What is the pathophysiology of pathological jaundice in neonates (newborns)?

From the Guidelines

Pathological jaundice in neonates is primarily caused by an imbalance between bilirubin production and clearance, which can lead to severe hyperbilirubinemia and potentially life-threatening complications, such as kernicterus, emphasizing the need for prompt diagnosis and treatment, as highlighted in a recent study published in 2024 1. The pathophysiology of pathological jaundice in neonates involves several key mechanisms, including:

• Increased bilirubin production due to hemolytic disorders, such as ABO/Rh incompatibility or G6PD deficiency
• Impaired bilirubin conjugation resulting from genetic disorders, like Crigler-Najjar or Gilbert syndrome
• Decreased bilirubin excretion caused by biliary obstruction or hepatocellular damage
• Increased enterohepatic circulation from conditions like pyloric stenosis or intestinal atresia According to the most recent guidelines, phototherapy is an essential intervention for severe hyperbilirubinemia, especially in neonates at high risk, and its use reduces the risk of bilirubin neurotoxicity as well as the need for exchange transfusions 1. The timing of intervention is guided by performing serial measurements of total serum/plasma bilirubin (TSB) concentrations and screening for the presence of intrinsic risk factors for bilirubin neurotoxicity. Key aspects of phototherapy include:
• Exposure to light in the blue-green wavelength range (460–490 nm), preferably at an optimal peak of 478 nm
• Irradiance of 25 to 35 mW/cm2/nm to at least 1 surface of the body (ventral or dorsal)
• Photoconversion of the unconjugated bilirubin molecule to the excretable water-soluble 4E,15Z photoisomer, peaking within 120 minutes Early intervention is critical, as excessive unconjugated bilirubin can cross the blood-brain barrier and cause kernicterus, resulting in permanent neurological damage, thus, prompt treatment with phototherapy, as recommended in the 2024 study 1, is crucial to prevent such complications and improve outcomes in neonates with pathological jaundice.

From the Research

Pathophysiology of Pathological Jaundice in Neonates

• Pathological jaundice in neonates is characterized by elevated bilirubin levels, which can lead to severe complications such as kernicterus if left untreated 2, 3, 4.
• The condition is caused by an increase in serum bilirubin levels, largely as a result of breakdown of red blood cells, and the liver's inability to convert bilirubin into a conjugated form that can be excreted in the bile 5.
• Newborns are particularly susceptible to jaundice due to increased red blood cell turnover, immature liver enzymes, and delayed stooling patterns 2.
• Very high levels of unconjugated bilirubin are neurotoxic and can cause brain damage if not treated promptly 3, 4, 5.

Risk Factors and Diagnostic Methods

• Risk factors for bilirubin-related neurotoxicity include prematurity, hemolytic diseases, and delayed stooling patterns 2, 4.
• Diagnostic methods include bilirubin screening, physical examination, and measurement of bilirubin levels in newborns who appear jaundiced 2, 4, 5.
• The American Academy of Pediatrics recommends universal neonatal hyperbilirubinemia screening in newborns 35 weeks' gestational age or greater 4.

Treatment and Management

• Treatment for pathological jaundice involves phototherapy and/or exchange transfusion of donor blood, as well as treatment of the underlying cause 3, 4, 6.
• Phototherapy is a simple and effective way to reduce bilirubin levels, but it can have short- and long-term adverse effects, including diarrhea and increased risk of seizures 4.
• Parental involvement is important to minimize the trauma of having a sick baby and its effect on bonding 6.
• Effective management relies on thorough assessment, parental education, and close postdischarge follow-up 2.