Jaundice and Infection

Chapter 35 Jaundice and Infection


Jaundice is the yellow discoloration of the skin and sclera that results from raised levels of bilirubin in the blood (hyperbilirubinaemia).



Conjugation of bilirubin


Bilirubin is a waste product from the breakdown of haem, most of which is found in red blood cells (RBCs). Ageing, immature or malformed RBCs are removed from the circulation and broken down in the reticuloendothelial system (liver, spleen and macrophages), and haemoglobin becomes the by-products of haem: globin and iron.



image Haem is converted to biliverdin and then to unconjugated bilirubin.


image Globin is broken down into amino acids that are reused by the body to make proteins.


image Iron is stored in the body or used for new red blood cells.


Two main forms of bilirubin are found in the body:



image Unconjugated bilirubin is fat soluble and cannot be excreted easily either in bile or urine.


image Conjugated bilirubin has been made water soluble in the liver and can be excreted in either faeces or urine.


Three stages are involved in the processing of bilirubin:



image transport


image conjugation


image excretion.




Transport


Unconjugated bilirubin is transported in the plasma to the liver, bound to the plasma protein albumin. If not attached to albumin, it can be deposited into extravascular fatty and nerve tissues in the body. The skin and the brain are the two most common sites.



image Staining of the skin is known as jaundice.


image Damage to the brain as a result of bilirubin staining and toxicity is known as kernicterus.



Conjugation


Once in the liver, bilirubin is combined with glucose and glucuronic acid, and conjugation occurs in the presence of oxygen. Uridine diphosphoglucuronyl transferase (UDP-GT or glucuronyl transferase) is the major enzyme involved in bilirubin conjugation. The conjugated bilirubin is now water soluble and available for excretion.



Excretion


The conjugated bilirubin is excreted via the biliary system into the small intestine, where it is catabolised by normal intestinal bacteria to form urobilinogen, then oxidised into orange-coloured urobilin. Most of the conjugated bilirubin is excreted in the faeces but a small amount is excreted in urine.



Jaundice


In term neonates, jaundice appears when serum bilirubin concentrations reach 85–120 μmol/l (5–7 mg/dl).



Physiological jaundice


This type of jaundice:



image never appears before 24 hours of life


image usually fades by 1 week of age.


Bilirubin levels never exceed 200–215 μmol/l (12–13 mg/dl).



Causes


Neonatal physiological jaundice is the result of a discrepancy between RBC breakdown and the baby’s ability to transport, conjugate and excrete unconjugated bilirubin. Neonates also have increased betaglucuronidase enzyme activity in the gut, which hydrolyses conjugated bilirubin back into the unconjugated state. If feeding is delayed, bowel motility is decreased, further compromising excretion of unconjugated bilirubin.



Exaggerated physiological jaundice in breastfed infants


The exact mechanisms are unknown. A reliable diagnosis can only be made by excluding pathological causes. Cessation of breastfeeding is unnecessary.



image Early-onset jaundice. It is thought that low fluid and calorie intake during colostrum production causes a slower intestinal transit time, which increases exposure to betaglucuronidase; this in turn adds more unconjugated bilirubin to the system.


image Prolonged jaundice occurs for unknown reasons in some healthy breastfed babies.



Exaggerated physiological jaundice in preterm babies


This is characterised by bilirubin levels of 165 μmol/l (10 mg/dl) or greater by day 3 or 4, with peak concentrations on days 5–7 that return to normal over several weeks. Preterm babies are more at risk of kernicterus. Contributing factors include:



image a delay in the expression of the enzyme UDP-GT


image shorter red cell life


image complications such as hypoxia, acidosis and hypothermia that can interfere with albumin-binding capacity.



Midwifery practice and physiological jaundice


It is important to distinguish between healthy babies with a normal physiological response who need no active treatment and those who require serum bilirubin testing. Transcutaneous bilirubinometry reduces the number of blood tests. Parents should be advised to report:



image excessive sleepiness


image reluctance to feed


image decrease in the number of wet nappies


image pale stools and yellow or orange urine.


Early, frequent feeding assists newborns to cope with an increased bilirubin load.



Pathological jaundice


Pathological jaundice in newborns usually appears within 24 hours of birth, and is characterised by a rapid rise in serum bilirubin. Criteria are listed in Box 35.1.



Box 35.1 Diagnosis of pathological jaundice




• Jaundice within the first 24 hours of life


• A rapid increase in total serum bilirubin > 85 μmol/l (5 mg/dl) per day


• Total serum bilirubin > 200 μmol/l (12 mg/dl)


• Conjugated (direct-reacting) bilirubin > 25–35 μmol/l (1.5–2 mg/dl)


• Persistence of clinical jaundice for 7–10 days in term babies, or 2 weeks in preterm babies



Causes


The underlying aetiology of pathological jaundice is some type of interference with bilirubin production, transport, conjugation or excretion. Any disease or disorder that increases bilirubin production or that alters the transport or metabolism of bilirubin is superimposed upon normal physiological jaundice.



Production


Factors that increase haemoglobin destruction also increase bilirubin levels. Causes of increased haemolysis include:



image Rhesus anti-D, anti-A, anti-B and anti-Kell and ABO blood group incompatibility


image haemoglobinopathies – sickle cell disease and thalassaemia


image spherocytosis – fragile RBC membrane


image extravasated blood – cephalhaematoma and bruising


image sepsis – can lead to increased haemoglobin breakdown


image polycythaemia – blood contains too many red cells, as in maternofetal or twin-to-twin transfusion.



Transport


Factors that lower blood albumin levels or decrease albumin-binding capacity include:



image hypothermia, acidosis or hypoxia (can interfere with albumin-binding capacity)


image drugs that compete with bilirubin for albumin-binding sites, e.g. aspirin, sulphonamides and ampicillin.



Conjugation


As well as immaturity of the neonate’s enzyme system, other factors can interfere with bilirubin conjugation in the liver:



image Dehydration, starvation, hypoxia and sepsis (oxygen and glucose are required for conjugation).


image TORCH infections (toxoplasmosis, others, rubella, cytomegalovirus, herpes).


image Other viral infections, e.g. neonatal viral hepatitis.


image Other bacterial infections, particularly those caused by Escherichia coli.


image Metabolic and endocrine disorders that alter UDP-GT enzyme activity, e.g. Crigler–Najjar disease and Gilbert syndrome.


image Other metabolic disorders, such as hypothyroidism and galactosaemia.



Excretion


Factors that can interfere with bilirubin excretion include:



image hepatic obstruction caused by congenital anomalies


image obstruction from increased bile viscosity


image saturation of protein carriers needed to excrete conjugated bilirubin into the biliary system


image infection, other congenital disorders and idiopathic neonatal hepatitis (can also cause an excess of conjugated bilirubin).



Haemolytic jaundice


Rhesus (RhD) isoimmunisation causes haemolytic disease of the newborn (HDN). Few antibodies to blood group antigens other than those in the Rh system cause severe HDN; fetal transfusion is unusual for multiple maternal antibody isoimmunisation without anti-D. ABO incompatibility is possibly the most frequent cause of mild to moderate haemolysis in neonates.



Rhesus d incompatibility


RhD incompatibility can occur when a woman with Rh-negative blood type is pregnant with a fetus with Rh-positive blood type.



image The placenta normally prevents fetal blood entering the maternal circulation. However, during pregnancy or birth, small amounts of fetal Rh-positive blood cross the placenta and enter the circulation of the mother, who has Rh-negative blood.


image The woman’s immune system reacts by producing anti-D antibodies that cause sensitisation.


image In subsequent pregnancies these maternal antibodies can cross the placenta and destroy fetal erythrocytes.


image Usually, sensitisation occurs during the first pregnancy or birth, leading to extensive destruction of fetal red blood cells during subsequent pregnancies.


Rh isoimmunisation can result from any procedure or incident where maternal blood leaks across the placenta or from the inadvertent transfusion of Rh-positive blood to the woman.



Prevention of RhD isoimmunisation


This is by routine antenatal anti-D immunoglobulin (Ig) prophylaxis, within 72 hours of birth or after any other sensitising event. Anti-D Ig is a human plasma-based product that prevents the production of anti-D antibodies by the mother.



Administration of anti-D Ig


Anti-D Ig is administered to Rh-negative women who are pregnant with, or have given birth to, an Rh-positive baby. It destroys any fetal cells in the mother’s blood before her immune system produces antibodies. The process for non-sensitised women is set out in Box 35.2.



Box 35.2 Administration of anti-D Ig to non-sensitised women




1. Women who are Rh-negative are screened for Rh antibodies (indirect Coombs’ test). A negative test shows an absence of antibodies or sensitisation


2. Blood is retested at 28 weeks of pregnancy. In countries where antenatal prophylaxis is routine (at 28 and 34  weeks’ gestation), the first injection of anti-D Ig is given just after this blood sample is taken


3. Where a policy of routine antenatal anti-D Ig prophylaxis is not in place, blood is retested for antibodies at 34  weeks of pregnancy


4. When anti-D Ig prophylaxis is given at 28  weeks, blood is not retested, as it is difficult to distinguish passive anti-D Ig from immune anti-D


5. Following the birth, cord blood is tested for confirmation of Rh type, ABO blood group, haemoglobin and serum bilirubin levels and the presence of maternal antibodies on fetal red cells (direct Coombs’ test). Again, a negative test indicates an absence of antibodies or sensitisation. The postnatal dose of anti-D Ig is still given if passive anti-D Ig is present


6. A Kleihauer acid elution test is also carried out on an anticoagulated maternal blood sample immediately after birth to estimate the number of fetal cells in a sample of maternal blood


7. Anti-D Ig must always be given as soon as possible, and in any case within 72 hours of any sensitising event and the birth. Anti-D Ig is injected into the deltoid muscle, from which absorption is optimal

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Related posts:

  1. The Placenta
  2. Prolonged Pregnancy and Disorders of Uterine Action
  3. The Third Stage of Labour
  4. Problems of Pregnancy

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Jul 11, 2016 | Posted by in MIDWIFERY | Comments Off on Jaundice and Infection

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