Neonatal Hyperbilirubinemia Visible jaundice: Adults: >2mg% Newborns: >6mg Up to 50% of all newborns may develop jaundice
Source of Bilirubin Metabolism of heme. 6-10 mg/kg/day. (adults 3- 4mg/kg/day) 1gr Hemoglobine produces 34mg of bilirubin 75%: from old RBCs released from RES 25%: from ineffective erythropoyesis, myoglobine, cytochromes, catalase, peroxidase.
Metabolism Heme Biliverdin + CO + Fe Heme Oxygenase + O2 Biliverdin reductase Indirect (unconjugated) bilirubin Binds to albumin in plasma
Conjugation Liver Uptake (binds to ligandin) Endoplasmic reticullum Liver Uptake (binds to ligandin) Endoplasmic reticullum Bilirubin Mono and diconjugated bilirubin Bilirubin Mono and diconjugated bilirubin UDPG-T Stool Beta glucuronidase Bacteria Excretion Gut Elimination Enterohepatic recirculation Urobilinoids Indirect bilirubin Liver
Jaundice: Physical examination Blanch skin with a finger Jaundice Significant when appears at palms or below knees. Significant when appears at palms or below knees. Transcutaneous bilirubinometer Bruising, cephalohematoma, others. Organomegaly
Dermal Zones of Jaundice After leaving RES bilirubin binds to albumin, initially with low affinity, thus bilirubin precipitates in the proximal parts of the body before it does it distally. So jaundice appears first proximally, and later distally.
Jaundice: Laboratory Total serum bilirubin Blood type, Rh, Coombs infant and mother Smear (morphology and reticulocytes) Hematocrit
Jaundice: Laboratory Antibody identification Direct bilirubin: When more than 2 weeks old or signs of cholestasis If prolonged: LFT, TORCH, sepsis work-up, metabolic, thyroid G6PD
Non Physiologic Jaundice Onset at < 24 hs Onset at < 24 hs Bilirubin over levels for phototherapy Bilirubin over levels for phototherapy Bilirubin rise > 0.5 mg%/hr Bilirubin rise > 0.5 mg%/hr Signs of underlying illness Signs of underlying illness Vomiting, lethargy, poor feeding, weight Vomiting, lethargy, poor feeding, weight Age > 8 days in term or 15 days in premature Age > 8 days in term or 15 days in premature
Non Physiologic Jaundice: Anamnesis Familial: G6PD, spherocytosis, metabolic, enzymes. Siblings: Immune, breast milk. Immune, breast milk.Pregnancy: Infections, drugs, diabetes. Delivery: Trauma, cord clumping, asphyxia.
Bilirubin toxicity: Disrupted BB barrier HyperosmolarityAnoxiaHypercarbiaPrematurity Cerebral Penetration: As free indirect bilirubin or bound when disrupted BBB
Bilirubin toxicity: Factors Unbound indirect bilirubin Unbound indirect bilirubin Albumin concentration Albumin concentration 1gr albumin binds 8.5mg bilirubin Displacement from albumin site FFA Drugs: Sulfonamides Correction of acidosis
Bilirubin toxicity: Kernicterus Basal ganglia Cranial nerve and cerebral nuclei Hippocampus Anterior horn of spinal cord Neuronal injury + yellow staining of brain incidence in hemolytic disease (especially RH) Localization
Bilirubin toxicity: Acute encephalopathy I) Hypotonia, lethargy, high pitched cry, poor suck II) Hypertonia of extensor muscles opistotonus, rigidity, oculogyric crises, retrocollis III) Return of hypotonia after 1 week
Bilirubin toxicity Healthy full-term infants: Abnormality in ABR Hypotony: reverses with bilirubin levels Very rarely kernicterus Low birth weight infants: Damage most probably due to accompanying factors than to high bilirubin. Damage most probably due to accompanying factors than to high bilirubin.
Breast Feeding Jaundice Bilirubin after 4 days of age. Healthy infants Resolves after holding breast milk for 1-2 days Presentation Early: 2-4 days of age Late: after 4 days of age
Breast Feeding Jaundice: Mechanism Interference with hepatic conjugation Beta glucuronidase in milk Reduced bacterial colonization of gut Caloric intake intestinal motility recirculation FFA suggested to reduce bilirubin metabolism
Treatment Options for Jaundiced Breast-fed Infants
Isoimmune hemolytic disease of the newborn Rh, or minor types (Kell, Duffy, E, C,c) 15% of people are Rh- Coombs + Maternal sensitization d/t previous pregnancy, transfusion, amniocentesis, abortion
IHDN: Pregnancy Management Coombs titers >1/16 or previous history of severe disease Amniocentesis for optical density High levels, and clinical signs of hydrops Intrauterine transfusion Intraperitoneal, intravascular or intracardiac Repeated transfusions switched fetal blood type
IHDN: Newborn Management Check immediately after birth HematocritBilirubin Blood type 50% will only need phototherapy 24% will be anemic and cord bilirubin >4mg% exchange transfusion
IHDN: Prevention Anti D (Rh) immune globulin indications At 28 weeks At 28 weeks within 72 hours since birth. within 72 hours since birth. Procedures or suspected transplacental hemorrhage.
ABO hemolytic disease of the newborn 15% of pregnancies mother O infant A or B 20% will develop significant jaundice 10% will need phototherapy. Presentation: Early jaundice (<24hs of life) Many times Combs -, but there are antibodies Blood smear: spherocytes
Treatment: Phototherapy Bilirubin best absorbs light at 450 m. The best is to provide it with blue light. White range: 380-700 m also adequate. Irradiation generates photochemical reaction in the extravascular space of the skin A higher illuminated area increases effectiveness
Treatment: Phototherapy Mechanism Photoisomerization: Natural Isomer 4Z,15Z 4Z,15E hydrosoluble blood biliar secretion (unconjugated) Slow excretion and fast reisomerization reabsorbed. Slow excretion and fast reisomerization reabsorbed. Photooxydation: Small polar products. Slow
Treatment: Phototherapy mechanism Structural isomerization: Ciclization to lumirubin (irreversible) bile and urine Fast excretion not reabsorption. Related to dose of phototherapy (intensity of light)
Treatment: Phototherapy mechanism BilirubinLumirubin Main Pathway
Phototherapy: Technique Fluorescents,spots or biliblankets More than 5 w/cm2 at 425-475 m Naked, covering eyes Increase fluids 10-20% Check bilirubin every 12-24hs Stop: 13 ± 1mg% in term, 10 ± 1mg% in preterm Check 12-24hs later for rebound
Phototherapy: Side effects Increased water loss Diarrhea Retinal damage Bronze baby, tanning Mutations in DNA? shield scrotum Disturb of mother-infant interaction.
Exchange transfusion: Technique Irradiated PC < 7 days + FFP. Warmed Double of blood volume. Open incubator, monitors Route UV: push-pull, over > 1hr Artery-vein: Isovolumetric
Exchange transfusion: Complications Bleeding Thrombocytopenia, loss of factors. Thrombocytopenia, loss of factors.InfectionsHemolysisGVHDOther Fever, hypothermia, NEC?
Neonatal Jaundice: Other treatments Phenobarbital: conjugation Oral agar: enterohepatic circulation Metalloporphyrins: inhibit bilirubin production. Competitors of heme oxygenase IVIGg: inhibits hemolysis. Binds to FC receptor of reticuloendothelial cells
Management of Hyperbilirubinemia in the Healthy Term Newborn*
Diagnostic approach to neonatal jaundice Jaundice Measure Bilirubin Non physiologic Blood type, Rh, Coombs Hematocrit, Smear, Reticulocytes Increased direct bili Increased indirect bili Coombs + Coombs - ABORh minor group SepsisTORCH Biliary Atresia Cholestasis Inspissated Bi HepatitisCFTyrosinosisGalactosemia or ¯Hematocrit Hematocrit Polycytemia RC shape Normal Abnormal BleedingsEnterohepaticMetabolicDrugsOther Specific and non specific Abnormalities