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Neonatal Jaundice Flashcards

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1
Q

What is icterus?

A

Another word for neonatal jaundice comes from yellow bird

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2
Q

What is physiologic jaundice?

A

This is normal jaundice of the newborn that is due to breakdown of fetal hb, immature liver metabolism of bilirubin, absence of gut flora which impedes elimination of bile and exclusive breast feeding

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3
Q

Why might exclusive breast feeding lead to physiological jaundice?

A

If there are feeding difficulties in the early stages the neonate is at risk of dehydration and therefore decreased bilirubin elimination

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4
Q

When does physiological jaundice normally occur?

A

After 24 hours from birth

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5
Q

If jaundice develops in what timeframe does it indicate that it is pathological?

A

Within 24 hours from birth- majority due to prehepatic cause

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6
Q

What may cause pathological jaundice within 24 hours of birth?

A

Rhesus Haemolytic Disease
ABO Incompatibility between mother any baby
Red Cell Anomalies- Spherocytosis, G6PD deficiency

Note- causes are pre-hepatic mostly

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7
Q

What test should be done to investigate pathological neonatal jaundice?

A

Split Bilirubin- Conjugated and Unconjugated
Coombs Test- If positive indicates maternal antibodies are attacking the neonates red cells due to Rh or ABO incompatibility

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8
Q

What does a positive Coomb’s Test indicate?

A

Maternal antibodies are against an antigen expressed on the neonates red cells

The Coomb’s Test is used to investigate for autoimmune haemolytic anaemia

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9
Q

What test is used to investigate for an autoimmune cause for haemolytic anemia?

A

Coomb’s Tests

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10
Q

What does the direct Coomb’s Test indicate?

A

The DCT indicates that antibodies are present against an antigen expressed on the red cells. This is indicated by the blood clumping due to cross linking between Ig. It does not however tell us the type of antibody present and what it is targetting

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11
Q

What does the indirect Coomb’s Test indicate?

A

The indirect Coomb’s Test tells us which antibodies are present, for example it will indicate if there is Anti A Abs present. This is done by exposing the serum (which contains the antibodies) to known blood group antigens and any clumping indicates that the antibody is present

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12
Q

Which pregnancy will be affected by rhesus haemolytic anaemia?

A

The second pregnancy- if the mother is Rh -ve and the father Rh +ve the baby will be Rh +ve also. During the first pregnancy some of the baby’s red cells will be exposed to the maternal immune system and the mother will generate anti Rh antibodies following exposure. During the second pregnancy these anti Rh antibodies will target the Rh positive fetal blood.

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13
Q

When does sensitisation occur for mothers who are Rh -ve with an Rh +ve child?

A

During birth of the first child

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14
Q

What should be done to sensitisation to rhesus antigen in Rh +ve mothers who are pregnant with an Rh-ve child?

A

Anti Rh Abs should be given to the mother during pregnancy- at 28 weeks of gestation and again within 72 hours postpartum. These should target the fetal red cells for immune destruction preventing an immune response being generated by the maternal immune system.

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15
Q

What can be given to mothers who have been sensitised to Rh antigen expecting an Rh +ve child?

A

Antibodies against the Anti-Rh Ab

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16
Q

What two conditions may lead to pathological neonatal jaundice due to autoimmune haemolysis?

A

Rhesus Haemolytic Disease

ABO Incompatibility

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17
Q

Explain the blood types of mother and baby involved in ABO incompatibility

A

Mother is most often group O (both anti A or B) and baby is group A or B or AB

Maternal antibodies against the blood group antigens enter the fetal circulation and attack the fetal red cells

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18
Q

Which pregnancy will be affected for ABO incompatibility between mother and baby?

A

The first pregnancy- antibodies against the blood group antigens are already present without the need for sensitisation to occur following exposure during the first pregnancy in the way as Rhesus Haemolytic Disease occurs

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19
Q

What should be investigated if the Coomb’s Test comes back negative?

A

Negative Coombs Test indicates that the cause of the jaundice is not due to an autoimmune haemolytic anaemia

Investigate Hb level

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20
Q

What might a low Hb indicate?

A

That there is a blood collection outside the blood vessels and the breakdown of this is causing the bilirubin load. for example this may be due to cephalohematoma due to trauma during delivery.

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21
Q

What is a cephalohematoma?

A

A haematoma that occurs following trauma to the head during pregnancy. There is pooling of blood in the periosteum of the skull. The breakdown of the blood causes a bilirubin rise leading to jaundice.

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22
Q

What might a high Hb indicate?

A

Increased haemoglobin levels indicate there is an increased load of red blood cells that may be slowly broken down resulting in the bilirubin rise.

Common in babies of diabetic mothers, when there’s a transfusion (twin-twin, maternal-fetal) or delayed cord clamping

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23
Q

What should be done if Hb comes back as normal?

A

Check Reticulocyte count, LDH and haptoglobin

High reticulocytes indicates increased red cell production which may be due to red cells- Sickle, Spherocytes

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24
Q

What is haptoglobin?

A

Haptoglobin is a protein that binds to Hb and so reduced haptoglobin indicates increased levels of free Hb due to red cell breakdown

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25
How does the reticulocyte count, LDH and haptoglobin change with haemolysis and why?
Reticulocyte count goes up- due to increased red cell production to compensate for haemolysis LDH goes up- it is an intracellular enzyme and so is released with cell breakdown Haptoglobin goes down- haptoglobin binds free Hb and so increased levels of free Hb bind to haptoglobin reducing it.
26
Why is haptoglobin unreliable in newborns?
It is very often undetectable as there is already a large amount of fetal Hb breakdown
27
What tests should be done to investigate for haemolysis and why?
Blood Smear- To look at the physical characteristics of RBCs Reticulocyte Count- Increases with haemolytic processes LDH- Increases with haemolytic processes Haptoglobin- Decreases with haemolytic processes Coombs- Investigate for autoimmune causes G6PD Levels- Oxidative stress causes red cell lysis
28
What does a blood smear investigate for?
Membrane defected in the red cells E.g. Spherocytes, Elliptocytes, Sickle Cell
29
What enzymes levels should be checked if investigating for a haemolytic process?
Pyruvate kinase | G6PD
30
What investigation might be done to quantify the different types of Hb present?
Haemoglobin electrophoresis This might reveal haemoglobinopathies present.
31
What test can be done to investigate for haemoglobinopathies?
Hb Electrophoresis Indicates the different levels of Hb present
32
What might you suspect if reticulocytes, LDH and Haptoglobin are all normal?
Breast Feeding Jaundice Breast Milk Jaundice Hepatocellular Causes- Enzyme issues If all reticulocytes, LDH and haptoglobin are normal it indicates the cause is unlikely to be a haemolytic one.
33
What causes breast feeding jaundice?
Insufficient quantity or frequency of feedings which causes reduced GI transmission and there is less excretion of conjugated bilirubin. This conjugated bilirubin builds up in the bowel lumen and is converted back to unconjugated bilirubin and reabsorbed back into circulation.
34
When does breast feeding jaundice commonly present?
First 7 days of life
35
What type of bilirubin is elevated in breast feeding jaundice and why?
Unconjugated Poor feeding leads to reduced GI transmission and there is a build up of conjugated bilirubin in the bowel. This is converted to unconjugated bilirubin which is then absorbed back into the infants enterohepatic circulation
36
How does breast feeding jaundice normally resolve?
Typically feeding issues resolve, feeding increases or formula may be needed to increase the intake. Note it is important to monitor weight centiles closely.
37
What causes breast milk jaundice?
Substances within the breast milk itself that inhibit the enzyme that converts unconjugated to conjugated bilirubin in the liver (called glucuronyl transferase). These substances include metabolites of progesterone.
38
What is recommended for breast milk jaundice?
Keep breastfeeding but may be paused if bilirubin levels raise too high- monitor closely.
39
What enzyme is responsible for converting unconjugated bilirubin into conjugated bilirubin?
Glucuronyl Transferase
40
What hepatocellular conditions may cause neonatal jaundice with rises in unconjugated bilirubin?
Enzyme deficiencies meaning hepatocytes are less effective at conjugating bilirubin Gilbert's Syndrome (low glucuronyl transferase) Crigler-Najjar Syndrome (absence of glucuronyl transferase)
41
How can an enzyme deficiency diagnosis leading to a hepatic cause of neonatal jaundice be confirmed?
Genetic Testing
42
What complication can occur with prolonged hyperbilirubinemia?
Kernicterus
43
Which form of bilirubin causes kernicterus?
Prolonged elevated levels of unconjugated bilirubin- as it is fat soluble it can cross the blood brain barrier and deposit in the basal ganglia
44
What does kernicterus causes?
``` Lethargy Poor feeding Hypotonia Seizures Death ```
45
What is treatment the treatment for severe unconjugated hyperbilirubinemia?
Phototherapy or Exhchange Transfusion if indicated
46
What is Kernicterus?
Kernicterus is the clinical features of acute or chronic bilirubin encephalopathy Risks are greater if there is a severely elevated unconjugated bilirubin or prolonged raised unconjugated bilirubin.
47
How does phototherapy work?
It converts the unconjugated bilirubin into the more soluble form lumirubin which can then be excreted more easily. Therefore doesn't rely on hepatic conjugation.
48
What is important to monitor during phototherapy?
Temperature to avoid overheating and burns | Eye protection must be used
49
When might an exchange transfusion be indicated?
If phototherapy has failed to adequately reduce bilirubin levels Extremely high bilirubin levels Any clinical signs of kernicterus regardless of bilirubin levels
50
What is an exchange transfusion?
Small amounts of blood are withdrawn and replaced with packed red cells by an umbilical vein intravenous infusion
51
What is indicated by raised levels of conjugated bilirubin with normal AST, ALT, ALP, GGT?
Hepatic Jaundice due to conditions such as Dubin Johnsons and Rotor Syndrome. Due to defective proteins of bilirubin storage and transport. Conjugation process works but cannot be excreted into the bile canaliculi, causing it to leak into the bloodstream. Normal ALT/AS/ALP/GGT indicates no liver injury.
52
What is Dubin-Johnson Syndrome?
Genetic condition where there is a defect in conjugated bilirubin transport out of hepatocytes into bile canaliculus causing it to accumulate and leak out into the bloodstream. Causes raised conjugated bilirubin.
53
How is Dubin-Johnson syndrome diagnosed?
Urinary Coproporphyrin Excretion- normal in quantity but not quality. This is a product of haem synthesis, in Dubin-Johnson syndrome there is a large amount of coproporphyrin 1 in the urine (which is normally excreted in the bile). Coproporphyrin 1 is normally excreted in the bile and coproporphyrin III is normally excreted in the urine. To diagnose Dubin-Johnson syndrome there needs to be an increase in the ratio of 1:3 in the urine, as the protein for transporting conjugated bilirubin out of hepatocytes is defunct. A liver biopsy may also be done which appears black.
54
What is rotor syndrome?
Genetic condition where there is a defect in proteins that store conjugated bilirubin in the hepatocyte, build up occurs and then leak into the bloodstream. Note quantity of coproporphyrin is increased but ratios are normal. Liver biopsy is normal
55
What should be considered if there is a raised conjugated bilirubin and raised ALT/AST but normal ALP?
Raised ALT and AST indicates there has been hepatic injury but there lack of a raised ALP/GGT means there is not a post-hepatic obstructive cause. Investigate for Hep B, Hep C and TORCH (Congenital infections)
56
Why might IgM Abs be used rather than IgG Abs when investigating for certain conditions?
IgG may be maternal IgG which crosses the placenta.
57
What are some hepatic causes for neonatal jaundice?
Probably best to use a surgical sieve E.g. Infection- Heb B, Hep C, TORCH, VZV Enzymes- Dubin Johnsons, Rotor Syndrome, Alpha 1 antitrypsin deficiency Haemochromatosis- Serum Iron, Transferrin, Ferritin Wilson's Disease- Ceruloplasmin
58
``` What should be considered if there is a: Raised conjugated bilirubin Normal AST/ALT Raised ALP Normal LFTs- INR, PT, PTT, Albumin ```
Post hepatic causes should be considered- there is an obstruction to bile outflow.
59
Describe the lab results for Dubin Johnsons and Rotor syndrome?
These conditions involve proteins defective in: Excreting conjugated bilirubin into the bile canaliculi for Dubin Johnsons Storing conjugated bilirubin in the hepatocytes for Rotor Syndrome Leads to raised levels of conjugated bilirubin but there is: No Liver Injury (Normal AST/ALT) No Liver Dysfunction (Normal INR, Albumin, PT, PTT)
60
Describe the lab results, including the normal investigations for this, for a pre-hepatic jaundice?
Raised unconjugated bilirubin Cause may be haemolytic anaemia or poorly formed red cells that break down Raised reticulocyte count +ve Coomb's Test for AI causes Raised LDH due to red cell breakdown Reduced haptoglobin due to increased free Hb Blood Smear may show issues with red cell physical properties e.g. spherocytosis Hb Electrophoresis may reveal haemoglobinopathies Enzymes- G6PD or pyruvate may be deficient
61
Describe the lab result for hepatic causes of jaundice where there would be liver injury but no evidence of dysfunction? What could cause this picture?
Raised Total and Conjugated Bilirubin Raised ALT and AST Normal INR, Albumin, PT and PTT Hepatitis B and C Haemochromatosis Wilson's Disease
62
What investigation is done for Wilson's Disease?
Ceruloplasmin
63
What investigations should be done to investigate for haemochromatosis?
Serum Iron Transferrin Ferritin
64
Describe the lab results for a post-hepatic jaundice?
Raised Conjugated and Total Bilirubin Raised ALT and AST Raised ALP and GGT No evidence of liver dysfunction
65
What other features may you see with an obstructive jaundice?
Pale fatty stools Dark urine- conjugated bilirubin is water soluble and so excreted in the urine RUQ pain in adults
66
Why might clotting be deranged in an obstructive jaundice?
Vitamins A, D, E and K are fat soluble and require fat to be absorbed. Obstructive jaundice reduces the release of bile required for the emulsification of fats in the GI tract. This reduces the absorption of the fat soluble vitamins. Vitamin K has an important role in clotting and so clotting can become deranged.
67
What must be checked to investigate for Dubin Johnsons and Rotor Syndrome? Describe the results
Urinary Coproporphyrins Dubin Johnsons- Raised ratio of coproporphyrin:III in the urine (I is normally excreted in the bile). Also liver biopsy is black. Rotor Syndrome- Increased levels of urinary coproporphyrins as it is a defective storage proteins in the hepatocytes. Liver biopsy normal. Note- AST and ALT are normal in this hepatic cause of jaundice.
68
What should be done to investigate for post-hepatic causes of jaundice in the neonate?
Abdominal USS- Dilation of the biliary tree and absent gallbladder indicates biliary atresia
69
What is seen on abdominal USS for biliary atresia?
Absent Gallbladder | Dilated biliary tree
70
What imaging can be done to investigate the biliary tree structure?
Cholangiogram- may be done intraoperatively in neonates where dye is injected MRCP?
71
What surgical procedure is done to fix biliary atresia?
Kasai procedure- portion of small intestine used to connect bile out flow to small intestine
72
What is a choledochal cyst?
Congenital dilations of the bile ducts which can cause bile outflow obstruction
73
If there is evidence of post-hepatic jaundice in children with specific dysmorphic facial features which syndrome should be considered?
Alagille syndrome Facial features- triangular face, large forehead, wide nasal bridge, deep set eyes, small pointed chin Chronic cholestasis Cardiac Abnormalities- e.g. pulmonary stenosis Skeletal Abnormalities- e.g. butterfly vertebra Ocular abnormalities- e.g. posterior embryotoxon
74
Describe the lab results for a neonatal jaundice?
Raised conjugated and total bilirubin Raised ALT/AST - Evidence of Liver Injury Further lab results depend on cause
75
What are the causes of neonatal hepatitis?
``` Congenital Infections- Think TORCH Toxoplasmosis Hep A Hep B Hep C Syphilis CMV VZV Rubella ``` Genetic causes- Alpha 1 Antitrypsin deficiency Hemochromatosis Wilsons Disease

Paediatrics (6 decks)

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