12: Neonatal Jaundice

Question 1

What is the description and cause of Jaundice?

Answer 1

The accumulation of bilirubin in the skin -yellow tones
Becomes apparent when bilirubin level is >5-7
Advances Head to toe

Rise in bilirubin from 1.5 in cord blood to 5-6 on the third day of life, declining to a normal level (<1.3-1.5) by 10-12 days in Caucasian and AA infants

Asian infants reach 8-12 on day 4-5 and decline more slowly

Breastmilk jaundice: inadequate feeding can lead to increased jaundice because of slow moving bowels and inability to clear bili

Question 2

What is Non-physiologic (pathologic) Jaundice?

Answer 2

Appears at <24 hours and may last longer than 8 days

The rate of increase is >0.5 mg/dL/hr

Total bili >12.5 before 48 hours old or direct bili exceeds 1.5-2

Kernicterus (bilirubin encephalopathy) involves toxicity of the nervous system resulting from high levels of bili

Consider exchange transfusion when bili levels reach 25-30

Question 3

What are the causes of jaundice?

Answer 3

Increased rate of hemolysis
Decreased rate of conjugation
Abnormalities of excretion or absorption

Question 4

What increases the rate of hemolysis to cause jaundice?

Answer 4

ABO incompatibility
Rh incompatibility
Abnormal RBC shapes
RBC enzyme abnormalities

Question 5

What decreases the rate of conjunction and causes jaundice?

Answer 5

Immaturity of bilirubin conjugation (physiologic jaundice)
Congenital familial nonhemolytic jaundice
Breast milk jaundice

Question 6

What are the abnormalities of excretion and absorption that cause jaundice?

Answer 6

Sepsis
Hepatitis
Metabolic abnormalities
Biliary atresia
Choledochal cyst
Obstruction of ampulla of Vater
Drugs

Question 7

What family factors increase the risk of jaundice?

Answer 7

Significant hemolytic disease/anemia
Inborn errors of metabolism
Early or severe jaundice
Ethnic or geographic origin associated with hemolytic anemia
Hepatobiliary disease
Sibling received phototherapy

Question 8

What maternal history factors can increase the risk of jaundice?

Answer 8

ABO or Rh incompatibilities in previous pregnancy
Sepsis risk for the infant - Prolonged ROM
Macrosomic infant of a diabetic mother

Question 9

What color of skin is an infant suffering from the deposition of indirect bili in the skin?

Answer 9

Bright yellow or orange

Question 10

What color of skin is an infant suffering from the obstructive type (direct bili)

Answer 10

Greenish or muddy yellow

Question 11

Physical exam of an infant with jaundice?

Answer 11

Petechia
Bruising
Hepatosplenomegaly
Signs of infection
Lethargy
Hypotonia
Poor feeding
Loss of Moro reflex - signs of bili toxicity to the brain
Diminished DTR's
Respiratory distress
Failure to suck
Opisthotonos
Bulging fontanelle
Twitching of face or limbs
Seizures
Shrill, high pitched cry
Signs of kernicterus

Question 12

What are diagnostic studies for jaundice?

Answer 12

TcB Noninvasive Transcutaneous bilirubin
TSB (indirect and direct) for infants with TcB >15, for darker skinned infants or for infants under phototherapy
Fractionated bili: provides the concentration of both unconjugated and conjugated bili

Additional Labs:
ABO
Rh
Blood type
Isoimmmune antibodies of mother
Coombs test on infant
HgB
Hct
Reticulocyte count

Question 13

Elevated indirect (unconjugated) serum bili with a normal reticulocyte count and negative Coombs test

Answer 13

physiologic jaundice
breast milk jaundice
congenital familial nonhemolytic jaundice

Question 14

Elevated indirect and direct serum bili with a negative Coombs test and a normal reticulocyte count

Answer 14

hepatitis
metabolic abnormalities
biliary atresia
choledochal cyst in the bile duct
GI or pancreatic obstruction
sepsis
drugs

Question 15

How is jaundice managed?

Answer 15

Monitoring of TcB and TSB
Frequent breast feeding, supplementation feeding
Phototherapy with overhead light, bili blanket and bilibed
Exchange transfusion

Question 16

How is jaundice prevented?

Answer 16

Frequent breast feeding
Systematic assessment of the new born for the risk of hyperbilirubinemia
Early and focused follow-up based on risk assessment
Supplement feeding if infant is inadequate intake, weight loss >10%, infant dehydration

Question 17

How is bilirubin produced?

Answer 17

The breakdown of RBC –> Heme –> bilirubin
1g of Hgb produces 24 mg of bilirubin

Unconjugated bilirubin binds to albumin and is taken to the liver where it becomes conjugated, conjugated bilirubin is then excreted from the liver via the bile duct into the intestine. There it is further metabolized and excreted in the stool. Without appropriate gut flora or prolonged time in the intestine it is turned back into unconjugated bili and absorbed by the intestines back into circulation.

Question 18

What is Unconjugated Bilirubin?

Answer 18

Or indirect bilirubin

Bilirubin not yet conjugated and reversibly bound to albumin.

Unconjugated bilirubin builds up when glucouronyl transferase is deficient and conjugation is slow

Question 19

What is conjugated bilirubin?

Answer 19

Or direct bilirubin

Bilirubin conjugated with glucuronide

Water soluble so it’s easily excretable. It builds up with obstruction of bile flow (cholestasis)

Question 20

What is free bilirubin?

Answer 20

A small amount of unconjugated bilirubin not bound to albumin so it can cross the BBB and cause damage to neurons

Question 21

What causes physiologic jaundice?

Answer 21

Increased RBC mass in the newborn
Decreased activity of UDP glucuronyl transferase that correlates with gestational age, leading to decreased conjugation and excretion
Increased enterohepatic circulation due to lack of intestinal flora, decrease gut motility and small enteral intake

Question 22

What increases the chances of nonphysiological jaundice?

Answer 22

Early jaundice: infants with jaundice in first 24-36 hours of life likely have increased production of bili (hemolysis) or excessive blood cell breakdown from polycythemia or bruising

Significant jaundice in a previous infant

Exclusive breast feeding: due to small intake in first few days, delayed institution of intestinal flora and increased enterohepatic circulation of bilirubin

Gestational age <38 weeks

East Asian race

Cephalhematomas and bruising

Maternal age >25

Male sex

Question 23

What is hyperbilirubinemia?

Answer 23

Hemolysis leading to increased bilirubin production?

Question 24

What are the leading causes of hyperbilirubinemia?

Answer 24

Excessive production of bilirubin
Decreased bilirubin clearance
Breastfeeding-Associated Jaundice

Question 25

What causes excessive production of bilirubin?

Answer 25

Hemolysis leading to increased bilirubin production
Nonantibody-mediated hemolysis
Nonhemolytic causes of increased Bilirubin production

Question 26

What causes hemolysis leading to increased bilirubin production?

Answer 26

Antibody-mediated: Directed Coombs test or indirect Coombs test - Positive
ABO incompatibility: Mother Type O, Baby type A or B

Rh incompatibility: Mom Rh neg, baby Rh pos - Usually prevented with RhoGam

Question 27

What is nonantibody-mediated hemolysis: Direct Coombs test or direct antibody test - Negative

Answer 27

Red cell membrane defects

Red cell enzyme defects

Question 28

What is nonhemolytic causes of increased bilirubin production?

Answer 28

Bruising: related to birth trauma
Polycythemia: Can be due to delayed cord clamping, twin-twin or maternal-fetal transfusion, or secondary to chronic intrauterine hypoxia, IUGR, or maternal diabetes

Question 29

What can cause decrease bilirubin clearance?

Answer 29

Bowel obstruction/delayed passing of meconium

Inborn errors of metabolism:
Galactosemia
Hypothyroidism
Glycuronyl transferase deficiency - Crigler-Najjar Syndrome, Gilbert Syndrome

Question 30

How does phototherapy work?

Answer 30

Light energy is absorbed by the bilirubin molecule and changes its stereochemical shape making it more water soluble. This can be excreted in the bile without conjugation. This makes the bilirubin less toxic as the serum levels fall.

Question 31

What are the possible complications of phototherapy?

Answer 31

Retinal Effects: Wear an eye patch
Diarrhea
Dehydration
Bronze-baby syndrome: transient gray-bronze discoloration of infants with cholestatic jaundice treated with photo therapy. Usually, disappears after stopping phototherapy. No known long last effects.

Question 32

What are guidelines for therapy?

Answer 32

Screening TSB >95%

TSB >8 mg % at 24 hours
TSB >13 mg % at 48 hours
TSB >16 mg % at 72 hours

Question 33

What are some future medications to treat hyperbilirubinemia?

Answer 33

Heme oxygenase inhibitors (tin-protoporphyrin and tin-mesoporphyrin): suppress formation of bilirubin

Phenobarbital: When administered before birth, to mother of infant with known severe hemolytic disease, it will induce the infant’s hepatic enzymes and increase hepatic uptake of bili and excretion of bili into the bile.

Question 34

What is the pathology of Kernicterus?

Answer 34

yellow staining of brain nuclei (kerns), with current management of hyperbilirubinemia, this is a rare complication

Question 35

What are the clinical manifestations of Kernicterus?

Answer 35

Lethargy
Hypotonia
Poor suck to severe
Largely irreversible disease associated with coma and seizures

Question 36

What is the root cause of re-emergence of kernicterus?

Answer 36

Early discharge (<48 hrs) without early follow-up

Failure to check the bili level in an infant noted to be jaundiced before 24 hours of age

Failure to recognize the presence of risk factors

Underestimating the severity of jaundice by clinical (visual) assessment

Lack of concern regarding the presence of jaundice

Delay in measuring serum bili despite marked jaundice

Failure to respond to parental concerns regarding jaundice, poor feeding or lethargy.