Neonatal Jaundice and Kernicterus | Medical Science Optional Notes for UPSC PDF Download

Introduction

• Around 60% of term newborns develop visible jaundice within the first week of life, typically benign without requiring intervention.
• Pathological Jaundice is characterized by:
  • Onset within 24 hours
  • Total serum bilirubin (TSB) levels exceeding expected normal range in term babies:
    • 5 mg/dl on the first day
    • 10 mg/day on the second day
    • 15 mg/day thereafter
  • Persistence of clinical jaundice beyond 3 weeks
  • Presence of conjugated bilirubin (dark urine staining the nappy)
• Important causes of neonatal jaundice include:
  • Hemolytic factors: Rh incompatibility, ABO incompatibility, G6PD deficiency, thalassemias, hereditary spherocytosis
  • Non-hemolytic factors: prematurity, extravasated blood, inadequate feeding, polycythemia, idiopathic, breast milk jaundice, hypothyroidism

Investigations

• The purpose of conducting investigations is to verify the extent of jaundice, pinpoint its cause, and monitor the response to treatment.

First line

• Measurement of total serum bilirubin.
• Determination of blood groups for both the mother and the baby.
• Examination of a peripheral smear.

Second line

• Performance of a Direct Coombs test.
• Evaluation of hematocrit levels.
• Assessment of reticulocyte count.
• Measurement of G6PD levels in red blood cells.

Schematic approach to the diagnosis of neonatal jaundice

Principles of Management

• Antenatal Monitoring:
  • Conduct serial ultrasound and Doppler examinations during pregnancy to detect fetal anemia signs, such as increased blood flow velocities, and monitor for Hydrops Fetalis.
  • Quantitative analysis of maternal anti-Rh D antibodies is essential, with rising levels indicating fetal Rh disease.
  • Early delivery is typically recommended, usually around 36 weeks' gestation.
• Postnatal Care for Neonatal Jaundice:
  • Employ phototherapy for mild neonatal jaundice, converting insoluble bilirubin into soluble isomers for excretion in urine and feces.
  • Structural isomerization, an irreversible reaction converting bilirubin into lumirubin, is a key mechanism responsible for the decline in total serum bilirubin (TSB) during phototherapy.
• Advanced Treatment for Moderate or Severe Disease:
  • Consider exchange transfusion for neonates with moderate or severe disease.
  • Utilize the pull and push technique through the umbilical venous route for exchange transfusion, ensuring a proper insertion of the umbilical catheter for free blood flow.
• Intravenous Immunoglobulin (IVIG) Therapy:
  • IVIG has demonstrated success in treating Hemolytic Disease of the Newborn, not only for anti-D but also anti-E cases.
  • Use IVIG to reduce the necessity for exchange transfusion and shorten the duration of phototherapy.

Complications of Hemolytic Disorder of the Newborn

• Kernicterus:
• Irreversible brain damage caused by direct toxicity induced by elevated serum bilirubin.
• Hydrops Fetalis:
• Accumulation of fluid in fetal compartments such as the scalp, pleura, and peritoneum.
• Stillbirth:
• Fetal death before delivery.
• Hepatosplenomegaly:
• Enlargement of the liver and spleen.
• Cerebral Palsy:
• Neurological disorder affecting movement and posture.

Preventive Measures

• Early Pregnancy:
  • Use IVIG/Plasmapheresis to lower autoantibody levels.
• Mid to Late Pregnancy:
  • Consider intrauterine transfusion.
• Rho (D) Immunoglobulin Administration:
  • Administer anti-Rh antibodies to the mother via intramuscular route to prevent Rh disease.
  • Administer 100ug (500IU) of anti-D at 28 weeks and 34 weeks of gestation in the first pregnancy to reduce the risk to about 0.2%, with no reported adverse effects.

Kernicterus

Etiopathogenesis of Kernicterus

• Nature of Kernicterus:
  • Kernicterus, also known as bilirubin encephalopathy, is a neurological syndrome characterized by the accumulation of unconjugated (indirect) bilirubin in the basal ganglia and brainstem nuclei.
• Threshold for Kernicterus:
  • Kernicterus is observed only in infants with a bilirubin level exceeding 20 mg/dL, as indicated by large series studies.
• Duration of Exposure:
  • The precise duration of exposure to elevated bilirubin levels required to induce toxic effects remains unknown.
• Multifactorial Pathogenesis:
  • The development of kernicterus involves a multifaceted process, including:
    a) Levels of unconjugated bilirubin
    b) Interaction between albumin binding and unbound bilirubin levels
    c) Passage of bilirubin across the blood-brain barrier
    d) Neuronal susceptibility to injury
• Factors Influencing Blood-Brain Barrier Disruption:
  • Disruption of the blood-brain barrier can be influenced by diseases, asphyxia, maturational changes in blood-brain barrier permeability, and other factors.
• Risk Factors for Severe Hyperbilirubinemia in Infants ≤35 Weeks of Gestation:
  • Certain factors increase the risk of severe hyperbilirubinemia, including:
  • Jaundice observed within the first 24 hours
  • Blood group incompatibility with positive direct antiglobulin test
  • Known hemolytic diseases (e.g., glucose-6-phosphate dehydrogenase deficiency)
  • Elevated end-tidal CO concentration
  • Gestational age between 35-36 weeks
  • Previous sibling receiving phototherapy
  • Cephalohematoma or significant bruising
  • Exclusive breastfeeding, particularly if nursing is challenging and weight loss is excessive
  • East Asian race

Clinical Manifestations: Acute Form

• Phase 1 (1st 1-2 days):
  • Poor suck, stupor, hypotonia.
  • Seizures.
• Phase 2 (Middle of 1st Week):
  • Hypertonia of extensor muscles.
  • Opisthotonos, retrocollis.
  • Fever.
• Phase 3 (After the 1st Week):
  • Hypertonia.

Chronic Form

• 1st Year:
  • Hypotonia.
  • Active deep tendon reflexes.
  • Obligatory tonic neck reflexes.
  • Delayed motor skills.
• After 1st Year:
  • Movement disorders (choreoathetosis, ballismus, tremor).
  • Upward gaze.
  • Sensorineural hearing loss.
• By 3 Years of Age:
  • Complete neurologic syndrome apparent, including bilateral choreoathetosis, involuntary muscle spasms, extrapyramidal signs, seizures, mental deficiency, dysarthric speech, high-frequency hearing loss, squinting, and defective upward eye movements.

Complications

• More than 75% of infants die.
• 80% of survivors have bilateral choreoathetosis with involuntary muscle spasms.
• Common complications include mental retardation, deafness, and spastic quadriplegia.

Prevention

• Universal screening for hyperbilirubinemia within the first 24-48 hours after birth.
• Jaundiced infants before 24 hours require total and direct serum bilirubin level measurement, with elevated levels prompting evaluation for possible hemolytic disease.
• Promote ongoing lactation with education, support, and follow-up services during the neonatal period.
• Advise mothers to nurse infants every 2-3 hours, avoiding routine water or glucose supplementation for adequate hydration and caloric intake.
• Conduct a hearing assessment (BERA) at 3 months of age.

IMNCI Guidelines-Jaundice

Neonatal Jaundice/Kernicterus-Repeats

Q1: Enumerate various causes of jaundice in a new born child. Write briefly the laboratory investigations and management of hemolytic jaundice in a new born. (2002) 

Q2: A newborn comes with deep jaundice at the age of 48 hours. What history would you like to take? What all investigations will you advise? How will you treat the case if a serum bilirubin (indirect) level is 18 mg/dl? (2007) 

Q3: Enumerate the clinical factors predisposing to bilirubin toxicity in newborn infants. (2013) 

Q4: Discuss the etiology and pathophysiology of kernicterus in newborns. How can you prevent kernicterus? (2014) 

Q5: A term neonate born to Rh negative mother is brought at 22 hours of life with jaundice, fever and one episode of convulsion. (2015)
i. What are the most likely diagnosis and its basis?
ii. Enumerate the key investigations and principles of management.
iii. List four important long term complications of this disease.
iv. Mention the preventive measures. 

Q6: Describe the clinical features of bilirubin encephalopathy in early neonatal period. Enumerate the predisposing factors contributing to bilirubin encephalopathy in newborn infants. Name the long-term pathological and clinical sequelae of bilirubin encephalopathy. (2016)