Neonatal Jaundice Li weizhong

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.

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.

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

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.

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

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

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

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

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.

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.

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).

Causes of Pathologic Jaundice Infective jaundice Neonatal hepatitis TORCH infection Neonatal sepsis

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

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.

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

Hemolytic Disease of the Newborn Li weizhong

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.

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

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

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

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.

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

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

Clinical Manifestations Clinical Features Of Hemolytic Disease Clinical Features Rh ABO Frequency Unusual Common Anemia Marked Minimal Jaundice Marked Minimal to moderate Hydrops Common Rare Hepatosplenomegaly Marked Minimal Kernicterus Common Rare

Laboratory Diagnosis Laboratory Features Rh ABO Laboratory Features Of Hemolytic Disease Laboratory Features Rh ABO blood type of Mother Rh negative O blood type of Infant Rh positive A or B Anemia Marked Minimal Direct Commb’s test Positive Negative Indirect Commb’s test Positive Usually positive Hyperbilirubinemia marked Variable RBC morphology Nucleated RBC Spherocytes

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

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

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

Differential Diagnosis Congenital nephrosis Neonatal anemia Physiological jaundice

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

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

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

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

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

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

Treatment Exchange transfusion Indication Hemoglobin＜120g/L Hydrops, hepatosplenomegaly and heart failure Bilirubin in the 1st 12 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

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

Treatment Drug treatment Intravenous immune globulin (IVIG) Human albumin Protoporphyrins : Sn-PP; Zn-PP Glucocorticoids: Dexamethasone Inducer of liver enzyme: Luminal

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