Differential diagnosis of neonatal jaundices. Hemolytic disease of newborn. Lecturer: Sakharova Inna.Ye., M.D., Ph.D. Lecture plan: 1. Classification of neonatal jaundices. 2. Evaluation of jaundice severity. 3. Principles of the newborns management of different types of jaundices. 4. Complications of neonatal jaundices. 5. Treatment of neonatal jaundices. 6. Hemolytic disease of the newborn Neonatal jaundice (jaundice of newborns) вЂ“ appearance of a yellowish coloration of the skin, sclerae and/or mucouses of the infant because of serum bilirubin level increase. Classification of jaundices: I. In general jaundice should be distinguished on: вЂў вЂў physiological pathological. II. According to the time from birth there are: пЂ Early jaundice (< 36 hours of age) п‚· always pathological п‚· usually due to haemolysis, with excessive production of bilirubin п‚· babies can be born jaundiced with o very severe haemolysis o hepatitis (unusual) п‚· causes of haemolysis (decreasing order of probability) o ABO incompatibility o Rh incompatibility o sepsis п‚· Rare causes пЃЇ red cell enzyme defects e.g. G6PD deficiency пЃЇ red cell membrane defects, e.g., hereditary spherocytosis - Physiological (appears after 36 hours of age, usually on the 3-5 th day, lasts up to 14-th day of life) Total serum bilirubin concentration doesnвЂ™t exceed 205 mkmol/L (12 mg/dL). This type of jaundice can be complicated and uncomplicated, that is why observation and bilirubin level control are very important. Nota bene вЂ“ 1 mg/dL of bilirubin = 17,1 mkmol/L of bilirubin пЂ Prolonged (protracted) jaundice is present after 14 days of life in term newborns and after 21 days of life in premature infant. вЂў breast milk jaundice (diagnosis of exclusion, cessation of brest feeding not necessary) вЂў continued poor milk intake вЂў haemolysis вЂў infection (especially pre-natal) вЂў hypothyroidism пЂ Late jaundice which appears after 7-th day of life. вЂў It is necessary to perform careful inspection of the newborn to find the reason of this jaundice. Differential diagnostic of jaundices Criterion Type of jaundice Conjugated Appearance Hepatosplenomegaly Stool Hemolytic 2-3-rd day 1-st day вЂ” Mecha Parenchynical matous 1-2-nd week End of the 1-st week Urea Gradu+ ally Yellow Coloured Acholic Coloured or light Light yell. Coloured Dark Dark п‚ Bilirubin Indirect Anemia,reticulocytosis + вЂ” + Indirect + + Direct вЂ” вЂ” Both;direct вЂ” вЂ” Estimation of the risk of severe hyperbilirubinemia development (Bhutani). Kramer scale (jaundice appearance stages) Zone 1 TSB 58 mg/L 2 3 4 88 117 146 5 > 146 Criteria of the вЂњdangerousвЂќ jaundice of newborns (WHO, 2003) Age of newborn (in hours) 24 24-48 > 48 Localization of jaundice Any Extremities (zone 4) Feet, wrists (zone 5) Conclusion вЂњDangerousвЂќ jaundice The reasons of physiological jaundice (transient jaundice) are: пѓј increased production (1 gram of hemoglobin produces 35 mgr of bilirubin when hemolysed) пѓј decreased uptake and binding by liver cells пѓј decreased conjugation ( low activity of glucuronil transferase) пѓј decreased excretion пѓј increased enterohepatic circulation of bilirubin Principles of the management of patient with physiological jaundice Clinical features вЂў Appears not earlier than end of the second day of life, is present in the 1-2 zones only вЂў Active baby вЂў Liver and spleen not enlarged вЂў Light-yellow uria, normal urination, coloured stool Examination and treatment вЂў Transcutaneous bilirubinometry (level of skin bilirubin вЂў Adequate brest feeding вЂў Further observation for the child Principles of the management of patient with complicated physiological jaundice Examination and treatment In normal newbornвЂ™s state Appears not earlier than end of the second вЂў Estimate TSB level day of life, is present in вЂў Decide fototherapy the 3-4 zones necessitivity вЂў Adequate brest feeding May be worsening of newbornвЂ™s state вЂў Further observation for the child Liver and spleen may be enlarged In worsening of newbornвЂ™s state Light-yellow urine, normal urination, вЂў Immediate phototherapy coloured stool Clinical features вЂў вЂў вЂў вЂў Principles of the management of patient with early or вЂњdangerousвЂќ jaundice вЂў To start phototherapy immediately вЂў To estimate total and conjugated serum bilirubin concentration вЂў Baby's blood group, direct antiglobulin (Coombs') test (detects antibodies on the baby's red cells), and elution test to detect anti-A or anti-B antibodies on baby's red cells (more sensitive than the direct Coomb's test) вЂў Full blood examination, looking for evidence of haemolysis, reticulocytes level, unusually-shaped red cells, or evidence of infection Principles of the management of patient with prolonged (protracted) and late jaundices вЂў вЂў вЂў вЂў Examination and treatment To estimate total and conjugated serum bilirubin concentration (TSB and CSB) In hepatomegaly to estimate AlT, AsT Adequate brest feeding Further observation for the child Immediate hospitalization in the case of: вЂў Worsening of newbornвЂ™s state вЂў TSB > 11,7 mg/dL вЂў CSB > 1,9 mg/dL (> 20 % of TSB) вЂў Liver or spleen enlargement вЂў Dark urine and/or acholic stool Toxic action of unconjugated bilirubin in fullterm newborns appears in 18-20 mg/dL(in premature newborns вЂ“ in 12-14 mg/dL), it can lead to the bilirubin encephalopathy and kernicterus. Kernicterus is a preventable neurologic disorder caused by newborn jaundice that can result in cerebral palsy, mental development retardation, auditory processing problems (AN), gaze and vision abnormalities, and dental enamel hypoplasia. Bilirubin staining of brain tissue In newborns with jaundice there are specific clinical signs, which can appear in bilirubin encephalopathy. The early symptoms of brain injury are poor feeding, decreased alertness, alteration of muscle tone, and a high-pitched cry. Later symptoms of bilirubin toxicity include shrill cry, inability to feed, mild or deep stupor, abnormal or uncoordinated movements, and seizures. Risk Factors for High Bilirubin Levels: вЂў Blood group incompatibility вЂў Gestational age less than 37 weeks вЂў Previous sibling received phototherapy/family history of jaundice вЂў East Asian ethnicity вЂў Presence of bruising or cephalohematoma вЂў Exclusive breastfeeding, particularly if nursing is not going well and weight loss is excessive (> 10% of birth weight) Risk factors for kernicterus appearance: вЂў Asphyxia вЂў Acidosis вЂў Prematurity вЂў Acute hemolysis вЂў Not effective therapy of jaundice вЂў Hypoalbuminemia. American Academy of Pediatrics recommendations for healthy term newborns (TSB, mg/dL) Age, hours Consider Photo- Exchange photo- therapy transfusion if intensive therapy phototherapy fails Exchange transfusion and intensive photother apy 25-48 п‚і 12 п‚і 15 п‚і 20 п‚і 25 49-72 п‚і 15 п‚і 18 п‚і 25 п‚і 30 > 72 п‚і 17 п‚і 20 п‚і 25 п‚і 30 There are several types of phototherapy: - fiber-optical (using of special matress or diaper), - classic (ultra-violet lamps), - spotted (local) - intensive. Intensive phototherapy suggests at least two sources of light: photomattress and lamp. вЂў Intensive phototherapy should produce a decline of TSB of 1-2 mg/dl within 4-6 hours, and the TSB level should continue to fall. If this doesnвЂ™t occur, itвЂ™s considered a failure of phototherapy. Hemolytic disease of the newborn (HDN, erythroblastosis fetalis) п‚· Common causes for HDN - Rh blood group incompatibility - ABO blood group incompatibility п‚· Uncommon causes - Kell system antibodies presence п‚· Rare causes - Duffy system antibodies presence Clinical types of HDN: Icteric type is the most frequent type of jaundice. Clinical feature is jaundice of skin and mucoses. Anemic type is present in 10-20 % of newborns. Diagnostic criteria are paleness, HB level <120 g/L, haematocrit < 40% in birth. Hydropic type (hydrops foetalis) is the most severe type, approximately always is connected with Rh blood group incompatibilitiy. Clinical features are generalized edemas and anemia in birth. Mixed type. HDN diagnosis criteria: 1. 2. Family history of hemolitic disease. Generalized edemas, HB level <120 g/L, haematocrit < 40% in birth, reticulocytosis 3. Onset of jaundice before 24 hours, positive direct antiglobulin (Coombs') test. 4. Level of unconjugated bilirubin in umbilical blood > 2,9 (50 mkmol/L) mg/dL, bilirubin rise in serum > 0.5 mg/dL/hour (> 8,55 mkmol/L). 5. Changes in peripheral smear (microspherocyrosis, anisocytosis, terget cells). This photograph shows normal RBCs, damaged RBCs, and immature RBCs that still contain nuclei. Principles of the management of the newborn with hemolytic disease вЂў To start phototherapy immediately вЂў To estimate total and conjugated serum bilirubin concentration (TSB and CSB) вЂў To decide exchange blood transfusions necessitivity according to special tables вЂў In the case of intensive phototherapy fails after 4-6 hours to performe exchange blood transfusions (under the control of TSB according to special tables) Indications for exchange blood transfusions in term babies with HDN Factors Level of total bilirubin level in umbilical blood Bilirubin rise in serum (during phototherapy) - Rh incompatibility - ABO incompatibility Anemia in the first day of life Indexes > 80 mkmol/L в‰Ґ 7 mkmol/L в‰Ґ 10 mkmol/L РќbпЂј 100 g/Р», Ht <35% Indications for exchange blood transfusions in term babies with HDN continuation Factors Ratio of TSB (mkmol/L) and albumin (g/L) depending on the weight of baby < 1250 g 1250-1499 g 1500-1999 g 2000-2500 g > 2500 g Indexes Bilirubin mkmol/L Albumin g/L 6,8 8,8 10,2 11,6 12,2 In the case of Rh blood group incompatibility can be used Rh negative blood of the same group (with baby) or Rh negative packed red cells Рћ (I) in the plasma of AB (IV). In the case of ABO blood group incompatibility can be used the Rh same (with baby) packed red cells Рћ (I) in the plasma of AB (IV). In the case of both of Rh blood group incompatibility and ABO blood group incompatibility can be used Rh negative packed red cells Рћ (I) in the plasma of AB (IV).