Neonatal Jaundice

Day 1 of life ( < 24 hours) Day 2 – day 21 (3rd week)Prolonged or Persistent

Neonatal Jaundice ( > 3 weeks)

Always pathological Never physiological ↑↑ chance of Hemolytic DDx

[1] Physiological: Breast Feeding:

(day 3 – 7) not receiving enough milk Breast Milk: receiving enough milk

[2]Pathological:Usually conjugated but it may start unconjugated then conjugated.

5 – 10 % of newborn infants are still jaundiced at more than 3 weeks of age.

This is usually unconjugated hyperbilirubinemia , which resolves shortly after wards.

Pathological is "conjugated" or it might be "unconjugated" thenconjugated caused by liver disease.

Causes:

Hemolytic disorders:Enzyme defect: Rh incompatibility ABO incompatibility G6PD deficiency

Cell membrane defect: Hereditary

Spherocytosis

Congenital Infection

Causes:

- Physiological jaundice- Breast milk jaundice- Infection, e.g. UTI- Hemolysis, e.g. G6PD deficiency, ABO incompatibility- Bruising- Polycythemia- Crigler-Najjar $

Causes:

Unconjugated: Physiological or

breast milk jaundice Infection (particularly

UTI) Hypothyroidism Hemolytic anemia High gastrointestinal

obstruction

Conjugated: Bile duct obstruction Neonatal hepatitis

Conjugated hyperbilirubinemia = direct bilirubin > 20% of total.

In general, jaundice may either be:

[unconjugated]:

- Hemolytic (G6PD deficiency, hereditary spherocytosis, Rh incompatibility, ABO incompatibility)

- Hypothyroid- High gastrointestinal obstruction Pyloric stenisos- Infection UTI- Breast milk induced jaundice- Physiological jaundice- Crigler-Najjar $, Gilbert $, not common in neonate

[conjugated]:

- Bile duct obstruction Biliary atresia Choledocal cyst

- Neonatal hepatitis Congenital infection (TORCH, hepatitis) Metabolic disorders:

o α1-antitrypsin deficiencyo Galactosemiao Tyrosinemia

Cystic fibrosis TPN induced hepatitis (cholestasis) especially in Preterm.

- Intrahepatic biliary hypoplasia Alagille's syndrome

DDx of unconjugated hyperbilirubinemia in the 1st week:

1. Hemolytic disease of the newborn2. Physiological jaundice3. Cephalhematoma4. Jaundice of prematurity5. Breast milk jaundice

UNCONJUGATED HYPERBILIRUBINEMIA

(1) Rh incompatibility:

- It's the most serious of the hemolytic type, but less common than ABO incompatibility

- It's due to blood group incompatibility between [maternal] Rh- & [fetal] Rh+ IgG antibody reaction

- Hx of blood transfusion to mother is important, also previous pregnancy, & previous delivery of Rh+ baby .

- O/E: The affected baby will have pallor [due to hemolytic anemia), hepatosplenomegaly

- Investigations: +ve Coomb's test, ↑ retic count, rapidly ↑ bilirubin with ↑ direct.

- Nowadays, this type [Rh] is not common, due to availability of anti-Rhogam Ab / Anti-D Ab for the sensitized Rh- mother

(2) ABO incompatibility:

- The mother has blood group O & the infant has either group A, B.- Most ABO Abs are IgM & don't cross the placenta, but some group

O women have IgG anti-(either A or B)-hemolysin in the blood which can cross the placenta & hemolyse the red cells.

- More common than Rh incompatibility, but less severe.- Anemia is less severe- Direct Ab test (Coomb's test) is not always +ve, weakly +ve,

might be –ve.- Spherocytes in blood film is a feature.

Both Rh + ABO ttt by:

1. Phototherapy ttt is important to prevent bilirubin encephalopathy [Kernicterus].

2. Sometimes, we use exchange transfusion if bilirubin level is 20 in all term infants.

(3) G6PD deficiency:

- X-linked disease, only seen in males.- Family Hx (e.g. brother) is IMPORANT- Diagnosed by measuring RBC enzyme / enzyme assay- Associated with (precipitating factors):

1. Medications:o primaquine (antimalarial)o synthetic vit. Ko some antibiotics like sulphonamideso nitrofurantoino furazolidineo para-aminosalicylic acid (aspirin)o phenacetibo nephthalene

2. fava baens favism (anemia)3. infections [infectious mononucleosis, viral hepatitis]

- ttt: packed RBC transfusion in severe cases avoid precipitating factors treat infection properly

(4) Hereditary spherocytosis

- It's autosomal dominant- 25% new mutations- +ve family Hx (e.g. brother + sister) of splenectomy, anemia & gall

bladder disease.- Presentation: anemia, jaundice, dark urine, pale stool- Aplastic crisis by parvovirus B19- Diagnosis:

Blood film show spherocytes Osmotic fragility test IMPORTANT

- Pathophysiology (see the hand written sheet or Nasser Jamal Text Book)

Both disease is ttt by phototherapy

(5) Physiological jaundice

- It occurs in about 60% of normal full term infants during the 1st

week of life.- Why do we see jaundice & consider it to be normal, physiologic:

Due to:1. ↑ RBC production catabolism of extra-hemoglobin.2. Shorter RBC life span in neonate [70 days] whereas in

adulthood 120 days.3. ↓ uptake by of bilirubin from plasma, due to transient

immaturity of binding proteins So, ↑ chance for destruction

4. ↓ uridine diphosphate glucouronyl transferase enzyme5. ↓ bacteria that convert bilirubin to uroblinigen

- It's diagnosed by exclusion:Criteria:

1. Baby must be looking normal + active2. No anemia or organomegaly 3. Jaundice not be seen at day 1 of life4. Usually seen on in 3rd day in full term, & at day 5 in preterm5. Not persistent for more than 1 week in term, & 2 weeks in

preterm6. Bilirubin level is maximally 13 mg/dl in full term & 15 mg/dl

in preterm7. Bilirubin daily rise should never exceed 5 mg/dl. مھم

8. There should be no family Hx of splenectomy or gall bladder surgery

- Prolonged physiological jaundice:1. Hypothyroidism (thyroxin is important for maturation of the

enzymes) & constipation leads to increase unconjugated bilirubin enterohepatic circulation

2. Congenital hypertrophic pyloric stenosis (most probably due to hypoglycemia as glucose is essential for formation of the glucuronic acid)

3. Breast milk jaundice4. Constipation

5. Polycythemia6. IDM7. SGA

(6) Breast milk jaundice:

I- Early onset hyperbilirubinemia associated with breast feeding: Onset: Occurs before the 7th day in breast-fed babies. May be due to:

↓ Milk intake dehydration hemoconcentration ↑ bilirubin, or

↓ Caloric intake in babies given glucose 5% (low caloric) instead of breast milk.

Management: frequent breast feeding ( > 10 times/day) & discouraging giving 5% glucose.

II- Late onset hyperbilirubinemia associated with breast milkaka Breast Milk (Induced) Jaundice: Unconjugated jaundice, occurring in .5% of exclusively

breast-fed full term babies. Onset: 7th day, Peak: 14th to 21st day. Causes:

Pregnandiol may be present in breast milk inhibits glucuronyl transferase.

Non-esterified fatty acids in milk may compete with bilirubin for liver conjugation.

No putrefactive intestinal flora ↓ transformation of bilirubin to stercobilinogen ↑ enterohepatic circulation of bilirubin.

β-glucuronidase in breast milk deconjugation & ↑ enterohepatic circulation of bilirubin.

Do we recommend breast feeding, & WHY?Cessation of breast feeding for 1-2 days & replacement by formula feeding rapid decline in serum bilirubin to normal levels, after which breast feeding can be given without ↑ in bilirubin.

If breast feeding is NOT stopped, hyperbilirubinemia decreases gradually, & may persist for 3-10 weeks at lower level.

The condition is benign. Kernicterus does not occur.

(7) hypothyroidism

- They have jaundice + umbilical hernia + open posterior fontanel- Why do they have jaundice? (see the mechanism from Text Book)

ttt of all types of unconjugated jaundice:

1) Phototherapy: Purplish blue light wave length 540 nanometer (425 – 475) It converts unconjugated bilirubin into polar photoisomers

which are less lipophilic During phototherapy: temperature & hydration must be

monitored. Side effects of phototherapy:

1. Water loss + dehydration2. Diarrhea, over heating [Bronze baby syndrome]3. Hyperpigmentation4. Retinal damage especially when eyes are not covered

during ttt.2) Phenobarbitone:

It may be used in ttt of unconjugated jaundice as it stimulate the synthesis of bilirubin binding proteins glucuronyl transferase enzyme.Given in the 1st day or to the mother before delivery.Dose: 8 mg/kg/day in 2 doses, IM

3) Exchange transfusion: Umbilical vein catheter after cord cutting, through a special

valve, over 45 – 60 minutes period. Aim: exchange of double the blood volume of the infant

(2 x 85 ml x body weight in kg)

In case of Rh incompatibility, blood group of the donor should be the same of the infant but Rh-, while in ABO incompatibility it should be group O.

Side effects of exchange transfusion: Cardiac arrhythmias Electrolyte disturbance Embolism (blood clots, or air) Portal or splenic vein thrombosis Infection

Complications of unconjugated jaundice:

Bilirubin is lipophilic can cross the Blood Brain Barrier (BBB) can cause [Kernicterus]

KERNICTERUS

Encephalopathy resulting from the deposition of unconjugated bilirubin in the basal ganglia & brain stem nuclei.

# It can be seen with ↑↑ level, especially more than 25 mg/dl in full-term babies & 15 mg/dl in prematures.

# Stages of Kernicterus:

Stage (1) Kernicterus Stage:

Poor Moro Reflex, high pitched crying, fever & opisthotonos (arched position)

Stage (2) Lucid Stage:

↓ Tone at about 1 week of age.

Stage (3) Post-Kernicterus Stage:

Spasticity + Hearing loss

CP [mixed type choreoathetosis]

CONJUGATED JAUNDICE

Prolonged neonatal jaundice is the most common presentation of liver disease in the neonatal period.

Categories:

(1) Bile duct obstruction: Biliary atresia Choledocal cyst

(2) Neonatal hepatitis: Congenital infection Inborn error of metabolism Cystic fibrosis TNP induced jaundice, especially in preterm

(3) Intrahepatic biliary hypoplasia Alagille's syndrome

Conjugated jaundice:

- Pale stool- Dark urine- Failure to thrive- Bleeding tendency ↓ vit. K

(1) Biliary atresia: + case history 20.1, page 339 (illustrated textbook)

- It's a progressive disease CLD liver failure, if not treated within 60 days of life. If ttt done after 60 days poor prognosis "unsuccessful ttt"

- Biliary atresia means: obstruction or absence of intrahepatic ducts + extrahepatic tree intact gall bladder.

- Biliary atresia & Choledocal cyst must be differentiated:

Abdominal US

If

Gall bladder is intact but the biliary tree is dilated [cyst]

Gall bladder is intact but the biliary tree is not visualized.

Intraoperative cholaniogram

HIDA scanor TBIDA

Surgery[cyst removal]

+Roux-en-Y

anastomosis

If there's good uptake to the

dye, but show no excretion

Intraoperative cholaniogram

+Biopsy↓

It'll show fibrosis &

ductal proliferation

Choledocal Cyst

Biliary Atresia

So, intraoperative cholangiogram is diagnostic.

# If we diagnose biliary atresia Surgery, called Kasai Procedure[HepatoPortoEnteroStomy] jejunum is attached to portahepatis in the gall bladder after operation the stool color will become back to normal Green [bile will drain through anastomosis].

(2)α1-antitrypsin deficiency:

- Autosomal recessive disease. It causes liver disease in infancy & emphysema in adulthood.

- It's due to: protease deficiency ↑ protease inhibitor (Pi)

- There are many phenotypes for Protease Inhibitor. When liver disease is associated, the phenotype will be PiZZ on chromosome 14.

- Clinical features: Prolonged neonatal jaundice Bleeding (vit. K ↓) especially in breast-fed. Hepatomegaly, splenomegaly Cirrhosis Portal hypertension

- Diagnosed by: Enzyme level (α1-antitrypsin) in the blood Phenotype: PiZZ on chromosome 14

(3) Galactosemia:

- Due to: deficiency of the enzyme galactose-1-phosphate uridyl transferase galactose-1-phosphate accumulate in the blood toxic effect on the brain, lens, liver & kidney.

- Clinical picture: Hypoglycemia convulsion jaundice, hepatomegaly (especially when they're fed milk) cataract developmental delay

- Diagnosed by:1. Tandem MS [metabolic screen]2. Measuring the enzyme (galactose-1-phosphate uridyl

transferase) level in RBCs

(4) Alagille's syndrome:

- Autosomal dominat condition.

- Clinical picture:1. ∆ facies Triangular2. Pulmonary hypertension3. Eye defect4. Intrahepatic biliary hypoplasia jaundice, severe pruritus +

FTT5. Renal tubular disorders.6. Butterfly vertebrae in X-Ray.

DISEASES OF THE LIVER

Viral Hepatitis

See Prof. Tahir Toonisi's Book (pages 68 – 70)

Acute Liver Failure (Fulminant Hepatitis)

Causes:

1. Infection: Viral hepatitis A, B, C2. Poisons/drugs: Paracetamol, isoniazid, halothane, poisonous

mushroom (Amanita phalloides) 3. Metabolic: Wilson's disease, tyrosinemia4. Autoimmune hepatitis5. Reye's Syndrome

Reye's $:

It's seen when giving aspirin for a child aged less that 12 years of those who have some genetic problems.

Acute NON-Inflammatory Encephalopathy with micro-vesicular fatty liver infiltration.

The commonest beta oxidant defect is Medium Chain Acyl-CoA Dehydrogenase deficiency (MCAD).

Chronic liver disease

Causes:

1. Chronic hepatitis: Post-viral hepatitis B,C Autoimmune hepatitis Drugs (nitrofurantoin, NSAIDs) Inflammatory bowel disease Primary sclerosing cholangitis (± ulcerative colitis)

2. Wilson's disease ( > 3 years )3. α1-antitrypsin deficiency4. Cystic fibrosis5. Secondary to:

Neonatal liver disease Bile duct lesions

(1) Wilson's disease (hepatolenticular degeneration):

- Autosomal recessive disease- Only diagnosed after age of 3 years- Copper will accumulate in brain, liver & kidney.- Children who have the disease will have hepatic problem, but

in adulthood neurological symptoms.- Clinical Picture:

Jaundice, hepatomegaly, ascites, portal hypertension, dysarthria, tremors, & Kayser Fleisher rings in the cornea.

- Investigations:1. In serum:

↓ Copper ↓ ceruloplasmin LFTs

2. In urine: ↑ Copper

↑ Ceruloplasmin3. Liver biopsy:

↑ Copper- Treatment:

D-penicillamine (copper chelatic agent) orally for life ↑ urine excretion of copper, but it's toxic. So, add zink to reduce copper absorption.

Urso for pruritus.

(2) Congenital Hepatic Fibrosis (CHF):

- Children over 2 years old- Present with: hepatosplenomegaly + abdominal distension +

portal hypertension bleeding varices- Liver function can be Normal in early stage

By: angelic_doc

Sources:

Dr. Hassan Moria summery sheet 2008, Illustrated Textbook of Pediatrics, Manual of Pediatrics, Pediatrics for Undergraduates…