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Neonatal JaundiceJoel Cadrin

MD Candidate 2016, French StreamCHEO ~ Children’s Hospital of Eastern Ontario

Wednesday, June 3, 2015

Case Study

A full term male infant, born by Emergency Caesarean section following failed forceps-assisted delivery, is now 4 days old and is ready for discharge.

His birth weight was 3.3kg. He is being breastfed every 3 to 4 hours, which seems to be going well. This is the mother’s second child. The family is of Greek origin. You are called, because, on exam, the bedside nurse noticed the baby to be jaundiced. His mother thinks she noticed the jaundice at around 24 hours of life, but isn’t certain. It appears to be worse today. His weight is now 3.1kg. He is alert on exam. You notice a Band-Aid on his right heel. Jaundice is visible on his head, trunk, legs and sclerae. You can palpate his liver 2 cm below the right costal margin, and the spleen seems palpable. How do you approach this program?

Reflections

What particular characteristics do you find pertinent in this case?

How you would begin to approach this case?

Remember to keep this case study in mind as we proceed through the presentation

Objectives

To review the physiology of bilirubin metabolism and recognize the significance of jaundice in newborn infants.

To explore the differential diagnosis of jaundice according to timing of occurrence.

To review the important clues on history and important physical findings (antenatal, perinatal and postnatal) to assist with diagnosis

To elaborate an appropriate plan of management and discuss the currently available therapies

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Objective #1Review the physiology of bilirubin

metabolism and recognize the significance of jaundice in newborn infants.

Physiological Mechanism of Bilirubin Metabolism

UGT1A1 and Conjugation of Bilirubin

Uridine diphospate glucuronosyl transferase (UGT1A1) conjugates the unconjugated bilirubin in the liver

At 30 - 40 weeks’ gestation UGT1A1 is at ~1% of adult levels

At 14 weeks of age, the levels rise to adult concentration

The Pathways of Conjugated Bilirubin

Excreted into the intestine through the gallbladder and bile duct, and follows one of two following paths:

Pathway 1: Bilirubin excreted with the stool

Pathway 2: Bilirubin may be de-conjugated by bacteria and then reabsorbed into the blood via the enterohepatic circulation

Jaundice

What is jaundice?

Bilirubin deposition in skin and mucous membrane

Results in yellow color on the skin and mucous membranes

Cephalocaudal progression

Significance of Neonatal Jaundice

May be indicative of physiologic or pathologic origins

Most cases: Bilirubin deposition and according jaundice has little consequence on the neonate

However, there is potential for severe consequences as bilirubin may cross the BBB

Kernicterus

Severe jaundice may lead to kernicterus

Kernicterus is the staining of the basal ganglia with bilirubin

A rare, but preventable cause of athetoid cerebral palsy, and other neurological pathologies

Significance of Neonatal Jaundice

Factors to consider:

Many causes of jaundice

Timing of onset

Rate of rise of bilirubin

Maximum levels of bilirubin

Persistent jaundice

Acute Symptoms of Kernicterus

Lethargy

Hypotonia

Poor Suck

Hypertonia of extensor muscles (retrocolis, opisthotonus)

High-pitched cry

Fever

Seizures

Comas

Chronic Symptoms of Kerniterus

Athetoid cerebral palsy

Seizures

Developmental delay

Hearing deficits

Oculomotor disturbances

Dental Dysplasia

Mental deficiency

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Objective #2Explore the differential diagnosis of

jaundice according to timing of occurrence.

Differential diagnosis of jaundice according to timing

of occurrence

The differential diagnoses in neonatal jaundice has much to do with the timing of the onset of the jaundice.

Timing can indicate physiologic vs. pathologic jaundice

Timing can indicate the presence of unconjugated vs. conjugated bilirubin in the system

DDx

Hemolytic Disease: Isoimmune: ABO, Rh, Minor group incompatibility Structural or RBC abnormalities (Spherocytosis,

Glucose-6-Phosphate Dehydrogenase Deficiency) Hereditary of defects in bilirubin conjugation (Gilbert

Syndrome, Crogler-Najjar Syndrome)

DDx

Bacterial Sepsis

Breastfeeding jaundice

Breast milk jaundice

Congenital biliary atresia

Extrahepatic Biliary Obstruction

Neonatal Hepatitis (Bacterial, Viral, Not Specific)

Onset of Jaundice

Specific Timings of Onset to Consider:

First 24h of life

Between 24h to 2 weeks of age

After 2 weeks of age

Reflections

What do you think is significant about timing in the DDx of neonatal jaundice?

How do you think jaundice before 24h of life differs from jaundice after the 24h mark?

Requires IMMEDIATE Attention

Hemolysis

Rh incompatibility: Identified antenatally. Hydrops, anemia, Hepatosplenomegaly

ABO incompatibility: O women have IgG anti A or B that cross placenta

G6PD Deficiency: Mediterranean, Asian, Middle-Eastern, African American

Hemorrhage and Bruising

Sepsis

Congenital Infection

Bilirubin is conjugated & abnormal clinical signs

Growth restriction

Hepatosplenomegaly,

Thrombocytopenia purpura

First 24h of Life

Between 24h to 2 Weeks

Physiological jaundice (usually most noticeable around days 2-5)

Breast milk jaundice

Infection (UTI)

Hemolysis

Bruising

Polycythemia

Crigler-Najjar Syndrome (UTB1A1 deficiency)

After 2 Weeks of Age

Unconjugated

Physiological or breast milk jaundice

Infection (UTI)

Hypothyroidism

Hemolytic Anemia

High GI obstruction (i.e. pyloric stenosis)

Conjugated

Bile duct obstruction

Neonatal hepatitis

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Objective #3Review the important clues on history and

important physical findings (antenatal, perinatal and postnatal) to assist with

diagnosis

History

Newborn history

Delivery history

Risk Factors for Hyperbilirubinemia PreTerm Previous sibling with severe hyperbilirubinemia Bruising Cephalhematoma Male Asian or European background Dehydration Maternal blood type

Signs of cholestasis: Acholic stools, dark urine, weight loss

Back to the Case

A full term male infant, born by Emergency Caesarean section following failed forceps-assisted delivery, is now 4 days old and is ready for discharge.

His birth weight was 3.3kg. He is being breastfed every 3 to 4 hours, which seems to be going well. This is the mother’s second child. The family is of Greek origin. You are called, because, on exam, the bedside nurse noticed the baby to be jaundiced. His mother thinks she noticed the jaundice at around 24 hours of life, but isn’t certain. It appears to be worse today. His weight is now 3.1kg. He is alert on exam. You notice a Band-Aid on his right heel. Jaundice is visible on his head, trunk, legs and sclerae. You can palpate his liver 2 cm below the right costal margin, and the spleen seems palpable. How do you approach this program?

Pertinent points in the history

Full term : lower risk

Male sex: increased risk

Emergency C-Section following failed forceps: Trauma (cephalhematoma?)

4 days old and ready for discharge: 96 hours old

Breastfed every 3-4 hours, going well: exclusive breastfeeding

Greek origin: higher risk for G6PD deficiency in people of Mediterranean descent

Physical Exam

What should we be examining for?

Where would you start your physical exam in neonatal jaundice?

Physical Exam

Vital Signs

General appearance

Measurements

Respiratory, CVS

Abdo

Neuro

Findings on Physical Exam

Vital Signs are normal

Birth Weight was 3.3 kg, now 3.1 kg: Weight loss <10%

At Day 4, nurse finds baby to be jaundiced: 96 hours

Mother thinks it began at 24 h of life: Significance of 24h

Baby is on alert on exam, no abnormal neurological signs

Jaundice visible on head, trunk, legs, sclera: Moves in cephalocaudal direction

Band-Aid on right heel: metabolic screening underway

Hepatosplenomegaly : sign of possible intrauterine infection, Rh incompatibility (extravascular hemolysis)

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Objective #4To elaborate an appropriate plan of

management and discuss the currently available therapies

Plan of Management

When to measure bilirubin concentration? CPS recommendations

How do we predict hyperbilirubinemia?

How does phototherapy lower unconjugated bilirubin levels?

When should we consider exchange transfusions?

Investigations

TSB (or Transcutaneous measurement if available) Universal screening

CBC, Reticulocytes, Film, LDH, Haptoglobuline, DAT, Blood type

Electrolytes, Urea, Creatinine

LP

LFTs

Ultrasound (hepatobiliary anatomy)

CXR

Metabolic screen

Guideline 1

To be used to determine if phototherapy , follow up or if routine care is required.

Direct antiglobulin test (Coombs test) should be performed in infants with early jaundice and mother of blood group O in order to identify risk group (presently, in Ottawa this is done for all O mothers)

Guideline 2

To be used to determine if intensive phototherapy is required.

Guideline 3

Used to determine if exchange transfusion required

Immediate exchange tranfusion is recommended if signs of acute bilirubin encephalopathy (hypertonia, arching, retrocolis, fever, high pitched cry)

Available Therapies

Breastfeeding support programs

Phototherapy

Supplemental fluids (PO,IV)

IVIg

Exchange transfusion

Management of this case

If our patient’s bilirubin was measured to be 300 micromol/L, with a negative DAT (DAT performed since mother was O+), and no other risk factors

If our patient’s bilirubin was measured to be 400 micromol/L, with a positive DAT.

If our patient’s bilirubin was measured to be 350 micromol/L, with a positive DAT

Case 2

Female infant born at 39 weeks. Mother AB+

Spontaneous vaginal delivery, no complications

At 36 hours, weight is stable, baby is feeding well, she is alert on exam, she is ready for discharge.

No jaundice at present time, bilirubin at 96 micromol/L

What action is to be taken?