Neonatal Jaundice - Bowen University Breast milk jaundice ¢â‚¬¢ Breastmilk...

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Transcript of Neonatal Jaundice - Bowen University Breast milk jaundice ¢â‚¬¢ Breastmilk...

  • Neonatal Jaundice


    Bowen University Teach Hosp Ogbomoso

  • Introduction

    • Most common medical problem in the newborn. Affects between 40 – 80% of newborn babies.

    • Most cases are benign

    • Potential for severe adverse consequences – Cerebral palsy – Mental retardation – Death

  • Source of Bilirubin

    Haemoglobin 75-80%


    Haem-containing enzymes


    -Catalase /Peroxidases

    -Tryptophan pyrrolase

    -In-effective erythropoiesis


  • Bilirubin Metabolism

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    • Breakdown product of haemoglobin – 1gm of Hb gives 35mg

    Bilirubin • Enzyme action in the RES

    – Heme oxygenase: Biliverdin, Fe & CO

    – Biliverdin reductase: Bilirubin

    – Bilirubin carried in blood bound to plasma albumin

    • Uptake and Conjugation in the LIVER – Ligandin facilitates hepatic

    uptake – Uridine

    diphosphoglucuronyl transferase (UDPGT) catalyses conjugation with glucuronic acid

    • Excretion in Bile and the GIT • Enterohepatic circulation

    – Deconjugation by Beta- glucuronidase

  • Bilirubin Metabolism con’t

    • Unconjugated bilirubin is carried in blood bound to plasma albumin

    – Small fraction is “free”. This fraction increases when other molecules compete with bilirubin for albumin binding.

    • Bilirubin conjugation is the biologically critical activity

    – Converts water insoluble to water soluble bilirubin

    • Activity of UDPGT is low at birth

    – Rises to adult levels by 4 – 8 weeks of life

    – Many variants of the encoding gene with varying levels of activity

    – Links in the activity of UDPGT1 and pathogenesis of jaundice in G-6PD deficient neonates

  • Bilirubin Metabolism con’t

    • Free Bilirubin in Plasma – Hydrophobic and lipophilic in character – Crosses biological membranes e.g blood-brain


    – Binding stable in molar concentration ratio of bilirubin:albumin of 0.5-1: 1 and normal plasma pH (solubility of bilirubin is very low at pH 7.4).

    – Acidosis, Hypoalbuminaemia and Hyperbilirubinaemia destabilize the binding and lead to high levels of “free” unbound bilirubin.

  • Common Aetiology of NNJ

    • Physiological Hyberbilirubinaemia

    • Glucose-6-Phosphate Dehydrogenase Deficiency

    • ABO Incompatibility

    • Rhesus Iso-immunization

    • Bacterial Infections /UTI

    • Preterm/ Low Birthweight

    • Breastfeeding/ Breast-milk Jaundice

  • Uncommon Causes of NNJ

    • Crigler-Najjar Syndrome types I and II

    • Gilbert’s disease

    • Hypothyroidism

    • Hypopituitarism

    • Hereditary spherocytosis

  • Causes of Prolonged Indirect Hyperbilirubinaemia

    • Breast milk jaundice

    • Haemolytic disease

    • Hypothyroidism

    • Pyloric stenosis

    • Crigler-Najjar sydrome

    • Gilbert syndrome in breast-fed infants

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  • Causes of Prolonged direct Hyperbilirubinaemia

    • Septicaemia

    • Rotor syndrome

    • Dubin–Johnson Syndrome

    • Progressive Familial Intrahepatic Cholestasis Syndromes

    • Alagille Syndrome

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  • Physiologic jaundice

    • Diagnosis of exclusion after excluding infection, haemolysis, and metabolic diseases.

    • Multifactorial: RBC mass, RBC life span, decreased UDP-glucuronyl transferase and ligandin, increased enterohepatic circulation

    • Begins at >24 hrs

    • Peaks at

  • Physiologic Hyperbilirubinaemia

    • Diagnosis of exclusion after excluding infection, haemolysis, and metabolic diseases.

    • Multifactorial: RBC mass, RBC life span, decreased UDP-glucuronyl transferase and ligandin, increased enterohepatic circulation

    • Begins at >24 hrs

    • Peaks at

  • Breastfeeding jaundice

    • Breastfeeding jaundice – Infant of mothers with difficulty in establishing

    breastfeeding decreased PO intake

    – Inadequate fluid and nutrient intake with significant weight loss

    – Increased enterohepatic circulation with increased risks of hyperbilirubinaemia

    – Onset 2-4dys’ peaks at 3-6dys

    – Returns to normal after 3weeks

  • Breast milk jaundice

    • Breastmilk jaundice – Increased enterohepatic circulation

    • Increased beta-glucuronidase in BM & • Delay in establishment of intestinal microflora

    – Metabolite of progesterone (pregnane-3-alpha 20 β-diol) • Inhibits UDPGT activity

    – Inflammatory cytokines in BM (IL-1 beta; IL-6) • Reduction in uptake, metabolism & excretion of


    – High epidermal growth factor (EGF) in BM • Reduces GI motility • Onset 4-7days peaks at 5-15day • Returns to normal after 9weeks

  • Jaundice and the Brain

    • Neonatal jaundice & Brain dysfunction – Unconjugated hyperbilirubinaemia the cause of bilirubin


    • Factors contributing to persistence (or resurgence) – Lack of adequate concern for the risks

    – Early hospital discharges

    – Limitations in our health care system to provide continuity of care

  • Management – Unconjugated Hyperbilirubinaemia

    • Aim of management – Prevent bilirubin encephalopathy

    • Important Facts to Note: – Only the “free” unconjugated bilirubin is toxic to the

    newborn brain. – Lab. Measurement of free bilirubin is difficult. – TSB is used for decision making – No absolute safe level of bilirubin.

  • Management – Unconjugated Hyperbilirubinaemia

    • Important Facts to Note:

    – Risk of toxicity is increased by factors that destabilize the bilirubin-albumin binding and/or integrity of the BBB

    – Jaundice in 1st 24hrs is almost always pathological (it should never be dismissed as physiological jaundice). • (note that bilirubin is an antioxidant and in low

    levels play useful role in the overall wellbeing of the infant esp. in LBW, preterms)

  • Management: Important Steps

    • Clinical evaluation

    – History & Physical Exam.

    – Lab. Investigations & Imaging Studies

  • Evaluation of Newborn with Jaundice.

    • History should be thorough- (keeping in mind key epidemiological risk factors)

    – Pregnancy and delivery, drugs.

    – Asphyxia, trauma, cephalohaematoma

    – Family hx., Hx of NNJ in older sibs, mother’s blood group

    – Baby- feeding, general activity

    Physical Examination of Baby should also be thorough- Assess jaundice (note cephalocaudal progression of jaundice), pallor, general activity, signs of encephalopathy etc (non-invasive methods of bilirubin estimation (transcutaneous bilirubinometry) if available should be used: Icterometer, Jaundice meter etc-physician estimates of severity may be misleading).

  • Cephalopedal Representation of Progression in

    NNJ (Kremer et al).

    Zone SBR mg/dl

    • 1 = 5 mg/dl

    • 2 = 10 mg/dl

    • 3 = 15 mg/dl

    • 4 = 20 mg/dl

    • 5 > 25 mg/dl

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  • Clinical Features of Kernicterus ACUTE FORM

    Phase 1 (1st 1–2 days): poor sucking, stupor, hypotonia, seizures

    Phase 2 (middle of 1st wk): hypertonia of extensor muscles, opisthotonos, retrocollis, fever

    Phase 3 (after the 1st wk): hypertonia CHRONIC FORM

    First year: hypotonia, active deep tendon reflexes, obligatory tonic neck reflexes, delayed motor skills

    After 1st yr: movement disorders (choreoathetosis, ballismus, tremor), upward gaze, sensorineural hearing loss


  • Evaluation contd. • Lab. Investigations:

    – Total serum bilirubin (TSB), Conjugated bilirubin (CB).

    • Wide variations - inter- &intra- Lab.

    • TSB values used in decision making except when conjugated levels are high

    – Haemoglobin, Haematocrit

    – Blood groups (baby & mother) Rh. Factor

    – Coomb’s test,G6PD Assay, Serum albumin

    – Urinalysis for reducing substances.

    – End-tidal carbon monoxide (ETCO) in breath. An index of bilirubin production. (an apparatus for this exists)

  • Management Option-1

    • Re-assurance and Observation on Outpatient basis:

    – Otherwise healthy term newborn

    – Presenting after 72hrs.

    – Mild jaundice (TSB< 10mg/dl or 170umol/l)

    – Available for review within 24-48hrs – very important.

  • Management Option-2 • Pharmacotherapy.

    Phenobarbital increases bilirubin conjugation and excretion

    – Limited by slow action (takes 72hrs to become effective). No use in acute jaundice

    – May be useful for prophylaxis in at risk neonates

    – Can be combined with option 1 to accelerate excretion.

    Tin-mesoporphyrin (SnMP) and Tin-protoporphyrin (SnPP) which inhibit the action of the microsomal enzyme-heme oxygenase and therefore prevent production of bilirubin have shown promise in clinical trials (has been