1. Neonatal Health Assoc Prof Zsuzsoka Kecskes Dept of Neonatology The Canberra Hospital

2. Topics covered Jaundice Hips Cardiac/Oxygen Saturation Monitoring

3. Neonatal jaundice What is jaundice?

4. Jaundice is bilirubin that is deposited in the skin and mucous membranes. It is the end product of haem breakdown. Lysis of red blood cells releases haem from haemoglobin, haem is then converted to bilirubin and excreted.

5. Bilirubin metabolism Enterohepatic circulation Uridine diphosphate glucuronyl transferase (UDPGT)

6. 65% of term newborns develop clinical jaundice in first week 80% of preterm infants Prevalence of neonatal jaundice

7. Types of neonatal jaundice Bilirubin exists in two main forms in serum 1.Unconjugated bilirubin reversibly bound to albumin 2.Conjugated bilirubin readily excretable via the renal and biliary systems

8. Best classified by age of onset and duration: 1.Early: within 24 hrs of life 2.Intermediate: 2 days to 2 weeks 3.Late: persists for >2 weeks Causes of neonatal jaundice

9. EarlyIntermediateLate/prolonged Haemolytic causes: –Rh isoimmunisation –ABO incompatibility –G6PD deficiency Congenital infection Physiological jaundice Breast milk jaundice (inadequate intake) Sepsis Haemolysis Crigler-Najjar syndrome (glucuronyl transferase absent/reduced) Polycythaemia, bruising Conjugated (dark urine, pale stools): –Bile duct obstruction –Biliary atresia –Neonatal hepatitis Unconjugated: –Physiological –Breast milk jaundice –Infection –Hypothyroidism

10. Causes of neonatal jaundice EarlyIntermediateLate/prolonged Haemolytic causes: –Rh isoimmunisation –ABO incompatibility –G6PD deficiency Congenital infection Physiological jaundice Breast milk jaundice (inadequate intake) Sepsis Haemolysis Crigler-Najjar syndrome (glucuronyl transferase absent/reduced) Polycythaemia, bruising Conjugated (dark urine, pale stools): –Bile duct obstruction –Biliary atresia –Neonatal hepatitis Unconjugated: –Physiological –Breast milk jaundice –Infection –Hypothyroidism

11. Apparent before 24 hours of age Always pathological The main cause for early jaundice is haemolysis such as: –Rhesus isoimmunisation –ABO incompatibility –G6PD deficiency Early jaundice

12. Investigations for early jaundice Serum bilirubin level FBC and film Blood group Maternal blood group Direct coombs test Consider G6PD level

13. Causes of neonatal jaundice EarlyIntermediateLate/prolonged Haemolytic causes: –Rh isoimmunisation –ABO incompatibility –G6PD deficiency Congenital infection Physiological jaundice Breast milk jaundice (inadequate intake) Sepsis Haemolysis Crigler-Najjar syndrome (glucuronyl transferase absent/reduced) Polycythaemia, bruising Conjugated (dark urine, pale stools): –Bile duct obstruction –Biliary atresia –Neonatal hepatitis Unconjugated: –Physiological –Breast milk jaundice –Infection –Hypothyroidism

14. Physiological jaundice Physiological jaundice is jaundice that is present between day 2 and day 10

15. Physiological jaundice Physiological jaundice is due to: -High bilirubin production (fetal Hb, high Hb) -Reduced bilirubin excretion (UDPGT concentrations at term are 1% of adult concentrations)

16. What are the factors that exacerbate ‘physiological jaundice’?

17. Factors that can increase the severity of physiological jaundice Prematurity Sepsis Bruising Cephalohematoma Polycythaemia Delayed passage of meconium Breast feeding Certain ethnic groups, esp Chinese

18. Causes of neonatal jaundice EarlyIntermediateLate/prolonged Haemolytic causes: –Rh isoimmunisation –ABO incompatibility –G6PD deficiency Congenital infection Physiological jaundice Breast milk jaundice (inadequate intake) Sepsis Haemolysis Crigler-Najjar syndrome (glucuronyl transferase absent/reduced) Polycythaemia, bruising Conjugated (dark urine, pale stools): –Bile duct obstruction –Biliary atresia –Neonatal hepatitis Unconjugated: –Physiological –Breast milk jaundice –Infection –Hypothyroidism

19. Prolonged Jaundice Jaundice persisting after 14 days in the term infants Or Jaundice persisting after 21days in the preterm infant

20. When to start phototherapy?

21. Serum bilirubin level Conjugated fraction of bilirubin Liver function test (GGT, ALT, AST, Albumin) Coagulation profile (PT, PTT, INR) Abdominal ultrasound (gallbladder) DISIDA / HIDA scan (with follow through) Thyroid function test (TSH, free T4) Metabolic screen (urine for reducing substance) Hepatitis screen (TORCH) Liver biopsy (bile duct proliferation) FBC and film Blood group Maternal blood group Direct coombs test Investigations for prolonged jaundice

22. Kernicterus Also called bilirubin encephalopathy Neurological syndrome resulting from neurotoxic affects of unconjugated bilirubin on basal ganglia and brainstem nuclei Though infrequent, has at least 10% mortality and 70% morbidity

23. Mechanism of neurotoxicity in kernicterus Unbound (unconjugated) bilirubin is: –neurotoxic at high levels –lipophilic and can cross the blood-brain-barrier Long term clinical sequelae Bilirubin staining of affected areas Dysfunction and death of neurons Impairs mitochondrial functions neurotransmitter synthesis Binds to cell components Bilirubin accumulates at nerve terminals

24. Kernicterus: signs and symptoms (first 24 hours) Phase 1: –Poor suck, hypotonia and lethargy Phase 2: –Hypertonia and opisthotonos Phase 3: –Less hypertonia, high pitched cry, hearing and visual loss, poor feeding and athetosis

25. Kernicterus: signs and symptoms (long term) Choreoathetoid cerebral palsy Upward gaze palsy Sensorineural hearing loss Intellectual delay (less common)

26. Depends on the cause and level and type of bilirubin Unconjugated hyperbilirubinaemia: –Ensure adequate fluid intake –Phototherapy –IV immunoglobulin –Exchange transfusion Conjugated hyperbilirubinaemia: –Ensure adequate nutrition –Treat underlying problem Treatment of Neonatal Jaundice

27. Phototherapy Biliblanket Phototherapy lights

28. Phototherapy Spectrum of light Blue is most effective (460 - 490 nm) Ultraviolet light (10 – 400 nm) Infrared light (400 – 700 nm) Phototherapy is NOT: Ultraviolet light Infrared light Bilirubin absorbance and transmittance Maisels MJ et al. N Engl J Med 2008;358:920-8 Bilirubin absorbance

29. When to start phototherapy? Decision is based on: 1.Level of bilirubin 2.Rate of rise of bilirubin 3.Gestational age 4.Chronological age 5.Wellness of the baby

30. When to start phototherapy?

31. Take home message Jaundice before 24 hours is always pathological Kernicterus is rare but serious complication of Unconjugated hyperbilirubin Early diagnosis of biliary atresia impacts on long-term outcome

32. Examination of the hips - Recommendations All newborns are to be screened by physical examination (AAP) –properly trained health care provider with regular re- assessment of skills –evidence is good, expert consensus is strong –pre term babies at d/c health check or when acute needs have settled Examination at 2-4 days, 1, 2, 4, 6, 9 & 12 months - (CTFPHC) –fair evidence

33. Examination of the hips Be aware of changes of physical exam with age –by 8-12 weeks Barlow & Ortolani tests are negative regardless of the status of the femoral head –at 3 months limitation of abduction is the most reliable sign associated with DDH (AAP). Asymmetry of thigh folds, leg length discrepancy & Galeazzi sign are also signs. Hips continue to dislocate through out the first year of life 1/5000 children have a dislocated hip detected at 18 months

34. Examination of the hips – High Risk Family history Breech presentation Foot deformities Oligohydramnios Primiparity Females

35. Examination of the hips - Incidence White neonates: 1% CDH Varies with Race:  Blacks/Koreans/Chinese F:M 4:1 LHS60% RHS20% Bilat20%

36. Examination of the hips Identify at Risk infants: Examine the Hips for Dislocation and/or dislocatibility If hips are stable and there are no risk factors  no further action If there is a strong family history (parents or siblings) of CDH, delivery was as breech, or other deformities are present:  hip ultrasound at 6 weeks and appointment at the post-natal clinic even if hips are stable during the immediate postnatal period. All babies with clicky hips MUST be reviewed by the Neonatal Registrar and NOT simply referred for U/S and follow-up. Clicky but stable hips are quite common in the first 48 hours of life!

38. Heart Examination Congenital heart disease (CHD) commonest congenital malformation (9 in 1000 live births) Contributes significantly to infant mortality and morbidity. Current post-natal screening CHD: physical examination after birth and repeat examination at 6-8weeks of age. Can miss up to 25% of infants with critical CHD Delayed or missed diagnosis associated with significant morbidity, the most significant being hypoxic / ischaemic brain injury.

39. Observational studies suggest that there may be some benefit in screening with pulse oximetry To date no randomised controlled trials Rarity of undiagnosed cyanotic CHD and large number of patients required for studies a randomised controlled trial may not be feasible. Heart Examination

40. Systematic reviews found overall sensitivity of 63% and specificity of 99.8% for pulse oximetry in diagnosing congenital heart disease in asymptomatic newborns False positives 0.2-0.9% Sensitivity of pulse oximetry screening 72% compared to 58% for clinical examination.

41. Heart Examination 2 other studies found that in asymptomatic babies a significantly higher number of babies with duct dependent heart disease were detected during screening by physical examination and pulse oximetry (86.2%) compared with those regions not using pulse oximetry screening (72%).  benefit of screening with pulse oximetry in addition to clinical examination. False positives for congenital heart disease will occur but may be expected to detect some other important medical problems, such as sepsis or RDS

42. Heart Examination PULSE OXIMETRY SCREENING Within 4-24 hours of life on PNW or DS If SaO2 < 90% Medical review If asymptomatic, repeat pulse oximetry in 2- 3 hours If symptomatic further investigations (bloods, CXR, ECG and echocardiography), consider admission)

43. Heart Examination Screening introduced to TCH 12 months ago Audit after 4 months (976 neonates)

44. Heart Examination 40 (4%) of infants were missed 15 (1.5%) were found to have saturations<90% –3 (0.3%) incorrect assignment –7 (0.7%) -passed on screen 2 –1 (0.1%) other diagnosis (Pierre Robin sequence) 4 (0.41%) failed both screens –3 (0.31%) had sepsis with normal sats on discharge –1 (0.1%) had PPHN and non critical congenital heart defect (ASD)

45. Take home messages Nutrition (weight, urine output) Jaundice Physical exam (heart, hips) We are just at the end of the phone!!!!!