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Kernicterus
Short Analytical Essay
Department of
Physiology
W.M.P. Weerasingha
MD/2016/4912
39th Batch
Content
1 ) Medical definition of kernicterus
2) What is kernicterus?
3 ) Bilirubin & kernicterus
3.1) Unconjugated bilirubin 
3.2) Conjugated bilirubin
4) What Causes kernicterus?
5) Risk factors of kernicterus
6) Symptoms of Kernicterus
7) Diagnosis & Tests
8) cerebral palsy
8.1) Athetoid Cerebral Palsy
8.2) Dystonic Cerebral Palsy
9) Treatment for kernicterus
9.1) Photopherapy
9.2) A Complications of phototherapy
9.3) Exchange transfusion
9.4) Risks factors of exchange transfusions
9.5) Modern therapies
10 )Acknowledgement11) References
1. Medical definition of kernicterus
Kernicterus is a disorder that is due to severe jaundice in newborn, with accumilation
of the pigment named as bilirubin in the brain that leads to damage the brain, potentially leading to athetoid cerebral palsy, hearing loss, vision problems, or mental retardation. Also known as bilirubin encephalopathy.1
2.What is kernicterus?
K e r n i c t e r u s  is a rare kind of preventable brain damage that can happen in newborns with jaundice.

Jaundice is a yellow coloring of the skin and other tissues that affects about 60%-80% of infants in the United States. It happens when babies accumilate too much of a chemical called bilirubin in their blood.When is not treated it turns into kernicterus.2
Bilirubin is the final product of red blood cell breakdown occurs in spleen, liver& naturally occurring process in both babies and adults.But normally, this condition goes away on its own. If this condition persist for a long time when the bilirubin level stays too high that condition known as hyperbilirubinaemia.In hyperbilirubinemia bilirubin can accumulate in the gray matter a area which is located in the central nervous system(CNS)and is not treated immediately that jaundice becomes kernicterus and causes brain damage & other irreversible neurological damages.3, 4.

3.Bilirubin & kernicterus
There are two types of functional bilirubin in the body.

3.1.Unconjugated bilirubin 
This bilirubin type travels through the blood to the liver. It’s not water soluble means it doesn’t dissolve in water. so it can build up in the body.It transport within the blood binding with albumin.

3.2.Conjugated bilirubin
This is synthesized from unconjugated bilirubin in human liver. Conjugated bilirubin is water soluble & it can be removed from the body through the intestines urinary track.

If unconjugated bilirubin isn’t converted into its unconjugated form in the liver, unconjugated form can build up in the baby’s body. When the unconjugated bilirubin level is very high, it can come out from the blood and then can enter into the brain tissue through immature blood brain barrier of the infants.Increasement of the unconjugated bilirubin can lead up to kernicterus if something can aid it to build up. Conjugated bilirubin doesn’t enter into the brain usually and can be removed from the body. Therefore, conjugated bilirubin doesn’t lead to kernicterus.5
If the serum bilirubin concentration is below 428 ?mol/L in term babies then there is a high tendency to get away from kernicterus.The factors that influence the occurance of kernicterus in infants with hyperbilirubinaemia are
A serum bilirubin level higher than 340 ?mol/L in term babies
A rapidly rising bilirubin level is higher than 8.5 ?mol/L per hour. 6
4.What Causes kernicterus?
Increase heamolysis
Babies have many more red blood cells than a adult, as a result of the sudden transition from the uterus to the external world. Fetal red blood cells have a shorter lifespan than adult and can be destroyed rapidly in newborn period.It often results an highly increasement of bilirubin in the blood and tissues of newborns.Particularly infants having Glucose 6-Phosphate dehydrogenase enzyme deficiency who are exposed to mothballs.If this condition persist for a long time it causes kernicterus.3,7
Enzyme Deficiency of conjugation
uridinediphosphateglucuronosyltransferase isoform 1A1 (UGT1A1) enzyme induce a reaction called “glucuronidation”. This reaction turns a large load of sugar into the bilirubin and convert it water soluble, so it can excreted through the urine or the feces.Otherwise babies cannot eliminate bilirubin.This is the only pathway excretes bilirubin.So decrease of UGT1A1 enzyme increases unconjugated bilirubin in blood.4
Decreasing of albumin in blood
Factors that leads to decrease the albumin levels may cause to reduce albumin binding & transportation of unconjugated bilirubin to the liver and therefore larger load of free bilirubin present in the serum…Due to lack of development of the liver, blood albumin level are inadequate in early infancy to transport enough unconjuged bilirubin.8
Immaturity of the blood brain barrier
Occurance of Kernicterus is significantly changed by the changes of physiological permeability of the blood brain barrier.The permeability of the blood brain barrier is induced by acidosis and hypoxic ischemic damages, .In early infancy blood brain barrier is fully permeable to the unconjugated bilirubin due to its immaturity. Then bilirubin enters the brain, it can permanently stay in the brain’s gray matter resulting Kernicterus. Gray matter is essential for eye movement, hearing, balance, and coordination.3.8
5.Risk factors of kernicterus
When any of the risk factors are present . it is important that the doctor must treat jaundiced babies quickly, because there is a great potential for long term complications.3
Rh disease or ABO incompatibility
Sometimes both baby’s and mother’s blood types are not compatible. If a mother is Rh-negative, that means her red blood cells don’t have a certain type of protein that reasonable for Rh positiveness attached to them. It is possible for her baby to having a another type of Rh factor than her. If her baby is Rh-positive, it means they do have that protein attached to their red blood cells. This incident is commonly called as incompatibility.In Rh incompatibility, a part of fetus red blood cells can cross via the placenta and enters to the mother’s blood. The mother’s immunity system recognizes these cells as foreign bodies. It produces proteins called antibodies & attack the baby’s red blood cells. The mother’s antibodies can enter into the baby’s body through the placenta and then destroy the baby’s red blood cells.5
Incompatibility of the ABO system is more common & similar but less severe clinical situation.The mother is usually group O & the baby can be either A or B.There is a marked elevation in the titres of the naturally occurring anti A & anti B haemolysins but these level drop to normal level after pregnancy is not at greater risk.Not like Rh disease.9
Premature babies 
A child born before 37th week of gestation is having a greater risk of developing jaundice because of his or her liver may not be ful functional and have ability to get rid itself of excess bilirubin.10
Crigler-Najjar& Gilbert’s syndrome
Babies with this inherited condition lack of an enzyme needed to convert unconjugated bilirubin to conjugated bilirubin for removal.As a result excess amount of unconjugated bilirubin build up in the blood.5
Hypothyroidism
Permanent jaundice might be an earliest sign of hypothyroidism in an infant.Fortunately; all babies are screened for this with the newborn screening test at 48-72 hours of age. If other signs predict it as hypothyroidism, further investigation is mandatory because appropriate early treatment may prevent profound developmental delay.

Hepatitis
Hepatitis can be caused by infection like Toxoplasmosis, Cytomegalovirus, Rubella, Herpes or disorders like galactosaemia.7
Have a parent or sibling who had jaundice as an infant
A newborn that has famly member who had kernicterus early is more likely to develop the condition.5, 10
Infection
If the baby has other signs as well as excessive jaundice bacterial infection must be excluded.Infections acquired early pregnancy might cause neonatal hepatitis, but other clinical signs are obvious and a substantial fraction of the jaundice is conjugated (; 15 per cent).7
East Asian or Mediterranean descent 
A child born to a family of these two origins is more likely than others to develop jaundice at birth. Certain families inherit conditions like glucose-6-phosphate dehydrogenase deficiency most probably resulting in a higher likelihood that a child will develop jaundice as a newborn.10
Sulfonamides
Unconjugated bilirubin normally transport through the blood to the liver bind with albumin. In the liver it’s converted to conjugated bilirubin so it can be removed from the body as feces & urine.Sulfonamides can release bilirubin from albumin & increases bloodbilirubin level. The unbound bilirubin can cross into the brain and cause kernicterus.5
Bruising 
A baby who is born with bruising at birth has more tendency to develop jaundice than others. A bruise happens when blood goes out of a blood vessel due to a trauma or using of medical instruments to facilitate the delivery, and leads the colour of the skin to appear black & blue.When healing large bruises, they can cause excess levels of bilirubin to form in the body, resulting in jaundice10
Breast-milk jaundice
In third day of life, the Serum bilirubin concentration of infants who are breastfed is higher than infants who are fed by formulas.Content of the breast milk which produce excessive jaundice is not known but unsaturated fatty acids or a lipase that inhibits conjugating glucuronyltransferase enzyme have been suspected.7
Difficulty with feeding 
A child who is not eating and passing urine or stool within the first few days of life is at a high risk of developing jaundice, because those mechanisms aid in the excretion of excess bilirubin from the body.10
Biliary atresia
Biliary atresia is a rare complication in which the bile duct is absent, it leads to an obstructive jaundice which is fatal in most cases.Pale colour stools and dark colour urine usually can be seen in this babies.7
Cephalohaematoma
Macrosomia3
Any kind of deficiency or syndrome that either decrease the removal of bilirubin, or increases the amount of red blood cells(RBC) which are broken down can lead to jaundice.If jaundice is remain untreated or is treated too late can cause kernicterus.3
6
Linked pathological causes of infants who presented due to kernicterus in America.The number of babies with each of the pathologies are presented.6
6.Symptoms of Kernicterus
The symptoms of jaundice initially manifest on the face and then spread to the whites of the eyes, abdomen, arms, chest, and legs as the bilirubin levels continue to increase.child suffering from kernicterus may shows following symptom.10
Very yellow skin color that begin from the head and spread to the toes.

lethargic. This means they are unusually sleepy. lethargic babies sleep even more than a typical baby and are very hard to wake up.5
Irritability
Trouble feeding2
Fever
Extreme fussiness
Dehydration
Seizures
A high pitched and inconsolable cry.5,10
lack of wet or dirty diapers
A body arched like a bow,the head or neck and heels are bent backwards while the body protrudes forward
Hearing and other sensory problems
Limpness, stiffness or a floppy body
Irregular eye movements.10
If a baby has these symptoms, must see a doctor or take the baby to the nearest hospital.2,5,10
A baby having kernicterus with yellowish skin.7
7.Diagnosis & Tests
Babies usually have their highest bilirubin level when the age is3 to 5 days old. Newborns must be watched for jaundice every 8 to 12 hours within the first 2 days of their lives & again must be rechecked before they are 5 days old.2
Before the baby get discharged from the hospital a doctor checks the baby’s bilirubin levels.There are two tests.

Transcutaneous bilirubin, or TcB, level test – This procedure is done by a light meter that is placed on a newborn’s head in order to determine the child’s bilirubin level. If the meter reading is high, then the blood test is performed.

Total serum bilirubin, or TSB, level test – This test is done if the TcB level is high.The best test to check the excess bilirubin levels is taking a sample of blood from the baby. If a child’s blood bilirubin levels are too high, repeat blood testings will be done to predict the most reasonable way of treatment. If a child has jaundice,child must be tested repeatedly to treat the condition. 5,10
measuring serum bilirubin levels in the first 24 hours predicted hyperbilirubinaemia (? 290?mol/L) at days 3 to 5& serum bilirubin > 102 ?mol/L within the first 24 hours of life is predict the serum bilirubin > 290 ?mol/L within 3 and 5 days.

Also there is a method called Kramer’s rule which predict blood bilirubin level considering skin discolouration.6
8.cerebral palsy
The most significant complication of kernicterus is cerebral palsy.It occurs when bilirubin accumulate in the gray matter of brain.There are 2 kind of cerebral palsies.

8.1. Athetoid Cerebral Palsy
Athetoid/dyskinetic cerebral palsy  is characterized by involuntary movements of muscle with variable muscle tone .Children with athetoid cerebral palsy often show spastic motions.They need steady position for sitting or walking. and. Some children have trouble with fine motor skills. it takes more time ; energy to move the limbs into specific position.

8.2.Dystonic Cerebral Palsy
In this case causes involuntary muscle spasms and slow, rhythmic, twisting movements.Children dystonic cerebral palsy switch from a floppy and loose muscle tone to a tight one. Dystonic Cerebral pulsy can also cause difficulty in moving the tongue and vocal cords muscles.It leads to spoken inabilities. botulinum toxin uses as a treatment for this condition.3
11
A brain X-Ray which was effected by Kernicterus
9.Treatment for kernicterus
While treating to kernicterus, the doctors will consider the following factors.

baby’s bilirubin concentration
age of the baby
Whether the baby is a born preterm or not
bilirubin level rising rate.3
There are several recommended treatments for kernicterus
9.1.PhotopherapyPhototherapy is the most suitable treatment for kernicterus due to immature
Liver function &can be used prophylactically in infants with heamolitic anaemia.When the skin of jaundice infants is exposed to light in the spectrum of blue to green(420-450nm) bilirubin can be transformed into isomers which can be excreted without conjugation.The water soluble isomers of bilirubin is produced in human infants undergoing phototherapy are bound to albumin before being excreted in bile or urine.In human infants lumirubin appears to be the major photodegradation product of the pyrrole rings which make up the original porphyrin of the haem molecule.phototherapy is done in a incubator exposing whole body of the child to light apart from eyes.Photopherapy produce a light source usually wavelength of 425-475nm which reduce the plasma albumin level.Treatment should be given to infants as soon as their unconjugated bilirubin reaches 250 ?mol/L(15mg/100ml) in term infants & 170 ?mol/L(10mg/100ml) in preterm infants. In phototherapy body fluid level decrease rapidly.so It is important infant to get enough fluids during phototherapy. Breast or bottle feeding should continue. If a baby is severely dehydrated during procedure IV fluids would be needed.2,12.

9.2.A Complications of phototherapy
Overheating
excessive water loss
Severe diarrhoea
retinal damage
ileus in preterm infants
parental anxiety
rash.7
9.3.Exchange transfusion
Babies with a very high bilirubin level treated with blood exchange transfusion. At 1stbaby’s blood is removed a bit at a time. Then blood is replaced by matched blood from a donor.5
Exchange transfusion should be considered in infants with Rh disease who
have not received blood transfusions in utero
are visibly jaundiced within 12 hours of birth
have cord bilirubin ; 80 micromol/L
have cord blood haemoglobin ; 100 g/L
.Exchange transfusion takes place with the children at high risk of kernicterus..The effects of intrauterine blood transfusions are unpredictable, but haemolysis is usually less severe because more of the baby’s blood is Rh negative donor blood.6
9.4.Risks factors of exchange transfusions
Bradycardia
Apnea
Infection
Cyanosis
Air embolism
Vasospasm
Death (not oftenly).

After an exchange transfusion continuous inspection for haemoglobin is necessary because further haemolysis may causes anaemia,and the babies still need a number of blood transfusions.7
Regular feedings to the baby can decrease the bilirubin levels. Bilirubin is removed through the gut system as feces. The more babies eat, the more waste they produce, and the more bilirubin is removed from body.5
9.5.Modern therapies
Intravenous Gama globulin in immunehemolytic jaundice, Tin-mesoporphyrin and Bilirubin-oxidase are some of the modalities used in experimental or limited clinical trials by various workers.Antenatal phenobarbitone given to the mother in doses of 30 mg three times a day have been shown to reduce exchange transfusion in neonates with hemolytic disease.8
10.AcknowledgementI owe my deep gratitude to my instructor Dr.Mahinda Kommalage,who took keen interest on my study & guided me all along ,till the completion of the work by providing all the necessary information to succeed my study……
11.References1.medterms medical dictionary a-z list Medical Author and Editor Medical Author Tse-Ling Fong, M.D.

https://www.medicinenet.com/script/main/art.asp?articlekey=4100
2.WebMD Medical Reference Reviewed by Roy Benaroch, MD on March 14, 2017.

https://www.webmd.com/children/what-is-kernicterus – 1
3.Jaundice neonatal hyperbilirubimemia by Reiter & Walsh.

https://www.abclawcenters.com/frequently-asked-questions/can-jaundice-cause-cerebral-palsy/
4.Kernicterus From Wikipedia, the free encyclopedia.

https://en.wikipedia.org/wiki/Kernicterus
5.Medically reviewed by Karen Gill, MD on June 13, 2017 — Written by Stephanie Watson.

https://www.healthline.com/health/kernicterus
6. Neonatal screening for Kernicterus
External review against programme appraisal criteria for the UK National Screening Committee (UK NSC) Version: 3
file:///C:/Users/Guest/Downloads/Kernicterus_review_consultation_version%20(1).pdf
7.Department of Health & Human Services, State Government of Victoria, Australia.

https://www2.health.vic.gov.au/hospitals-and-health-services/patient-care/perinatal-reproductive/neonatal-ehandbook/conditions/jaundice
8. INDIAN JOURNAL OFPRACTICAL PEDIATRICS by Dr. A. Balachandran & Dr. K.Nedunchelian. Vol.7 No.4
9.Essential Paediatrics.Third Edition By Churchill Livingstone.63-64.

10.TheCPLawyer at TheCPLawyer.com
11.Neuroimaging in neonatal seizures.volume 17,issued 1,March 2015 By The Educational Journal of the International league against epilepsy.

https://www.jle.com/en/revues/epd/e-docs/neuroimaging_in_neonatal_seizures_303808/article.phtml?tab=texte#xref_box_fig2
12.Children’s Medicine ; surgery By Forrester Cockburn,Robert Carachi,Krishna N Goel ; Danial G Young.47-48.

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