Approach to jaundice (newborn and infant): Clinical sciences

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Introduction0:00–0:27

Jaundice is a yellowish discoloration of the skin and sclera 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 two weeks of age or if there is evidence of cholestasis.
If a newborn or infant presents with jaundice first perform an ABCD E assessment to determine if they are unstable or stable if unstable, stabilize their airway breathing and circulation.

Unstable Patient0:27–1:31

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 lifethreatening condition manifests with lethargy, hypotonia and a high pitched cry if left untreated can lead to opisthotonus seizures, death or chronic bilirubin encephalopathy known as ICTERUS due to permanent brain damage.
Once you recognize severe jaundice, consider an urgent exchange transfusion. Ok.

Stable Patient1:31–3:43

Let's return to the ABCD E 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 and 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 mg per deciliter over 24 hours is considered pathologic. First, let's discuss newborns whose jaundice started before two weeks of age.

Onset before 2 Weeks/Conjugated Hyperbilirubinemia3:43–4:55

In this case, you'll need to assess the direct serum bilirubin level. If it's 2 mg 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 mix or FTS 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 mg per deciliter, your patient has unconjugated hyperbilirubinemia.

Unconjugated Hyperbilirubinemia4:55–5:27

Next order a reticulocyte count, blood group and Coombs test also called direct anti-globulin 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 coomb's test result.
Uh positive Coombs indicates isoimmune hemolytic disease of the newborn, which usually results from A B or Rh incompatibility to assess for maternal infant blood incompatibility order, an anti B anti A and anti B antibodies and review the maternal history.

Coombs +5:27–6:27

Now, if the mother is Rh negative and didn't receive prenatal RD 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 A bo 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.

Coombs -6:27–8:27

This could result from a hemoglobinopathy, RBC membranal 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 membrane 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 membraned. You can confirm the diagnosis with further testing like an osmotic fragility test.
Finally, if your patient is of middle eastern or sub Saharan African ancestry and the peripheral smear reveals hinds bodies or bite cells.
They probably have an RBC enzyme defect, specifically glucose, six phosphate dehydrogenase deficiency, you'll need to assess RBC enzymatic activity for confirmation.
Keep in mind that glucose, six phosphate dehydrogenase activity shouldn't be measured during an acute hemolytic episode as it can result in false negative results.
Here's a clinical pearl. Other conditions that are associated with non immune mediated hemolysis can also cause jaundice in newborns.
For example, polycythemia can cause intravascular hemolysis and minor birth trauma like cephalohematoma can cause extravascular hemolysis.

Non-Hemolytic8:27–11:29

Now let's go back to reticulocytes If the reticulocyte count is not elevated. Consider non hemolytic processes and assess for onset of jaundice within the 1st 24 hours of life.
If jaundice began within the 1st 24 hours, consider Kriegler Najar syndrome type one, which is associated with a complete absence of UDP glucuronosyl transferase activity and an inability to conjugate bilirubin.
Affected infants have rapidly progressive jaundice and extreme levels of indirect hyperbilirubinemia order a percutaneous liver biopsy.
And if hepatic UDP glucuronosyl transferase activity is absent, it confirms the diagnosis. These infants are at risk of Cicis and require urgent exchange transfusion.
Here's a high yield fact, Gilbert syndrome is another genetic condition associated with mildly reduced UDP glucuronyl cyl transferase activity, this condition can cause transient neonatal hyperbilirubinemia but isn't usually diagnosed before adolescence.
Now, if the jaundice started after the 1st 24 hours of life, think about conditions that transiently impair hepatic bilirubin excretion.
These are diagnoses of exclusion. Some infants develop jaundice 2 to 3 days after birth that resolves within two weeks and are well appearing on exam.
These findings suggest physiologic jaundice which is caused by the breakdown of fetal red blood cells combined with a transiently reduced ability to effectively conjugate bilirubin.
Others developed jaundice during the first week of life and experienced difficulty breastfeeding and decreased stooling.
The exam reveals significant weight loss in dry mucous membranes, which is consistent with breastfeeding jaundice in this transient condition.
Suboptimal breast milk intake causes decreased stooling, which leads to increased enterohepatic circulation of bilirubin.
Lastly, in some cases, jaundice begins after the first week of life. In exclusively breastfed infants with normal intake and stool output.
The exam reveals a well appearing infant with adequate weight gain. These findings suggest breast milk jaundice.
A benign condition thought to be caused by increased enterohepatic circulation. Combined with factors in breast milk that disrupt bilirubin conjugation, breast milk jaundice can persist up to three months and resolves spontaneously.
Here's another clinical pearl. In some cases, unconjugated hyperbilirubinemia persisting longer than two weeks indicates a pathologic condition such as congenital hypothyroidism or intestinal obstruction.
All right, let's go back and discuss jaundice that begins or persists after two weeks of age, which suggests a pathologic condition associated with cholestasis.

Jaundice after 2 Weeks/Conjugated Hyperbilirubinemia11:29–13:52

In this case, you should assess direct serum bilirubin levels. A level of 2 mg per deciliter or higher indicates conjugated hyperbilirubinemia.
Next review, your patient's history in greater detail, symptoms like pruritus, dark urine and pale clay colored stools should make you consider cholestasis to evaluate further order.
An abdominal ultrasound, abnormal ultrasound suggests an extrahepatic cause. So, if it demonstrates an absent or atrophic gallbladder and a triangular cord sign, which is a triangular echogenic structure in the liver hilum, diagnose biliary atresia, which is the most common and severe cause of neonatal cholestasis.
In this condition, extrahepatic bile ducts are present at birth but an idiopathic inflammatory process gradually destroys them.
However, if ultrasound reveals a dilated cystic lesion, separate from the gallbladder that communicates with the bile duct, diagnose a choledochal cyst.
Ok. If ultrasound findings are normal, consider intrahepatic causes and assess the newborn screen for evidence of metabolic liver disease.
Elevated succinylacetone levels suggest tyrosinemia while absent gault activity suggest galactosemia. Finally, if the newborn screen is normal, consider alagille syndrome also known as arteriohepatic dysplasia, which is associated with a paucity of intrahepatic bile ducts.
The physical exam commonly reveals a triangular face, a prominent forehead, deep set eyes and a pointed chin. You may detect a soft blowing systolic ejection murmur, suggesting peripheral pulmonic stenosis.
These findings suggest alagille syndrome. You can confirm the diagnosis with genetic testing.
Here's one final clinical pearl. Other conditions associated with neonatal cholestasis include alpha one antitrypsin deficiency Gaucher disease and cystic fibrosis.
All right. As a quick recap.

Review13:52–14:53

When a patient under two weeks of age presents with jaundice, order a total and direct serum bilirubin levels. Cbc reticulocyte count blood group and Coombs test conjugated hyperbilirubinemia suggests congenital infection unconjugated hyperbilirubinemia suggest immune mediated hemolysis like ABO or Rh incompatibility or non immune mediated hemolysis like hemoglobinopathies.
RBC membranous or an RBC enzyme defect. A normal reticulocyte count indicates non hemolytic causes such as physiologic breastfeeding or breast milk, jaundice, conjugated hyperbilirubinemia beginning after two weeks of age indicates cholestasis which could have extrahepatic causes like biliary atresia or choledochal cyst or intrahepatic causes such as tyrosinemia galactosemia or alagille
Approach to jaundice (newborn and infant): Video | Osmosis