1. Continuity Clinic Hyperbilirubinemia in the Newborn

2. Continuity Clinic Objectives Understand the physiology of hyperbilirubinemia Be able to define kernicterus Know the associated risk factors for jaundice Be able to appropriately assess the risk of harm from jaundice Be familiar with current therapies

3. Continuity Clinic Epidemiology 50-70% of newborns have jaundice Moderate (>12 mg/dL) develops in 4% of bottlefed compared to 14% of breastfed Severe jaundice (>15 mg/dL) occurs in 0.3% bottlefed vs 2% of breastfed Groups more susceptible – Chinese, Japanese, Korean, Native American

4. Continuity Clinic Case 1 You are called by the nurse that a newborn’s TcB is 11.1. Is this concerning? What information do you need to answer that question?

5. Continuity Clinic Case 2 You are called by the ER to see an infant whose bili is 22. Must you admit? What information do you need to answer this question?

6. Continuity Clinic BILIRUBIN Non-polar, water insoluble compound requiring conjugation with glucuronic acid to form a water soluble product that can be excreted. It circulates to the liver reversibly bound to albumin

7. Continuity Clinic The Skinny on Heme Catabolism RBC’s are broken down in the reticuloendothelial system Heme groups are removed from globin groups

8. Continuity Clinic Overview of Bilirubin Production

9. Continuity Clinic In Phagocyte

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11. Conjugation Since conjugated bilirubin crosses the placenta very little, conjugation is not active in the fetus with levels of UDPGT about 1% of adult levels at 30 - 40 weeks gestation After birth, the levels of UDPGT rise rapidly but do not reach adult levels until 4-6 weeks of age. Ligandins, which are necessary for intracellular transport of bilirubin, are also low at birth and reach adult levels by 3-5 days.

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13. Enterohepatic Circulation Meconium contains 100-200mg of conjugated bilirubin at birth. Conjugated bilirubin is unstable and easily hydrolyzed to unconjugated bilirubin. This process occurs non-enzymatically in the duodenum and jejunum and also occurs in the presence of beta-glucuronidase, an enteric mucosal enzyme, which is found in high concentration in newborn infants and in human milk.

14. Continuity Clinic 2 Types of Jaundice Unconjugated and Conjugated Definition of direct hyperbilirubinemia Causes of direct hyperbilirubinemia

15. Continuity Clinic Etiology of Direct Hyperbilirubinemia Infection,Infection, Infection Biliary Atresia Choledochal cyst Hepatitis – infection OR maternal meds Alpha-1-antrypsin Tyrosinemia Galactosemia Cystic Fibrosis Dubin Johnson Rotors Syndrome

16. Continuity Clinic Indirect Hyperbilirubinemia Why do we care? Kernicterus: Early symptoms –Hypoglycemia, ICH, lethargy, poor feeding, decreased reflexes Late symptoms –Opisthotonos, twitching, convulsions, muscle rigidity

17. Continuity Clinic Etiology of Indirect Hyperbilirubinemia Polycythemia –Maternal fetal transfusion –Twin-twin transfusion –Delayed Cord Clamping –Intrauterine hypoxia RBC Breakdown 1.Extravascular 2.Intravascular Kleihauer Betke Tests Cephalohematoma, bruising Immune: ABO, Rh, minor antigens Enzyme deficiencies: G6PD, Pyruvate Kinase Membrane Deficiencies: spherocytosis, ellipocytosis

18. Continuity Clinic Etiology of Indirect Hyperbilirubinemia Breastfeeding vs. Breastmilk jaundice Metabolic: Down’s syndrome, Gilbert’s syndrome, Hypothyroidism, and Crigler- Najjar Physiologic

19. Continuity Clinic Clinical Evaluation 5 mg/dL 15 mg/dL 20 mg/dL

20. Continuity Clinic ALBUMIN A low albumin level could possibly be the reason behind kernicterus occurring in some infants at relatively low bilirubin levels. There was a report of a 29 week infant whose peak bilirubin level was only 15.7 and yet developed classic kernicterus with spasticity, dystonia, ballismus, and gaze abnormalities. Her bilirubin/albumin molar ratio was 0.67. It has been suggested that a ratio of >0.5 might be a threshold in sick preterm infants.

21. Continuity Clinic Time to Get to Work Signs you need to actually stop being lazy and have to be a doctor: –Jaundice in first 24 hours –Hemolysis is suggested by rate of rise of bili >0.5 mg/dL/hour –Jaundice beyond 10-14 days of life –Direct bili > 2 mg/dL

22. Continuity Clinic RISK FACTORS FOR SIGNIFICANT JAUNDICE Gestational Age Race Family history of jaundice requiring phototherapy Hemolysis (ABO or other) Severe bruising Breastfeeding

23. Continuity Clinic Gathering Data History – what do you want to know? Laboratory Tests –CBC with retic –Total and Direct Bilirubin –Blood type of mom and child –Direct antiglobin test (DAT)

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25. To Treat or Not to Treat -Bhutani Curve-

26. Continuity Clinic ASSESSING THE RISK OF JAUNDICE BY THE NUMBERS www.bilitool.org Palm downloadable!

27. Continuity Clinic Treatment Hydration/Feeding Phototherapy Exchange Transfusion

28. Continuity Clinic PHOTOTHERAPY Phototherapy has been the mainstay of treating hyperbilirubinemia since the 1960s. Phototherapy causes structural isomerization, forming lumirubin, which is then excreted in the bile and urine. Since photoisomers are water soluble, they should not be able to cross the blood-brain barrier, so starting phototherapy should decrease the risk of kernicterus by turning 20-25% of bilirubin into a form unable to cross, even before the level has lowered significantly.

29. Continuity Clinic PHOTOTHERAPY Bilirubin absorbs light best at 450 nm, but longer wavelenths penetrate skin better. Make sure skin is as exposed as possible and that light is not too far from baby. Fiberoptic light (bili blanket) is much less efficacious on its own.

30. Continuity Clinic EXCHANGE TRANSFUSION Double volume exchange transfusion was a common procedure prior to advent of Rhogam and phototherapy. Now fortunately a rare occurrence Used for bilirubin >25 in a term infant and not decreasing despite phototherapy

31. Continuity Clinic Review of Case 1 You are called by the nurse that a newborn’s TcB is 11.1. Is this concerning? What information do you need to answer that question?

32. Continuity Clinic Review of Case 1 How old is the patient? What is the gestational age? What other risk factors are present? –1–12 hours old –F–Full term –A–ABO incompatible

33. Continuity Clinic Review of Case 2 You are called by the ER to see an infant whose bili is 22. Must you admit? What information do you need to answer this question?

34. Continuity Clinic Review of Case 2 How old is the patient? What is the fractionation? Breast or bottle fed? Other risk factors? –1–10 days –2–22 total / 0.8 direct –B–Breast fed –N–None

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