Neonatal Jaundice (Hyperbilirubinemia) 单补技大字同济等学西
Neonatal Jaundice (Hyperbilirubinemia)
Introduction all babies develop elevated serum bilirubin(SBR) levels, to a greater or lesser degree, in the first week of life. This is due to: increased production(accelerated rBC breakdown) decreased removal (liver enzyme insufficiency) Increased reabsorption(enterohepatic circulation)
Introduction All babies develop elevated serum bilirubin (SBR) levels, to a greater or lesser degree, in the first week of life. This is due to: ➢ increased production (accelerated RBC breakdown); ➢ decreased removal (liver enzyme insufficiency) ➢ Increased reabsorption (enterohepatic circulation)
Introduction >60%of infants become clinically jaundiced in 1st wk Bili levels peak at 3 5 days in full term infants >1/6 of formula fed infants have bili levels over 12 1/3 of breast fed infants have bili levels over 12 Over 80% of all infants with bili levels>129 mg/dl in the first four days of life are breast fed
Introduction ➢ ~60% of infants become clinically jaundiced in 1 st wk ➢ Bili levels peak at 3~5 days in full term infants ➢ ~1/6 of formula fed infants have bili levels over 12 ➢ ~1/3 of breast fed infants have bili levels over 12 ➢ Over 80% of all infants with bili levels>12.9 mg/dl in the first four days of life are breast fed
Bilirubin metabolism derived from the catabolism of proteins that contain heme the most important source is the breakdown of Hb from rbC native bilirubin is relatively insoluble in water at physiologic ph, but it is very lipid soluble bilirubin circulates bound to albumin in equilibrium with its unbound or free fraction the unbound fraction that readily crosses the blood-brain barrier and results in neurotoxicity
Bilirubin Metabolism ➢ derived from the catabolism of proteins that contain heme ➢ the most important source is the breakdown of Hb from RBC ➢ native bilirubin is relatively insoluble in water at physiologic pH, but it is very lipid soluble ➢ bilirubin circulates bound to albumin in equilibrium with its unbound or "free" fraction ➢ the unbound fraction that readily crosses the blood-brain barrier and results in neurotoxicity
Bilirubin metabolism Bilirubin is made more water-soluble in the liver by conjugation with glucuronic acid to form conjugated"or direct-reacting bilirubin, then cleared through the bile into the intestines and out through the feces Phototherapy works by producing photoisomers of bilirubin that are more water soluble, and that can be cleared directly in bile or urine without conjugation in the liver “ enterohepatic circulation”:β- glucuronidase in the gut hydrolysis the conjugated bilirubin into unconjugated bilirubin. and reabsorbed into liver
Bilirubin Metabolism ➢ Bilirubin is made more water-soluble in the liver by conjugation with glucuronic acid to form "conjugated" or "direct-reacting" bilirubin, then cleared through the bile into the intestines and out through the feces. ➢ Phototherapy works by producing photoisomers of bilirubin that are more water soluble, and that can be cleared directly in bile or urine without conjugation in the liver. ➢ “enterohepatic circulation”: b-glucuronidase in the gut hydrolysis the conjugated bilirubin into unconjugated bilirubin, and reabsorbed into liver
Characteristics of neonatal Bilirubin metabolism Increased bilirubin production 8.8mg/kg daily vs 3.8mg/kg in adults Insufficiency of bilirubin transportation acidosis, hypoalbuminemia Immature of liver function lower ingestion(y, z protein); lower UDPGT activity Increased“ enterohepatic circulation” lower in gut bacteria; higher B-glucuronidase activity
Characteristics of Neonatal Bilirubin Metabolism ➢ Increased bilirubin production 8.8mg/kg daily vs 3.8mg/kg in adults ➢ Insufficiency of bilirubin transportation acidosis, hypoalbuminemia ➢ Immature of liver function lower ingestion (y, z protein); lower UDPGT activity ➢ Increased “enterohepatic circulation” lower in gut bacteria; higher b-glucuronidase activity
"Physiological Jaundice Seen in 60% of term infants and over 80% of preterm Serum values reaches maximum at 6mg/dl on 4.5d in term and 10-12 mg/dl on 5-7d in premature infants Jaundice declines gradually, reaching normal values within 2 wks in term, and 34w(1-2m)in preterm Causes no damage in term infants Up limit for abnormal? Undefined (Term <12mg/dl, or term<13, preterm<15mg/dI)
“Physiological” Jaundice ➢ Seen in 60% of term infants and over 80% of preterm ➢ Serum values reaches maximum at 6mg/dl on 4~5d in term and 10~12mg/dl on 5~7d in premature infants ➢ Jaundice declines gradually, reaching normal values within 2 wks in term, and 3~4w (1~2m) in preterm ➢ Causes no damage in term infants Up limit for abnormal? Undefined (Term <12mg/dl, or term<13, preterm<15mg/dl)
Factors likely to make “ physiological/ jaundice” worse prematurity bruising cephalohematoma polycythaemia delayed passage of meconium breast feeding certain ethnic groups, esp Chinese
Factors likely to make “physiological jaundice” worse ➢ prematurity ➢ bruising ➢ cephalohematoma ➢ polycythaemia ➢ delayed passage of meconium ➢ breast feeding ➢ certain ethnic groups, esp Chinese
Characteristics of Pathological Jaundice Jaundice appears within 24 hrs of life Severe jaundice: SBR>12-15mg/dl, or >5mg/dl/day Sustained jaundice(term>2w, preterm>4w Recurrence of jaundice Increased serum conjugated bilirubin(1.5-2 mg/dI)
Characteristics of Pathological Jaundice ➢ Jaundice appears within 24 hrs of life ➢ Severe jaundice: SBR>12~15mg/dl, or >5mg/dl/day ➢ Sustained jaundice (term>2w, preterm>4w ) ➢ Recurrence of jaundice ➢ Increased serum conjugated bilirubin (>1.5~2mg/dl)
Pathological Jaundice Infectious diseases Neonatal hepatitis(Torch infection) Neonatal septicemia Non-infectious diseases Hemolytic diseases Biliary atresia Breast milk jaundice Genetic metabolic diseases: G6PD, al-antitrypsin, CF Drugs induced: vitamin K3, K4
Pathological Jaundice ➢ Infectious diseases • Neonatal hepatitis (Torch infection) • Neonatal septicemia ➢ Non-infectious diseases • Hemolytic diseases • Biliary atresia • Breast milk jaundice • Genetic metabolic diseases: G6PD, a1-antitrypsin, CF • Drugs induced: Vitamin K3, K4