Neonatal Jaundice

1. Neonatal Jaundice Li weizhong

2. Introduction • Neonatal Jaundice is known as the visible clinical manifestation of dying skin and sclera yellow during the neonatal period, resulting from deposition of bilirubin in the neonatal bodies.

3. Introduction • Jaundice is observed during the 1st wk in approximately 60% of term infant and 80% of preterm infant. • Hyperbilirubinemia can be toxic, with high levels resulting in an encephalopathy known as kerni-cterus.

4. Metabolism of Bilirubin • Increased bilirubin production • Less effective binding and transportation • Less efficient hepatic conjugation • Enhanced absorption of bilirubin via the enterohepatic circulation

5. Clinical Manifestation • Jaundice may be present at birth or at any time during the neonatal period. • Jaundice usually begins on the face and, as the serum level increases, progresses to the chest and abdomen and then the feet. • Jaundice resulting from deposition of indirect bilirubin in the skin tends to appear bright yellow or orange; jaundice of the obstructive type (direct bilibrubin), a greenish or muddy yellow.

6. Methods of Diagnosis • A complete diagnostic evaluation • Determination of direct and indicrect bilirubin fractions • Determination of hemoglobin • Reticulocyte count • Blood type • Coombs’ test • Examination of the peripheral blood smear

7. Classifications • Direct-reacting hyperbilirubinemia • Hepatitis • Cholestasis • Inborn errors of metabolism • Sepsis

8. Classifications • Indirect-reacting hyperbilirubinemia • Hemolysis • Reticulocytosis • Evidences of red blood cell destruction • A positive Coomb’s test • Blood group incompatibility • Positive results of specific examination

9. Classifications • Direct and indirect- reactin hyperbilirubinemia • Hepatitis • Sepsis • Liver damage complicated by Hemolysis

10. Classifications • Physiologic jaundice • Clinical jaundice appears at 2-3 days. • Total bilirubin rises by less than 5 mg/dl (86 umol/L) per day. • Peak bilirubin occurs at 3-5 days of age. • Peak bilirubin concentration in Full-term infant <12mg/dl (205.2 umol/L) • Peak bilirubin concentration in Premature infant <15mg/dl (257umol/L) • Clinical jaundice is resolved by 2 weeks in the term infant by 3-4 weeks in the Preterm infant.

11. Classifications • Pathologic jaundice • Clinical jaundice appears in 24 hours of age. • Total bilirubin rises by higher than 5 mg/dl (86 umol/L) per day. • Peak concentration of total bilirubin is more than 12 mg/dL in the term infant and 15 mg/ dL in the preterm infant.

12. Classifications • Pathologic jaundice • Clinical jaundice is not resolved in 2 weeks in the term infant and in 4 weeks in the Preterm infant. • Clinical jaundice appears again after it has been resolved. • Direct bilirubin concentration is more than 1.5 mg/dL (26umol/L).

13. Causes of Pathologic Jaundice • Infectivejaundice • Neonatal hepatitis • TORCH infection • Neonatal sepsis

14. Causes of Pathologic Jaundice • Jaundice associated without infection • Hemolytic disease of the newborn • ABO incompatibility • Rh incompatibility • Biliary atresia • Jaundice associated with breast- feeding

15. Causes of Pathologic Jaundice • Breast milk jaundice • It is caused by prolonged increased enterohepatic circulation of bilirubin. (β-GD↑) • The hyperbilirubinemia peaks at 10-15 days of age. • The level of unconjugated hyperbilirubinemia is at 10-30 mg/dL (172-516 umol/L). • If nursing is interrupted for 72 hours, the bilirubin level falls quickly.

16. Causes of Pathologic Jaundice • Genetic disease • Congenital deficiencies of the enzymes • glucose-6-phosphate dehydrogenase (G-6-PD) • Thalassemia • Cystic fibrosis • Drug • Vitamin k • Novobiocin

17. Hemolytic Disease of the Newborn Li weizhong

18. Introduction • Hemolytic disease of the newborn • It is an isoimmunity hemolysis associated with ABO or Rh incompatibility. • It results from transplacental passage of maternal antiboddy active against RBC antigens of the infant, leading to an increased rate of RBC destruction. • It is an important cause of anemia and jaundice in newborn infant.

19. Etiology and Pathogenesis • ABO hemolytic disease • ABO incompatibility • Type O mothers • Type A or B fetuses • Presence of IgG anti-A or Anti-B antibodies in type O mother • Frequently occurring during the first pregnancy without prior sensitization

20. Etiology and Pathogenesis • Rh hemolytic disease • Rh blood group antigens (C, c, D, d, E, e) • D>E>C>c>e • Pathophysiology of alloimmune hemolysis resulting from Rh incompatibility • An Rh-negative mother • An Rh-positive fetus • Leakage of fetal RBC into maternal circulation • Maternal sensitization to D antigen on fetal RBC

21. Etiology and Pathogenesis • Production and transplacental passage of maternal anti-D antibodies into fetal circulation • Attachment of maternal antibodies to Rh-positive fetal RBC • Destruction of antibody-coated fetal RBC

22. Etiology and Pathogenesis • Rh hemolytic disease was rare during the first pregnancy involving an Rh-positive fetus. • Once sensitization has occurred, re-exposure to Rh D RBC in subsequent pregnancies leads to an anamnestic response, with an increase in the maternal anti-Rh D antibody titer. • The likelihood of an infant being affected increased significantly with each subsequent pregnancy.

23. Etiology and Pathogenesis • Significant hemolysis occurring in the first pregnancy indicates prior maternal exposure to Rh-positive RBC. • Fetal bleeding associated with a previous spontaneous or therapeutic abortion • Ectopic pregnancy • A variety of different prenatal procedures • Transfusion of some other blood product containing Rh D RBC in an Rh-negative mother

24. Clinical Manifestations • Jaundice • Anemia • Hydrops • Massive enlargement of the liver and spleen • Bilirubin encephalopathy (Kernicterus)

25. Clinical Manifestations Clinical Features Of Hemolytic Disease

26. Laboratory Diagnosis Laboratory Features Of Hemolytic Disease

27. Diagnosis • The definitive diagnosis requires demonstration of blood group incompatibility and of corresponding antibody bound to the infant’s RBC.

28. Diagnosis • Antenatal Diagnosis • History • Expectant parents’ blood types • Maternal titer of IgG antibodies to D or E (>1:32) • At 12～16 wk • At 28～32 wk • At 36 wk • Fetal Rh and ABO status • Fetal jaundice level

29. Diagnosis • Postnatal diagnosis • Jaundice at < 24 hr • Anemia (Hematocrit and hemoglobin examination) • Rh or ABO incompatibility • Coomb’s test positive • Examination for RBC antibodies in the mother’s serum

30. Differential Diagnosis • Congenital nephrosis • Neonatal anemia • Physiological jaundice

31. Treatment • Main goals • To prevent intrauterine or extrauterine death of fetal or infant form severe anemia and hypoxic • To avoid neurotoxicity from hyperbilirubinemia

32. Treatment • Treatment of the unborn infant • Utero transfusion • Indication • Hydrops • Anemia (Hematocrit<30%) • Method • Packed RBC matching with the mother’s serum • Umbilical vein transfusion

33. Treatment • Delivery in advance • Indication • Pulmonary maturity • Fetal distress • Maternal titer of Rh antibodies > 1:32 • 35～37 wk of gestation

34. Treatment • Treatment of the liveborn infant • Immediate resuscitation and supportive therapy • Temperature stabilization • Correction of acidosis: 1-2mEq/kg of sodium bicarbonate • A small transfusion compatible packed RBC • Volume expansion for hypotension • Provision of assisted ventilation for respiratory failure

35. Treatment • Phototherapy • Blue spectrum of 427-475 nm (or White or Green) • Irradiance:10-12μW/cm2 • Protection of eyes and genital • Indication Bilirubin≥10mg/dl at ＜12 hr Bilirubin≥12-14mg/dl at ＜18 hr Bilirubin≥15mg/dl at ≥24 hr

36. Treatment • Side effect of phototherapy • Diarrhea • Dehydration • Riboflavin destruction • Hypocalcemia • Bronze-baby syndrome

37. Treatment • Exchange transfusion • Indication • Hemoglobin＜120g/L • Hydrops, hepatosplenomegaly and heart failure • Bilirubin in the 1st12 of life>0.75mg/dl/hr • Bilirubin concentration>20mg/dl • Factors supporting early exchange transfusion: Previous kernicterus in a sibling, reticulocyte counts greater than 15%, asphyxia of neonate and premature infant

38. Treatment • Blood volume of exchange transfusion • Double-volume exchange transfusion :150-180ml/kg • Blood choose of Rh incompatibility • Rh in accordance with mother • ABO in accordance with neonate • Blood choose of ABO incompatibility • Plasm of AB type • RBC of O type

39. Treatment • Drug treatment • Intravenous immuneglobulin (IVIG) • Human albumin • Protoporphyrins : Sn-PP; Zn-PP • Glucocorticoids: Dexamethasone • Inducerof liver enzyme: Luminal

40. Prevention • Intramuscular injection of 300ug of human anti-D globulin to an Rh-negative mother • Within 72 hr of delivery of an ectopic pregnancy • Abdominal trauma in pregnancy • Amniocentesis • Chorionic villus biopsy • Abortion