Jaundice is usually noted by yellow discoloration of the skin and sclera with the naked eye.[35]Queensland Clinical Guidelines. Maternity and neonatal clinical guideline: neonatal jaundice. Jun 2019 [internet publication].
https://www.health.qld.gov.au/__data/assets/pdf_file/0018/142038/g-jaundice.pdf
[36]National Institute for Health and Care Excellence. Jaundice in newborn babies under 28 days. Oct 2023 [internet publication].
https://www.nice.org.uk/guidance/cg98
[37]National Association of Neonatal Nurses. Prevention of acute bilirubin encephalopathy and kernicterus in newborns. Position Statement #3049. NANN Board of Directors, March 2010. Adv Neonatal Care. 2010 Jun;10(3):112-8.
http://www.ncbi.nlm.nih.gov/pubmed/20505419?tool=bestpractice.com
[38]New South Wales Government. Neonatal - jaundice identification and management in neonates ≥32 weeks gestation. November 2016 [internet publication].
http://www1.health.nsw.gov.au/pds/ActivePDSDocuments/GL2016_027.pdf
All infants should be visually assessed for jaundice at least every 12 hours following delivery until discharge.[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
However, visual estimation of the degree of jaundice can lead to errors, particularly in darkly pigmented neonates. Transcutaneous bilirubin (TcB) measurement or total serum bilirubin (TSB) should be measured between 24 and 48 hours after birth (or before discharge if that occurs earlier) in all infants, but as soon as possible in those noted to be jaundiced within 24 hours of birth.[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
The Bilistick (a point-of-care device) measuring TcB has been suggested as a screening tool, though the results have not always been consistent.[39]Boo NY, Chang YF, Leong YX, et al. The point-of-care Bilistick method has very short turn-around-time and high accuracy at lower cutoff levels to predict laboratory-measured TSB. Pediatr Res. 2019 Aug;86(2):216-220.
https://www.nature.com/articles/s41390-019-0304-0
http://www.ncbi.nlm.nih.gov/pubmed/30696987?tool=bestpractice.com
[40]Greco C, Iskander IF, Akmal DM, et al. Comparison between Bilistick System and transcutaneous bilirubin in assessing total bilirubin serum concentration in jaundiced newborns. J Perinatol. 2017 Sep;37(9):1028-1031.
https://www.nature.com/articles/jp201794
http://www.ncbi.nlm.nih.gov/pubmed/28617429?tool=bestpractice.com
[41]Rohsiswatmo R, Oswari H, Amandito R, et al. Agreement test of transcutaneous bilirubin and bilistick with serum bilirubin in preterm infants receiving phototherapy. BMC Pediatr. 2018 Sep 29;18(1):315.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6162930
http://www.ncbi.nlm.nih.gov/pubmed/30268107?tool=bestpractice.com
[42]Kamineni B, Tanniru A, Vardhelli V, et al. Accuracy of Bilistick (a point-of-care device) to detect neonatal hyperbilirubinemia. J Trop Pediatr. 2020 Dec 1;66(6):630-636.
https://academic.oup.com/tropej/article-abstract/66/6/630/5841166?redirectedFrom=fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32433770?tool=bestpractice.com
TSB should be measured if the TcB exceeds or is within 52 micromol/L (3 mg/dL) of the phototherapy treatment threshold or if the TcB is ≥256 micromol/L (≥15 mg/dL). Jaundice is physiological if it happens on postnatal day 2 and resolves by a week of life. All neonates with jaundice in the first 24 hours of life and those with increased transcutaneous bilirubin after 24 hours of life need further evaluation.
Infants with risk factors for hyperbilirubinaemia require closer monitoring. Risk factors for hyperbilirubinaemia include lower gestational age, jaundice in the first 24 hours of life, known or suspected haemolysis of any cause, scalp haematoma or significant bruising, Down syndrome, an infant with macrosomia in a mother with diabetes, exclusive breast feeding with suboptimal intake, family history suggestive of inherited red blood cell disorders including glucose-6-phosphate dehydrogenase (G6PD) deficiency, and history of a parent or sibling requiring phototherapy or exchange transfusion.[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
Determining the presence of these risk factors requires a detailed history including obtaining a family history of blood disorders or neonatal jaundice, examining the infant and assessing laboratory investigations.[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
Decisions regarding management are guided by the gestational age, the hour-specific TSB, and the presence of risk factors for bilirubin neurotoxicity (gestational age <38 weeks, albumin <30 g/L [<3.0 g/dL], serious illness in the newborn infant, [e.g., sepsis or significant clinical instability in the previous 24 hours], or isoimmune haemolytic disease, G6PD deficiency, or other haemolytic conditions).[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
Evaluation of pathological jaundice
If the child is younger than 24 hours of age, if the TcB exceeds or is within 52 micromol/L (3 mg/dL) of the phototherapy treatment threshold, or if the TcB measurement is ≥256 micromol/L (≥15 mg/dL), TSB should be measured. Where there is more than one TcB or TSB measurement available, a rapid rate of increase (≥5 micromol/L [≥0.3 mg/dL] per hour in the first 24 hours or ≥3 micromol/L [≥0.2 mg/dL] per hour thereafter) suggests haemolysis with a higher risk of subsequent hyperbilirubinaemia. In these circumstances, a direct antiglobulin test (DAT)/Coombs' test should be done if not previously carried out.[1]Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999 Jan;103(1):6-14.
http://www.ncbi.nlm.nih.gov/pubmed/9917432?tool=bestpractice.com
[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
If the DAT test is positive, mother's and neonate's ABO and Rh blood groups must be checked. If there is no incompatibility (incompatibility occurs when mother is blood group O and neonate is A or B or when the mother is Rhesus -ve and the neonate is Rhesus +ve), minor blood group antigens incompatibility should be considered. If negative, direct serum bilirubin must be checked. Indirect bilirubin is the unconjugated fraction, derived by subtracting the direct bilirubin value from the TSB.
Causes of unconjugated hyperbilirubinaemia (such as haemolytic anaemias, extravasation of blood, causes of increased enterohepatic circulation, or conjugation defects) should be checked by doing a full blood count. If haematocrit is >65%, polycythaemia should be confirmed by obtaining the haematocrit level (either with a venous or an arterial sample). If the haematocrit is normal or decreased, the reticulocyte count and peripheral smear should be checked. If the reticulocyte count is increased, causes of haemolytic anaemia (blood group incompatibility, red blood cell enzyme deficiencies) should be considered. Tests include blood groups and glucose-6-phosphate dehydrogenase screening. If the blood smear is abnormal, specific red blood cell membrane defects should be identified by the osmotic fragility test.
For breastfed infants who are still jaundiced at 3-4 weeks of age, and for formula-fed infants who are still jaundiced at 2 weeks of age, the total and direct-reacting (or conjugated) bilirubin concentrations should be measured, if not already measured previously.[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
A joint recommendation from the North American and European Societies for Pediatric Gastroenterology, Hepatology, and Nutrition defines a direct serum bilirubin concentration >17.1 micromol/L (>1.0 mg/dL) as abnormal.[43]Fawaz R, Baumann U, Ekong U, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2017 Jan;64(1):154-68.
https://journals.lww.com/jpgn/fulltext/2017/01000/Guideline_for_the_Evaluation_of_Cholestatic.23.aspx
http://www.ncbi.nlm.nih.gov/pubmed/27429428?tool=bestpractice.com
It is recommended to repeat the measurement within a few days to 2 weeks.[9]Kemper AR, Newman TB, Slaughter JL, et al. Clinical practice guideline revision: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2022 Sep 1;150(3):e2022058859.
https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
Various causes of conjugated hyperbilirubinaemia including hepatocellular disease secondary to infections/metabolic or genetic causes and extrahepatic biliary disease need to be considered and investigated.[44]Benchimol EI, Walsh CM, Ling SC, et al. Early diagnosis of neonatal cholestatic jaundice: test at 2 weeks. Can Fam Physician. 2009 Dec;55(12):1184-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793221
http://www.ncbi.nlm.nih.gov/pubmed/20008595?tool=bestpractice.com
Tests may include liver function tests, blood culture, urine for reducing substances, plasma amino acids, urine amino acids, urine culture, abdominal ultrasound, and percutaneous liver biopsy. When taking bloods in practice, it may be clinically appropriate to carry out a wide range of tests during the initial investigations, and to reduce the need for taking repeated bloods from neonates.