Differential diagnosis of neonatal jaundices. Hemolytic disease of newborn.

Differential diagnosis of Differential diagnosis of neonatal jaundices.neonatal jaundices.

Hemolytic disease of newborn.Hemolytic disease of newborn.

Lecturer:

Prof. H.A. Pavlyshyn

Neonatal jaundice (jaundice of newborns) – 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:

• physiological • pathological. II. According to the time from birth there are: Early jaundice (< 36 hours of age) always pathological  usually due to haemolysis, with excessive production of bilirubin  babies can be born jaundiced with o    very severe haemolysis o    hepatitis (unusual)  causes of haemolysis (decreasing order of probability) o    ABO incompatibility o     Rh incompatibility o sepsis

- 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 doesn’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 – 1 mg/dL of bilirubin = 17,1 mkmol/L of bilirubin

Prolonged (protracted) jaundice is present after 14 days of life in term newborns and after 21 days of life in premature infant.

• breast milk jaundice (diagnosis of exclusion, cessation of brest feeding not necessary)

• continued poor milk intake • haemolysis  • infection (especially pre-natal) • hypothyroidism Late jaundice which appears after 7-th day of life.• It is necessary to perform careful inspection of the newborn to

find the reason of this jaundice.

Estimation of the risk of severe hyperbilirubinemia development (Bhutani).

Kramer scale (jaundice appearance stages)

Zone 1 2 3 4 5

TSB

mg/L

58 88 117 146 > 146

Criteria of the “dangerous” jaundice of newborns (WHO, 2003)

Age of newborn (in

hours)

Localization of jaundice

Conclusion

24 Any “Dangerous” jaundice

24-48 Extremities (zone 4)

> 48 Feet, wrists (zone 5)

Сomplications HDN

The reasons of physiological jaundice (transient jaundice) are:

increased production (1 gram of hemoglobin

produces 35 mgr of bilirubin when hemolysed) decreased uptake and binding by liver cells decreased conjugation ( low activity of glucuronil

transferase) decreased excretion increased enterohepatic

circulation of bilirubin

Principles of the management of patient

with physiological jaundice Clinical features

• Appears not earlier than end of the second day of life, is present in the 1-2 zones only

• Active baby• Liver and spleen not

enlarged• Light-yellow uria,

normal urination, coloured stool

Examination and

treatment• Transcutaneous bilirubinometry

(level of skin bilirubin

• Adequate brest feeding

• Further observation for the child

Principles of the management of patient with complicated physiological jaundice

Clinical features• Appears not earlier than

end of the second day of life, is present in the 3-4 zones

• May be worsening of newborn’s state

• Liver and spleen may be enlarged

• Light-yellow urine, normal urination, coloured stool

Examination and treatmentIn normal newborn’s state

• Estimate TSB level• Decide fototherapy

necessitivity• Adequate brest feeding• Further observation for the

childIn worsening of newborn’s

state• Immediate phototherapy

Principles of the management of patient with early or “dangerous” jaundice

• To start phototherapy immediately• To estimate total and conjugated serum bilirubin

concentration • 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)

• 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

jaundicesExamination 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:

• Worsening of newborn’s state

• TSB > 11,7 mg/dL• CSB > 1,9 mg/dL (> 20 %

of TSB)• Liver or spleen

enlargement• Dark urine and/or acholic

stool

Toxic action of unconjugated bilirubin in full-term newborns appears in 18-20 mg/dL(in premature newborns – 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

Risk Factors for High Bilirubin Levels:• Blood group incompatibility

• Gestational age less than 37 weeks • Previous sibling received phototherapy/family history of jaundice • East Asian ethnicity • Presence of bruising or cephalohematoma • Exclusive breastfeeding, particularly if nursing is not going well and weight loss is excessive (> 10% of birth weight)

Risk factors for kernicterus appearance:• Asphyxia• Acidosis• Prematurity• Acute hemolysis• Not effective therapy of jaundice• Hypoalbuminemia.

Preterm baby

Baby with asphyxia

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. 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 doesn’t occur, it’s considered a failure of phototherapy.

Hemolytic disease of the newborn (HDN, erythroblastosis fetalis)

 Common causes for HDN

- Rh blood group incompatibility

- ABO blood group incompatibility Uncommon causes - Kell system antibodies presence

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.     Family history of hemolitic disease.

2.     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

• To start phototherapy immediately

• To estimate total and conjugated serum bilirubin concentration (TSB and CSB)

• To decide exchange blood transfusions necessitivity according to special tables

• 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)