Approach to jaundice (newborn and infant): Clinical sciences

Jaundice is a yellowish discoloration of the skin and sclerae caused by elevated serum bilirubin, or hyperbilirubinemia. While jaundice is a common and benign physiologic phenomenon in newborns, it's considered pathologic if it progresses rapidly, begins within the first day of life, persists beyond 2 weeks of age, or if there is evidence of cholestasis.

If a newborn or infant presents with jaundice, first perform an ABCDE assessment to determine if they are unstable or stable. If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access, and begin IV fluids if needed. Put your patient on continuous vital sign monitoring and lastly, provide supplemental oxygen, if needed.

Here’s a high-yield fact! Because unconjugated bilirubin is a lipid-soluble neurotoxic substance that crosses the blood-brain barrier, excessively high levels can lead to acute bilirubin encephalopathy. This life-threatening condition manifests with lethargy, hypotonia, and a high-pitched cry. If left untreated, it can lead to opisthotonos, seizures, death, or chronic bilirubin encephalopathy, known as kernicterus, due to permanent brain damage. Once you recognize severe jaundice, consider an urgent exchange transfusion.

Okay, let’s return to the ABCDE assessment and discuss stable patients. In this case, obtain a focused history and physical examination. Caregivers usually notice jaundice in the face first, followed by the trunk and lower extremities. The exam may reveal scleral icterus and yellowish skin, suggesting unconjugated hyperbilirubinemia; or yellowish-green skin, suggesting conjugated hyperbilirubinemia. These findings confirm the presence of jaundice.

Remember that a visual assessment of jaundice isn’t always reliable in newborns with deeply pigmented skin; so obtain a transcutaneous bilirubin level, which estimates the total serum bilirubin. Then, plot the result on a nomogram, using the patient’s age in hours. If it falls within the high or high-intermediate risk zone, also known as the treatment threshold, they will need further evaluation of hyperbilirubinemia. So, order fractionated serum bilirubin levels, which include total, direct, and indirect bilirubin. Then, assess the age of onset to determine your next steps.

Here’s a clinical pearl! Infants who meet treatment threshold should begin phototherapy, to convert unconjugated bilirubin into a form that’s more easily excreted. However, phototherapy can’t treat conjugated hyperbilirubinemia, and in these infants, phototherapy can produce a grayish-brown skin discoloration, called “bronze baby syndrome”. Before starting treatment, check a conjugated bilirubin level, and avoid phototherapy if it’s elevated.

Let’s follow that up with a high-yield fact! The terms conjugated and unconjugated bilirubin are often used interchangeably with direct and indirect, respectively. Elevated conjugated or direct bilirubin always indicates a pathologic process. Also, any form of bilirubin that rises more than 5 milligrams per deciliter over 24 hours is considered pathologic.

First, let’s discuss newborns whose jaundice started before two weeks of age. In this case, you’ll need to assess the direct serum bilirubin level. If it’s 2 milligrams per deciliter or greater, your patient has conjugated hyperbilirubinemia. This should make you consider congenital TORCH infections. Newborns with TORCH infections often have low birth weight, and physical exam commonly demonstrates hepatosplenomegaly, rash, and possibly, chorioretinitis.

Next, order LFTs and viral serologies or PCR. Results may include elevated transaminases; while viral serology or PCR testing might be positive for rubella, cytomegalovirus, toxoplasma, or herpes simplex virus, which confirms congenital TORCH infection.

Time for a clinical pearl! Conjugated hyperbilirubinemia in a neonate with a fever or hemodynamic instability may indicate other types of infections, like E. coli sepsis or urinary tract infection.

On the other hand, if the direct bilirubin level is below 2 milligrams per deciliter, your patient has unconjugated hyperbilirubinemia. Next, order a reticulocyte count; blood group; and Coombs test, also called direct antiglobulin test; and a CBC with peripheral blood smear. Then, assess for hemolysis by reviewing the reticulocyte count. If it’s elevated, consider a hemolytic process, and assess the Coombs test result.

A positive Coombs indicates isoimmune hemolytic disease of the newborn, which usually results from ABO or Rh incompatibility. To assess for maternal-infant blood incompatibility, order anti-D, anti-A, and anti-B antibodies; and review the maternal history.

Now, if the mother is Rh-negative and didn’t receive prenatal Rho-D-immunoglobulin; and the infant is Rh-positive and anti-D antibodies are detected, diagnose Rh incompatibility. This is associated with severe hemolysis, resulting in anemia and jaundice within the first day of life. However, if the mother’s blood type is O; the infant has blood type A or B; and anti-A or anti-B antibodies are positive, diagnose ABO incompatibility. In this case, hemolysis is less severe and does not usually cause anemia or jaundice within the first day of life.

Now, if the Coombs is negative, assess the family history and the peripheral smear, to look for evidence of non-immune-mediated hemolysis. This could result from a hemoglobinopathy; RBC membranopathy; or RBC enzyme defect.

The family history might be positive for sickle cell disease or thalassemia; and the peripheral smear could reveal sickled cells, suggesting sickle cell disease; or hypochromia and microcytosis with target cells, suggesting thalassemia. In this case, your patient probably has a hemoglobinopathy, which you can confirm with hemoglobin electrophoresis.

On the flip side, there might be a family history of RBC membranopathy, and the peripheral smear could demonstrate spherocytes, suggesting hereditary spherocytosis; or elliptocytes, suggesting hereditary elliptocytosis. In this case, it’s likely your patient has an RBC membranopathy. You can confirm the diagnosis with further testing, like an osmotic fragility test.