1. Hyperbilirubinemia Monica Stemmle

2. Objectives Understand pathway where bilirubin comes from Physiologic vs Pathologic Hyperbilirubinemia Understand the risk for Kernicterus Understand why we care about hyperbilirubinemia

3. Physiology

4. Physiologic hyperbilirubinemia 1. Increased production: Increased RBC volume and decreased lifespan of RBC in neonates 2. Decreased Excretion: UGT activity is decreased in neonates for first few days. Also increased enterohepatic circulation

5. Pathologic Hyperbilirubinemia Can you name some of the risk factors : 1. Increased bilirubin load? 2. Decreased bilirubin clearance?

6. Increased bilirubin load Hemolysis – Immune mediated (ABO, rH, minor antigens) – Heritable defects (RBC membrane defect, RBC enzyme defects, hemoglobinopathies) Sepsis/DIC Hematomas Polycthemia Macrosomia Increased enterohepatic ciculation

7. Decreased bilirubin clearance G6PD deficiency Meconium plug Imperforate anus

8. Risk of Hyperbilirubinemia KERNICTERUS

9. Kernicterus Physiology not well understood Believed that exposure to bilirubin at a sensitive window of neuronal development may lead to apoptosis Requires PROLONGED HIGH bilirubin

10. Kerniticus studies 1. Outcomes among Newborns with Total Serum Bilirubin Levels of 25 mg per Deciliter or More Thomas B. Newman N Engl J Med 354;18 may 4, 2006 – Kaiser data. Infants with bili >24. No cases of kernicterus and no neurologic difference 2. Outcomes in a Population of Healthy Term and Near-Term Infants With Serum Bilirubin Levels of >19 mg/dL Who Were Born in Nova Scotia, Canada, Between 1994 and 2000. Pediatrics. Jangaard et al. 122 (1): 119. (2008). – Babies in Nova Scotia bw 1994-2000. No dif in neuro problems or deafness between severe hyperbili (>19) and no hyperbili (<13). 3. Synopsis report from the Pilot USA Kernicterus Registry VK Bhutani and L Johnson Journal of Perinatology (2009) 29, S4–S7. – No cases of kernicterus at bili <20, very usual at 20-25 and 25-35 could be reversible if acted on quickly

11. So who do you screen AAP recommends universal screening either with TcB or TSB USPSTF recommends against universal screening. – Risks: treating unneccesarily, interrupting breastfeeding, increased treatment and cost of hospitalization. Summary: Screen with TcB or TSB with clinical judgment and weighing baby risk factors!

12. Risk Factors to Consider Can you name a few for hyperbilirubinemia needing photo AND nuerotoxicity?

13. Risk Factors for Hyperbili Predischarge TSB or TcB in the HR or HIR zone Lower Gestational age Exclusive breasfeeding (esp if not going well or weight loss excessive) Jaundice in first 24 hours Isoimmune or other hemolytic disease Cephalohematoma or significant bruising East Asian Race

14. Risk factors for neurotoxicity Isoimmune hemolytic disease G6PD Asphyxia Sepsis Acidosis Albumin <3

15. Charts To help Do you know what the 3 charts and what they look at are that we use?

16. AAP Charts Risk Zones Phototherapy Exchange Transfusion

17. Risk Zones

18. Phototherapy

19. So what does all this mean? Approach each baby individually Importance is WHY the baby is jaundiced not that the baby is jaundiced Use clinical judgment and think about risks when deciding when to recheck and when to treat.

20. Questions You are the junior on at Valley and have a baby that is being admitted for hyperbili. Meanwhile 3 other kids hit the floor at the same time. In order to triage you send the intern to see the hyperbili first while you see the sicker patients. When you reunite with the intern what are your 4 top questions you want to ask the intern?

21. Gestational age and chronologic age Bili level (and hours that it was taken) Baby vital signs and general appearance Baby blood type and mom blood type

22. Intern Response 6 day old ex 36 0/7 with a bili of 15.8. Vitals not done yet. Mom is A +, Ab neg. Which places the baby at risk for severe hyperbili? – Late preterm – Mom’s blood type – Male – 6 days old

23. Late preterm And Male

24. A little more history Baby is 3% down from BW currently drinking breast and bottle. Baby looks “fine”. Why do you think the baby has hyperbili? Breastfeeding jaundice Breastmilk Jaundice Exaggerated physiologic jaundice Other

25. Exaggerated physiologic jaundice or other reason What labs do you want? CBCd Retic Direct bili Type and cooms

26. You get all because you don’t have a good explanation for the high bili level. While you are waiting for the results the nurse mentions the baby has low tone. You go to examine the baby and notice the baby does not suck much. You look back at the vitals and note the temp was low. You also notice his perfusion is poor. What next?

27. Rule out Sepsis Evaluation!

28. What would you order? – LP – CBCd – Blood culture – Urine culture – CRP

29. You correctly order the full workup. During the tap the baby has respiratory arrest. You then transfer to the NICU. In transport you get a call that the CBC shows a white count of 3.7 but the smear says “many bacteria”. What were your warning signs that this was not a simple case of neonatal jaundice?

30. Abnormal vital signs (low temp). No clear cause for jaundice (older baby, not that far from BW, not a risk with mom blood type) Poor perfusion.

31. Objectives reviewed Understand pathway where bilirubin comes from Physiologic vs Pathologic Hyperbilirubinemia Understand the risk for Kernicterus Understand why we care about hyperbilirubinemia

32. Questions?

33. References Hyperbilirubinemia in the Newborn Infant >35 Weeks’ Gestation: An Update With Clarifications M. Jeffrey Maisels Vinod K. Bhutani, Debra Bogen, Thomas B. Newman, MD, Ann R. Stark, and Jon F. Watchko PEDIATRICS Volume 124, Number 4, October 2009 Screening of Infants for Hyperbilirubinemia to Prevent Chronic Bilirubin Encephalopathy: US Preventive Services Task Force Recommendation Statement US Preventive Services Task Force Pediatrics 2009; 124;1172-1177 Neonatal Jaundice M. Jeffrey Maisels Pediatr. Rev. 2006;27;443-454 Trends in Hospitalizations for Neonatal Jaundice and Kernicterus in the United States, 1988_2005 Bryan L. Burke, James M. Robbins, T. Mac Bird, Charlotte A. Hobbs, Clare Nesmith and John Mick Tilford Pediatrics 2009;123;524-532