Jaundice

Jaundice PEDIATRICS

1. JAUNDICE PEDIATRICS G.ERIC™ MD4

2. Jaundice is an important problem in the first week of life. High bilirubin levels may be toxic to the developing central nervous system and may cause neurological impairment even in term newborns. Nearly 60% of term newborn becomes visibly jaundiced in the first week of life. In most cases, it is benign and no intervention is required. Approximately 5-10% of them have clinically significant jaundice requiring use of phototherapy or other therapeutic options

3. Physiological jaundice represents physiological immaturity of the neonates to handle increased bilirubin production. Visible jaundice usually appears between 24-72 hr of age. Total serum bilirubin (TSB) level usually peaks by 3 days of age and then falls in term neonates. TSB levels are below the designated cut-offs for phototherapy. It does not require any treatment. Physiological Versus Pathological Jaundice

4. Pathological jaundice is referred to as an elevation of TSB levels to the extent where treatment of jaundice is more likely to result into benefit than harm. There is no clear cut demarcation between pathological and physiological jaundice. TSB levels have been arbitrarily defined as pathological if it exceeds 5 mg/ dl on first day, 10 mg/ dl on second day, or 15 mg/ dl thereafter in term babies. Such jaundice warrants investigation for the cause and therapeutic intervention such as phototherapy. Appearance of jaundice within 24 hr, TSB levels above the expected normal range, presence of clinical jaundice beyond 3 weeks and conjugated bilirubin (dark urine staining the nappy) would be categorized under this category.

5. Exclusively breastfed infants have a different pattern of physiological jaundice as compared to artificially-fed babies. Jaundice in breastfed babies usually appears between 24-72 hr of age, peaks by 5-15 days of life and disappears by the third week of life. One-third of all breastfed babies are detected to have mild clinical jaundice in the third week of life, which may persist into the 2nd to 3rd month of life in a few babies. This increased frequency of jaundice in breastfed babies is not related to characteristics of breast milk but rather to inadequate breastfeeding (breastfeeding jaundice). Ensuring optimum breastfeeding would help decrease this kind of jaundice Breastfeeding Jaundice

6. Approximately 2-4% of exclusively breastfed term babies have jaundice in excess of 10 mg/ dl beyond third-fourth weeks of life. These babies should be investigated for prolonged jaundice. A diagnosis of breast milk jaundice should be considered if this is unconjugated (not staining nappies); and other causes for prolongation such as inadequate feeding, continuing hemolysis , extravasated blood, G6PD deficiency and hypothyroidism have been ruled out. Mothers should be advised to continue breastfeeding at frequent intervals and TSB levels usually decline over a period of time. Some babies may require phototherapy. Breastfeeding should not be stopped either for diagnosis or treatment of breast milk jaundice Breast Milk Jaundice

7. Originally described by Kramer, dermal staining of bilirubin may be used as a clinical guide to the level of jaundice. Dermal staining in newborn progresses in a cephalocaudal direction. The newborn should be examined in good daylight. The skin of forehead, chest, abdomen, thighs, legs, palms and soles should be blanched with digital pressure and the underlying color of skin and subcutaneous tissue should be noted. Serum levels of total bilirubin are approximately 4-6 mg/dl (zone 1), 6-8 mg/dl (zone 2), 8-12 mg/dl (zone 3), 12-14 mg/dl (zone 4) and >15 mg/dl (zone 5) Clinical Estimation

8. Dermal zones for estimation of total serum bilirubin levels

9. Yellow staining of palms and soles is a danger sign and requires urgent serum bilirubin estimation and further management. In general, the estimation of bilirubin levels by dermal zones is unreliable particularly at higher TSB levels, after phototherapy and when it is carried out by an inexperienced observer. Total serum bilirubin can be assessed non invasively by a transcutaneous handheld device.

10. Measurement of Billrubin Levels Newborns detected to have yellow discoloration of the skin beyond the legs, or when their clinically assessed TSB levels approach phototherapy range, should have lab confirmation of total serum bilirubin . TSB assessment has a marked interlaboratory variability.

11. Important causes of jaundice in neonates include: i . Hemolytic: Rh incompatibility, ABO incompatability , G6PD deficiency, thalassemias , hereditary spherocytosis ii. Non-hemolytic: prematurity, extravasated blood, inadequate feeding, polycythernia , idiopathic, breast milk jaundice Risk factors for development of severe hyper bilirubinernia include: i . Jaundice observed in the first 24 hr ii. Blood group incompatibility with positive direct antiglobulin test, other known hemolytic disease (e.g. G6PD deficiency). iii. Gestational age 35-36 weeks. iv. Previous sibling received phototherapy. v. Cephalohematoma or significant bruising. vi. If breastfeeding is inadequate with excessive weight loss Causes

12. All the neonates should be visually inspected for jaundice every 12 hr during initial 3 to 5 days of lifeTranscutaneous bilirubin ( TcB ) can be used as an aid for initial screening of infants. Visual assessment (when performed properly) and TcB have reasonable sensitivity for initial assessment of jaundice. As a first step, serious jaundice should be ruled out. Phototherapy should be initiated if the infant meets the criteria for serious jaundice. Total serum bilirubin should be determined subsequently in these infants to determine further course of action. Approach to a Jaundiced Neonate

13. Investigations The aim of performing investigations is to confirm the level of jaundice, identify the cause and follow response to treatment. First line • Total serum bilirubin (and its fractions, if jaundice is prolonged or there is yellow staining of nappies): All cases with suspected pathological levels either clinically or by trancutaneous measurements need confirmation by blood examination of serum bilirubin levels. • Blood groups of mother and baby (if the mother is 'O' or Rh negative): detects any incompatibility • Peripheral smear: evidence of hemolysis Management

14. Second line • Direct Coombs test: detects presence of antibody coating on fetal RBC • Hematocrit : decreased in hemolysis • Reticulocyte count: increased in hemolysis • G6PD levels in RBC • Others: sepsis screen; thyroid function test; urine for reducing substances to rule out galactosernia ; specific enzyme/ genetic studies for Crigler-Najjar , Gilbert and other genetic enzyme deficiencies

15. Physiological Jaundice The parents should be explained about the benign nature of jaundice. The mother should be encouraged to breastfeed frequently and exclusively. Mother should be told to bring the baby to the hospital if the baby looks deep yellow or palms and soles have yellow staining. There is no use to expose the baby to direct sunlight to reduce hyperbilirubinemia . Any newborn discharged prior to 72 hr of life should be evaluated again in the next 48 hr for assessment of adequacy of breastfeeding and progression of jaundice.

16. Prolonged Jaundice Beyond 3 Weeks This is defined as persistence of significant jaundice (10 mg/dl) beyond three weeks in a term baby. The common causes include inadequate feeding, breast milk jaundice, extravasated blood ( cephalohematoma ), ongoing hemolytic disease, G6PD deficiency and hypothyroidism. One should rule out cholestasis by noting the urine and stool color and checking the level of direct bilirubin . If the baby has dark urine or significant jaundice, investigations should be initiated to rule out: i . Cholestasis (stool color, urine color, direct and indirect bilirubin levels) ii. Ongoing hemolysis , G6PD screen iii. Hypothyroidism iv. Urinary tract infectionA

17. Phototherapy Phototherapy remains the mainstay of treating hyperbilirubinemia in neonates. Photocopy is highly effective and carries an excellent safety track record of over 50 yr. It acts by converting insoluble bilirubin ( unconjugated ) into soluble isomers that can be excreted in urine and feces. Many review articles have provided detailed discussion on phototherapy related issues. The bilirubin molecule isomerizes to harmless forms under blue-green light (460-490 nm); and the light sources having high irradiance in this particular wavelength range are more effective than the others.

18. For phototherapy to be effective, bilirubin needs to be present in skin so there is no role for prophylactic phototherapy. Phototherapy acts by several ways: Configurational isomerization : Here the Z-isomers of bilirubin are converted into E-isomers. The reaction is instantaneous upon exposure to light but reversible as bilirubin reaches into the bile duct. After exposure of 8-12 hr of phototherapy, this constitutes about 25% of TSB, which is nontoxic. Since this is excreted slowly from body this is not a major mechanism for decrease in TSB. • Structural isomerization : This is an irreversible reaction where the bilirubin is converted into lumirubin . The reaction is directly proportional to dose of phototherapy. This product forms 2-6% of TSB which is rapidly excreted from body thus is mainly responsible for phototherapy induced decline in TSB. • Photo oxidation : This is a minor reaction, where photo-products are excreted in urine.

19. A jaundiced baby receiving phototherapy with two overhead units and biliblanket pad (arrow)

20. Monitoring and stopping phototherapy. Monitor temperature of the baby every 2 to 4 hr. Measure TSB level every 12 to 24 hr. Discontinue phototherapy once two TSB values 12 hr apart fall below current age specific cut offs. The infant should be monitored clinically for rebound bilirubin rise within 24 hr after stopping phototherapy for babies with hemolytic disorders.

21. Exchange Transfusion Double volume exchange transfusion (DVET) should be performed if the TSB levels reach to age specific cut-off for exchange transfusion (Fig. 8.52 and Table 8.25) or the infant shows signs of bilirubin encephalopathy irrespective of TSB levels. Indications for DVET at birth in infants with Rh isoimmunization include: i . Cord bilirubin is 5 mg/ dl or more ii. Cord Hb is 10 g/ dl or less At birth, if a baby shows signs of hydrops or cardiac decompensation in presence of low PCV (<35%), partial exchange transfusion with 50 ml/kg of packed red blood cells should be done to quickly restore oxygen carrying capacity of blood. The ET should be performed by pull and push technique using umbilical venous route. Umbilical catheter should be inserted just enough to get free flow of blood.

22. Followup Babies with serum bilirubin ;?.20 mg/dl and those who require exchange transfusion should be kept under followup in the high-risk clinic for neurodevelopmental outcome. Hearing assessment (BERA) should be done at 3 months of age. With prompt treatment, even very elevated serum bilirubin levels within the range of 25 to 29 mg/ dl are not likely to result in longterm adverse effects on neurodevelopment.

23. Prevention • Antenatal investigation should include maternal blood grouping. Rh positive baby born to a Rh negative mother is at higher risk for hyperbilirubinemia and requires greater monitoring. Anti D ( RhoGam ) injection after first obstetrical event ensures decreased risk of sensitization in future pregnancies. • Ensuring adequate breastfeeding • Parent education regarding danger signs should include yellowish discoloration below knees and elbows or persistent jaundice beyond 15 days as reason for immediate checkup by health personnel. • High risk babies such as ones with large cephalohematoma or family history of jaundice should be followed up after 2-3 days of discharge