Jaundice Dr David Tickell Consultant Paediatrician

Physiology Heme (RBC) breakdown releases bilirubin (BR) Half life of HbF (α2γ2) <70 days Half life days for adult Hb – HbA (α2β2) & HbA 2 (α2δ2) BR binds to albumin & taken to hepatocyte BR conjugated by UGT, water-soluble form secreted into bile BR in bile either excreted or deconjugated by beta- glucuronidase & reabsorbed (enterohepatic circ.)

The risks Hyperbilirubinaemia can lead to Acute bilirubin encephalopathy Kernicterus (post mortem description, although often applied to the chronic clinical manifestations) Neurologic damage from BR Blood-brain barrier impermeable to BR until a certain BR concentration Blood brain barrier becomes more competent in the first few days of life – this reflects the rising cut off for phototherapy

Physiological jaundice Causes Higher neonatal Hb Faster RBC turnover (shorter half life of HbF) Slow hepatic UGT conjugating activity Increased enterohepatic circulation Peak jaundice levels hours, umol/L Higher and later in Asians Resolution in 1-2 weeks

Classification Early (1 st 24hrs) vs. physiological vs. late (>2wks) Early mostly haemolytic Late generally also pathological Conjugated vs. unconjugated >15% conjugated fraction = conjugated Physiological vs. Pathological

Unconjugated causes Haemolytic ABO incompatability (A & B antibodies) Rhesus, anti-D (negative mother vs. positive baby) Other antibodies (anti-c, -E, -Kell, etc) Membrane defects e.g. spherocytosis Enzyme defects e.g. G6PD/PK deficiency Cephalhaematoma & other bruising Polycythaemia Sepsis

Unconjugated causes cont. Non-haemolytic Physiological Breast milk Conjugation disorders e.g. Gilbert, Criggler-Najjar Hypothyroid Drugs Increased enterohepatic circulation Breast milk jaundice Intestinal obstruction

Mixed causes Infective Viruses (hepatitis A, B & C, Echo, EBV & CMV) Reye syndrome Chemicals & drugs Alcohol Isoniazid, rifampicin Methotrexate Paracetamol Autoimmune

Conjugated causes Intrahepatic Intrahepatic cholestasis e.g. Alagille syndrome Post-hepatic Biliary atresia Choledochal cyst Bilirubin excretion disorders Dubin-Johson syndrome Rotor syndrome

High risk groups Rh(D)-negative mothers Blood group O mothers Severe bruising/cephalhaematoma High neonatal Hb or Hct Prematurity or LBW/SGA Sepsis or severely unwell Previous children with severe jaundice (Breast feeding) (Polycythaemia)

Prevention Managing Rh(D)- mothers Cord blood for DCT & neonatal blood group Giving anti-D when exposed to foetal blood Managing potential ABO incompatability Early DCT & neonatal blood group if clinical concern Early investigation if anti-c, -E, -Kell A/N ultrasound for hydrops ?in utero transfusions Cord SBR & DCT at time of birth Early SBR & aggressive phototherapy Caution other antibodies anti-C, -e, -Jk, -Fy, -S, -s

Management Phototherapy When SBR in range (NICE guidelines) Green/blue light wavelengths isomerise BR to lumirubin, which is soluble & excreted into bile/urine Safe, effective Minimal side effects: eyes (only proven in animals), water loss (not with new lights), rash (uncommon), loose stools, increased temperature Bilibeds/blankets useful, not as powerful Increased number of lights has reduced exchange transfusion amounts, although no difference in studies

Management Phototherapy – monitoring Repeat testing every 6-8 hours with severe hyper- bilirubinaemia (transfusion range, <24 hours old) Otherwise repeat daily Think about haemolysis causing lowered Hb & higher risk of rebound after ceasing Exchange transfusion If SBR rising with maximal phototherapy or signs of bilirubin induced neurologic dysfunction Done in tertiary neonatal institutions Dual IV access: blood removed as blood transfused

Other therapies IVIG Reduces need for exchange transfusion with haemolytic jaundice (unknown mechanism) mg/kg over 2 hours if rising SBR despite maximal phototherapy OR within 50mmol/L of transfusion limit Can be repeated after 12 hours Phenobarbitone Increases conjugation & excretion of BR Not routinely used given neurological SFX Ursodeoxycholic acid Increased bile flow, used in conjugated jaundice

The End Thank You