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{{SK}}  [[Chronic]] [[bilirubin]] [[encephalopathy]]
{{SK}}  [[Chronic]] [[bilirubin]] [[encephalopathy]]
==Overview==
==Overview==
'''Kernicterus''' is [[irreversible]] [[brain]] [[damage]] due to [[chronic]] high levels of [[unconjugated]] [[bilirubin]] in the baby`s [[blood]] which is not treated early. [[Hyperbilirubinemia]] frequently occurs in [[majority]] of [[newborn]] [[infants]] but mostly it is [[benign]] and in [[severe]] [[cases]] can [[progress]] to kernicterus and [[developmental]] [[abnormalities]]. The [[risk]] of [[bilirubin]] [[induced]] [[neurologic]] [[damage]] and kernicterus are more in [[preterm]] than [[term]] [[neonates]] and the [[former]] [[suffer]] [[adverse]] [[effects]] at [[lower]] [[total]] [[bilirubin]] [[levels]] with [[worse]] [[long-term]] [[outcomes]]. [[Liver]] [[metabolizes]] and [[excretes]] [[bilirubin]]. [[During]] [[pregnancy]], the [[mother`s]] [[liver]] does it for the [[baby]]. After [[birth]], some of the [[baby`s]] [[liver]] [[enzyme]] not well [[developed]] [[specially]] in [[preterm]], [[bilirubin]] [[raises]] in the [[baby`s]] [[blood]] and [[accumulates]] in the [[skin]] and [[sclera]] of [[eyes]] and [[cause]] [[jaundice]]. When the [[jaundice]] gets [[severe]], The [[tissues]] [[protecting]] the [[brain]] (the [[blood-brain barrier]]) are [[immature]] in [[newborns]]. [[Bilirubin]] [[penetrates]] the [[brain]] and is [[deposited]] in the [[basal ganglia]],[[hippocampus]], [[geniculate bodies]] and [[cranial nerve nuclei]] causing [[irreversible]] [[damage]]. Depending on the [[level]] of [[exposure]], the [[effects]] [[range]] from [[unnoticeable]] to [[severe]] [[brain damage]]. When the [[jaundice]] occurs within ([[24 hours]]) of [[life]] is always [[pathological]], whereas it [[happens]] after 24 hours of [[life]], it can be [[physiological]]. [[Several]] [[underlying]] [[pathologic]] [[processes]] [[responsible]] for [[hyperbilirubinemia]] are [[G6PD]] [[deficiency]], [[Crigler-Najjar]] [[syndrome]], [[Gilbert]] [[syndrome]], [[hemolytic]] [[disorders]], and a [[decreased]] [[ability]] to [[conjugate]] [[bilirubin]] in [[neonates]] and [[infants]]. [[Newborn]] [[babies]] are often [[polycythemic]], meaning they have too many [[red blood cell]]s. When they [[break]] [[down]] the [[cells]], one of the [[byproducts]] is [[bilirubin]], which [[circulates]] in the [[blood]] and [[causes]] [[Neonatal_jaundice|jaundice]]. When [[hyperbilirubinemia]] occurs in [[adult]] and [[older]] [[children]], it is [[frequently]] due to [[liver]] [[abnormalities]].  
'''Kernicterus''' is defined as [[irreversible]] [[brain]] [[damage]] due to [[chronic]] high levels of [[unconjugated]] [[bilirubin]] in the baby's [[blood]]. It will develop if the high levels of [[unconjugated bilirrubin]] are not treated early. [[Hyperbilirubinemia]] frequently occurs in [[newborns]], but it is mostly [[benign]]. [[Severe]] [[cases]] can [[progress]] to kernicterus and [[developmental]] [[abnormalities]]. The [[risk]] of [[bilirubin]]-[[induced]] [[neurologic]] [[damage]] and kernicterus is higher in [[preterm]] than [[term]] [[neonates]], and the former, suffer [[adverse effects]] at lower [[total bilirubin]] levels with worse [[long-term]] [[outcomes]]. [[Liver]] [[metabolizes]] and [[excretes]] [[bilirubin]]. During [[pregnancy]], the mother's liver metabolizes it for the [[baby]]. After [[birth]], some newborns may have [[liver]] [[enzymes]] that are still immature, especially if they are [[preterm]]. This causes [[bilirubin]] to [[rise]] in the baby's [[blood]] and [[accumulates]] in the [[skin]] and [[sclera]] of [[eyes]], causing [[jaundice]]. The [[tissues]] [[protecting]] the [[brain]] (the [[blood-brain barrier]]) are [[immature]] in [[newborns]], therefore, they are vulnerable to increased levels of [[unconjugated bilirubin]]. [[Bilirubin]] [[penetrates]] the [[brain]] and is [[deposited]] in the [[basal ganglia]], [[hippocampus]], [[geniculate bodies]], and [[cranial nerve nuclei]] causing [[irreversible]] [[damage]]. Depending on the [[level]] of [[exposure]], the [[effects]] [[range]] from [[unnoticeable]] to [[severe]] [[brain damage]]. Many conditions may cause [[jaundice]], but when it occurs within ([[24 hours]]) of life it is always [[pathological]]. If it [[happens]] after 24 hours of life, it can be [[physiologic]]. Some of the several underlying [[pathologic]] [[processes]] responsible for [[hyperbilirubinemia]] are [[G6PD]] [[deficiency]], [[Crigler-Najjar]] [[syndrome]], [[Gilbert]] [[syndrome]], [[hemolytic]] [[disorders]], and [[decreased]] ability to [[conjugate]] [[bilirubin]] in [[neonates]] and [[infants]]. [[Newborn]] babies are often [[polycythemic]], meaning they have too many [[red blood cell]]s. When red cells are destroyed, one of the [[byproducts]] is [[bilirubin]], which [[circulates]] in the [[blood]] and [[causes]] [[Neonatal_jaundice|jaundice]]. When [[hyperbilirubinemia]] occurs in [[adult]]s and [[older]] [[children]], it is [[frequently]] due to [[liver]] [[abnormalities]].  
Some [[medications]], such as the [[antibiotic]] [[co-trimoxazole]] (a combination of [[trimethoprim]]/[[sulfamethoxazole]]) may [[induce]] this [[disorder]] in the [[baby]], either when taken by the [[mother]] or given [[directly]] to the [[baby]], due to [[displacement]] of [[bilirubin]] from binding [[sites]] on [[serum albumin]]. The [[bilirubin]] is then [[free]] to [[pass]] into the [[Central Nervous System]], because the [[baby's]] [[blood-brain barrier]] is not fully [[developed]]. In the ([[first 48 hrs of life]]), A [[baby]] should be [[checked]] for [[jaundice]] and if it is [[discharged]] before 72 hrs, the [[baby]] should be seen after 2 days. The [[treatment]] is [[phototherapy]] and [[exchange]] [[transfusion]].
Some [[medications]], such as the [[antibiotic]] [[trimethoprim]]/[[sulfamethoxazole]] may [[induce]] this [[disorder]] in the [[newborn]], either when taken by the [[mother]] or given [[directly]] to the [[patient]], due to [[displacement]] of [[bilirubin]] from binding [[sites]] on [[serum albumin]]. The [[bilirubin]] is then [[free]] to [[pass]] into the [[central nervous system]]. In the ([[first 48 hrs of life]]), a [[baby]] should be [[checked]] for [[jaundice]] and if it is [[discharged]] before 72 hrs, the [[baby]] should be seen after 2 days. The [[treatment]] is [[phototherapy]] and [[exchange]] [[transfusion]].


==Historical Perspective==
==Historical Perspective==
*Kernicterus was first discovered by Christrian Georg [[Schmorl]], a German [[Pathologist]], in 1904 <ref name="urlKernicterus: Past, Present, and Future | American Academy of Pediatrics">{{cite web |url=+https://doi.org/10.1542/neo.4-2-e33 |title=Kernicterus: Past, Present, and Future &#124; American Academy of Pediatrics |format= |work= |accessdate=}}</ref>.
*Kernicterus was first discovered by Christrian Georg [[Schmorl]], a German [[Pathologist]], in 1904<ref name="urlKernicterus: Past, Present, and Future | American Academy of Pediatrics">{{cite web |url=+https://doi.org/10.1542/neo.4-2-e33 |title=Kernicterus: Past, Present, and Future &#124; American Academy of Pediatrics |format= |work= |accessdate=}}</ref>.


*The [[association]] between [[hyperbilirubinemia]] and kernicterus was made in 1875<ref name="urlKernicterus: Past, Present, and Future | American Academy of Pediatrics">{{cite web |url=+https://doi.org/10.1542/neo.4-2-e33 |title=Kernicterus: Past, Present, and Future &#124; American Academy of Pediatrics |format= |work= |accessdate=}}</ref>.
*The [[association]] between [[hyperbilirubinemia]] and kernicterus was made in 1875<ref name="urlKernicterus: Past, Present, and Future | American Academy of Pediatrics">{{cite web |url=+https://doi.org/10.1542/neo.4-2-e33 |title=Kernicterus: Past, Present, and Future &#124; American Academy of Pediatrics |format= |work= |accessdate=}}</ref>.
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==Classification==
==Classification==
*Based on the duration of symptoms, [[bilirubin]] [[encephalopathy]] may be classified as either [[acute]], [[subtle]] or [[chronic]].  
*Based on the duration of symptoms, [[bilirubin]] [[encephalopathy]] may be classified as either [[acute]], [[subtle]] or [[chronic]].  
**[[Acute]] [[bilirubin]] [[encephalopathy]]: comprises the [[cute]] [[illness]] caused by [[severe]] [[hyperbilirubinemia]]. The [[sign]] and [[symptom]] includes [[decreased]] [[feeding]], [[lethargy]], [[hypotonia]] and/or [[hypertonia]], [[high]]-[[pitched]] [[cry]], [[retrocollis]] and [[opisthotonus]], [[setting]]-[[sun]] [[sign]], [[fever]], [[seizures]], and may be [[death]].
**[[Acute]] [[bilirubin]] [[encephalopathy]]: comprises the [[acute]] [[illness]] caused by [[severe]] [[hyperbilirubinemia]]. The [[signs]] and [[symptoms]] includes [[decreased]] [[feeding]], [[lethargy]], [[hypotonia]] and/or [[hypertonia]], high-pitched cry, [[retrocollis]] and [[opisthotonus]], setting-sun [[sign]], [[fever]], [[seizures]], and may cause [[death]].
**[[Subtle]] [[bilirubin]] [[encephalopathy]]/[[Bilirubin]] [[induced]] [[neurologic]] [[dysfunction]]: defined by the presence of [[insidious]] [[developmental]] [[disorders]] without the [[classical]] [[findings]] of [[kernicterus]]. This may presents with [[neurodevelopmental]] [[disorders]] such as [[sensory]] and [[sensorimotor]] [[integration]] [[disorders]], [[hypotonia]], [[ataxia]] or [[clumsiness]], [[aphasia]], and [[auditory]] [[neuropathy]] which is [[impaired]] [[auditory]] [[brainstem]] [[reflexes]] with normal [[otoacoustic]] [[emissions]] or [[cochlear]] [[microphonic]] [[responses]].
**[[Subtle]] [[bilirubin]] [[encephalopathy]]/[[Bilirubin]] [[induced]] [[neurologic]] [[dysfunction]]: defined by the presence of [[insidious]] [[developmental]] [[disorders]] without the classical findings of [[kernicterus]]. This may presents with [[neurodevelopmental]] [[disorders]] such as [[sensory]] and [[sensorimotor]] [[integration]] [[disorders]], [[hypotonia]], [[ataxia]] or [[clumsiness]], [[aphasia]], and [[auditory]] [[neuropathy]] which is [[impaired]] [[auditory]] [[brainstem]] [[reflexes]] with normal [[otoacoustic]] [[emissions]] or [[cochlear]] [[microphonic]] [[responses]].
**[[Chronic]] [[bilirubin]] [[encephalopathy]]: the [[long]]-[[term]] [[outcome]] of [[acute]] [[bilirubin]] [[encephalopathy]] and composed of a [[tetrad]] of [[clinical]] [[characteristics]] that are [[typically]] appear after one [[year]] of [[age]]:  
**[[Chronic]] [[bilirubin]] [[encephalopathy]]: the [[long]]-[[term]] [[outcome]] of [[acute]] [[bilirubin]] [[encephalopathy]] and composed of a [[tetrad]] of [[clinical]] [[characteristics]] that are [[typically]] appear after one [[year]] of [[age]]:  
***[[Abnormal]] [[motor]] [[control]], [[movements]], and [[muscle]] [[tone]];  
***[[Abnormal]] [[motor]] [[control]], [[movements]], and [[muscle]] [[tone]];  
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Kernicterus [[happens]] in [[all]] [[parts]] of the [[world]]. [[Geographic]] [[areas]] where [[glucose]]-6-[[phosphate]] [[dehydrogenase]]-[[deficiency]] is [[common]], the [[risk]] of kernicterus is [[higher]]. The [[incidence]] rate of kernicterus in [[Sweden]] is 1.3 per 100 000 [[births]] which is [[slightly]] [[higher]] than that in [[other]] [[population]]-[[based]] [[studies]] in [[high]]-[[resource]] [[settings]]. The [[incidence]] [[rate]] of kernicterus in [[Canada]], [[California]], and [[Denmark]], has been [[reported]] to be 0.5 to 1 per 100 000 [[births]], whereas in [[Norway]], the [[incidence]] [[rate]] has been [[estimated]] to be less than 0.5 per 100 000 [[births]]<ref name="pmid30901042">{{cite journal| author=Alkén J, Håkansson S, Ekéus C, Gustafson P, Norman M| title=Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden. | journal=JAMA Netw Open | year= 2019 | volume= 2 | issue= 3 | pages= e190858 | pmid=30901042 | doi=10.1001/jamanetworkopen.2019.0858 | pmc=6583272 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30901042  }} </ref>. The [[risk]] of kernicterus is [[higher]] in [[male]] [[newborns]] than [[female]]. However, the [[mechanism]] is [[unknown]]<ref name="pmid34277071">{{cite journal| author=Freudenberger DC, Shah RD| title=A narrative review of the health disparities associated with malignant pleural mesothelioma. | journal=J Thorac Dis | year= 2021 | volume= 13 | issue= 6 | pages= 3809-3815 | pmid=34277071 | doi=10.21037/jtd-20-3516 | pmc=8264689 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34277071  }} </ref>.
Kernicterus [[happens]] in [[all]] [[parts]] of the [[world]]. [[Geographic]] [[areas]] where [[glucose]]-6-[[phosphate]] [[dehydrogenase]]-[[deficiency]] is [[common]], the [[risk]] of kernicterus is [[higher]]. The [[incidence]] rate of kernicterus in [[Sweden]] is 1.3 per 100 000 [[births]] which is [[slightly]] [[higher]] than that in [[other]] [[population]]-[[based]] [[studies]] in [[high]]-[[resource]] [[settings]]. The [[incidence]] [[rate]] of kernicterus in [[Canada]], [[California]], and [[Denmark]], has been [[reported]] to be 0.5 to 1 per 100 000 [[births]], whereas in [[Norway]], the [[incidence]] [[rate]] has been [[estimated]] to be less than 0.5 per 100 000 [[births]]<ref name="pmid30901042">{{cite journal| author=Alkén J, Håkansson S, Ekéus C, Gustafson P, Norman M| title=Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden. | journal=JAMA Netw Open | year= 2019 | volume= 2 | issue= 3 | pages= e190858 | pmid=30901042 | doi=10.1001/jamanetworkopen.2019.0858 | pmc=6583272 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30901042  }} </ref>. The [[risk]] of kernicterus is [[higher]] in [[male]] [[newborns]] than [[female]]. However, the [[mechanism]] is [[unknown]]<ref name="pmid34277071">{{cite journal| author=Freudenberger DC, Shah RD| title=A narrative review of the health disparities associated with malignant pleural mesothelioma. | journal=J Thorac Dis | year= 2021 | volume= 13 | issue= 6 | pages= 3809-3815 | pmid=34277071 | doi=10.21037/jtd-20-3516 | pmc=8264689 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34277071  }} </ref>.
==Risk Factors==
==Risk Factors==
*[[preterm]] [[babies]]
*[[Preterm]] [[babies]]
**[[Babies]] with [[Darker]] [[Skin]] [[Color]]
*[[Babies]] with [[darker]] [[skin]] [[color]]
***[[East]] [[Asian]] or [[Mediterranean]] [[Descent]]
*[[East]] [[Asian]] or [[Mediterranean]] [[descent]]
****[[Feeding]] [[Difficulties]]
*[[Feeding]] [[difficulties]]
*****[[Sibling]] with [[Jaundice]]
*[[Siblings]] that presented with [[jaundice]]
******[[Bruising]]
*[[Bruising]]
*******[[Blood]] [[Type]]<ref name="urlWhat are Jaundice and Kernicterus? | CDC">{{cite web |url=https://www.cdc.gov/ncbddd/jaundice/facts.html#:~:text=Kernicterus%20is%20a%20type%20of,sometimes%20can%20cause%20intellectual%20disabilities. |title=What are Jaundice and Kernicterus? &#124; CDC |format= |work= |accessdate=}}</ref>
*[[Blood]] type (Rh or [[ABO]] incompatibility)<ref name="urlWhat are Jaundice and Kernicterus? | CDC">{{cite web |url=https://www.cdc.gov/ncbddd/jaundice/facts.html#:~:text=Kernicterus%20is%20a%20type%20of,sometimes%20can%20cause%20intellectual%20disabilities. |title=What are Jaundice and Kernicterus? &#124; CDC |format= |work= |accessdate=}}</ref>


==Screening==
==Screening==
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[[Hepatomegaly]] or [[splenomegaly]] on [[phyical]] [[examination]] are [[indicative]] of a [[hemolytic]] cause.<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>
[[Hepatomegaly]] or [[splenomegaly]] on [[phyical]] [[examination]] are [[indicative]] of a [[hemolytic]] cause.<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>


===physical Examination===
===Physical Examination===
*[[vital]] [[signs]]: [[Afebrile]], [[tachycardia]], [[dyspnea]], and [[impaired]] [[oxygen]] [[saturation]].
*[[Vital]] [[signs]]: [[afebrile]], [[tachycardia]], [[dyspnea]], and [[impaired]] [[oxygen]] [[saturation]].
**[[Head]] and [[Neck]]: [[icteric]] [[sclera]].
*[[Head]] and [[Neck]]: [[icteric]] [[sclera]].
***[[Skin]]: [[yellowish]] [[discoloration]] of the [[body]].
*[[Skin]]: [[yellowish]] [[discoloration]] of the [[body]].
****Neurologic: [[bulging]] [[fontanelles]] and [[setting]] [[sun]] [[sign]]([[upward]]-[[gaze]] [[paresis]])<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
*Neurologic: [[bulging]] [[fontanelles]] and [[setting]] [[sun]] [[sign]] ([[upward]]-[[gaze]] [[paresis]])<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.


===Laboratory Findings===
===Laboratory Findings===
[[Total]] and [[direct]] [[bilirubin]], [[Blood]] [[type]] [[mother]] and [[infant]], [[Coomb]] [[test]], [[Reticulocyte]] [[count]] and [[transcutaneous]] [[bilirubin]] [[measurement]] is helpful in a few cases<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
[[Total]] and [[direct]] [[bilirubin]], [[blood]] [[type]] [[mother]] and [[infant]], [[Coomb]] [[test]], [[reticulocyte]] [[count]] and [[transcutaneous]] [[bilirubin]] [[measurement]] is helpful in a few cases<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
 
===ECG===
===ECG===
There are no [[ECG]] findings [[associated]] with Kernicterus.
There are no [[ECG]] findings [[associated]] with Kernicterus.
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There are no [[x-ray]] findings [[associated]] with Kernicterus.
There are no [[x-ray]] findings [[associated]] with Kernicterus.
===Echocardiography or Ultrasound===
===Echocardiography or Ultrasound===
There are no [[Echocardiography]] findings [[associated]] with Kernicterus.
There are no [[echocardiography]] findings [[associated]] with Kernicterus.
 
===CT Scan===
===CT Scan===
[[CT]] [[Scan]] is not [[routinely]] [[indicated]] to [[diagnose]] [[kernicterus]]. It may help in [[ruling]] out other causes of [[encephalopathy]]<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
[[CT]] [[Scan]] is not [[routinely]] [[indicated]] to [[diagnose]] [[kernicterus]]. It may help in [[ruling]] out other causes of [[encephalopathy]]<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
===MRI===
===MRI===
[[MRI]] is not [[routinely]] [[indicated]] to [[diagnose]] [[kernicterus]]. It may help in [[ruling]] out other causes of [[encephalopathy]]<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
[[MRI]] is not [[routinely]] [[indicated]] to [[diagnose]] [[kernicterus]]. It may help in [[ruling]] out other causes of [[encephalopathy]]<ref name="urlKernicterus - StatPearls - NCBI Bookshelf">{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK559120/ |title=Kernicterus - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref>.
 
===Other Imaging Findings===
===Other Imaging Findings===
[[Advanced]] [[MRI]] including [[diffusion]]-[[weighted]] [[imaging]], [[magnetic]] [[resonance]] [[spectroscopy]], and [[diffusion]] [[tensor]] [[imaging]] with [[tractography]] may give good understanding of the [[pathogenesis]] of [[bilirubin]]-[[induced]] [[brain]] [[injury]] and the [[neural]] [[basis]] of [[long]]-[[term]] [[disability]] in [[infants]] and [[children]] with [[chronic]] [[bilirubin]] [[encephalopathy]]<ref name="pmid25267277">{{cite journal| author=Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF| title=Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise. | journal=Semin Perinatol | year= 2014 | volume= 38 | issue= 7 | pages= 422-8 | pmid=25267277 | doi=10.1053/j.semperi.2014.08.005 | pmc=4250342 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25267277  }} </ref>..
[[Advanced]] [[MRI]] including [[diffusion]]-[[weighted]] [[imaging]], [[magnetic]] [[resonance]] [[spectroscopy]], and [[diffusion]] [[tensor]] [[imaging]] with [[tractography]] may give good understanding of the [[pathogenesis]] of [[bilirubin]]-[[induced]] [[brain]] [[injury]] and the [[neural]] [[basis]] of [[long]]-[[term]] [[disability]] in [[infants]] and [[children]] with [[chronic]] [[bilirubin]] [[encephalopathy]]<ref name="pmid25267277">{{cite journal| author=Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF| title=Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise. | journal=Semin Perinatol | year= 2014 | volume= 38 | issue= 7 | pages= 422-8 | pmid=25267277 | doi=10.1053/j.semperi.2014.08.005 | pmc=4250342 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25267277  }} </ref>..
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The [[mainstay]] of [[treatment]] for kernicterus is [[medical]] [[therapy]]. [[Surgery]] is may be needed to [[treat]] the causes of [[hyperbilirubinemia]] such as in [[biliary]] [[atresia]]<ref name="pmid28878446">{{cite journal| author=Sumida W, Uchida H, Tanaka Y, Tainaka T, Shirota C, Murase N | display-authors=etal| title=Review of redo-Kasai portoenterostomy for biliary atresia in the transition to the liver transplantation era. | journal=Nagoya J Med Sci | year= 2017 | volume= 79 | issue= 3 | pages= 415-420 | pmid=28878446 | doi=10.18999/nagjms.79.3.415 | pmc=5577027 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28878446  }} </ref>.
The [[mainstay]] of [[treatment]] for kernicterus is [[medical]] [[therapy]]. [[Surgery]] is may be needed to [[treat]] the causes of [[hyperbilirubinemia]] such as in [[biliary]] [[atresia]]<ref name="pmid28878446">{{cite journal| author=Sumida W, Uchida H, Tanaka Y, Tainaka T, Shirota C, Murase N | display-authors=etal| title=Review of redo-Kasai portoenterostomy for biliary atresia in the transition to the liver transplantation era. | journal=Nagoya J Med Sci | year= 2017 | volume= 79 | issue= 3 | pages= 415-420 | pmid=28878446 | doi=10.18999/nagjms.79.3.415 | pmc=5577027 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28878446  }} </ref>.
===Primary Prevention===
===Primary Prevention===
[[Preventing]] [[jaundice]] by [[advising]] the [[mother]] to [[breasting]] [[feed]] her [[baby]] every 2-3 hrs a day. Giving [[water]] or [[dextrose]] [[water]] for [[breast]] [[feeding]] [[infants]] is not [[recommeded]] because it will not [[prevent]] [[hyperbilirubinemia]]<ref name="urlA Practical Approach to Neonatal Jaundice - American Family Physician">{{cite web |url=https://www.aafp.org/afp/2008/0501/p1255.html |title=A Practical Approach to Neonatal Jaundice - American Family Physician |format= |work= |accessdate=}}</ref>.
Promote and support [[breast]] [[feeding]]<ref name="urlA Practical Approach to Neonatal Jaundice - American Family Physician">{{cite web |url=https://www.aafp.org/afp/2008/0501/p1255.html |title=A Practical Approach to Neonatal Jaundice - American Family Physician |format= |work= |accessdate=}}</ref>.


===Secondary Prevention===
===Secondary Prevention===
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[[Treat]] [[jaundiced]] [[neonates]] [[based]] on the [[bilirubin]] leves with [[phototherapy]] or [[exchange]] [[transfusion]]<ref name="urlA Practical Approach to Neonatal Jaundice - American Family Physician">{{cite web |url=https://www.aafp.org/afp/2008/0501/p1255.html |title=A Practical Approach to Neonatal Jaundice - American Family Physician |format= |work= |accessdate=}}</ref>.
[[Treat]] [[jaundiced]] [[neonates]] [[based]] on the [[bilirubin]] leves with [[phototherapy]] or [[exchange]] [[transfusion]]<ref name="urlA Practical Approach to Neonatal Jaundice - American Family Physician">{{cite web |url=https://www.aafp.org/afp/2008/0501/p1255.html |title=A Practical Approach to Neonatal Jaundice - American Family Physician |format= |work= |accessdate=}}</ref>.


[[Category:Up to Date]]
==References==
==References==
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Latest revision as of 18:38, 12 October 2023

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdulkerim Yassin, M.B.B.S[2]

Synonyms and keywords: Chronic bilirubin encephalopathy

Overview

Kernicterus is defined as irreversible brain damage due to chronic high levels of unconjugated bilirubin in the baby's blood. It will develop if the high levels of unconjugated bilirrubin are not treated early. Hyperbilirubinemia frequently occurs in newborns, but it is mostly benign. Severe cases can progress to kernicterus and developmental abnormalities. The risk of bilirubin-induced neurologic damage and kernicterus is higher in preterm than term neonates, and the former, suffer adverse effects at lower total bilirubin levels with worse long-term outcomes. Liver metabolizes and excretes bilirubin. During pregnancy, the mother's liver metabolizes it for the baby. After birth, some newborns may have liver enzymes that are still immature, especially if they are preterm. This causes bilirubin to rise in the baby's blood and accumulates in the skin and sclera of eyes, causing jaundice. The tissues protecting the brain (the blood-brain barrier) are immature in newborns, therefore, they are vulnerable to increased levels of unconjugated bilirubin. Bilirubin penetrates the brain and is deposited in the basal ganglia, hippocampus, geniculate bodies, and cranial nerve nuclei causing irreversible damage. Depending on the level of exposure, the effects range from unnoticeable to severe brain damage. Many conditions may cause jaundice, but when it occurs within (24 hours) of life it is always pathological. If it happens after 24 hours of life, it can be physiologic. Some of the several underlying pathologic processes responsible for hyperbilirubinemia are G6PD deficiency, Crigler-Najjar syndrome, Gilbert syndrome, hemolytic disorders, and decreased ability to conjugate bilirubin in neonates and infants. Newborn babies are often polycythemic, meaning they have too many red blood cells. When red cells are destroyed, one of the byproducts is bilirubin, which circulates in the blood and causes jaundice. When hyperbilirubinemia occurs in adults and older children, it is frequently due to liver abnormalities. Some medications, such as the antibiotic trimethoprim/sulfamethoxazole may induce this disorder in the newborn, either when taken by the mother or given directly to the patient, due to displacement of bilirubin from binding sites on serum albumin. The bilirubin is then free to pass into the central nervous system. In the (first 48 hrs of life), a baby should be checked for jaundice and if it is discharged before 72 hrs, the baby should be seen after 2 days. The treatment is phototherapy and exchange transfusion.

Historical Perspective

Classification

Pathophysiology

The neonatal hyperbilirubinemia occurs due to increased production or limited excretion of indirect or unconjugated bilirubin. Newborns baby, especially preterm neonates, have higher rates of bilirubin production than adults, because an increased red cells turnover and a shorter life span. In newborn neonates, unconjugated bilirubin is not easily excreted, and there is limited bilirubin congugation which lead to physiologic jaundice. Excessive physiologic jaundice occurs at values above 7 to 17 mg/dl [104 to 291 μmol/l]). Serum bilirubin concentrations greater than 17 m/dl in full-term infants are no longer considered physiologic and pathologic causes should be identified, of which the most common are Crigler-Najjar syndrome, Gilbert syndrome, hemolytic disorders, and a reduced ability to conjugate bilirubin in newborn babies[3].

Causes

Bilirubin is a yellow pigment produced by the breakdown of hemoglobin in old or hemolyzed red blood cells. High levels of bilirubin is due to either increased production, decreased hepatic uptake, impaired conjugation, or increased enterohepatic circulation. Kernicterus is caused by very high levels of indirect or unconjugated bilirubin in the blood which crosses blood brain barrier and yellow staining of brain tissues that leads to brain damage and hearing loss[3].

Differentiating Kernicterus from other Diseases

Kernicterus must be differentiated from other diseases that cause movement disorder, visual or auditory impairment such as Cerebral palsy, Head trauma, Neonatal sepsis, Congenital TORCH infections, Hypoxic-ischemic brain injury in the newborn, Fetal alcohol syndrome and Cretinism/pediatric hypothyroidism[4].

Epidemiology and Demographics

Kernicterus happens in all parts of the world. Geographic areas where glucose-6-phosphate dehydrogenase-deficiency is common, the risk of kernicterus is higher. The incidence rate of kernicterus in Sweden is 1.3 per 100 000 births which is slightly higher than that in other population-based studies in high-resource settings. The incidence rate of kernicterus in Canada, California, and Denmark, has been reported to be 0.5 to 1 per 100 000 births, whereas in Norway, the incidence rate has been estimated to be less than 0.5 per 100 000 births[5]. The risk of kernicterus is higher in male newborns than female. However, the mechanism is unknown[6].

Risk Factors

Screening

There is insufficient evidence to recommend routine screening for kernicterus[8].

Natural History, Complications, Prognosis

Kernicterus is a very rare type of brain damage that occurs in a newborn with severe jaundice.The term kernicterus, which refers to yellow staining of the brainstem nuclei (Greek for ‘jaundice of the nuclei’). The prognosis of kernicterus depends on the severity and time to intervention. With early intervention, there may be full recovery. However, a late diagnosis can cause Permanent brain damage, enamel dysplasia, paralysis of upward gaze and, intellectual deficits, Hearing loss and Death..[9]

Diagnosis

History and Symptoms

Weakness lethargy poor feeding Extensor hypertonia retrocollis opisthotonus and hypotonia are generally seen in this phase.

Hypotonia Hyperreflexia Delayed achievement of milestones Visual and auditory defects Choreathetoid cerebral palsy Hepatomegaly or splenomegaly on phyical examination are indicative of a hemolytic cause.[4]

Physical Examination

Laboratory Findings

Total and direct bilirubin, blood type mother and infant, Coomb test, reticulocyte count and transcutaneous bilirubin measurement is helpful in a few cases[4].

ECG

There are no ECG findings associated with Kernicterus.

x-ray

There are no x-ray findings associated with Kernicterus.

Echocardiography or Ultrasound

There are no echocardiography findings associated with Kernicterus.

CT Scan

CT Scan is not routinely indicated to diagnose kernicterus. It may help in ruling out other causes of encephalopathy[4].

MRI

MRI is not routinely indicated to diagnose kernicterus. It may help in ruling out other causes of encephalopathy[4].

Other Imaging Findings

Advanced MRI including diffusion-weighted imaging, magnetic resonance spectroscopy, and diffusion tensor imaging with tractography may give good understanding of the pathogenesis of bilirubin-induced brain injury and the neural basis of long-term disability in infants and children with chronic bilirubin encephalopathy[10]..

Other Diagnostic Studies

Brainstem evoked auditory response (BEAR) aid to diagnose the most common complication of bilirubin toxicity i.e., hearing impairmen. Complete blood count, Serum electrolytes and lumbar puncture to rule out sepsis[4]..

Treatment

Medical Therapy

Fluid supplementation in term infants presenting with severe hyperbilirubinemia decreases the rate of exchange transfusion and duration of phototherapy. The management of kernicterus is to prevent neurotoxicity by reducing bilirubin levels. The mainstays of therapy to prevent and treat hyperbilirubinemia are:

Surgery

The mainstay of treatment for kernicterus is medical therapy. Surgery is may be needed to treat the causes of hyperbilirubinemia such as in biliary atresia[11].

Primary Prevention

Promote and support breast feeding[12].

Secondary Prevention

Identify and evaluat jaundice.

Post delivery, check serum bilirubin levels in all newborns with jaundice in the first 24 hours.

Know that visual estimation of bilirubin levels is inaccurate.

Monitor preterm( i.e less than 37 weeks) newborns closely.

Do a thorough risk assessment for all newborns.

Educate the parents about jaundice and alarm them.

Schedule follow up visit.

Treat jaundiced neonates based on the bilirubin leves with phototherapy or exchange transfusion[12].

References

  1. ↑ 1.0 1.1 [+https://doi.org/10.1542/neo.4-2-e33 "Kernicterus: Past, Present, and Future | American Academy of Pediatrics"] Check |url= value (help).
  2. ↑ Das S, van Landeghem FKH (2019). "Clinicopathological Spectrum of Bilirubin Encephalopathy/Kernicterus". Diagnostics (Basel). 9 (1). doi:10.3390/diagnostics9010024. PMC 6468386. PMID 30823396.
  3. ↑ 3.0 3.1 Dennery PA, Seidman DS, Stevenson DK (2001). "Neonatal hyperbilirubinemia". N Engl J Med. 344 (8): 581–90. doi:10.1056/NEJM200102223440807. PMID 11207355.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 "Kernicterus - StatPearls - NCBI Bookshelf".
  5. ↑ Alkén J, Håkansson S, Ekéus C, Gustafson P, Norman M (2019). "Rates of Extreme Neonatal Hyperbilirubinemia and Kernicterus in Children and Adherence to National Guidelines for Screening, Diagnosis, and Treatment in Sweden". JAMA Netw Open. 2 (3): e190858. doi:10.1001/jamanetworkopen.2019.0858. PMC 6583272 Check |pmc= value (help). PMID 30901042.
  6. ↑ Freudenberger DC, Shah RD (2021). "A narrative review of the health disparities associated with malignant pleural mesothelioma". J Thorac Dis. 13 (6): 3809–3815. doi:10.21037/jtd-20-3516. PMC 8264689 Check |pmc= value (help). PMID 34277071 Check |pmid= value (help).
  7. ↑ "What are Jaundice and Kernicterus? | CDC".
  8. ↑ Trikalinos TA, Chung M, Lau J, Ip S (2009). "Systematic review of screening for bilirubin encephalopathy in neonates". Pediatrics. 124 (4): 1162–71. doi:10.1542/peds.2008-3545. PMID 19786450.
  9. ↑ "Kernicterus Article".
  10. ↑ Wisnowski JL, Panigrahy A, Painter MJ, Watchko JF (2014). "Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise". Semin Perinatol. 38 (7): 422–8. doi:10.1053/j.semperi.2014.08.005. PMC 4250342. PMID 25267277.
  11. ↑ Sumida W, Uchida H, Tanaka Y, Tainaka T, Shirota C, Murase N; et al. (2017). "Review of redo-Kasai portoenterostomy for biliary atresia in the transition to the liver transplantation era". Nagoya J Med Sci. 79 (3): 415–420. doi:10.18999/nagjms.79.3.415. PMC 5577027. PMID 28878446.
  12. ↑ 12.0 12.1 "A Practical Approach to Neonatal Jaundice - American Family Physician".
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