Neonatology Neonatal Jaundice

Contents Billirubin metabolism in normal neonates Special problems in neonates The diseases in relation with Neonatal Jaundice Dangerous of the Hyperbillirubinemia

Billirubin + plasm albumin --- in blood Capillary bile duct breakdown of hemoglobin 80% ineffective erythropoiesis Reticulo- endothelial system liver Bilirubin + Protein Y 、 Z conjugative conjugated Bi Reabsoption:90% — Hepatic cells Glucuronic acid 90% Glucose conjugates Xylose conjugates intestine lumen Bacteria urobilinogen 80% excrete Kidney 10% Portal vein Urine ： urobilinogen （ 0-4mg/d ） Fecal : urobilinogen (40-280mg/d) breakdown of hemoproteins Normal Billirubin Metabolism in neonates Intrahepatic hemachrome Tissue hemachrome Smooth endoplasmic reticulum Hepato- enteral circulation

Specificity of Billirubin Metabolism in newborns Increased bilirubin formation –Excesive RBCs after birth –Shorter half life of fetal hemoglobin –Heme oxygenase  –Increased bilirubin originated from bypass

Specificity of Billirubin Metabolism in newborns Insufficient in transiting bilirubin –albumin linking/transporting bilirubin 

Specificity of Billirubin Metabolism in newborns Insufficient in treating bilirubin by liver –Y. Z protein  –Hepatic Enzyme under developed –Activity of hepatic enzyme easily being undermined –Serums glucose rapidly 

Specificity of Billirubin Metabolism in newborns Load of hepatoenteral circulation  –Intestine flora  –Activity of β- Glucuronidase within mesocaval  –High quantity of bilirubin in meconium

Physiological Jaundice Pretermterm Beginning presence2-3 d, peak on 4-6 d Serum Billirubin level<12mg/dl<15mg/dl Duration7-10 d 2 － 3 w Physical statusUsual

Pathological Jaundice Presenting earlier, <24-48 h after birth Higher Serum Billirubin level –TBI >12mg/dl –increasing rapidly, >5mg/dl/d Longer duration: –Term:>2 w preterm:>4 w Persistently progressing, or re-presence after disappearing

Etiology of Pathological Jaundice Unconjugated –Hemolytic Disease of the Newborn alloimmune hemolytic (ABO and Rh types) deformity of RBC RBC Enzyme deficiency Extravascular Hemolysis –Breastfeeding Jaundice –Erythrocytosis

Etiology of Pathological Jaundice Conjugated –Neonatal Hepatic diseases –Congenital bile duct disorders –Congenital metabolic disorders

Etiology of Pathological Jaundice Mixed by Unconjugated with Conjugated –Infectious

Hemolytic disease of newborn ABO type incompatability alloimmune hemolytic disease –50% happened in first pregnancy –20 ％ ABO type incompatability ， incidence 10 ％ –majority maternal type O and infant type A or B RH type incompatability alloimmune hemolytic disease –No Occurrence in first pregnancy, except the one had history of abortion and transfusion –Antigenic: D>E>C>c>e –RH D most commonly seen

Hemolytic disease of newborn Clinical manifestation Jaundice –Present at different time: ABO 2-3d. RH<24H –Level of TBi: ABO: light elevated RH: severely elevated and progressing Anemia: severe in RH and may complicated with heat failure Hepatosplenomegaly Hydrops fetalis (universal edema of the fetus)

Hemolytic disease of newborn Laboratory investigation Prompt hemolysis indicators –RBC Hb  –Reticulocyte  –Nuclear RBC> 10% blood type incompatibility –Maternal: O, newborn: A,B –Maternal: Rh-, newborn: Rh+

Hemolytic disease of newborn Laboratory investigation Coomb’s test –Rh: Direct: positive Indirect: positive (Ab. present and the type) –ABO: Direct: positive Free antibody present Ab. Release test: positive

Hemolytic disease of newborn Diagnosis –History: Past production history of the mother Newborn with hyperbilirubinemia, anemia Stillbirth Hydrops fetalis –Clinical manifestation –Laboratory evidences

Hemolytic disease of newborn Prenatal diagnosis –Mother with Rh-negative: measure Rh Ab in GA 28,32,36 w –Examining amniotic fluid: bilirubine level

Hemolytic disease of newborn Prevention –Mother with Rh-negative delivering the first fetus given anti-D Ab.

Neonatal Hepatitis Intrauterine, intrapartum and during delivering infected –Virus: common: CROTCHS/CMV Pathogenesis –Cholestasis: Capillary bile duct and hepatic duct obstruction –Liver cells and mesenchymal inflammatory change –portal area hyperplasia

Neonatal hepatitis Clinical manifestation Obstructive jaundice –Jaundice represent following the fading of physiological jaundice –Dark yellow urine and grey-white stool Gastrointestinal symptoms: –anorexia, hyperphagia, vomiting, diarrhea Anemia hepatosplenomegaly

Neonatal hepatitis Laboratory investigation TBi , VDB: direct and indirect positive Hepatic function: –ALT , serum proteins , albumin  Serous virology –Positive: CMV IgG/M, TOXO IgG/M –HBV: antigens and antibodies

Biliary atresia cholestasis Severe obstructive jaundice with high Conjugated Bi Persistent grey-white stool Severe hepatosplenomegaly Progressive worsening in hepatic function Diagnosis based on ultrasound, CT and MRI Isotope ECT may helpful

Jaundice with Infection When there are no find in particular General manifestation of the infection Blood stream infection or organ infection Both conjugated and unconjugated Bi  Jaundice subsided when infection controled

Breastfeeding Jaundice Babies with exclusive breast feeding Jaundice persists Unconjugated Bi predominant Without hepatosplenomegaly and injury of hepatic function Jaundice fading or disappearing after suspending breast feeding Good outcome

Kernicterus Pathology –staining and necrosis of neurons in the basal ganglia, hippocampus, and subthalamic nucleus of the brain

Kernicterus For a healthy term infant with a STB concentration less than 30mg/dl (513μmol/L) will usually not suffer neurologic damage No certainty that lower STB levels under some circumstances eliminates the possibility of permanent injury, in particular with respect to auditory function. The neurologic consequences of prolonged exposure to moderate hyperbilirubinemia are uncertain.

Kernicterus Major risk factor –Albumin binding of bilirubin. –1 gram of albumin can bind 8.2mg of bilirubin –A serum albumin concentration of 3g/dl could theoretically bind approximately 25mg/dl of bilirubin Not cross the blood-brain barrier –Albumin-bound bilirubin –Conjugated bilirubin Premature –low serum albumin concentrations –frequency of acidosis

Kernicterus Clinical manifestation –First 1 to 2 d: poor sucking, stupor, hypotonia, seizures –In the middle of the first week: hypertonia of extensor muscles, opisthotonus ， retrocollis, and fever –After the first week: hypertonia –Survivors: appeared with hypotonia, active deep tendon reflexes, obligatory tonic neck reflexes, delayed motor skills and after the first year, movement disorder

Clinical management Phototherapy Plasma or albumin Exchange transfusion Enzyme inducer: phenobarbital Original diseases treatment The other symptomatic treatment

Summery Almost all newborns have jaundice and the majority are transient or physiological Certain diseases causing neonatal jaundice have prolong and serious presentation Kernicterus is the most severe complication and has very poor outcome and sequelae

Thanks and questions?