APPROACH TO A CHILD WITH JAUNDICE

S.BALASANKAR

2009 MBBS

APPROACH TO A CHILD WITH JAUNDICE

S.BALASANKAR2009 MBBS

JAUNDICE

Jaundice is the visible manifestation of increased level of bilirubin in the body.

It is not a disease rather a symptom of diseases.

In adults sclera appears jaundiced when serum bilirubin exceeds 2 mg/dl.

However it is difficult to see sclera in newborn due to difficulty in opening eye. But in new born it is very easy to see jaundice in skin.

BURDEN

Important problem in the 1st week of life.Almost all neonates (60% Term and 80%

Preterm) will have bilirubin > 5 mg/dl in the 1st week of life and become visibly jaundiced, vast majority being benign

Some of the term babies (8 to 9%) have levels exceeding 15 mg/dl in 1st 7 days of life.

High bilirubin level is toxic to the developing CNS.(KERNICTERUS; Bilirubin≥25mg/dl)

BILIRUBINEnd product of hemoglobin metabolism

that is excreted in bile.In neonates -75% : from catabolism of circulating

RBCs -25% :*from ineffective erythropoiesis (bone marrow) *from turnover of heme

proteins & free heme( liver).

Hyperbilirubinemia -Direct( Conjugated) -Indirect( Un-conjugated)

Conjugated Hyperbilirubinemia is present, * >20% of total bilirubin is conjugated * >2mg/dl is conjugated

If neither criteria is met, hyperbilirubinemia is classified as Un-conjugated.

NEONATAL JAUNDICE

Jaundice after 1 week:

a) Prolonged direct Jaundice› Neonatal hepatitis (common)› Extra-hepatic biliary atresia› Breast milk jaundice› Metabolic disorders› Intra-hepatic biliary atresia› Amino acid toxicity› Inspissated bile syndrome

(uncommon)

b) Prolonged Indirect Jaundice

> Criggler Najjar Syndrome> Breast milk jaundice> Hypothyroidism> Pyloric stenosis> Ongoing hemolysis, malaria

CLINICAL CLASSIFICATION:

PHYSIOLOGICAL JAUNDICE

PATHOLOGICAL JAUNDICE

PHYSIOLOGICAL JAUNDICE:

• In new born babies bilirubin metabolism is immature which results in the occurrence of hyperbilirubinemia in the first few days of life. Also there is increased bilirubin load on the hepatic cell due to physiological polycythemia.

Immaturity could be at various steps of bilirubin metabolism like:

Defective uptake from plasma into liver cell( deficiency of LIGANDIN)

Defective conjugation( UDP-glucoronosyl transferase: <1% of adult activity during the first 10 days of life)

Decreased excretion Increased entero-hepatic circulation

Increased Bilirubin production:

Larger circulating red blood cell volume

Shortened RBC lifespan (70-90 days vs 120 days in adult)

Substantial production from other sources

Characteristics:

First appears between 24-72 hours of age

Maximum intensity seen on 4-5th day in term and 7th day in preterm neonates

Does not exceed 15 mg/dlClinically undetectable after 14 days.No treatment is required but baby

should be observed closely for signs of worsening jaundice.

PATHOLOGICAL JAUNDICEPresence of any of the following signs denotes that the jaundice is pathological.

Clinical jaundice detected before 24 hours of age

Rise in serum total bilirubin by more than 5 mg/dl/ day (>5mg/dl on first day , 10 mg/dl on second day and 12- 13 mg/dl thereafter in term babies)

Serum bilirubin more than 15 mg/dlClinical jaundice persisting beyond 14

days of lifeClay/white colored stool and/or dark

urine staining the nappy yellowDirect bilirubin >2 mg/dl at any time.

Treatment is required in the form of phototherapy or exchange blood transfusion. One should investigate to find the cause of pathological jaundice.

It can be

Overproduction Hyperbilirubinemia

Under-secretion Hyperbilirubinemia

Overproduction Hyperbilirubinemia:

Blood group incompatibilitiesMaternal-fetal or feto-fetal transfusionsNon Immune Hemolytic anemiasStructurally Abnormal Red cellsExtra-vascular Hemolysis

Blood Group Incompatibilities:

Rh negative mother & Rh positive infant

ABO incompatibilities

Strongly considered if there is jaundice in the first 24 hours of life

Non-Immune Hemolytic Anemias:

1. G6PD Deficiency: Deficiency-decreased NADPH-

decreased reduced Glutathione –decreased protection of RBCs from oxidants-hemolysis.

2. Excess of Vitamin K given IM

Structurally Abnormal RBCs:

Spherocytosis

Pyknocytes ( irregular borders)

Under-secretion Hyperbilirubinemia:

Enzymatic Deficiency( Glucoronyl transferase)

Hormonal suppression (Breast milk jaundice)

Inhibition of conjugationHepatic cell injury due to InfectionsSubstrate deficiency (hypoglycemia)Mechanical obstruction (biliary atresia)

Hormonal Suppression:

Pregnandiol present in maternal breast milk suppresses bilirubin conjugation.

Breast feeding may be stopped and restarted in a period of 48hours.

Thyroxine Deficiency:

Thyroxine increases the activity of Glucoronyl transferase which promotes conjugation of bilirubin.

Inhibition of Conjugation:

Sulfonamides and Vitamin K results in competitive conjugation inhibition of bilirubin.

GALACTOSEMIA: Absent or deficient Galactose 1-

phosphoate uridyl transferase which is needed in glucoronidaton of indirect bilirubin.

APPROACH

HISTORYMaternal and Perinatal History:Delivery at period of gestation,

Postnatal age in hours.Maternal illness during pregnancy which

also includes diabetes; drug use.Previous history of malaria.Traumatic delivery, delayed cord

clamping, oxytocin use.Birth asphyxia, delayed feeding, delay

in meconium passage.

Family history of jaundice, liver disease

Previous sibling with jaundice for blood group incompatibility.

Kernicterus: Lethargy, poor feeding, and hypotonia. Some advanced signs are seizures, retrocollis, paralysis of upward gaze and shrill cry.

Breast feeding.

ON EXAMINATION:Baby lethargic, poor feeding, temperature instability, with apnea: Sepsis

Small for gestation: polycythemia

Cataract, rash: TORCH infections

Extra vascular bleed: Cephalhematoma

Pallor: hemolysis, blood loss

Petechiae: sepsis, TORCH infections.

Hepatosplenomegaly: Rh-isoimmunization, sepsis, TORCH infections.

Dysmorphic features, congenital heart disease (pulmonary stenosis), Intra-hepatic biliary atresia :Alagille syndrome

HOW DO YOU LOOK FOR ICTERUS?

1. Dermal staining :progresses from head to toeExamined in good day light skin of

forehead, chest, abdomen, thigh, legs, palms, and soles.

Blanched with digital pressure and the underlying color of the skin and subcutaneous tissue should be noted.

2. Trans-cutaneous bilirubinometer .

Clinical Jaundice

Measure Bilirubin

> 12 mg/dl and infant < 24 hr old

Fraction of Bilirubin

Indirect

Direct

< 12 mg/dl and infant > 24 hr old

Follow bilirubin level

Direct bilirubin

Evaluate for treatable causes 1.Infections-blood, urine culture, VDRL. 2.Metabolic disorders-urine reducing substances, serum amino acids,T4,TSH.If no abnormality ;screen for Identifiable causes *α-1 antitrypsin deficiency *cystic fibrosis *congenital viral infectionsIf no abnormality; evaluate for anatomical abnormalities *Stool color *USG *Hepato-biliary scintigraphy *Liver biopsy

Indirect

High(>65%)Polycythemia

Hematocrit

Low/Normal

Reticulocyte count

Blood TypeCoomb’s test

PlateletsEvaluate smear

Normal Reticulocyte countLook for evidence of,

*Infections-blood, urine culture*Enclosed hemorrhage

*Congestive cardiac failure*Hypoxia

*Hypothyroidism*Drugs/toxins

None found

Familial Disorders*Criggler Najjar

*Gilbert

Elevated Reticulocyte Count

Consider:1.Iso-immunization

2.Erythrocyte membrane defect

3.Erythrocyte enzyme defect

MANAGEMENT

PHYSIOLOGICAL JAUNDICE

Explain about benign nature of the disease

Encourage to breastfeed frequently & exclusively

Ask Mother to bring baby back if baby looks deep yellow or palms & soles have yellow staining.

PATHOLOGICAL JAUNDICE

Mainly 2 modalities of Treatment:

PHOTOTHERAPY

EXCHANGE TRANSFUSION

PHOTOTHERAPY

Mainstay of treatmentUnder blue-green light(460-490nm),

insoluble bilirubin is converted into soluble isomers that can be excreted in urine & feces.

To be effective, bilirubin must be present in skin; hence nor role for prophylactic phototherapy

Term & near term neonates:

The American Academy of Pediatrics (AAP) has laid down criteria for managing babies with elevated serum bilirubin based on gestational age and other risk factors( hemolysis , asphyxia, low albumin level, hypothermia)

MECHANISMS:

CONFIGURATIONAL ISOMERIZATION

STRUCTURAL ISOMERIZATION

PHOTO OXIDATION

Configurational Isomerization

Z-isomer converted to E-isomerReaction is instantaneous but

reversible.After exposure of 8-12 hrs, this

constitutes about 25% of the TSB which is non-toxic.

Excreted slowly from the body; hence not a major mechanism for decrease in TSB.

Structural Isomerization

Irreversible reactionBilirubin is converted into Lumirubin.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

Minor reaction

Administering Phototherapy:

Optimum ambient room temperature( 25-28celcius) to prevent hypothermia.

Remove all clothes of baby except diaper

Cover baby’s eyes with an eye patch(to prevent retinal degeneration) ensuring that it does not block the baby’s nostrils.

Place the baby under the lights in a cot if weight is more than 2kg or in an incubator if baby is small(<2kg)

Keep the distance between the baby & the light 30-45cm.

Ensure optimum breastfeeding as intermittent feeding sessions.

Monitor temperature of the baby every 2-4hrs

Measure TSB every 12-24hrs.Discontinue, once 2 TSB values 12hr

apart fall below current age-specific cut-offs.

Monitor for rebound bilirubin rise within 24hrs.

Complications of Phototherapy:Loose stoolsErythematous macular rashPurpuric rash associated with transient

porphyrinemiaOver-heatingDehydrationBronze baby syndrome

Bronze Baby Syndrome

Intense grey-brown discoloration of the skin, serum, and urine, especially in premature infants; when phototherapy was used to reduce hyperbilirubinemia. Pre-existing hepatic disease is suspected as a cause of the jaundice and may have prevented the biliary excretion of the photo oxidation products of bilirubin; their retention resulted in the bronze discoloration.

EXCHANGE TRANSFUSION

Double Volume Exchange Transfusion (DVET) : 160-180ml/kg; is to be performed if TSB levels reach age-specific cut-offs or if the infant shows signs of bilirubin encephalopathy, irrespective of TSB levels.

If baby shows signs of cardiac decompensation at birth, partial exchange transfusion with 50ml/kg of packed red cells should be done to quickly restore oxygen carrying capacity of blood.

Umbilical venous route.

FOLLOWUP

Babies with serum bilirubin>20 mg/dl & those who required ET should be kept under follow-up in high-risk clinic for neuro-developmental outcome.

Hearing assessment should be done at 3months of age.

PREVENTIONAnte-natal screening to detect Rh iso-

immunization & prompt administration of Anti D after first obstetric event.

Ensure adequate breast feeding.Educate parent about danger signs to

ensure immediate checkup.Follow-up high risk babies( large

cephalo-hematoma, family history of jaundice) for 2-3 days of discharge.

JAUNDICE IN THE CHILD & ADOLESCENT

HISTORY:Age at onset of symptoms. E.g.:

Wilson’s disease commonly manifests in pre-adolescents & adolescents.

Past/present use of any drugsH/o of blood transfusion/ dialysisExposure to viral hepatitisAny h/o of chronic illness;

hemoglobinopathies.Family h/o of inheritable disorders;

Wilson’s.

DDs of Un-conjugated Hyperbilirubinemia:Auto-immune hemolytic anemiasDrug induced hemolytic anemiasErythrocyte membrane defectsErythrocyte enzyme defectsHemoglobinopathiesCongestive cardiac failureSepsisGilbert syndrome.

DDs of Conjugated Hyperbilirubinemia:1. Obstructive Gall stones Primary sclerosing cholangitis Choledochal cyst Tumors2. Infections Hepatitis A, B, C, D, E EBV,CMV Varicella zoster HIV Leptospirosis

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