All unwell jaundiced infants require early evaluation:

Red flags:

• Known family history of significant hemolytic disease.
• Vomiting.
• Lethargy.
• Poor feeding.
• Fever.
• High-pitched cry.
• Dark urine.
• Light stools.

• Neonatal jaundice is a very common condition worldwide, occurring in up to 60% of term and 80% of preterm newborns in the first week of life with serum bilirubin levels >5 mg/dL (>85.5 µmol/L).
• Hyperbilirubinemia tends to occur in the first week after birth due to normal physiologic changes and is often harmless.
• Common cause of newborn readmission to hospital and emergency visits, especially in the first two weeks of life.
• Seen more commonly among preterm newborns.

The breakdown of hemoglobin in red blood cells releases unconjugated bilirubin (indirect bilirubin) into the bloodstream, which is then converted to conjugated bilirubin (direct bilirubin) in the liver.

• Indirect bilirubin is lipid-soluble and can cross the blood-brain barrier, thus making it a neurotoxic substance (kernicterus risk).
• Direct bilirubin is more easily excreted (if elevated, this is always pathological, requiring further investigation).

In newborns, excessive levels of indirect bilirubin in the blood can lead to encephalopathy (kernicterus).

• Kernicterus is a life-threatening infiltration of bilirubin into the brain, depositing in basal ganglia and brainstem nuclei.
• Penetration of the blood-brain barrier is more likely when bilirubin >25–30 mg/dL (425-510 µmol/L).

Figure 1: Signs of Bilirubin Encephalopathy.

The main causes of jaundice in neonates tend to be due to elevated indirect bilirubin, and include:

• Increase in hemolysis (increased RBC breakdown).
• Delayed maturation or inhibition of liver conjugation enzymes.
• Interference with liver uptake of indirect bilirubin.

Indirect bilirubin elevation = physiologic or pathologic.

Direct bilirubin elevation = pathologic.

Table 1. Initial Assessment Tips for Jaundice in Newborn.

Table 2. Etiologies of Jaundice in Newborn.

Evaluation:

• Newborns may be observed if they: are full-term, appear clinically well, are asymptomatic, have no warning signs, or have a presentation consistent with physiologic jaundice (Table 1).
• For jaundiced infants, order serum bilirubin and hemoglobin → no further testing needed if normal level in well-appearing, afebrile baby.
  • May consider getting a urinalysis and urine culture.
• Investigations for pathologic neonatal jaundice:
  • CBC
  • Total serum bilirubin (TSB)
    • Direct and Indirect Bilirubin
  • Direct Coombs’ test
  • Blood group testing (maternal and fetal)
  • Hemoglobin
  • Reticulocyte count
  • Liver function test
  • Alkaline phosphatase
  • Serum albumin
  • PTT/INR
  • TSH
  • Urinalysis
  • Full septic work-up (in addition to the above, do a WBC count, chemistry panel, CRP, urine culture, blood culture, and a lumbar puncture)

• TORCH infection panel – for infectious cause workup in direct hyperbilirubinemia.
• Consider abdominal ultrasound to investigate obstructive causes (biliary atresia is most common direct cause).
• If exchange transfusion is anticipated (see Table 3 below), obtain blood type and crossmatch.
• Hemolysis is suspected if there is: reticulocytosis, indirect hyperbilirubinemia, and a peripheral smear consistent with RBC destruction.

Management decisions should be made carefully, with consideration to the benefits and risks of each treatment as well as the neonate’s age, clinical appearance, bilirubin level, etiology, and jaundice onset/timing.

Admit the neonate and consult a neonatologist if:

• They are anemic, hyperbilirubinemia level indicates phototherapy or exchange transfusion treatment, or there is pathologic/conjugated hyperbilirubinemia.
• To find out which serum bilirubin levels phototherapy or exchange transfusion are indicated, see current Canadian Pediatric Society guidelines and nomogram (in-depth review section) as the value is age dependent.

The goal for indirect hyperbilirubinemia is to prevent kernicterus, as this can cause permanent brain injury or even death.

Table 3: Treatment of Indirect Hyperbilirubinemia.

The goal for managing direct hyperbilirubinemia is to immediately identify and treat the underlying cause of a patient’s symptoms:

• Start antibiotics if sepsis or urinary tract infection are suspected as the cause of jaundice.
• If obstruction or biliary atresia suspected, consult Pediatric Surgery regarding hepatic portoenterostomy.

Full-term, afebrile neonates that appear well and have a bilirubin level of low risk (based on nomogram) can be monitored closely and supported conservatively:

• Encourage frequent breastfeeds (8-10 times per 24 hours) and stools to support excretion of bilirubin.
• Administer IV bolus normal saline depending on weight if signs of dehydration.
• It is encouraged to not discontinue breastfeeding.
• Discuss different feeding options (e.g., continued breastfeeding, brief substitution with formula, and supplementing with formula) including their risks and benefits while considering parents’ preference.

1. https://cps.ca/en/documents/position/hyperbilirubinemia-newborn

   https://cps.ca/en/documents/position/hyperbilirubinemia-newborn#figure2

   https://www.healthlinkbc.ca/pregnancy-parenting/parenting-babies-0-12-months/newborns/jaundice-newborns-hyperbilirubinemia

   https://cps.ca/uploads/documents/hyperbilirubinemia_newborn_fig1.pdf

   https://cps.ca/uploads/documents/hyperbilirubinemia_newborn_fig2.pdf

   
   

1. Ansong-Assoku B, Shah SD, Adnan M, Ankola PA. Neonatal jaundice – statpearls – NCBI bookshelf [Internet]. 2023 [cited 2024 Jan 27]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532930/

   
   

2. Taylor T, Wheatley M. Jaundice in the Emergency Department: Meeting the Challenges of Diagnosis and Treatment [Internet]. 2018 [cited 2024 Jan 26]. Available from: https://www.ebmedicine.net/topics/hepatic-renal-genitourinary/jaundice-bilirubin

   
   

3. Maisels MJ. Managing the jaundiced newborn: A persistent challenge. Canadian Medical Association Journal. 2014 Nov 10;187(5):335–43. doi:10.1503/cmaj.122117

   
   

4. Colletti JE, Kothari S, Jackson DM, Kilgore KP, Barringer K. An emergency medicine approach to neonatal hyperbilirubinemia. Emergency Medicine Clinics of North America. 2007 Nov 22;25(4):1117–35. doi:10.1016/j.emc.2007.07.007