wong R. Metalloporphyrins in the management of neonatal hyperbilirubinemia. Semin Fetal Neonatal Med. 2010;15:164-8 pubmed publisher
    ..Use of phototherapy and/or exchange transfusion are the current modes for treating neonatal hyperbilirubinemia and preventing any neurologic damage...
  6. Randev S, Grover N. Predicting neonatal hyperbilirubinemia using first day serum bilirubin levels. Indian J Pediatr. 2010;77:147-50 pubmed publisher
    ..92%. First day TSB estimation can serve as a reliable screening test for neonates at risk for subsequent hyperbilirubinemia. Neonates with the first day TSB level of less than 6.4 mg/dl have minimum risk of subsequent hyperbilirubinemia. ..
  7. Boo N, Wong F, Wang M, Othman A. Homozygous variant of UGT1A1 gene mutation and severe neonatal hyperbilirubinemia. Pediatr Int. 2009;51:488-93 pubmed publisher
    ..Homozygous variant of nucleotide 211 G-->A mutation of UGT1A1 gene is a significant risk factor associated with severe hyperbilirubinemia among Malaysian Chinese newborns. ..
  8. De Luca D, Carnielli V, Paolillo P. Neonatal hyperbilirubinemia and early discharge from the maternity ward. Eur J Pediatr. 2009;168:1025-30 pubmed publisher
    ..Advice about things to avoid is provided together with a practical flowchart based on guidelines and recent evidence-based data. ..
  9. Wennberg R, Ahlfors C, Aravkin A. Intervention guidelines for neonatal hyperbilirubinemia: an evidence based quagmire. Curr Pharm Des. 2009;15:2939-45 pubmed
    ..A more comprehensive comparison of TSB and Bf, controlled for clinical confounders and photoiomers, is needed to formulate intervention guidelines with improved specificity that will reduce hospital admissions for unnecessary treatment. ..

More Information


  1. Engle W, Lai S, Ahmad N, Manning M, Jackson G. An hour-specific nomogram for transcutaneous bilirubin values in term and late preterm Hispanic neonates. Am J Perinatol. 2009;26:425-30 pubmed publisher
    ..Compared with the previous study, this report indicates that although differences were relatively small, significantly higher TcB values were observed in the Hispanic population. ..
  2. Maisels M. Neonatal hyperbilirubinemia and kernicterus - not gone but sometimes forgotten. Early Hum Dev. 2009;85:727-32 pubmed publisher
    ..Implementation of this approach might contribute to the prevention of severe hyperbilirubinemia and bilirubin encephalopathy...
  3. Davutoglu M, Garipardic M, Guler E, Karabiber H, Erhan D. The etiology of severe neonatal hyperbilirubinemia and complications of exchange transfusion. Turk J Pediatr. 2010;52:163-6 pubmed
    ..In order to prevent adverse effects of ECT, serum bilirubin levels should be closely monitored in newborns with ABO immunization. ..
  4. Dalal S, Mishra S, Agarwal R, Deorari A, Paul V. Does measuring the changes in TcB value offer better prediction of Hyperbilirubinemia in healthy neonates?. Pediatrics. 2009;124:e851-7 pubmed publisher
    ..Single TcB measurements at 30 to 48 hours predict hyperbilirubinemia with a reasonably high degree of accuracy. Changes in TcB levels do not offer any added clinical benefit. ..
  5. Karen T, Bucher H, Fauchere J. Comparison of a new transcutaneous bilirubinometer (Bilimed) with serum bilirubin measurements in preterm and full-term infants. BMC Pediatr. 2009;9:70 pubmed publisher
    ..Despite its new technology the Bilimed has no advantages, and more specifically no better agreement not only in term and near-term Caucasian infants, but also in non-Caucasian and more premature infants. ..
  6. Silva D, Martins R. Analysis of transient otoacoustic emissions and brainstem evoked auditory potentials in neonates with hyperbilirubinemia. Braz J Otorhinolaryngol. 2009;75:381-6 pubmed
  7. Ghersi Egea J, Gazzin S, Strazielle N. Blood-brain interfaces and bilirubin-induced neurological diseases. Curr Pharm Des. 2009;15:2893-907 pubmed
    ..Finally, we highlight the role of the blood-brain and blood-CSF barriers in regulating the brain biodisposition of candidate drugs for the treatment or prevention of bilirubin-induced brain injury. ..
  8. Fernandes A, Brites D. Contribution of inflammatory processes to nerve cell toxicity by bilirubin and efficacy of potential therapeutic agents. Curr Pharm Des. 2009;15:2915-26 pubmed
    ..Novel pharmacological strategies may reduce the incidence of UCB encephalopathy and prevent minor cerebral lesions that may result in mental illness...
  9. Brucknerova I, Behulova D, Sebova C, Bzduch V, Mach M, Dubovicky M, et al. Conjugated hyperbilirubinaemia as the first manifestation of mevalonic aciduria in a term newborn. Neuro Endocrinol Lett. 2009;30 Suppl 1:29-31 pubmed
    ..In cases of conjugated hyperbilirubinaemia of unknown aetiology it is important to exclude mevalonic aciduria by urine investigation for organic acids. ..
  10. Oh W, Stevenson D, Tyson J, Morris B, Ahlfors C, Bender G, et al. Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants. Acta Paediatr. 2010;99:673-678 pubmed publisher
    ..Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants. ..
  11. Woo H, Phornphutkul C, Laptook A. Early and severe indirect hyperbilirubinemia as a manifestation of galactosemia. J Perinatol. 2010;30:295-7 pubmed publisher
    ..We report an infant with galactosemia who presented with severe jaundice from indirect hyperbilirubinemia and met criteria for an exchange transfusion within 48 h after milk ingestion. ..
  12. Stillova L, Matasova K, Zibolen M, Stilla J, Kolarovszka H. Transcutaneous bilirubinometry in preterm neonates. Indian Pediatr. 2009;46:405-8 pubmed
    ..Close correlation (R=0.933) existed between total serum bilirubin and transcutaneous bilirubin values measured over sternum. ..
  13. De Luca D, Jackson G, Tridente A, Carnielli V, Engle W. Transcutaneous bilirubin nomograms: a systematic review of population differences and analysis of bilirubin kinetics. Arch Pediatr Adolesc Med. 2009;163:1054-9 pubmed publisher
    ..A bilirubin rate of rise higher than in the previous period implies that bilirubin production exceeds elimination and indicates high risk for subsequent hyperbilirubinemia in neonates. ..
  14. Watchko J, Lin Z, Clark R, Kelleher A, Walker M, Spitzer A. Complex multifactorial nature of significant hyperbilirubinemia in neonates. Pediatrics. 2009;124:e868-77 pubmed publisher
    ..Coexpression of the G6PD African A- mutation with UGT1A1 and SLCO1B1 variants was seen more often for case subjects. ..
  15. Adekunle Ojo A, Smitherman H, Parker R, Ma L, Caviness A. Managing well-appearing neonates with hyperbilirubinemia in the emergency department observation unit. Pediatr Emerg Care. 2010;26:343-8 pubmed publisher
    ..Low-risk neonates with hyperbilirubinemia can be managed more efficiently in an EDOU than in an inpatient unit. Phototherapy is initiated more rapidly, and patients are discharged sooner in the EDOU than in the inpatient setting. ..
  16. Smiechura M, Piontek A, Makowski A. [Hiperbilirubinemia- one of the high risk factor influence on hearing level in infants]. Przegl Lek. 2010;67:178-80 pubmed
    ..Hiperbilirubinemia was the only one factor of high risk of hearing loss in this group. The analysis of 53 patients showed that separate high level of bilirubina does not influence on hearing loss in children. ..
  17. Tołłoczko J, Kornacka M, Sonczyk A, Zapała Ł. Late preter cant neonatal problem?. Ginekol Pol. 2010;81:693-8 pubmed
    ..60%), p = 0.0000. (1) Respiratory disturbances, hiperbilirubinemia and intrauterine infections are more frequently observed in late preterms. (2) Increased morbidity in late preterm neonates prolongs the time of hospitalization. ..
  18. Sun G, Wang Y, Liang J, Du L. [Predictive value of umbilical cord blood bilirubin level for subsequent neonatal jaundice]. Zhonghua Er Ke Za Zhi. 2007;45:848-52 pubmed
    ..The use of UCS bilirubin values may help detect infants at low or high risk for hyperbilirubinemia and minimize an unnecessary prolongation of hospitalization. ..
  19. Hosseinpour Sakha S, Gharehbaghi M. Exchange transfusion in severe hyperbilirubinemia: an experience in northwest Iran. Turk J Pediatr. 2010;52:367-71 pubmed
    ..determine the indications for exchange transfusion (ECT) and the rates of ECT-related adverse events in neonatal hyperbilirubinemia. We reviewed retrospectively the medical charts of all newborns that had undergone ECT over three years ..
  20. Bakkeheim E, Bergerud U, Schmidt Melbye A, Akkök C, Liestøl K, Fugelseth D, et al. Maternal IgG anti-A and anti-B titres predict outcome in ABO-incompatibility in the neonate. Acta Paediatr. 2009;98:1896-901 pubmed publisher
  21. Liu F, Yu W, Song X, Yuan E, Li H. [Serum levels of insulin-like growth factor-1 in neonates with hyperbilirubinemia]. Zhongguo Dang Dai Er Ke Za Zhi. 2009;11:357-60 pubmed
    ..This study explored the potential role of serum IGF-1 in neonatal hyperbilirubinemia. Serum levels of IGF-1 were measured using ECLIA in 57 term neonates with hyperbilirubinemia and 25 ..
  22. Arhan E, Yusufoğlu A, Sayli T. Arc syndrome without arthrogryposis, with hip dislocation and renal glomerulocystic appearance: a case report. Eur J Pediatr. 2009;168:995-8 pubmed publisher
    ..Many patients with different associations of cholestasis, renal tubular acidosis, and dysmorphic morphology may be underdiagnosed...
  23. Vitek L, Ostrow J. Bilirubin chemistry and metabolism; harmful and protective aspects. Curr Pharm Des. 2009;15:2869-83 pubmed
    ..The regulation of cellular UCB content, by its conjugation, oxidation, and export, are, therefore of paramount importance to cellular health. ..
  24. Lease M, Whalen B. Assessing jaundice in infants of 35-week gestation and greater. Curr Opin Pediatr. 2010;22:352-65 pubmed publisher
    ..American Academy of Pediatrics officially recommended universal predischarge risk assessment for severe neonatal hyperbilirubinemia with the goal of minimizing subsequent risk of chronic bilirubin encephalopathy (formerly known as ..
  25. Chang P, Lin Y, Liu K, Yeh S, Ni Y. Prolonged unconjugated hyperbiliriubinemia in breast-fed male infants with a mutation of uridine diphosphate-glucuronosyl transferase. J Pediatr. 2009;155:860-3 pubmed publisher
    ..Male breast-fed infants had a higher risk than female infants for prolonged hyperbilirubinemia. Male breast-fed neonates with a variant nucleotide 211 in UGT1A1 have a high risk for developing prolonged hyperbilirubinemia. ..
  26. Watchko J. Hyperbilirubinemia in African American neonates: clinical issues and current challenges. Semin Fetal Neonatal Med. 2010;15:176-82 pubmed publisher
    ..Parental education at the time of birth hospitalization discharge combined with timely follow-up may help to reduce the risk of developing hazardous hyperbilirubinemia. ..
  27. Pakarinen M, Koivusalo A, Rintala R. Outcomes of intestinal failure--a comparison between children with short bowel and dysmotile intestine. J Pediatr Surg. 2009;44:2139-44 pubmed publisher
    ..Children with SB are more likely to wean off PN but more prone to cholestatic liver disease than those with DM as an etiology of IF. ..
  28. Kalakheti B, Singh R, Bhatta N, Karki A, Baral N. Risk of neonatal hyperbilirubinemia in babies born to 'O' positive mothers: a prospective cohort study. Kathmandu Univ Med J (KUMJ). 2009;7:11-5 pubmed
    ..significantly associated variables, ABO incompatibility was found to be a major risk factor for neonatal hyperbilirubinemia.It was seen that neonate with ABO incompatibility had two times higher chances of having ..
  29. Bellarosa C, Bortolussi G, Tiribelli C. The role of ABC transporters in protecting cells from bilirubin toxicity. Curr Pharm Des. 2009;15:2884-92 pubmed
    ..Since the Km of PGP for UCB is well above pathophysiological levels of Bf, it remains uncertain whether it has a role in protecting against UCB cytotoxicity. ..
  30. Rennie J, Sehgal A, De A, Kendall G, Cole T. Range of UK practice regarding thresholds for phototherapy and exchange transfusion in neonatal hyperbilirubinaemia. Arch Dis Child Fetal Neonatal Ed. 2009;94:F323-7 pubmed publisher
    ..Guidelines for England, Wales and Northern Ireland will be available from 2010, when the National Institute for Health and Clinical Excellence completes its review. ..
  31. Kuzniewicz M, Newman T. Interaction of hemolysis and hyperbilirubinemia on neurodevelopmental outcomes in the collaborative perinatal project. Pediatrics. 2009;123:1045-50 pubmed publisher
  32. Serber J, Stranzinger E, Geiger J, Teitelbaum D. Association of gastroschisis and choledochal cyst. J Pediatr Surg. 2009;44:e23-6 pubmed publisher
    ..The cases are a novel association not previously reported and should heighten the awareness that anatomical causes of a direct hyperbilirubinemia need to be ruled out in all neonates...
  33. Zhou Y, Lee L, Ng S, Hia C, Low K, Chong Y, et al. UGT1A1 haplotype mutation among Asians in Singapore. Neonatology. 2009;96:150-5 pubmed publisher
    ..Some of the polymorphisms have been associated with an increased risk of neonatal hyperbilirubinemia which may explain the increased incidence of jaundice in an Asian population as well as exaggerated ..
  34. Prachukthum S, Nunnarumit P, Pienvichit P, Chuansumrit A, Songdej D, Kajanachumpol S, et al. Genetic polymorphisms in Thai neonates with hyperbilirubinemia. Acta Paediatr. 2009;98:1106-10 pubmed publisher
    ..whether the variation of UGT1A1 gene, SLCO1B1 gene and GST gene may play a significant role in neonatal hyperbilirubinemia in Thai infants...
  35. Maisels M. Screening and early postnatal management strategies to prevent hazardous hyperbilirubinemia in newborns of 35 or more weeks of gestation. Semin Fetal Neonatal Med. 2010;15:129-35 pubmed publisher
    ..The application of these principles to the management of the jaundiced newborn might not eliminate every case of kernicterus, but should contribute to a reduction in its occurrence. ..
  36. Huang M, Lin M, Chen H, Chien K, Chen C. Risk factor analysis for late-onset neonatal hyperbilirubinemia in Taiwanese infants. Pediatr neonatol. 2009;50:261-5 pubmed publisher
    b>Neonatal hyperbilirubinemia is a recognized health risk for newborns. It can cause kernicterus and hearing impairment...
  37. Trikalinos T, Chung M, Lau J, Ip S. Systematic review of screening for bilirubin encephalopathy in neonates. Pediatrics. 2009;124:1162-71 pubmed publisher
    Severe neonatal hyperbilirubinemia is associated with chronic bilirubin encephalopathy (kernicterus). To systematically review the effectiveness of specific screening modalities to prevent neonatal bilirubin encephalopathy...
  38. Fouzas S, Mantagou L, Skylogianni E, Mantagos S, Varvarigou A. Transcutaneous bilirubin levels for the first 120 postnatal hours in healthy neonates. Pediatrics. 2010;125:e52-7 pubmed publisher
    ..We also present a percentile-based TcB nomogram designated for noninvasive and hour-specific evaluation of neonatal hyperbilirubinemia.
  39. Karakukcu C, Ustdal M, Ozturk A, Baskol G, Saraymen R. Assessment of DNA damage and plasma catalase activity in healthy term hyperbilirubinemic infants receiving phototherapy. Mutat Res. 2009;680:12-6 pubmed publisher
    ..The counteracting effect of higher catalase activities in hyperbilirubinemic newborns may be responsible for the inactivating toxic and DNA-damaging effects of PT. ..
  40. Stoniene D, Buinauskiene J, Markūniene E. The value of transcutaneous method of bilirubin measurement in newborn population with the risk of ABO hemolytic disease. Medicina (Kaunas). 2009;45:792-7 pubmed
    ..The hour-specific nomograms of transcutaneous bilirubin level should be used to evaluate hyperbilirubinemia using only a noninvasive method. ..
  41. Naderi S, Safdarian F, Mazloomi D, Bushehri E, Hamidian R. Efficacy of double and triple phototherapy in term newborns with hyperbilirubinemia: the first clinical trial. Pediatr neonatol. 2009;50:266-9 pubmed publisher
    Icterus is the most common medical problem in neonates and phototherapy is the standard treatment for neonatal hyperbilirubinemia. This study aimed to compare the efficacy and length of hospital stay of double and triple phototherapy in ..
  42. Silva I, Luco M, Tapia J, Pérez M, Salinas J, Flores J, et al. Single vs. double phototherapy in the treatment of full-term newborns with nonhemolytic hyperbilirubinemia. J Pediatr (Rio J). 2009;85:455-8 pubmed publisher
    ..However, our results suggest that double phototherapy may be more effective in those term newborns with higher bilirubin levels at admission. ..
  43. Profit J, Cambric Hargrove A, Tittle K, Pietz K, Stark A. Delayed pediatric office follow-up of newborns after birth hospitalization. Pediatrics. 2009;124:548-54 pubmed publisher
    ..Understanding reasons for delayed follow-up and providing guidance for jaundice management may promote a safer first week of life. ..
  44. Christensen R, Henry E. Hereditary spherocytosis in neonates with hyperbilirubinemia. Pediatrics. 2010;125:120-5 pubmed publisher
    ..We speculate that HS is underrecognized as a cause of neonatal hyperbilirubinemia. We speculate further that an MCHC of >or=36.0 g/dL can alert caregivers to the possibility of HS.
  45. Huang A, Tai B, Wong L, Lee J, Yong E. Differential risk for early breastfeeding jaundice in a multi-ethnic Asian cohort. Ann Acad Med Singapore. 2009;38:217-24 pubmed
    ..Chinese ethnic origin was an independent risk factor for hyperbilirubinaemia and phototherapy. Breastfeeding was not a risk factor for hyperbilirubinaemia/phototherapy in non-Chinese Asian infants. ..
  46. Bozkaya O, Kumral A, Yesilirmak D, Ulgenalp A, Duman N, Ercal D, et al. Prolonged unconjugated hyperbilirubinaemia associated with the haem oxygenase-1 gene promoter polymorphism. Acta Paediatr. 2010;99:679-683 pubmed publisher
    ..In this patient population, short repeat alleles of the HO-1 gene promoter polymorphism were associated with prolonged jaundice. ..
  47. Tønne A, Meberg A, Hager H. [Trends in the diagnosis and management of neonatal hyperbilirubinaemia]. Tidsskr Nor Laegeforen. 2010;130:18-20 pubmed publisher
    ..Far less exchange transfusions are performed nowadays than before 1994. ABO-immunization has been diagnosed more often after implementation of universal screening. ..
  48. Parlakgumus H, Durukan T. The relationship between cardiac adaptation to uteroplacental Doppler flow and perinatal outcome in pregnant women with diabetes. Clin Exp Obstet Gynecol. 2010;37:39-42 pubmed
    ..Neonatal complications were most common in this group. No relationship was found between echocardiographic findings, Doppler waveforms and poor perinatal outcome. ..
  49. Laosombat V, Viprakasit V, Dissaneevate S, Leetanaporn R, Chotsampancharoen T, Wongchanchailert M, et al. Natural history of Southeast Asian Ovalocytosis during the first 3 years of life. Blood Cells Mol Dis. 2010;45:29-32 pubmed publisher
    ..These babies had significant anemia at birth due to hemolysis with 51.6% of them developing neonatal hyperbilirubinemia. Co-inheritance of common UGT1A1 variants in such cases was not associated with their degree of ..
  50. Zuppa A, Sindico P, Antichi E, Carducci C, Alighieri G, Cardiello V, et al. Weight loss and jaundice in healthy term newborns in partial and full rooming-in. J Matern Fetal Neonatal Med. 2009;22:801-5 pubmed publisher
  51. Kurt A, Aygun A, Kurt A, Godekmerdan A, Akarsu S, Yilmaz E. Use of phototherapy for neonatal hyperbilirubinemia affects cytokine production and lymphocyte subsets. Neonatology. 2009;95:262-6 pubmed publisher
    ..from keratinocytes and on the expression of some lymphocyte subsets in the prevention or treatment of neonatal hyperbilirubinemia. The study group included 21 term newborns with hyperbilirubinemia and the control group included 16 ..
  52. Watchko J. Identification of neonates at risk for hazardous hyperbilirubinemia: emerging clinical insights. Pediatr Clin North Am. 2009;56:671-87, Table of Contents pubmed publisher
  53. Tell G, Gustincich S. Redox state, oxidative stress, and molecular mechanisms of protective and toxic effects of bilirubin on cells. Curr Pharm Des. 2009;15:2908-14 pubmed
    ..We then elucidate some of the molecular pathways that govern these effects. ..