Hyperbilirubinemia in the Newborn

1. Hyperbilirubinemia in the Newborn

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

8. Overview of Bilirubin Production

9. In Phagocyte

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.

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

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

17. Etiology of Indirect Hyperbilirubinemia Polycythemia Maternal fetal transfusion Twin-twin transfusion Delayed Cord Clamping Intrauterine hypoxia RBC Breakdown Extravascular Intravascular

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

19. Clinical Evaluation

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

23. 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)

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

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

27. Treatment Hydration/Feeding Phototherapy Exchange Transfusion

28. 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. 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. 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. 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. Review of Case 1 How old is the patient? What is the gestational age? What other risk factors are present? 12 hours old Full term ABO incompatible

33. 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. Review of Case 2 How old is the patient? What is the fractionation? Breast or bottle fed? Other risk factors? 10 days 22 total / 0.8 direct Breast fed None