Neonatal Jaundice by L. Veit | OPENPediatrics

Neonatal Jaundice, by Dr. Lauren Veit.

Learning Objectives.

By the end of this video, the viewer will be able to understand basic epidemiology of

neonatal jaundice, explain the pathophysiology of neonatal hyperbilirubinemia, recognize

the clinical presentation for a neonate with jaundice, conduct a diagnostic evaluation

for neonatal jaundice, describe the management of neonatal jaundice.

Introduction.

Neonatal jaundice is a common physiologic variant, as up to 60% of term, healthy newborns

exhibit some degree of jaundice in the first week of life.

Jaundice is a physical exam finding and refers to the yellow discoloration of the skin and

sclera caused by bilirubin deposition.

In contrast, hyperbilirubinemia refers to a total serum bilirubin measurement of greater

than the 95th percentile for age and requires treatment with photo therapy.

This is less common, but still affects about 5% of infants.

This video will focus on indirect hyperbilirubinemia, which encompasses the vast majority of hyperbilirubinemia

you will see in newborns.

Indirect and unconjugated hyperbilirubinemia refer to the same process, and you will see

these terms used interchangeably.

Direct and conjugated hyperbilirubinemia are also interchangeable and will be touched on

only briefly in this video.

Clinically, the progression to hyperbilirubinemia can be thought of as a spectrum.

To the left of the spectrum is simple jaundice-- isolated yellowing of the skin and sclera

without other symptoms.

As bilirubin continues to increase, we may see increased sleepiness and feeding difficulty.

Rarely, hyperbilirubinemia becomes severe-- typically, a total bilirubin of greater than

25 milligrams per deciliter.

This puts neonates at risk for bilirubin-induced neurologic dysfunction, or BIND, which occurs

when bilirubin crosses the blood brain barrier and binds to brain tissue, especially the

basal ganglia.

The term acute bilirubin encephalopathy is used to describe the acute manifestations

of BIND, which may initially include lethargy, hypotonia, and poor suck, and can evolve to

include irritability with high-pitched cry, hypertonia, fever, and seizures.

Kernicterus refers to the chronic and permanent sequelae of BIND, which are most often choreoathetoid

cerebral palsy, hearing loss, gaze abnormalities, and dental enamel dysplasia.

Fortunately, acute bilirubin encephalopathy and kernicterus are exceedingly rare in developed

countries such as the US, because we are almost always able to intervene before hyperbilirubinemia

becomes severe.

Bilirubin Metabolism.

Bilirubin is a product of red blood cell breakdown.

When red blood cells are broken down by macrophages, they release hemoglobin.

Hemoglobin is broken down to heme and globin.

And the heme is further metabolized to become unconjugated bilirubin.

Unconjugated bilirubin is water insoluble, so it is carried in the bloodstream on albumin

until it is delivered to the liver.

Once the unconjugated bilirubin is taken up by liver hepatocytes, it is conjugated by

the enzyme uridine diphosphate glucuronosyltransferase or UGT1A1 and then excreted by the hepatocytes

into the gallbladder and duodenum.

Once in the intestinal tract, most conjugated bilirubin is excreted in the feces.

But some is reverted back to the unconjugated form by the enzyme beta-glucuronidase and

reabsorbed into the bloodstream to start the cycle all over again, a process called enterohepatic

circulation.

Newborns are prone to what we call physiologic jaundice for a variety of reasons.

First, they typically have high hematocrits, on average around 60 and fetal red blood cells

with shorter lifespans.

Both of which increase their potential for red blood cell turnover, and, thus, unconjugated

bilirubin production.

Second, they are slow to metabolize unconjugated bilirubin, because they are just starting

to up regulate the UGT1A1 enzyme, which is not active in utero.

Third, as they are learning to feed and working toward a normal infant stooling pattern, excretion

of the bilirubin in the stool may be decreased.

These processes are present to some extent in almost all normal, healthy newborns, which

is why we call it physiologic.

Physiologic jaundice often peaks around day of life five and resolves by one to two weeks

of life.

Pathophysiology.

When physiologic jaundice progresses to hyperbilirubinemia, it is important to consider other mechanisms

that might also be contributing.

The first mechanism to consider is increased hemolysis of red blood cells, which leads

to increased production of unconjugated bilirubin.

Etiologies of increased hemolysis in a newborn include isoimmune mediated hemolysis, which

is to say ABO or Rh incompatibility.

Inherited red blood cell membrane defects, such as hereditary spherocytosis, arythrocyte

enzymatic defects, such as G6PD deficiency, and sepsis.

Of these etiologies, the one you will encounter most commonly is an ABO incompatibility, which

occurs when a mother is blood type O, and an infant is blood type A, B, or AB.

It is important to note that ABO incompatibility is present in about 15% of pregnancies, but

significant hemolysis only occurs in about 4% of ABO incompatible pregnancies.

So most newborns of ABO incompatible pregnancies will not have hyperbilirubinemia.

Polycythemia is more common in infants of diabetic mothers and extravasated blood, such

as in a cephalahematoma, can also lead to hyperbilirubinemia and are sometimes presented

as their own categories, though they ultimately lead to hyperbilirubinemia by increased hemolysis.

Increased enterohepatic circulation is another mechanism of hyperbilirubinemia in neonates.

Breastfeeding jaundice and breast milk jaundice are common etiologies under this umbrella.

Breastfeeding jaundice results from failure to establish adequate breastfeeding and typically

presents within the first week of life.

Reasons for inadequate breastfeeding can include poor milk supply, poor latch, cracked or painful

nipples, and poor positioning.

Inadequate feeding leads to dehydration and inadequate stooling.

As a result

there is decreased clearance of bilirubin via the stool.

Breast milk jaundice occurs later than breast feeding jaundice, often at two to four weeks

of life, and is thought to be due to an enzyme in the breastmilk itself, beta glucuronidase,

that promotes enterohepatic circulation.

It is important to note that all of the above etiologies should lead to an indirect hyperbilirubinemia.

Direct hyperbilirubinemia, which in a newborn is defined as a direct bilirubin of greater

than 20% of total or of greater than 1 milligram per deciliter, is never normal and should

prompt urgent consideration of other ideologies, including biliary atresia.

History and Physical Exam.

History should focus on the newborns feeding, voiding, stooling, and mental status.

Some questions you may ask on the history include, "Is the baby exclusively breastfed?

If so, does mom feel like breastfeeding is going well?

Has her milk come in?

Is the baby latching?

How many times has the baby fed in the last 24 hours?"

"How long does the baby feed at the breast?

Has the baby gotten any formula feeds?

How many wet diapers has the baby had in the last 24 hours?

How many stools in the last 24 hours?

Have the stools transitioned from meconium to yellow and seedy?

Is the baby waking to feed?

Does the baby seem hungry?"

Other history questions should focus on risk factors for hyperbilirubinemia.

"What is the baby's gestational age?

Were there complications with the pregnancy or the delivery?

Did a sibling require photo therapy?

Is there a family history of red blood cell disorders, such as G6PD deficiency?

Is the family of East Asian ancestry?"

It is also good practice to confirm that the baby had a newborn screen as hypothyroidism

and galactosemia are two uncommon causes of hyperbilirubinemia that are screened for in

all states.

Physical exam should be comprehensive but we'll discuss highlights here.

Weight is an important vital sign in these patients and should be reported as percentage

change from birth weight.

General appearance is also very important.

Is the infant well appearing and vigorous?

Does he wake appropriately with exam?

Skin and sclera should be examined for jaundice.

Head should be examined for cephalohematoma or caput succedaneum.

The abdomen should be assessed for organomegaly.

A neurologic exam should be performed with a focus on suck and tone.

Diagnostic Testing.

Diagnostic testing should always include a total and direct serum bilirubin level.

In cases of ABO incompatibility, a DAT, also known as a Coombs, should also be sent.

CBC, reticulocyte count, G6PD activity, peripheral smear, and type and screen should be considered

in cases of severe hyperbilirubinemia, early onset of hyperbilirubinemia, within the first

24 hours of life, rapid rate of bilirubin rise, greater than 0.5 milligrams per deciliter

per hour, failure to respond appropriately to photo therapy, or persistent hemolysis.

The AAP nomogram, which can be downloaded from the primary literature or found at www.bilitool.org,

defines treatment thresholds for hyperbilirubinemia in infants born at gestational age greater

than or equal to 35 weeks.

Enter the total serum bilirubin level and the age in hours at which it was measured,

and the nomogram will give you the bilirubin threshold at which to initiate photo therapy.

There are three curves, or three different thresholds at which to initiate, designated

low risk, medium risk, and high risk.

A gestational age of less than 38 weeks or the presence of neurotoxicity risk factors,

such as isoimmune hemolytic disease, or ABO incompatibility, should prompt infants to

be evaluated on the medium or high risk curves.

If your patient is below the photo therapy threshold, the nomogram and BiliTool will

risk stratify the likelihood of the patient needing photo therapy in the future.

Finally, when you are calculating your patient's photo therapy threshold, it is good practice

to determine the exchange transfusion threshold, which can be done on the AAP nomogram, but

is not part of BiliTool.

Management.

The cornerstones of hyperbilirubinemia management are phototherapy and feeding.

Neonates with severe hyperbilirubinemia may also require exchange transfusion, but this

is rare and outside the scope of this lecture.

Phototherapy uses blue light to convert unconjugated bilirubin into bilirubin photoproducts.

It can be delivered overhead in a closed crib or via bili blanket.

Response to phototherapy is dose dependent, so it is crucial that maximal skin surface

area is exposed and that interruptions are minimized.

Feeding is also critical to management.

Infants should be fed at least every two to three hours.

Breastfeeding mothers should be offered the help of a lactation consultant.

Supplemental formula feeding-- that is, offering formula after the baby has attempted to breastfeed--

can help decrease bilirubin levels and may be considered on a case-by-case basis with

input from parents.

IV fluids are not routinely indicated in hyperbilirubinemia but should be considered in newborns who are

unable to maintain adequate hydration orally or are approaching the exchange transfusion

threshold.

Once phototherapy has been initiated, total serum bilirubin should be re-measured at 4

to 12 hour intervals.

Most often, the bilirubin level will drop nicely on phototherapy.

If this response is not achieved, more extensive diagnostic testing and NICU consult for potential

exchange transfusion may be considered.

When the total serum bilirubin level has dropped below the phototherapy threshold and the newborn

is demonstrating good feeding, he can be discharged, ideally with next-day follow up with a pediatrician.

Rebound bilirubin testing-- that is re-checking a bilirubin level after phototherapy has been

discontinued-- is not recommended by the AAP and in many cases is not indicated.

Rebound bilirubin testing should be considered in neonates born at gestational age less than

38 weeks, phototherapy initiation at less than 72 hours of life, or if there is clinical

concern for ongoing hemolysis.

For example, in a neonate who is DAT positive-- because neonates in these categories are at

higher risk for rebound hyperbilirubinemia.

With this approach, newborns with hyperbilirubinemia have excellent outcomes, and kernicterus has

become exceedingly rare.

Thank you for watching this video on neonatal jaundice.