34eaNeonatal jaundice edited.ppt
- 2. Teaching Aids: NNF NJ- Neonatal Jaundice
- 3. Facts & figures Commonest abnormal physical finding during I week of life > 2/3 of NBBs develop clinical jaundice Visible form of bilirubinemia – Adult sclera >2mg / dl – Newborn skin >5 mg / dl Occurrence - 25 – 50% of term, 80% of preterm NBBBs Yellow discoloration – First evident on skin of face, naso-labial folds and tip of nose Masked by physiological plethora Assess by blanching Assess in good daylight – No yellow light, clothes or curtains
- 4. Clinical assessment of jaundice With increase in jaundice – Cephalo-pedal progression of yellow discoloration of skin - Area of body Bilirubin levels mg/dl Face 4-8 Upper trunk 5-12 Lower trunk & thighs 8 - 16 Arms & lower legs 11 - 18 Palms & soles > 15 Imp! – Screen all NBBs x BD in good day light
- 6. Sources of Bilirubin Haem containing proteins RBC Hb – Major source. 1 gm Hb 34 mg of Bilirubin - Haem from ineffective erythropoiesis in bone marrow - Other haem containing proteins – myoglobin, cytochromes, catalase, peroxidase - Free haem
- 7. Bilirubin turnover in Newborn Hb Haem + Globin Other sources BILIRUBIN UCB binds to S albumin Dissociates from albumin UDPG - T Bil monoglucoronide + Bil Diglucoronide Water sol Bil Binds to cytoplasmic Ligandin (Y protein) Excreted into bile canaliculi Enters Gut Excreted in stool Biliverdin + CO + Fe Bilirubin Reductase Haem oxygenase Beta Glucoronidase UCB Production Transport Uptake Excretion Conjugation
- 8. Physiological handicaps causing increased Bilirubin turnover 1. Increased production of bilirubin Physiological Polycythemia Shorter life span of HbF (90 days) 1ml/kg (approx 1% ) of blood hemolyse everyday 0.15 gm/ kg of Hb released everyday 1 gm Hb yields 35 mg of bilirubin Hence, a 3 kg infant produces 15 mg bil/ day from Hb sources + 1 mg/kg from non Hb sources Thus, daily load to the liver – 20 mg bil 2. Defective uptake from plasma Non availability of albumin binding sites
- 9. Physiological handicaps… 3. Defective conjugation Transient deficiency of Y & Z acceptor proteins 4. Reduced hepatic clearance Reduced UDPG enzymes >ed unconjugated bil in early days of life in preterms 5. Enhanced enterohepatic circulation 100 – 200 mg of bil in gut as 1 mg/gm of meconium Reduced gut motility & poor evacuation Paucity of bacterial flora in gut of NBB Over activity of intestinal glucoronidase enzyme Conj Bil rapidly deconjugated and recirculated through blood to liver for reconjugation
- 10. Bilirubin load causing jaundice in Newborn >ed RBC vol & <ed RBC survival >ed Bil monoglucoronide <ed Bil Diglucoronide UCB Production Transport Uptake Excretion Conjugation >ed Ineffective erythropoiesis & >ed Heam turnover Non availability of Albumin binding sites Defective conjugation <ed LIigandin Decreased excretion <ed gut motility Poor evacuation >>ed beta glucoronidase, <ed intestinal bacteria >ed BILIRUBIN load Defective uptake from plasma >ed Entero-hepatic circulation
- 12. Within 24 hours of birth Hemolytic disease of newborn - due to feto-maternal group incompatibility (Rh, ABO, other minor blood group systems) Intra-uterine infections (TORCH) Deficiency of red cell enzymes – G6 PD, pyruvate kinase, heokinase, phospho-glucose isomerase, unstable Hbs Admn of drugs in excess – Vit K, salycilates, sulfisoxazole to mother Hereditary spherocytosis Criggler Najjar syndrome Lucey Driscoll syndrome Homozygous alpha thalassemia
- 13. Between 24 – 72 hours of age Physiological jaundice May be aggravated/ prolonged by – Immaturity, birth asphyxia, acidosis, hypothermia, hypoglycemia, drugs, cephalhematoma, hge’/ bruising, Polycythemia, high altitude, cretinism, breast feeding, infections Mild hemolytic states – Feto maternal blood gp incompatibility, spherocytosis, deficiency of cell enzymes
- 14. After 72 hrs of age ( and within first 2 weeks) Septicemia Neonatal hepatitis Extra hepatic biliary atresia Breast milk jaundice Metabolic diseases – Galactosemia, tyrosinemia, fructosemia, organic acidemia, cyctic fibrosis, alpha 1 anti trypsin deficiency Hypertrophic pyloric stenosis & intestinal obstruction
- 15. Drugs causing increase in bilirubin Drugs Nature of action Vit K in larg doses Hemolysis Vit K and kanamycin Block Y acceptor protein Novobiocin, Moxalactam, Gentamycin, Kanamycin, Chloramphenicol Compete for Glucoronyl transferase Salicylates, long acting sulphonamides, sodium benzoate, furosamide, indomethacin, radiographic contract media Block bilirubin binding sites in albumin Oxytocin (induced labour) Hyponatremia & hypo osmolality Spinal block for mother using Bupivacaine
- 16. Risk factors for jaundice J - jaundice within first 24 hrs of life A - a sibling who was jaundiced as neonate U - unrecognized hemolysis N – non-optimal sucking/nursing D - deficiency of G6PD I - infection C – cephalhematoma /bruising E - East Asian/North Indian
- 17. Common causes in Sri Lanka Physiological Blood group incompatibility Intrauterine and postnatal infections G-6PD deficiency Bruising and cephalhematoma Breast milk jaundice
- 18. Jaundice – Physiological & Pathological
- 19. Physiological jaundice Appears between 30 – 72 hrs of age in term babies (earlier in preterms) Maximum intensity by 4th-5th day in term & 7th day in preterm Serum level less than 15 mg / dl Disappears by 10 days of life (reaches 15 days in preterms) Disappears without any treatment Note: Baby should, however, be watched for worsening jaundice Alert in preterms…danger of brain damage!
- 20. Features of physiological jaundice (all of the following Jaundice that first appears between 24-72 hours of age Maximum intensity is seen on 4-5th day in term and 7th day in preterm neonates Does not exceed 15 mg/dl (255μmol/l) Clinically undetectable after 14 days Physiological jaundice is a diagnosis by exclusion. No treatment is required but baby should be observed closely for signs of worsening jaundice
- 21. Pathological jaundice In 5% of newborns Appears within 24 hours of age Serum bilirubin > 15 mg / dl after 24h Jaundice persisting after 14 days Stool clay / white colored and urine staining clothes yellow Direct bilirubin> 2 mg / dl Total serum bilirubin (TSB) increasing by > 5mg/dl/day(85 μmol/l/day) or 0.5 g/dl/hr (8.5μmol/l/hr)
- 22. Dangers of hyperbilirubinemia Unconjugated hyperbilirubinemia Bil encephalopathy/ Kernicterus C/F – Refusal of feeds, shrill cry, setting sun sign, convulsions, retrocollis and opisthotonus - Sluggish Moro’s response, lethsrgy, poor feeding - Preterms – Non specific. Die due to apneic attacks - Infancy – Athetoid cerebral palsy, choreo-athetosis, brownish staining of teeth, dental dysplasia, deafness, paralysis of upward gaze, intellectual retardation & learning disabilities
- 23. Pathogenesis of kernicterus Related to – Unconjugated bilirubin levels Gestational maturity of infant Integrity of blood-brain barrier Biochemical determinants – Bilirubin protein ratio – 3.5 or more HBABA (hydroxybenzene azo benzoic acid) dye binding capacity - < 50% Salicylate saturation index – 8 or moreRBC biuding of bilirubin - >4 mg%
- 24. Kernicterus
- 25. Assessment
- 26. Approach to a jaundiced baby Ask 4 questions - What is the birth weight? What is the gestation? What is the postnatal age in hours? Is the jaundice physiological or pathological? If jaundice is physiological and baby is well – only observe If deep jaundice – Assess for bil toxicity (kernicterus)
- 27. Indication for lab investigations (In high risk infants) H/O Jaundice, Exchange Blood transfusion / Kernicterus in previous sibling Mother – O group or Rh –ve Jaundice – Within 24 hrs or after 72 hrs Trunk distinctly yellow stained Sick jaundiced baby Jaundice persisting > 2 weeks Yellow coloured urine or clay coloured stools
- 28. Workup Maternal & perinatal history Physical examination Laboratory tests (must in all) Total & direct bilirubin (Total : 0.3 to 1.9 mg % , Direct : 0 to 0.3 mg %) Bil: protein ratio (< 3.4) Blood group and Rh for mother and baby Blood - Hematocrit, retic count and peripheral smear, Sepsis screen, Carboxy Hb Liver function - Vanden Bergh test Thyroid function TORCH titers, liver scan when conjugated hyperbilirubinemia Tests for – Pulmonary excretion rate of CO, OR End tidal CO (Etco) breath level
- 29. Assessment of severity of jaundice Assess in natural daylight for cephalo- pedal progression (Unreliable after phototherapy) Use of ‘Icterometer’ Transcutaneous bilimeter Bilimeter with microcentrifuge
- 31. Management
- 32. Management of jaundice A medical emergency Aim – Keep S bilirubin at a safe level and prevent bil toxicity Prevent brain damage Methods – Preventive and supportive measures Reduction of bilirubin levels – Phototherapy, Exchange transfusion (-most effective and reliable method), drugs
- 33. Preventive and supportive measures Prevention of Rh isoimmunization Withhold drugs that aggravate jaundice or block bilirubin binding sites in albumin Prevent perinatal distress factors Avoid phenolic detergents in nursery
- 34. Adequate feeding and hydration Aspiration of cephalhematoma (bil > 18 mg%) Treatment of sepsis and hepatitis Phenobarbitone Clofibrate – Enhances glucoronyl transferase
- 36. Measures to reduce Serum Bilirubin Phototherapy Drugs blocking entero-hepatic circulation of bilirubin Exchange transfusion Sunlight –NO!
- 37. Measures to reduce S Bilirubin - Phototherapy Safe and effective Bil absorbs light maximally at 420 – 460 nm Causes photo-oxidation & photo- isomerization of bilirubin Enhances hepatic exertion of unconjugated bil into the intestinal lumen Single & double surface system
- 38. Phototherapy equipment White light tubes 6-8*/ 4 blue light tubes Cradle or incubator Eye shades *May use 150 W halogen bulb
- 39. Babies under phototherapy Baby under conventional phototherapy Baby under triple unit intense phototherapy
- 40. Phototherapy Safe and effective Bil absorbs light maximally at 420 – 460 nm Causes photo-oxidation & photo-isomerization of bilirubin Enhances hepatic exertion of unconj bil into the intestinal lumen Single & double surface system 6 - 8 daylight tubes or 4 blue/ white tubes mounted on a stand with grounded electrical outlets. Change tubes every 1000 hours or after 3 months of use Alternate - 150 watt halogen bulb (life 1000 hours) OR Blue CFL lamps - change every 3000 h.. Maintain flux at 6-8 mw/cm2/nm with help of fluxmeter. Have Plexiglas shield to cover the tube lights. Nurse in cradle or incubator
- 41. Phototherapy Perform hand wash Place baby naked 45 cm away from the tube lights in a crib or incubator Fix eye shades - to prevent damage to the retina. Also cover gonads Keep baby at least 45 cm from lights, if using closer monitor temperature of baby Start phototherapy Frequent extra breast feeding every 2 hourly Turn baby every two hours or after each feed (in single surface) Monitor – Temp - 2 to 4 hourly, wt -daily, urine frequency, bilirubin - 12 hrly More frequent breastfeeding or 10-20% extra fluid is provided. Discontinue phototherapy - if two serum bilirubin values are < 10 mg/dl. Measure rebound bilirubin 6-8 hours after stopping phototherapy.
- 42. Turn baby every two hours or after each feed (in single surface) Monitor temperature of the baby x 2 – 4 hrly.. Monitor daily - Urine frequency and body wt More frequent breastfeeding or 10-20% extra fluid is provided. Monitor Serum bilirubin at least every 12 hours Measure rebound bilirubin 6-8 hours after stopping phototherapy. Remember - Baby appears bleached when under phototherapy. Hence clinical assessment of jaundice not reliable. Monitor S bilirubin.
- 43. Repeat serum bilirubin measurement 4–6 hours after initiating phototherapy. Repeat levels 4-6 hourly if serum bilirubin is rising or is not falling while under phototherapy. Repeat serum bilirubin measurement every 12-24 hours when the serum bilirubin level is stable or falling. • Stop phototherapy once bilirubin levels are below the phototherapy level by 2 -3 mg/dl (35 - 50μmol/l) as per postnatal age. • In case of haemolytic jaundice, check bilirubin levels after 12 hours of stopping phototherapy to check for rebound increase.
- 44. Side effects of phototherapy Increased insensible water loss Loose stools Skin rash Bronze baby syndrome Hyperthermia Upsets maternal baby interaction May result in hypocalcemia
- 46. Drugs blocking entero-hepatic circulation of bilirubin Drug Action Charcoal, Agar, Bind unconj bilirubin in gut and prevents entero- hepatic circulation Cholestyramine Enhances fecal exrcretion of bilirubin by binding unconj bil and bile salts Orotic acid Used to conjugate bilirubin Tin-mesoporphyrin (SnMP) Inhibit heam oxygenase & reduce productin of bilirubin Albumin infusion Improves bilirubin binding capacity
- 47. Exchange transfusion Most effective and reliable method to reduce serum bilirubin. Anticipation and early referral to a higher centre is important Indications – Cord Hb 10 gm% or less Cord bilirubin 5 mg% or more Unconj S bil 10 mg% within 24 hrs or 15 mg% within 48 hrs or rate of rise of 0.5 mg% per hr
- 48. Choice of blood for exchange blood transfusion ABO incompatibility – Use O cells of same Rh type, ideal - O cells suspended in AB plasma. Rh isoimmunization – In emergency 0 -ve blood. Ideal 0 -ve suspended in AB plasma or baby's blood group but Rh –ve blood also Other situations – Baby's blood group
- 49. Indications for Exchange Transfusion Hyperbilirubinaemia (Rhesus/ABO incompatibility) to prevent kernicterus Anaemia/ Hydrops Polycythemia ie. partial exchange Rare conditions Hyperkalaemia Drug toxicity/overdose Disseminated intravascular coagulation Maternal AntibodiesEY
- 50. The exchange equipment The volume of blood required - . 1. Single blood volume exchange for anaemia: – Term infant – 80 -100mls /kg – Preterm infant – 100mls/kg – Volume exchanged (ml) = Wt (kg) x Blood Volume x (Hb desired – Hb initial) 2. Double volume exchange for jaundice: (Approx 2 x 85 mls/kg) - Term infant – 200 -250 mls/kg or 80 – 85 mls/kg x 2/3 - Preterm infant – 300 mls/kg or 100 – 120 mls/kg x 2/3
- 51. Procedure 'PUSH-PULL METHOD’ via the umbilical vein. - Serial withdrawal and injection of aliquots (5-20 mls) – 1 mt for each cycle. Takes 60 – 120 minutes. - Used when arterial arterial access is a problem. ‘ISOVOLUMETRIC METHOD’ - slow removal of aliquots (10mls usually) from an artery (central or peripheral) and simultaneous infusion into a vein (central or peripheral). - preferred method - Does not cause wide fluctuations of blood volume and pressure. - Takes 60 – 90 minutes
- 52. First out specimen tested for - Haemoglobin, film, PCV Group, Rhesus, Direct Coomb's test PGL Urea and electrolytes, calcium, SBR, total and conjugated Blood gas Coagulations profile Newborn screening test Hold samples for other tests as indicated, eg. G6PD deficiency, Viral infection, hereditary spherocytosis, metabolic studies.
- 53. Set up for Push Pull method UAC tray and catheters Sterile drapes Blood administration set 3-way taps X 2 (white blood in, red for blood out to waste) Exchange transfusion recording sheet Blood warmer with appropriate coil Extension tubing, long - must be wide bore Drainage connecting tube 5ml, 10ml, and 20ml syringes depending on size of aliquots to be used Waste bag Calcium gluconate 10% ampoules Heparin ampoules1000 IU/ml or heparinised NaCl 0.9% 50 ml syringe
- 55. Hydrops fetalis
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