What are the causes of hepatomegaly in neonates?

Causes of Hepatomegaly in Neonates

Neonatal hepatomegaly demands immediate recognition of life-threatening cardiac and metabolic causes before considering other etiologies, with congestive heart failure from ductal-dependent lesions and neonatal sepsis being the most critical diagnoses to exclude first. 1

Life-Threatening Causes (Evaluate First)

Cardiac Causes

• Any neonate presenting with shock and hepatomegaly requires immediate prostaglandin infusion until complex congenital heart disease is excluded by echocardiography. 1
• Congestive heart failure from structural heart disease, particularly ductal-dependent lesions, is a primary cause of neonatal hepatomegaly. 1
• Look specifically for cyanosis, cardiac murmur, or differential upper/lower extremity blood pressures—these findings mandate immediate echocardiography and prostaglandin therapy. 1

Infectious Causes

• Neonatal sepsis presents with hepatomegaly alongside tachycardia, respiratory distress, poor feeding, poor tone, and reduced perfusion. 1
• Maternal risk factors include chorioamnionitis or prolonged rupture of membranes. 1
• Perinatal infections from hepatitis B virus, hepatitis C virus, and human immunodeficiency virus can cause neonatal hepatobiliary disorders. 2

Vascular Causes

• Diffuse hepatic infantile hemangiomas cause severe hepatomegaly before 4 months of age and can lead to abdominal compartment syndrome, compromised ventilation, renal failure, or high-output cardiac failure. 1
• Congenital hepatic arteriovenous malformations present with congestive heart failure, anemia, and hepatomegaly, though isolated massive hepatomegaly can occur in otherwise healthy neonates. 3
• Failure to recognize hepatic hemangiomas in infants with multiple cutaneous hemangiomas misses the opportunity for early treatment before cardiac decompensation. 1

Metabolic and Storage Disorders

Glycogen Storage Diseases

• Inborn errors of metabolism resulting in hyperammonemia or hypoglycemia can simulate septic shock and present with hepatomegaly. 1
• GSD Type III presents with hypoglycemia and hepatomegaly, with elevated transaminases and elevated CK levels. 1
• Pompe disease (GSD Type II) can rarely cause severe infantile cardiomyopathy with hepatomegaly from cardiac failure, distinguished by absence of hypoglycemia. 1
• Beta-hydroxybutyrate elevation at time of hypoglycemia distinguishes GSD from fatty acid oxidation disorders and hyperinsulinism—assuming all hepatomegaly with hypoglycemia is GSD without checking this can miss fatty acid oxidation disorders requiring completely different management. 1

Other Metabolic Disorders

• Galactosemia should be identified through newborn screening as it requires immediate dietary intervention. 1
• Gaucher disease and Niemann-Pick disease present with hepatomegaly but are distinguished by massive splenomegaly and absence of hypoglycemia. 1

Hepatobiliary Disorders

Cholestatic Conditions

• Biliary atresia presents with acholic stools and conjugated hyperbilirubinemia—missing this diagnosis delays surgical intervention. 1
• Neonatal hepatitis and intrahepatic cholestasis require differentiation from biliary atresia using hepatobiliary scintigraphy. 1, 2
• Primary liver disease, though rare in neonates, must be recognized promptly with treatment initiated in a timely manner to prevent unnecessary sequelae. 4

Nutritional Causes

• Kwashiorkor (severe protein-energy malnutrition) presents with edema, hepatomegaly, and dermatological changes. 5
• Vitamin A deficiency commonly accompanies protein-energy malnutrition and should be addressed in treatment. 5

Diagnostic Approach Algorithm

Initial Assessment

• When hepatomegaly coexists with hypoglycemia, obtain blood glucose, lactate, uric acid, hepatic profile, CK, plasma total and free carnitine, acylcarnitine profile, urinalysis, and urine organic acids. 1
• Abdominal ultrasound assesses liver size, texture, and focal lesions. 1, 6
• Echocardiography is mandatory to exclude structural heart disease and assess for cardiomyopathy. 1

Distinguishing Features

• Massive splenomegaly with hepatomegaly suggests Gaucher or Niemann-Pick disease rather than GSD. 1
• Hepatobiliary scintigraphy differentiates biliary atresia from intrahepatic cholestasis. 1
• Annual laboratory tests should include total bilirubin, AST, ALT, alkaline phosphatase, GGT, and platelet count to identify hepatobiliary involvement. 6

Critical Pitfalls to Avoid

• Failure to distinguish cardiac from metabolic causes can delay life-saving prostaglandin therapy in ductal-dependent lesions. 1
• Delaying treatment for potentially life-threatening conditions such as vascular malformations or acute liver failure can be fatal. 6
• Hepatomegaly secondary to systemic illness such as sepsis or hypoxic injury is common and must be differentiated from primary liver disease. 4