1. Hyperbilirubinemia

2. Case 1 5 day old former term male infant born to a 23 y.o. G1P0->1 woman. Is exclusively breastfeeding. Has total bilirubin of 25, direct is 0.7. Both mother and baby are O+, and coombs is negative. Phototherapy is started and baby is fed, 6 hours later the total bilirubin level is 19. Breastfeeding consult is done.

3. Physiologic Hyperbilirubinemia Increased production –Short RBC lifespan –Increased shunt bilirubin Decrease clearance –Portal vein shunting via ductus venosus Decreased conjugation –Decreased UDPGA synthesis –Decreased UDPG transferase Increased enterohepatic circulation –High concentration of bilirubin in meconium –Decreased bowel motility

4. Hyperbilirubinemia: Elevation in disease states Overproduction –Hemolysis Isoimmunization Genetic –Sequestered Blood –Polycythemia –Increased Enterohepatic Circulation Bowel obstruction Intestinal hypomotility Undersecretion –Decreased conjugation Congenital –Impaired hepatic transport Congenital Liver disease –Biliary obstruction Mixed –Infections Congenital infections Bacterial sepsis –Prematurity –Infant of a Diabetic Mother –Hypothyroidism

5. Bilirubin Neurotoxicity What is kernicterus? –Yellow staining of the brain –Neuronal necrosis microscopically Getting bilirubin from the blood to the brain cell isn’t easy “The numbers” keep changing Bilirubin encephalopathy vs. minor CNS deficits

6. Clinical Features of Kernicterus Acute –Phase 1 (first 1-2 days): poor sucking, stupor, hypotonia, seizures –Phase 2 ( mid first week): hypertonia of extensors, opisthotonus, retrocollis, fever –Phase 3 (after first week): hypertonia Chronic –First year: hypotonia, active DTRs, obligate tonic neck refles, delayed motor skills –After first year: movement disorders (choreoathetosis, ballismus, tremor), upward gaze, sensorineural hearing loss.

7. Vigintiphobia*: Fear of “20” Based on retrospective analysis of infants with hemolytic Rh disease…in the dark ages before intrauterine transfusion. –Hsia, et al. NEJM 1952;247:668-71 –Mollison and Cutbush. Blood 1951:777-88 *Term coined by the late Frank Oski, MD

8. Serum Bilirubin Level and Kernicterus in 229 Infants with Erythroblastosis Hsia, et al. NEJM 1952;247:668-71

9. AAP Guidelines for Hyperbilirubinemia - 2004 AMERICAN ACADEMY OF PEDIATRICS CLINICAL PRACTICE GUIDELINE Subcommittee on Hyperbilirubinemia Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation PEDIATRICS Vol. 114 No. 1 July 2004

10. Prevention of Kernicterus: Identifying infants at risk for Hyperbilirubinemia Prenatal maternal blood type and antibody screen Blood type and direct coombs on the baby –Or type only babies of: Rh negative mothers (necessary for Rhogam eval) Other antibody screen positive O mothers (for ABO incompatibility), or hold cord blood 5-7 days for testing Good follow up and check bilirubin levels

11. Risk Factors Without Hemolysis* Jaundice in first 24 hours Visible jaundice before discharge Previous jaundiced sibling Gestation 35-38 weeks Exclusive breastfeeding East Asian Race Bruising/cephalohematoma Maternal age >25 years Male sex *AAP subcommittee on Neonatal Hyperbili, Pediatrics, September 2001

12. Copyright ©2004 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316 Nomogram for designation of risk in 2840 well newborns at 36 or more weeks' gestational age with birth weight of 2000 g or more or 35 or more weeks' gestational age and birth weight of 2500 g or more based on the hour-specific serum bilirubin values

13. 4 Newborn Hyperbilirubinemias Exaggerated physiologic? –By exclusion Lack of Breast Milk Jaundice –Feeding History Prematurity –Assess maturity, review dating Hemolytic jaundice (ABO, DCcEe, et al) –Review prenatal and newborn labs

14. Evaluation of Hyperbilirubinemia Feeding history critical Assess breastfeeding –Sucking, swallowing, satisfaction, decrease in breast size –Stools (color and frequency) –Urine output –Weight loss (<10% at 5-7 days) –3-5 day office visit

15. Evaluation of Hyperbilirubinemia Mother’s blood type and antibody screen Baby’s blood type and Direct Coombs CBC, reticulocyte count (hemolysis) Total and Direct Bilirubin –Remember: “One bilirubin leads to another” Head to toe progression Transcutaneous bilirubin meter

16. Evaluation of Hyperbilirubinemia Head to Toe progression: Is it reliable? LI Kramer. AJDC. 1969;118:454-458

17. Breast Feeding (lack of) Jaundice Gradual increase in bilirubin –Presentation toward end of first week of life Clues are all in the feeding history No reported case of kernicterus(?) in healthy term infants –Even with levels of up to 30 –However, you must treat!?

18. Breast Feeding (lack of) Jaundice No reported case of kernicterus?* –Kernicterus in Otherwise Healthy, Breast-fed Term Newborns. Maisels & Newman. Pediatrics 1995;96:730-733 6 patients 4-10 days of age Bilirubin levels 39-50

19. Jaundice of Prematurity Jaundice appears at a level of 6-8 No relationship between kernicterus at autopsy and bilirubin level So if they are jaundiced treat them with phototherapy until it resolves

20. ABO Incompatibility: “UCLA Protocol” Age(h) Bilirubin Level Treatment <12<10 >10 Observe Phototherapy <18<12 >12 Observe Phototherapy <24<14 >14 Observe Phototherapy >24>15Phototherapy Rapid rise, then a plateau Osborn, et al. Pediatrics 1984;74:371-4

21. Non-ABO Hemolytic Jaundice Rh o is the same as “D” Don’t ignore: C, c, E, e, Duffy, Kell, Lewis… Rapid rate of rise: –Jaundice in the first 24 hours is abnormal –Bilirubin level >10 in first 24 hours is abnormal –Rate of rise >0.5 mg/dL/h Coombs test –Detects IgG antibodies on the baby’s RBCs Must keep bilirubin <20

22. Management of Hyperbilirubinemia Improve feeding Phototherapy Exchange Transfusion

23. Management of Hyperbilirubinemia Deal with feeding issues –Reverse catabolism and decrease enterohepatic circulation –Lactation consultation –Don’t supplement with water or dextrose water –For Non-preterm and non-hemolytic jaundice

24. Copyright ©2004 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316 Guidelines for phototherapy in hospitalized infants of 35 or more weeks' gestation

25. Phototherapy Fast application, available everywhere Use “blue light” 420-475 nm with spectral irradiance of at least 20 uW/cm 2 /nm All that is needed for most preemies, physiologic/ breast feeding jaundice, most ABO incompatibility Assess effectiveness of therapy

26. Phototherapy Intensive Phototherapy –Multiple lights for surface coverage –With a light blanket –Put lights close to baby for high radiance Intensive phototherapy failing to lower the bilirubin level suggests: –Hemolytic disease –Some other pathologic process –Weak lights, baby out from under too often

27. Management of Hyperbilirubinemia Exchange Transfusion –Reserve for hemolytic disease with bilirubin >20 –Those unresponsive to intensive phototherapy with bilirubin >25

28. Copyright ©2004 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316 Guidelines for exchange transfusion in infants 35 or more weeks' gestation

29. Case 2 6 day old term male born at home to a G6P5->6 woman. Noted to be jaundiced on 3 rd day of life. On day of admit had apneic/cyanotic episode. At local ED, total bili was 42.9 with direct of 4.4 and was coombs +. Baby was opisthotonic with tongue thrusting. 2 exchange transfusions and aggressive phototherapy performed. Total bili down to 16 after first exchange. Baby died of kernicterus several months later.

30. Case 3 8 day old former 36 week female born to a G4P2->3 woman with gestational diabetes. Brought to clinic with 22% wt loss. Total bili 28.5 with direct of 0.9. Na 178. Coombs -. Hydrated and aggressive phototherapy. 4 hours after admit bili down to 22. Feeding issues addressed and baby discharged home doing well.

31. Case 4 19 day old former term male recovering from extensive subgaleal hematoma. Has Total bilirubin level of 53.8. Treated with phototherapy only. Does he develop kernicterus? No, he has a direct bilirubin fraction of 37.0. (so, unconjugated fraction is only 16.2)