Neonatal Jaundice

Dr. Mohamed Haseen BashaAssistant professor ( Pediatrics)

Faculty of MedicineAl Maarefa College of Science and

Technology

Visible jaundice occurs in about 75% of term infants and 80% of preterm

infants during the first week of life. It is caused by a raised level of bilirubin, a

breakdown product of red blood cells.

Reasons for elevated bilirubin in newborns are:

• The hemoglobin concentration is high at birth so there is considerable heme

degradation

• Lifespan of newborn red blood cells is shorter than that of adult red blood cells

• Immaturity of liver enzymes impairs bilirubin conjugation and excretion

• Absorption of unconjugated bilirubin by intestines (enterohepatic circulation).

Metabolism of Bilirubin

Physiological Jaundice

• Jaundice attributable to physiological immaturity of neonates to handle

increased bilirubin production.

• Jaundice usually appears between 24-72 hours of age.

• Total serum bilirubin (TSB) level usually rises in full-term infants to a peak of 6

to 8 mg/dL by 3 days of age and then falls. A rise to 12mg/dL is in the

physiologic range.

• In premature infants, the peak may be 10 to 12 mg/dL on the 5 day of life,

possibly rising over 15 mg/dL without any specific abnormality of bilirubin

metabolism.

• Levels under 2mg/dL may not be seen until one month of age in both full term

and premature infants.

• Safe bilirubin levels in preterms vary according to gestational age.

Breast Milk Jaundice

• May persist as a prolonged physiological jaundice or appear de-novo

after 1st week

• Common in exclusively breast fed babies

• Maximum intensity is between 10-14 days

• If STB > 15 mg/dl, temporary cessation of breast feeding for 48 hours

leads to dramatic fall and does not rise thereafter

• For higher levels, phototherapy may be needed

• The exact cause is still not understood

Pathological Jaundice

• TSB concentrations have been defined as non-physiologic if concentration

exceeds 5 mg/dl on first day of life in term neonate, 10 mg/dL on

second day, or 12-13 thereafter.

• Any TSB elevation exceeding 17 mg/dL should be presumed pathologic

and warrants investigation for a cause and possible intervention, such as

phototherapy.

• Appearance of jaundice within 24 hours, peak TSB levels above the

expected normal range , presence of clinical jaundice beyond 3 weeks

and conjugated bilirubin (dark urine staining the clothes and light colored

stool) would be categorized under pathological jaundice.

Increased Bilirubin Load

• Elevated unconjugated bilirubin

• Hemolytic Disease

– Features: elevated reticulocytes, decreased Hgb

– Coomb’s + Rh incompatibility, ABO incompatibility, minor antigens

– Coomb’s - G6PD, spherocytosis, etc.

• Non-hemolytic Disease

– Features: normal reticulocytes

– Extravascular sources i.e. cephalhematoma

– Polycythemia

– Exaggerated enterohepatic circulation – I.e. CF

Decreased Bilirubin Conjugation

• Elevated unconjugated bilirubin

• Genetic Disorders

– Criggler-Najjar

• 2 types

• Severe hyperbilirubinemia

– Gilbert Syndrome

• Mild hyperbilirubinemia

• Hypothyroidism

Impaired Bilirubin Excretion

• Elevated unconjugated and conjugated bilirubin (> 2 mg/dL or > 20% of TSB)

• Biliary Obstruction

– Structural defects i.e. biliary atresia

– Genetic defects – Rotor’s & Dubin-Johnson syndromes

• Infection – sepsis, TORCH

• Metabolic Disorders – i.e. alpha1 antitrypsin deficiency

• Chromosomal Abnormalities – Turner’s syndrome

• Drugs – i.e. ASA, Sulfa, Erythromycin

Causes of jaundice by age of onset.

Clinical examination of jaundice• Dermal staining of bilirubin described by Kramer may be used as a

clinical guide to the level of jaundice.

• Dermal staining in newborn progresses in a cephalocaudal direction.

• The newborn should be examined in good daylight. The skin should be

blanched with digital pressure and the underlying color of skin and

subcutaneous tissue should be noted.

• The severity of jaundice cannot be reliably assessed by clinical Examination.

If jaundiced, also check for:

Is the newborn term or preterm?

• Basic pathophysiology of jaundice is same in term and preterm neonates but

at lower gestation babies are at higher risk of developing hyperbilirubinemia

and require closer surveillance and monitoring.

Is there evidence of hemolysis?

• In the setting of Rh or less frequently ABO incompatibility, onset of

jaundice within 24 hours, presence of pallor and hydrops, presence of

hepatosplenomegaly, presence of hemolysis on the peripheral blood smear,

raised reticulocyte count (>8%), rapid rise of bilirubin (>5 mg/dl in 24 hours

or >0.5 mg/dl/hr) or a suggestive family history of significant jaundice

should raise a suspicion of hemolytic jaundice.

Does the infant have an underlying serious disease? (sepsis,

Galactosemia)

• Presence of lethargy, poor feeding, failure to thrive, hepatosplenomegaly,

temperature instability or apnea may be a marker of an underlying serious

disease.

Does the infant have cholestatic jaundice?

• Presence of jaundice (>10 mg/dl) beyond 3 weeks, presence of dark urine

(staining the clothes) or pale colored stools would suggest cholestatic

jaundice.

Investigations

• Total bilirubin, Direct bilirubin, Indirect bilirubin

• Reticulocyte count, and smear for red cell morphology.

• Blood packed cell volume or hematocrit.

• Blood group (mother and baby).

• Sepsis Screen

• Liver function and Thyroid function tests

• TORCH Screening

• Direct antibody test (DAT or Coombs test).

• G6PD testing

• Microbiological cultures of blood, urine and/or cerebrospinal fluid for infection

Management

The need for treatment is ascertained by plotting the total bilirubin level on

a graph of bilirubin against age in hours. This will determine if:

• No treatment is needed

• Repeat bilirubin is required in 6 – 12 hours

• Phototherapy or exchange transfusion is indicated.

Treatment will change according to the absolute level of bilirubin reached and

the rate of rise on serial measurements (if bilirubin rising > 0.5 mg/dL/hour).

Different cut - off criteria are used for preterm infants, for whom the treatment

threshold is lower

Phototherapy

• Blue - green light (wavelength 425 – 475 nm) converts unconjugated

bilirubin to harmless isomers. The light is filtered to remove ultraviolet light.

• Conventional phototherapy is with a phototherapy light source above the

baby.

• Continuous multiple phototherapy is used if the serum bilirubin is rising

rapidly or is at a high level or does not fall within 6 hours of starting

conventional phototherapy.• Maintaining adequate hydration and good urine output should help to improve

the efficacy of phototherapy.

Phototherapy requires:• Effective light source• High irradiance (usually ≥ 30 μ W/cm 2 per nm)• Light as close to the infant as possible (if fluorescent tubes used, can be as

close as about 10 cm from infant)• Widespread skin exposure.

Nomogram for determination of risk of development of severe hyperbilirubinemia for infants ≥ 35 weeks ’ gestation and ≥ 2.5 kg birthweight.

Indications for phototherapy in infants ≥ 35 weeks ’ gestation

Management of neonatal hyperbilirubinemia in low birth weight babies based on bilirubin levels (mg/dl)

Disadvantages of Phototherapy

• Separates baby and parents.

• Eye coverage necessary, which may be disturbing to parents.

• Bronze - baby syndrome if phototherapy given with elevated conjugated bilirubin.

• Unstable body temperature possible while in open bassinet (cot) with majority of

skin exposed.

• Increased insensible water loss, but less with use of LED light sources.

• Slightly loose, more frequent stools which may contribute to water loss.

Exchange transfusion

• Baby’ s blood is removed and replaced with transfused blood. Removes

bilirubin and antibodies and corrects anemia. Blood used for exchange

transfusion in neonates with Rh isoimmunization should always have Rh

negative blood group.

• Complications include thrombosis, embolus, volume overload or depletion,

metabolic abnormalities, infection, coagulation abnormalities.

Phenobarbitone:

• It improves hepatic uptake, conjugation and excretion of bilirubin thus

helps in lowering of bilirubin. However its effect takes time.

• When used prophylactically in a dose of 5 mg/kg for 3-5 days after birth,

it has shown to effective in babies with hemolytic disease, extravasated

blood and in preterms without any significant side effects.

Intravenous Immunoglobulin ( IVIG )

• Can be used in rhesus disease or ABO incompatibility when total bilirubin

levels are rising despite continuous multiple phototherapy or level is near

exchange transfusion level.

Indications for exchange transfusion in infants ≥ 35 weeks ’ gestation

Prolonged jaundiceJaundice present at more than 2 weeks of age for term, 3 weeks for preterm

infants can be considered as prolonged jaundice.

It requires further assessment. First, it needs to be determined if the jaundice is

unconjugated or conjugated.

Unconjugated jaundice causes are:

• Breast milk jaundice – 15% of all breast fed infants are still jaundiced at 2

weeks, gradually decreasing over several weeks

• Hypothyroidism

• Gastrointestinal obstruction, e.g. pyloric stenosis

• Infection

• Liver enzyme disorders.

Conjugated jaundice ( > 1.5 mg/dL, 25 micrograms/L)

may be caused by:

• Biliary atresia – uncommon, but important to identify

as delay in surgery adversely affects outcome

• Neonatal hepatitis syndrome.

The infant will pass pale stools (no stercobilinogen) and

dark urine (from bilirubin).

Detailed investigation of infants with conjugated

jaundice is required.

Discharge and follow up

In view of the re emergence of kernicterus in otherwise healthy infants,

particularly at 35 – 37 weeks ’ gestation, a follow up assessment is considered

for jaundice depending on their length of stay in the nursery.

• Discharge at < 24 hours, follow - up by 72 hours of life

• Discharge at 24 – 48 hours, follow - up by 96 hours of life

• Discharge at 48 – 72 hours, follow - up by 120 hours of life.

Parents should also be given written and verbal information about jaundice.

Clinical judgment should be used in determining follow-up. Earlier or more

frequent follow-up should be provided for those who have risk factors for

hyperbilirubinemia

Kernicterus

Kernicterus describes acute or chronic bilirubin encephalopathy.

Kernicterus is rare in developed countries.

In acute bilirubin encephalopathy there may be hypotonia, lethargy, poor

feeding, irritability, high - pitched cry, fever, apnea, hypertonia with arching of

the neck and trunk (opisthotonus), seizures, coma, and death.

In chronic bilirubin encephalopathy there is permanent neurologic injury

resulting from the deposition of unconjugated bilirubin in the basal ganglia

and brainstem nuclei.

Long term consequences include dental dysplasia with yellow staining of the

teeth, high frequency sensori neural hearing loss, paralysis of upward gaze of the

eyes, choreoathetoid cerebral palsy, and learning difficulties.

Cross - section of the brain at autopsy showing yellow staining, predominantly in basal ganglia

from deposition of unconjugated bilirubin.

Prevention of Hyperbilirubinemia

1. Early and frequent feeding

2. Adequate hydration

3. Administration of Anti-D injection to Rh negative mother

Thank You