2 IntroductionNeonatal 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 IntroductionJaundice 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 productionLess effective binding and transportationLess efficient hepatic conjugationEnhanced 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 fractionsDetermination of hemoglobinReticulocyte countBlood typeCoombs’ testExamination of the peripheral blood smear
7 Classifications Direct-reacting hyperbilirubinemia Hepatitis CholestasisInborn errors of metabolismSepsis
8 Classifications Indirect-reacting hyperbilirubinemia Hemolysis ReticulocytosisEvidences of red blood cell destructionA positive Coomb’s testBlood group incompatibilityPositive results of specific examination
9 Classifications Direct and indirect- reactin hyperbilirubinemia HepatitisSepsisLiver 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 Infective jaundiceNeonatal hepatitisTORCH infectionNeonatal sepsis
14 Causes of Pathologic Jaundice Jaundice associated without infectionHemolytic disease of the newbornABO incompatibilityRh incompatibilityBiliary atresiaJaundice associated with breast- feeding
15 Causes of Pathologic Jaundice Breast milk jaundiceIt is caused by prolonged increased enterohepatic circulation of bilirubin. (β-GD↑)The hyperbilirubinemia peaks at days of age.The level of unconjugated hyperbilirubinemia is at mg/dL ( umol/L).If nursing is interrupted for 72 hours, the bilirubin level falls quickly.
16 Causes of Pathologic Jaundice Genetic diseaseCongenital deficiencies of the enzymesglucose-6-phosphate dehydrogenase (G-6-PD)ThalassemiaCystic fibrosisDrugVitamin kNovobiocin
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 diseaseABO incompatibilityType O mothersType A or B fetusesPresence of IgG anti-A or Anti-B antibodies in type O motherFrequently occurring during the first pregnancy without prior sensitization
20 Etiology and Pathogenesis Rh hemolytic diseaseRh blood group antigens (C, c, D, d, E, e)D>E>C>c>ePathophysiology of alloimmune hemolysis resulting from Rh incompatibilityAn Rh-negative motherAn Rh-positive fetusLeakage of fetal RBC into maternal circulationMaternal sensitization to D antigen on fetal RBC
21 Etiology and Pathogenesis Production and transplacental passage of maternal anti-D antibodies into fetal circulationAttachment of maternal antibodies to Rh-positive fetal RBCDestruction 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 abortionEctopic pregnancyA variety of different prenatal proceduresTransfusion of some other blood product containing Rh D RBC in an Rh-negative mother
24 Clinical Manifestations JaundiceAnemiaHydropsMassive enlargement of the liver and spleenBilirubin encephalopathy (Kernicterus)
25 Clinical Manifestations Clinical Features Of Hemolytic DiseaseClinical Features Rh ABOFrequency Unusual CommonAnemia Marked MinimalJaundice Marked Minimal to moderateHydrops Common RareHepatosplenomegaly Marked MinimalKernicterus Common Rare
26 Laboratory Diagnosis Laboratory Features Rh ABO Laboratory Features Of Hemolytic DiseaseLaboratory Features Rh ABOblood type of Mother Rh negative Oblood type of Infant Rh positive A or BAnemia Marked MinimalDirect Commb’s test Positive NegativeIndirect Commb’s test Positive Usually positiveHyperbilirubinemia marked VariableRBC morphology Nucleated RBC Spherocytes
27 DiagnosisThe 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 wkAt 28～32 wkAt 36 wkFetal Rh and ABO statusFetal jaundice level
29 Diagnosis Postnatal diagnosis Jaundice at < 24 hr Anemia (Hematocrit and hemoglobin examination)Rh or ABO incompatibilityCoomb’s test positiveExamination for RBC antibodies in the mother’s serum
31 TreatmentMain goalsTo prevent intrauterine or extrauterine death of fetal or infant form severe anemia and hypoxicTo avoid neurotoxicity from hyperbilirubinemia
32 Treatment Treatment of the unborn infant Utero transfusion Indication HydropsAnemia (Hematocrit<30%)MethodPacked RBC matching with the mother’s serumUmbilical vein transfusion
33 Treatment Delivery in advance Indication Pulmonary maturity Fetal distressMaternal titer of Rh antibodies > 1:3235～37 wk of gestation
34 Treatment Treatment of the liveborn infant Immediate resuscitation and supportive therapyTemperature stabilizationCorrection of acidosis: 1-2mEq/kg of sodium bicarbonateA small transfusion compatible packed RBCVolume expansion for hypotensionProvision of assisted ventilation for respiratory failure
35 Treatment Phototherapy Blue spectrum of 427-475 nm (or White or Green) Irradiance:10-12μW/cm2Protection of eyes and genitalIndicationBilirubin≥10mg/dl at ＜12 hrBilirubin≥12-14mg/dl at ＜18 hrBilirubin≥15mg/dl at ≥24 hr
36 Treatment Side effect of phototherapy Diarrhea Dehydration Riboflavin destructionHypocalcemiaBronze-baby syndrome
37 Treatment Exchange transfusion Indication Hemoglobin＜120g/L Hydrops, hepatosplenomegaly and heart failureBilirubin in the 1st 12 of life>0.75mg/dl/hrBilirubin concentration>20mg/dlFactors 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 : ml/kgBlood choose of Rh incompatibilityRh in accordance with motherABO in accordance with neonateBlood choose of ABO incompatibilityPlasm of AB typeRBC of O type
39 Treatment Drug treatment Intravenous immune globulin (IVIG) Human albuminProtoporphyrins : Sn-PP; Zn-PPGlucocorticoids: DexamethasoneInducer of liver enzyme: Luminal
40 PreventionIntramuscular injection of 300ug of human anti-D globulin to an Rh-negative motherWithin 72 hr of delivery of an ectopic pregnancyAbdominal trauma in pregnancyAmniocentesisChorionic villus biopsyAbortion