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{{CMG}} {{AE}}{{Ifeoma Anaya}}
{{CMG}} {{AE}}{{Ifeoma Anaya}}


{{SK}} [[Jaundice]] in kids; [[hyperbilirubinemia]]
{{SK}} [[Jaundice]] in kids, [[hyperbilirubinemia]]


==Overview==
==Overview==
The word '[[Jaundice]]' was derived from the french word for yellow which is '''''jaune'''''. [[Jaundice]] may be classified into two broad categories based on its time of onset and cause; [[physiologic]] and [[pathologic]] [[jaundice]]. [[Jaundice]] is caused by high [[concentrations]] of [[bilirubin]] in the [[bloodstream]]. A condition known as [[Hyperbilirubinemia]]. [[Hyperbilirubinemia]] can result from [[abnormalities]] in the [[metabolism]] of [[bilirubin]] which could occur at any stage from its [[production]] which is a result of the excessive breakdown of [[red blood cells]], defects in its [[hepatic]] [[metabolism]], and its post [[hepatic]] transport. [[Pathologic]] causes of [[jaundice]] can be classified into causes of conjugated and unconjugated [[hyperbilirubinemia]]. [[Differentials]] for [[jaundice]] are very limited however some [[skin]] discolorations in [[healthy]] individuals can look like [[jaundice]] in certain circumstances. The [[prevalence]] of [[jaundice]] varies among [[patient]] [[populations]]. In [[infants]] born at [[term]], 60% will develop [[jaundice]] in their first-week of [[life]]. This rises to 80% in [[preterms]]. Common [[risk factors]] in the development of [[Jaundice]] in [[children]] are a [[family history]] of [[jaundice]], [[family history]] of a child born with [[jaundice]], [[hyperthyroidism]] in mother, [[medication]] use by mother, etc. It is essential for every [[clinician]] to note that [[jaundice]] is not always a [[benign]] condition therefore, extensive [[investigation]] of a child with [[jaundice]] is necessary to [[prevent]] severe [[complications]]. [[Symptoms]] of [[Jaundice]] in [[children]] may include the following: yellowish discoloration of the [[skin]], [[sclera]], and [[mucous membrane]], time of onset, [[duration]], and [[progression]].  [[Patients]] with [[jaundice]] usually appear yellow on the [[skin]], [[mucous membranes]], and/or [[sclera]]. A useful [[technique]] in assessing the severity of [[jaundice]] is by using the [[principle]] of [[skin]] discoloration progressing in a cephalo-caudal direction in [[newborns]]. [[Laboratory]] findings include measuring the [[serum bilirubin]] from a [[blood]] sample. The total and conjugated portions are measured and the unconjugated fraction is measured by subtracting the conjugated fraction from the total. [[Echocardiography]] can detect [[cardiac]] [[abnormalities]] in [[patients]] with [[Alagille syndrome]] and [[biliary atresia]]. [[Ultrasonography]] of the [[abdomen]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]], or [[cholestatic]] workup in the setting of conjugated [[hyperbilirubinemia]]. [[Treatment]] options include [[phototherapy]], [[intravenous]] [[immunoglobulin]](IVIG), and [[exchange transfusion]]. [[Pharmacological]] options do exist. [[Surgery]] is the mainstay of [[therapy]] or the definitive [[treatment]] for most [[obstructive]] causes of conjugated [[hyperbilirubinemia]]. Several etiologies may be generally difficult to [[prevent]] however the [[prevention]] of [[complications]] from [[jaundice]] is equally crucial. Parents should be educated on how to recognize [[jaundice]] very early in a [[neonate]] so as to present promptly for management.
The word '[[Jaundice]]' is derived from the French word for [[Yellow discolouration|yellow]], which is '''''jaune'''''. [[Jaundice]] may be [[Classification|classified]] into two broad [[categories]] based on its [[Time series|time]] of onset and [[Causes|cause]] such as [[physiologic]] and [[pathologic]] [[jaundice]]. [[Jaundice]] is [[Causes|caused]] by high [[concentrations]] of [[bilirubin]] in the [[bloodstream]], a [[condition]] known as [[hyperbilirubinemia]]. [[Hyperbilirubinemia]] can [[result]] from [[abnormalities]] in the [[metabolism]] of [[bilirubin]] which could occur at any stage from its [[production]], which is a [[result]] of the excessive breakdown of [[red blood cells]], [[Defect|defects]] in its [[hepatic]] [[metabolism]], and its post [[hepatic]] [[Transporter|transport]]. [[Pathologic]] [[causes]] of [[jaundice]] can be [[Classification|classified]] into [[causes]] of [[Conjugated bilirubin|conjugated]] and [[Unconjugated bilirubin|unconjugated]] [[hyperbilirubinemia]]. [[Differentials]] for [[jaundice]] are very limited however, some [[Skin discoloration|skin discolorations]] in [[healthy]] [[Individual growth|individuals]] can look like [[jaundice]] in certain circumstances. The [[prevalence]] of [[jaundice]] varies among [[patient]] [[populations]]. In [[infants]] born at [[term]], 60% will develop [[jaundice]] in their first-week of [[life]], which rises to 80% in [[preterms]]. Common [[risk factors]] in the [[development]] of [[jaundice]] in [[children]] are a [[family history]] of [[jaundice]], [[family history]] of a [[child]] born with [[jaundice]], [[hyperthyroidism]] in the mother, [[medication]] use by the mother, etc. It is essential for every [[clinician]] to note that [[jaundice]] is not always a [[benign]] condition therefore, extensive [[investigation]] of a [[child]] with [[jaundice]] is necessary to [[prevent]] severe [[complications]]. [[Symptoms]] of [[jaundice]] in [[children]] may include the [[Yellow discolouration|yellowish discoloration]] of [[skin]], [[sclera]], and [[mucous membrane]]. A useful [[technique]] in assessing the severity of [[jaundice]] is by using the [[principle]] of [[skin discoloration]] progressing in a cephalo-caudal direction in [[newborns]]. [[Laboratory]] findings include measuring the [[serum bilirubin]] from a [[blood]] sample. The total and [[Conjugated bilirubin|conjugated]] portions are measured and the [[Unconjugated bilirubin|unconjugated fraction]] is measured by subtracting the [[Conjugated bilirubin|conjugated fraction]] from the total. [[Echocardiography]] can detect [[cardiac]] [[abnormalities]] in [[patients]] with [[Alagille syndrome]] and [[biliary atresia]]. [[Ultrasonography]] of the [[abdomen]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]], or [[cholestatic]] workup in the setting of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]]. [[Treatment]] options include [[phototherapy]], [[intravenous]] [[immunoglobulin]] ([[IVIG]]), and [[exchange transfusion]]. [[Pharmacological]] options are also there. [[Surgery]] is the mainstay of [[therapy]] or the definitive [[treatment]] for most [[obstructive]] [[causes]] of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]]. Several [[etiologies]] may be generally difficult to [[prevent]] however, the [[prevention]] of [[complications]] from [[jaundice]] is equally crucial. Parents should be educated on how to recognize [[jaundice]] very early in a [[neonate]] so as to present promptly for the management.


==Historical Perspective==
==Historical Perspective==
*The word '[[Jaundice]]' was derived from the french word for yellow which is '''''jaune'''''.<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
 
*Earliest known texts of '''''[[Icterus]] neonatorum''''' dates back to the [[medical]] [[records]] of the Providence Lying-in [[Hospital]] in the late 19th century. A phenomenon observed amongst several [[neonates]] in their first week of stay and attributed to [[breastfeeding]] which was the predominant way [[neonates]] were fed.
*The word '[[Jaundice]]' is derived from the French word for [[Yellow discolouration|yellow]] which is '''''jaune'''''.<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*A severe form termed '''''[[Icterus]] gravis''''' was better understood in the 1940s when advances in [[immunology]] and [[genetics]] led to the discovery of the Rh group of [[red cell]] [[antigens]] explaining its frequent recurrences in families after a first [[child]] becomes affected. These advances in [[hemolytic]] [[diseases]] birthed effective [[treatment]] modalities and [[screening]] methods that included [[maternal]] [[serology]] and [[amniocentesis]] in the [[perinatal]] period.  
*Very early records of '''''[[Icterus]] neonatorum''''' date back to the [[medical]] [[records]] of the Providence Lying-in [[Hospital]] in the late 19th century. A feature observed amongst several [[neonates]] in the first week of life and attributed to [[breastfeeding]].
*The Baby Boom Years of the 1960s which was flanked by an increase in [[birth]] rates led to the development of the Rh-immune [[antiglobulin]]. This was as a result of a corresponding rise in the rate of [[neonatal]] [[jaundice]]. Thus, Rh [[erythroblastosis]] became very rare with [[screening]] and [[immunoglobulin]] [[prophylaxis]] during the [[antenatal]] period. <ref>https://www.rimed.org/medhealthri/2010-05/2010-05-154.pdf</ref>
*'''''[[Icterus]] gravis''''', a more dire [[Presenting symptom|presentation]] was better understood in the 1940s when advances in [[immunology]] and [[genetics]] led to the discovery of the [[Rh disease|Rh]] group of [[red cell]] [[antigens]]. It explained its recurrent nature in families after a first [[child]] becomes affected. These advances also led to the [[development]] of [[Effective accessibility|effective]] [[treatment]] modalities along with [[screening]] methods such as [[maternal]] [[serology]] and [[amniocentesis]] in the [[perinatal]] period.
*The principles behind [[Phototherapy]] were first discovered at Rochford General [[Hospital]], Essex in the 1950s. [[Babies]] taken outside to the warm sunshine with the aim of taking a break from the confines of an [[incubator]] literarily became ''less yellow'' than before. Subsequently, [[lab]] [[results]] further confirmed this discovery. <ref>https://www.viapath.co.uk/news-and-press/the-birth-of-phototherapy</ref>
*An increase in [[birth]] rates during the Baby Boom period of the 1960s enabled the completion of [[clinical trials]] that led to the [[development]] of the [[Rh disease|Rh]]-[[immune]] [[antiglobulin]], following a corresponding rise in the [[rate]] of [[neonatal]] [[jaundice]]. With [[screening]] and [[immunoglobulin]] [[prophylaxis]], Rh [[erythroblastosis]] subsequently became very [[rare]].<ref name="pmid1846439">{{cite journal| author=Mittendorf R, Williams MA| title=Rho(D) immunoglobulin (RhoGAM): how it came into being. | journal=Obstet Gynecol | year= 1991 | volume= 77 | issue= 2 | pages= 301-3 | pmid=1846439 | doi=10.1097/00006250-199102000-00029 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1846439  }} </ref>
*The idea behind the [[development]] of [[phototherapy]] was first discovered at Rochford General [[Hospital]], Essex in the 1950s. [[Babies]] carried out to the warm sunshine with the aim of having a timeout from the [[incubator]] literally became ''less yellow'' than before. Subsequently, [[lab]] [[results]] further [[Confirmatory factor analysis|confirmed]] this [[Discovery Investigations|discovery]]. <ref name="pmid23650299">{{cite journal| author=Weiss EM, Zimmerman SS| title=A tale of two hospitals: the evolution of phototherapy treatment for neonatal jaundice. | journal=Pediatrics | year= 2013 | volume= 131 | issue= 6 | pages= 1032-4 | pmid=23650299 | doi=10.1542/peds.2012-3651 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23650299  }} </ref>


==Classification==
==Classification==
*[[Jaundice]] may be classified into two broad categories based on its time of onset and cause.
 
**'''[[Physiologic]] [[jaundice]]''':
*[[Jaundice]] may be [[Classification|classified]] into two broad [[categories]] based on its time of onset and [[Causes|cause]] as shown in the table below:
***Seen after the first 24 hours of life.
 
***[[Serum bilirubin]] levels never rise >5mg/dl daily and maximum [[concentration]] is about 12mg/dl and 14mg/dl in full terms and [[preterms]] respectively.
{| class="wikitable"
***Reaches the highest levels in the 4th-5th days and resolves within 2 weeks in both full-term and [[preterm]] [[infants]].  
|+Classification of Jaundice
***[[Infants]] usually appear well.
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Type of Jaundice
**'''Pathological [[jaundice]]''':
! style="background:#4479BA; color: #FFFFFF;" align="center" + |Details
***Appears anytime from the first few hours of life.
|-
***[[Serum bilirubin]] levels rise at a rate of >5mg/dl per day or 0.5mg/dl per hour and maximum [[concentration]] is usually >12mg/dl and >14mg/dl in full terms and [[preterms]] respectively.
| align="center" style="background:#DCDCDC;" + |'''[[Physiologic]] [[jaundice]]'''
***[[Infants]] appear [[ill]] and [[pale]] with abnormal discoloration of [[urine]] and [[stool]].<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
|
*Seen after the first 24 hours of [[life]].
*[[Serum bilirubin]] never exceeds >5mg/dl daily and the maximum [[concentration]] is about 12mg/dl and 14mg/dl in full terms and [[preterms]] respectively.
*The highest levels are attained in the first 4-5 days of [[life]] and resolve within 2 weeks in both full-term and [[preterm]] [[infants]].
*[[Infants]] usually [[Appearance|appear]] well.
|-
| align="center" style="background:#DCDCDC;" + |'''[[Pathological]] [[jaundice]]'''<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
|
*Seen anytime from the first few hours of [[life]].
*[[Serum bilirubin]] increases at a [[rate]] of >5mg/dl per day or 0.5mg/dl per hour and maximum [[concentration]] is usually >12mg/dl and >14mg/dl in full terms and [[preterms]] respectively.
*[[Infants]] appear [[ill]] and [[pale]] with [[abnormal]] discoloration of [[urine]] and [[stool]].
|}


==Pathophysiology==
==Pathophysiology==


*[[Jaundice]] is caused by high [[concentrations]] of [[bilirubin]] in the [[bloodstream]]. A condition known as [[Hyperbilirubinemia]].
*[[Jaundice]] is caused by high [[concentrations]] of [[bilirubin]] in the [[bloodstream]], a [[condition]] known as [[hyperbilirubinemia]].
*[[Hyperbilirubinemia]] can result from abnormalities in the [[metabolism]] of [[bilirubin]] which could occur at any stage from its [[production]] which is as a result of the excessive [[breakdown]] of [[red blood cells]], defects in its [[hepatic]] [[metabolism]], and its post [[hepatic]] transport.
*[[Hyperbilirubinemia]] can [[result]] from [[abnormalities]] in the [[metabolism]] of [[bilirubin]] which could occur at any stage from its [[production]], which is as a [[result]] of the excessive [[breakdown]] of [[red blood cells]], [[Defect|defects]] in its [[hepatic]] [[metabolism]], and its post [[hepatic]] [[Transporter|transport]].
*[[Hemoglobin]] released from the [[breakdown]] of old or defective [[red blood cells]] is composed of [[heme]] and [[globin]]. [[Globin]] is broken down into its component [[amino acids]] and [[recycled]] while [[heme]] is split into [[iron]] and [[biliverdin]] by the [[enzyme]], [[heme oxygenase]] in the [[reticuloendothelial]] [[system]]. [[Iron]] is transferred to [[ferritin]] and used again to make [[hemoglobin]] while [[biliverdin]] is converted to [[bilirubin]] by [[biliverdin reductase]]. <ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*[[Hemoglobin]] from the [[breakdown]] of effete [[red blood cells]] is composed of [[heme]] and [[globin]]. [[Globin]] is further dismantled into its component [[amino acids]] and [[recycled]] while [[heme]] is split into [[iron]] and [[biliverdin]] by the [[enzyme]], [[heme oxygenase]] in the [[reticuloendothelial]] [[system]]. [[Iron]] is transferred to [[ferritin]] and used again to make [[hemoglobin]] while [[biliverdin]] is converted to [[bilirubin]] by [[biliverdin reductase]]. <ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*[[Bilirubin]], which is [[water]]-insoluble becomes coupled to [[albumin]] and transported into [[hepatic]] [[cells]] for conjugation.  
*[[Water]]-insoluble [[bilirubin]] becomes coupled to [[albumin]] and transported into [[hepatic]] [[cells]] for [[conjugation]].
*This [[albumin]]-[[bilirubin]] compound is broken down and the unconjugated [[bilirubin]] enters the [[cytosol]] of [[hepatocytes]]to be conjugated to [[glucuronic acid]] in the [[endoplasmic reticulum]] by the [[enzyme]], Uridine diphosphate glucuronosyltransferase (UDPGT). <ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*This [[albumin]]-[[bilirubin]] compound is broken down and the [[unconjugated bilirubin]] enters the [[cytosol]] of [[hepatocytes]] to be [[Conjugated bilirubin|conjugated]] to [[glucuronic acid]] in the [[endoplasmic reticulum]] by the [[enzyme]], [[Uridine diphosphate glucuronyltransferase|uridine diphosphate glucuronyltransferase (UDPGT)]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*Conjugated [[bilirubin]] is secreted into [[bile]] and then into the [[small intestine]] after being stored in the [[gall bladder]]. It eventually gets to the [[colon]] where it is acted upon by [[bacterial]] [[flora]] and deconjugated to [[urobilinogen]]. Most of these are [[excreted]] into [[feces]] as the brown pigment, [[stercobilin]], and the rest is [[reabsorbed]] into the [[blood]], converted to yellow [[urobilin]] which is eventually excreted into the [[urine]]. <ref>https://www.rahulgladwin.com/noteblog/gastroenterology/jaundice.php</ref>
*This [[Conjugated bilirubin|conjugated]] form of [[bilirubin]] is [[Secretion|secreted]] into [[bile]] and then into the [[small intestine]] after being stored in the [[gall bladder]]. It subsequently reaches the [[colon]] where it is acted upon by [[bacterial]] [[flora]] and deconjugated to [[urobilinogen]]. Most are [[excreted]] into [[feces]] as the [[brown]] [[pigment]], [[stercobilin]], and the rest is [[reabsorbed]] into the [[blood]], converted to yellow [[urobilin]] which is eventually excreted into the [[urine]].
*Conjugated or unconjugated [[hyperbilirubinemia]] gives a clue as to the defective mechanism/point in the [[system]] responsible for the [[metabolism]] of [[bilirubin]].
*[[Hyperbilirubinemia]] whether [[Conjugated bilirubin|conjugated]] or [[Unconjugated bilirubin|unconjugated]] gives a clue as to the [[Defect|defective]] point in the [[metabolism]] of [[bilirubin]].
 
==Causes==


==Differentiating Jaundice in children from other Diseases==
*[[Causes]] of [[jaundice]] in [[children]] can be [[Classification|classified]] as follows:
{{familytree/start}}
{{familytree| | | | | | | A01 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |A01=[[Causes]] of [[jaundice]] in [[children]]}}
{{familytree| | | | |,|-|-|^|-|-|.| | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | B01 | | | | B02 | | | | | | | | | | | | | | | | | | | | | | | | | | |B01=[[Physiologic]]|B02=[[Pathologic]]}}
{{familytree| | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | |,|-|-|^|-|-|.| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | C01 | | | | C02 | | | | | | | | | | | | | | | | | | | | | | | |C01=Unconjugated [[hyperbilirubinemia]]|C02=Conjugated [[hyperbilirubinemia]]}}
{{familytree| | | | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | |,|-|-|^|-|-|.| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | D01 | | | | D02 | |!| | | | | | | | | | | | | | | | | | | | | | | | |D01=[[Hemolytic]]|D02=Non-[[hemolytic]]}}
{{familytree| | | | |!| | | | | |!| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | |!| | | | | |!| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | E01 | | | | E02 | |!| | | | | | | | | | | | | | | | | | | | | | | | |E01=•Rh incompatibility<br>•[[ABO]] incompatibility<br>•[[Hemoglobinopathies]] ([[Thalassemia]])<br>•Hematomas<br>•[[Polycythemia]]<br>•[[Sepsis]]|E02=•[[Crigler-Najjar syndrome]] I and II<br>•[[Gilbert syndrome]]<br>•[[Breast milk]] [[jaundice]]}}
{{familytree| | | | | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| |,|-|-|-|v|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| | | | | | | | | | | | | | | | |}}
{{familytree| |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | | | | | | | | | | | | | | |}}
{{familytree| F01 | | F02 | | F03 | | F04 | | F05 | | F06 | | | | | | | | | | | | | | | |F01=[[Infectious]]|F02=Obstructive|F03=[[Drugs]]|F04=[[Genetic]]/[[Metabolic]]|F05=Storage disorders|F06=Endocirnopathies}}
{{familytree| |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | | | | | | | | | | | | | | |}}
{{familytree| G01 | | G02 | | G03 | | G04 | | G05 | | G06 | | | | | | | | | | | | | | | | | | | | | |G01=•[[Viral]]<br>•[[Bacterial]]<br>•[[Parasitic]]|G02=•[[Biliary atresia]]<br>•[[Choledochal cyst]]<br>•Inspissated [[bile]] syndrome<br>•[[Neonatal]] [[sclerosing cholangitis]]<br>•[[Congenital]] [[hepatic fibrosis]]<br>•Intrinsic/extrinsic [[mass]]|G03=•[[Ceftriaxone]]<br>•[[Isoniazid]]<br>•[[Erythromycin]]<br>•[[Rifampin]]<br>•[[Sulfa]] [[drugs]]<br>•[[Parenteral nutrition]]<br>•[[Methotrexate]]|G04=•[[Alpha 1 antitrypsin]] [[deficiency]]<br>•[[Alagille syndrome]]<br>•[[Cystic fibrosis]]<br>•[[Tyrosinemia]]<br>•[[Galactosemia]]<br>•[[Rotor syndrome]]<br>•[[Trisomy 18]] and [[Trisomy 21]]|G05=•[[Gaucher's Disease]]<br>•Niemann-pick Disease<br>•[[Glycogen storage diseases]]<br>•[[Mucolipidoses]]|G06=•[[Hypopituitarism]]<br>•[[Hypothyroidism]]<br>•McCune Albright syndrome}}
{{familytree| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree/end}}


*Differentials for [[jaundice]] are very limited however some [[skin]] discolorations in [[healthy]] individuals can look like [[jaundice]] in certain circumstances.
==Differentiating jaundice in children from other diseases==
*Use of the [[antimalarial]] and [[antihelminthic]] [[drug]], [[Quinacrine]] can cause yellowish discoloration of the [[skin]] of individuals who take it.
 
*Excessive consumption of [[fruits]] and [[vegetables]] high in [[carotenes]] such as carrots and sweet potatoes can cause a [[skin]] discoloration termed as Carotenoderma.
*Alternative [[Diagnosis|diagnoses]] for [[jaundice]] are limited however, some [[Skin discoloration|skin discolorations]] in [[healthy]] individuals can resemble [[jaundice]] in certain circumstances.
*The above differentials spare the [[mucous membranes]] and [[sclera]]. <ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref><ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*Use of the [[antimalarial]] and [[antihelminthic|anti-helminthic]] [[drug]], [[Quinacrine]] can cause [[Yellow discolouration|yellowish discoloration]] of the [[skin]] of individuals who take it.
*Excessive consumption of [[fruits]] and [[vegetables]] high in [[carotenes]] such as carrots and sweet potatoes can cause a [[skin discoloration]] termed as Carotenoderma.
*The above differentials spare the [[mucous membranes]] and [[sclera]].<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref><ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>


==Epidemiology and Demographics==
==Epidemiology and Demographics==
*The [[prevalence]] of [[jaundice]] varies among [[patient]] [[populations]].
*The [[prevalence]] of [[jaundice]] varies among [[patient]] [[populations]].
*In [[infants]] born at [[term]], 60% will develop [[jaundice]] in their first-week life. This rises to 80% in preterms. <ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*In [[infants]] born at [[term]], 60% will develop [[jaundice]] in their first week of life which rises to 80% in preterms.<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*5-10% of [[neonates]] will require being admitted for the [[treatment]] of pathological [[jaundice]]. <ref name="pmid18334797">{{cite journal| author=Mishra S, Agarwal R, Deorari AK, Paul VK| title=Jaundice in the newborns. | journal=Indian J Pediatr | year= 2008 | volume= 75 | issue= 2 | pages= 157-63 | pmid=18334797 | doi=10.1007/s12098-008-0024-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18334797  }} </ref>  
*5-10% of [[neonates]] will require being admitted for the [[treatment]] of pathological [[jaundice]].<ref name="pmid18334797">{{cite journal| author=Mishra S, Agarwal R, Deorari AK, Paul VK| title=Jaundice in the newborns. | journal=Indian J Pediatr | year= 2008 | volume= 75 | issue= 2 | pages= 157-63 | pmid=18334797 | doi=10.1007/s12098-008-0024-7 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18334797  }} </ref>
*Causes of [[jaundice]] also vary with age groups. In [[newborns]], immature [[hepatic]] conjugation, [[hemolysis]], and certain [[congenital disorders]] are top causes while [[Hepatitis A]] [[infection]] is a cause seen more in older [[children]].
*Causes of [[jaundice]] also vary with [[age]] groups. In [[newborns]], immature [[hepatic]] [[conjugation]], [[hemolysis]], and certain [[congenital disorders]] are the top [[causes]], whereas [[Hepatitis A]] [[infection]] is a [[Causes|cause]] seen more in older [[children]].
*Death rate is 0.28 per 1 million live births. <ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*Death [[rate]] is 0.28 per 1 million [[Live birth|live births]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
   
   
===Age===
===Age===


*[[Patients]] of all age groups may develop [[jaundice]].
*[[Patients]] of all [[age]] groups may [[Development|develop]] [[jaundice]].
*It is more commonly observed in [[newborns]] and the [[elderly]] [[populations]]. <ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*It is more commonly observed in [[newborns]] and the [[elderly]] [[population]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
   
   
===Gender===
===Gender===


*[[Gender]] predilection can be observed in the [[etiology]] of [[jaundice]].  
*[[Gender]] preference can be observed in the [[etiology]] of [[jaundice]].
*An example is the documented [[male]] preponderance of Glucose-6-Phosphate dehydrogenase ([[G6PD]]) [[deficiency]] with an [[incidence]] of 4.5% [[males]] to 0.5% in [[females]]. <ref name="pmid29807950">{{cite journal| author=Chee YY, Chung PH, Wong RM, Wong KK| title=Jaundice in infants and children: causes, diagnosis, and management. | journal=Hong Kong Med J | year= 2018 | volume= 24 | issue= 3 | pages= 285-292 | pmid=29807950 | doi=10.12809/hkmj187245 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29807950  }} </ref>
*An example is the documented [[male]] preponderance of [[Glucose-6-phosphate dehydrogenase deficiency|glucose-6-Phosphate dehydrogenase (G6PD) deficiency]] with an [[incidence]] of 4.5% [[males]] to 0.5% in [[females]].<ref name="pmid29807950">{{cite journal| author=Chee YY, Chung PH, Wong RM, Wong KK| title=Jaundice in infants and children: causes, diagnosis, and management. | journal=Hong Kong Med J | year= 2018 | volume= 24 | issue= 3 | pages= 285-292 | pmid=29807950 | doi=10.12809/hkmj187245 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29807950  }} </ref>


===Race===
===Race===


*Racial predilection for [[jaundice]] is observed in a cause of unconjugated [[hyperbilirubinemia]], [[Gilbert syndrome]].  
*[[Racial]] predisposition for [[jaundice]] is observed in a [[Causes|cause]] of [[Unconjugated bilirubin|unconjugated]] [[hyperbilirubinemia]] such as [[Gilbert syndrome]].
*This is caused by a [[genetic]] [[mutation]] in the [[gene]] responsible for the production of the [[enzyme]], UDPGT. It is a [[diagnosis]] of exclusion and [[symptoms]] are triggered by stressful situations like [[dehydration]], illness.  
*A [[genetic]] [[mutation]] in the [[gene]] responsible for the [[Product (biology)|production]] of the [[enzyme]], UDPGT is its [[Causes|cause]]. [[Diagnosis]] is made only when alternative explanations have been ruled out. [[Symptoms]] are triggered by stressful situations such as [[dehydration]], and [[illness]].
*It has a [[prevalence]] of 5-10% in Caucasian and Asian [[populations]]. <ref name="pmid29807950">{{cite journal| author=Chee YY, Chung PH, Wong RM, Wong KK| title=Jaundice in infants and children: causes, diagnosis, and management. | journal=Hong Kong Med J | year= 2018 | volume= 24 | issue= 3 | pages= 285-292 | pmid=29807950 | doi=10.12809/hkmj187245 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29807950  }} </ref>
*It has a [[prevalence]] of 5-10% in Caucasian and Asian [[populations]].<ref name="pmid29807950">{{cite journal| author=Chee YY, Chung PH, Wong RM, Wong KK| title=Jaundice in infants and children: causes, diagnosis, and management. | journal=Hong Kong Med J | year= 2018 | volume= 24 | issue= 3 | pages= 285-292 | pmid=29807950 | doi=10.12809/hkmj187245 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29807950  }} </ref>


==Risk Factors==
==Risk Factors==


*Common [[risk factors]] in the development of [[jaundice]] in [[children]] are:  
*Common [[risk factors]] for the [[development]] of [[jaundice]] in [[children]] are:  
**[[Family history]] of [[jaundice]]
**[[Family history]] of [[jaundice]]
**[[Family history]] of a [[child]] born with [[jaundice]]
**[[Family history]] of a [[child]] born with [[jaundice]]
**[[Hyperthyroidism]] in [[mother]]
**[[Hyperthyroidism]] in the [[mother]]
**[[Medication]] use by [[mother]]
**[[Medication]] used by the [[mother]]
**Gestational Diabetes Mellitus ([[GDM]])
**[[Gestational diabetes|Gestational Diabetes Mellitus]] ([[GDM]])
**Race (Asian)
**[[Race]] (Asian)
**Age >25 years
**[[Age]] >25 [[Year|years]]
**[[ABO]] incompatibility
**[[ABO]] incompatibility
**Rh incompatibility
**[[Rh disease|Rh]] incompatibility
**Exclusive [[breastfeeding]]
**Exclusive [[breastfeeding]]
**Inability to breastfeed adequately
**Inability to [[Breastfeeding|breastfeed]] adequately
**Primiparity
**Primiparity
**[[Oxytocin]] use during [[labor]]
**[[Oxytocin]] use during [[labor]]
**[[Prematurity]]
**[[Prematurity]]
**[[Weight loss]](child)
**[[Weight loss]] ([[child]])
**[[Male]] gender
**[[Male]] gender
**[[Polycythemia]]
**[[Polycythemia]]
**[[Cephalhematoma]], [[hematoma]] in [[spleen]] or [[liver]], resulting in excessive [[hemolysis]] with [[red blood cell]] breakdown
**[[Hematoma]] in [[spleen]] or [[liver]], [[cephalhematoma]], causing excessive [[hemolysis]] with [[red blood cell]] breakdown
**[[Trisomy 21]]
**[[Trisomy 21]]
**[[G6PD]] [[deficiency]]
**[[G6PD]] [[deficiency]]
**[[Congenital]] [[infection]] ([[TORCHES]]) <ref name="pmid30159062">{{cite journal| author=Mojtahedi SY, Izadi A, Seirafi G, Khedmat L, Tavakolizadeh R| title=Risk Factors Associated with Neonatal Jaundice: A Cross-Sectional Study from Iran. | journal=Open Access Maced J Med Sci | year= 2018 | volume= 6 | issue= 8 | pages= 1387-1393 | pmid=30159062 | doi=10.3889/oamjms.2018.319 | pmc=6108787 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30159062  }} </ref> <ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
**[[Congenital]] [[infection]] ([[TORCHES]])<ref name="pmid30159062">{{cite journal| author=Mojtahedi SY, Izadi A, Seirafi G, Khedmat L, Tavakolizadeh R| title=Risk Factors Associated with Neonatal Jaundice: A Cross-Sectional Study from Iran. | journal=Open Access Maced J Med Sci | year= 2018 | volume= 6 | issue= 8 | pages= 1387-1393 | pmid=30159062 | doi=10.3889/oamjms.2018.319 | pmc=6108787 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30159062  }} </ref><ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>


==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==


*It is essential for every [[clinician]] to note that [[jaundice]] is not always a [[benign]] condition therefore, extensive investigation of a child with [[jaundice]] is necessary to prevent severe [[complications]].
*It is essential for every [[clinician]] to note that [[jaundice]] is not always a [[benign]] [[condition]] therefore, extensive [[Investigational product|investigation]] of a [[child]] with [[jaundice]] is necessary to [[Prevention (medical)|prevent]] severe [[complications]].
*[[Bilirubin]]-induced [[neurological]] dysfunction (BIND) seen in the setting of extremely high unconjugated [[bilirubin]] levels is a rare [[complication]].  
*In the setting of very high [[unconjugated bilirubin]] levels, a [[rare]] [[complication]] known as [[bilirubin]]-induced [[Neurological disorder|neurological dysfunction]] (BIND) is observed.
*It is a condition in which high levels of unconjugated [[bilirubin]] crosses the immature [[blood-brain-barrier]] of [[neonates]] and binds to [[glial]] [[tissue]] and [[brainstem]] [[nuclei]].  
*Elevated levels of [[unconjugated bilirubin]] crosses the immature [[blood-brain-barrier]] of [[neonates]] binding to [[glial]] [[tissue]] and [[brainstem]] [[nuclei]].
*Lack of [[colonic]] [[bacteria]] in [[neonates]] also predisposes them to this outcome due to increased [[enterohepatic]] [[reabsorption]] of deconjugated [[bilirubin]].  
*Lack of [[colonic]] [[bacteria]] in [[neonates]] also predisposes them to this [[outcome]] due to increased [[enterohepatic]] [[reabsorption]] of [[Unconjugated bilirubin|deconjugated bilirubin]].
*[[Bilirubin]] [[encephalopathy]], a catastrophic [[neurologic]] outcome known as [[Kernicterus]] or death are likely [[complications]] if [[treatment]] is either delayed or not promptly instituted.
*[[Bilirubin]] [[encephalopathy]], a catastrophic [[neurologic]] [[outcome]] known as [[kernicterus]] or death are likely [[complications]] if [[treatment]] is either delayed or not promptly instituted.
*Early [[symptoms]] of [[kernicterus]] are:
*Early [[symptoms]] of [[kernicterus]] are:
**Poor feeding
**Poor [[feeding]]
**Irritability
**[[Irritability]]
**High-pitched cry
**High-[[Pitch|pitched]] [[cry]]
**[[Apnea]]
**[[Apnea]]
**Floppy [[muscles]]
**[[Floppy muscles]]
*As the illness progresses, more severe [[symptoms]] are:
*As the [[illness]] progresses, more severe [[symptoms]] are:
**[[Seizures]]
**[[Seizures]]
**Muscular [[spasms]]
**[[Muscular]] [[spasms]]
**[[Cerebral palsy]]
**[[Cerebral palsy]]
**Learning problems
**[[Learning]] [[Problem Solved|problems]]
**Loss of [[hearing]] <ref>https://www.nhs.uk/conditions/jaundice-newborn/complications/</ref>
**Loss of [[hearing]]
*[[Complications]] from the causes of conjugated [[hyperbilirubinemia]] include:
*[[Complications]] from the [[causes]] of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]] include:
**[[Liver failure]]
**[[Liver failure]]
**[[Malabsorption]] of [[fat]] and fat-soluble [[vitamins]] from [[cholestasis]]
**[[Malabsorption]] of [[fat]] and [[fat-soluble]] [[vitamins]] from [[cholestasis]]
**[[Portal hypertension]]
**[[Portal hypertension]]
**[[Cirrhosis]]
**[[Cirrhosis]]
**Progression to [[hepatocellular carcinoma]] (HCC)
**Progression to [[hepatocellular carcinoma]] ([[Hepatocellular carcinoma|HCC]])
**[[Cholangiocarcinoma]] in [[patients]] with [[choledochal cyst]]
**[[Cholangiocarcinoma]] in [[patients]] with [[choledochal cyst]]
**Post Kasai procedure [[ascending cholangitis]]
**Post Kasai [[procedure]] [[ascending cholangitis]]
*[[Prognosis]] of [[jaundice]] in [[children]] especially is very good with prompt [[diagnosis]] and [[treatment]]. However, conjugated [[hyperbilirubinemia]] from obstructions of the [[hepatic]] and [[biliary]] tree have poorer outcomes. <ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*[[Prognosis]] is promising with prompt [[diagnosis]] and [[treatment]]. However, [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]] from the [[Obstruction|obstructions]] of [[hepatic]] and [[biliary]] tree have poorer [[Outcome|outcomes]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>


==Diagnosis==
==Diagnosis==
===Symptoms===


===Symptoms===
*[[Symptoms]] of [[jaundice]] in [[children]] may include the following:
*[[Symptoms]] of [[Jaundice]] in [[children]] may include the following:
**[[Skin]], [[sclera]] and [[mucous membrane]] discoloration
**Yellowish discoloration of the [[skin]], [[sclera]], and [[mucous membrane]]
**Time of onset and duration
**Time of onset and duration
**Progression. Involvement up to what body part?
**Progression (involvement up to which [[body]] part)
**Poor [[feeding]]
**Poor [[feeding]]
**Irritability
**[[Irritability]]
**[[Fever]]
**[[Fever]]
**[[Pruritus]]
**[[Pruritus]]
**[[Rash]]
**[[Rash]]
**[[Pains]] in the [[joints]]
**[[Pain]] in [[joints]]
**Recent [[travel history]]
**Recent travel history
**[[Diarrhea]]
**[[Diarrhea]]
**[[Urine]] and [[stool]] color change
**[[Urine]] and [[stool]] [[color]] change
**[[Anorexia]]
**[[Anorexia]]
**[[Weight loss]]
**[[Weight loss]]
**Body [[pains]] like [[abdominal]] discomfort/[[pains]]?
**[[Body]] [[pains]] such as [[abdominal]] [[discomfort]]/[[pains]]


===Physical Examination===
===Physical Examination===


*[[Patients]] with [[jaundice]] usually appear yellow on the [[skin]], [[mucous membranes]], and/or [[sclera]]. A useful technique in assessing the severity of [[jaundice]] is by using the principle of [[skin]] discoloration progressing in a cephalo-caudal direction in [[newborns]].  
*[[Patients]] appear yellow on the [[skin]], [[mucous membranes]] and/or [[sclera]]. A useful technique in assessing the severity of [[jaundice]] is by using the principle of [[skin discoloration]] progressing in a cephalo-caudal [[direction]] in [[newborns]].
*If [[discoloration]] has progressed to the [[thigh]] level, [[samples]] for urgent [[serum bilirubin]] should be taken.
*If [[discoloration]] has progressed to the [[thigh]] level, [[samples]] for urgent [[serum bilirubin]] should be taken.
*A limitation to this method is in [[infants]] who are already receiving [[phototherapy]] and those with darker colored [[skin]].
*This method is not necessary for [[infants]] who are already receiving [[phototherapy]] and those with darker colored [[skin]].
*[[Examination]] may be remarkable for other findings such as:
*Other findings on [[examination]] are:
**Irritable [[infant]]
**[[Irritable]] [[infant]]
**[[Fever]]
**[[Fever]]
**[[Rash]]
**[[Rash]]
**[[Examine]] [[urine]] and [[stool]]  
**[[Examine]] [[urine]] and [[stool]]
**Small or large for age
**Small or large for [[age]]
**[[Lymph node]] enlargement
**[[Lymph nodes enlarged|Lymph node enlargement]]
**[[Muscle]] [[spasms]]
**[[Muscle]] [[spasms]]
**Unconsolable cry
**Inconsolable [[cry]]
**[[Cardiac murmurs]]
**[[Cardiac murmurs]]
**[[Hepatomegaly]]
**[[Hepatomegaly]]
Line 245: Line 284:


*Measuring the level of [[bilirubin]].
*Measuring the level of [[bilirubin]].
**[[Serum bilirubin]] from a [[blood]] [[sample]]. The total and conjugated portions are measured and the unconjugated fraction is measured by subtracting the conjugated fraction from the total.
**[[Serum bilirubin]] from a [[blood]] [[sample]]. The total and [[Conjugated bilirubin|conjugated portions]] are measured first and the [[Unconjugated bilirubin|unconjugated fraction]] is measured by subtracting the [[Conjugated bilirubin|conjugated fraction]] from the total.
**Knowing the type of [[hyperbilirubinemia]] will guide further workup in identifying the cause of [[jaundice]]. Predominantly conjugated or mixed [[hyperbilirubinemia]] gives a clue of [[hepatic]] or post-[[hepatic]] [[etiology]].
**Knowing the type of [[hyperbilirubinemia]] will guide further workup in identifying the [[Causes|cause]] of [[jaundice]]. [[Conjugated bilirubin|Conjugated]] or mixed [[hyperbilirubinemia]] gives a speculation of [[hepatic]] or post-[[hepatic]] [[etiology]].
**Transcutaneous bilirubinometer. The accuracy of this can be altered by [[skin]] thickness and color.  
**Transcutaneous bilirubinometer. The [[accuracy]] of this can be altered by [[skin]] thickness and [[color]].
**Bilimeter
**Bilimeter
*[[Complete blood count]] with differentials and smear
*[[Complete blood count]] with differentials and [[Smear test|smear]]
*[[Blood]] and Rh group
*[[Blood]] and [[Rh (D) disease|Rh]] group
*[[G6PD]] levels
*[[G6PD]] levels
*[[Newborn screening]] for:
*[[Newborn screening]] for:
Line 257: Line 296:
**[[Galactosemia]]
**[[Galactosemia]]
**[[Hypothyroidism]]
**[[Hypothyroidism]]
*To assess [[liver]] synthetic function:
*To assess [[liver]] [[synthetic]] [[Function (biology)|function]]:
**[[Prothrombin time]] (PT)
**[[Prothrombin time]] ([[PT]])
**[[Serum albumin]]
**[[Serum albumin]]
*[[Liver function tests]]
*[[Liver function tests]]
Line 267: Line 306:
*[[Alpha 1 antitrypsin]] levels and [[phenotype]]
*[[Alpha 1 antitrypsin]] levels and [[phenotype]]
*[[Viral]] [[serologies]]
*[[Viral]] [[serologies]]
**Hepatitis A Virus ([[HAV]])
**[[Hepatitis A|Hepatitis A Virus]] ([[HAV]])
**[[HBV]]
**[[HBV]]
**[[HCV]]
**[[HCV]]
Line 276: Line 315:
**[[EBV]]
**[[EBV]]
**[[Parvovirus B19]]
**[[Parvovirus B19]]
*[[Serum]] [[ammonia]]  
*[[Serum]] [[ammonia]]
*[[Blood cultures]]
*[[Blood cultures]]
*[[Urinalysis]]
*[[Urinalysis]]
Line 287: Line 326:


===Electrocardiogram===
===Electrocardiogram===
*There are no [[ECG]] findings associated with [[Jaundice]] in [[children]].  
 
*It may be used to monitor [[cardiac]] rhythms during [[treatment]].
*There are no [[ECG]] findings [[Association (statistics)|associated]] with [[jaundice]] in [[children]].
*It may be used to monitor [[cardiac]] [[Rhythm|rhythms]] during [[treatment]].


===X-ray===
===X-ray===
*[[Chest radiograph]] can reveal [[cardiomegaly]] in individuals with [[Alagille syndrome]].
 
*A [[chest radiograph]] can reveal [[cardiomegaly]] in individuals with [[Alagille syndrome]].


===Echocardiography and Ultrasound===
===Echocardiography and Ultrasound===
*[[Echocardiography]] can detect [[cardiac]] abnormalities in patients with [[Alagille syndrome]] and [[biliary atresia]].
 
*[[Ultrasonography]] of the [[abdomen]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]] or [[cholestatic]] workup in the setting of conjugated [[hyperbilirubinemia]].<ref name="pmid29807950">{{cite journal| author=Chee YY, Chung PH, Wong RM, Wong KK| title=Jaundice in infants and children: causes, diagnosis, and management. | journal=Hong Kong Med J | year= 2018 | volume= 24 | issue= 3 | pages= 285-292 | pmid=29807950 | doi=10.12809/hkmj187245 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29807950  }} </ref>
*[[Echocardiography]] can detect [[cardiac]] [[abnormalities]] in [[patients]] with [[Alagille syndrome]] and [[biliary atresia]].
*[[Ultrasonography]] of the [[abdomen]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]] or [[cholestatic]] workup in the setting of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]].<ref name="pmid29807950">{{cite journal| author=Chee YY, Chung PH, Wong RM, Wong KK| title=Jaundice in infants and children: causes, diagnosis, and management. | journal=Hong Kong Med J | year= 2018 | volume= 24 | issue= 3 | pages= 285-292 | pmid=29807950 | doi=10.12809/hkmj187245 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29807950  }} </ref>


===CT scan===
===CT scan===
*[[CT scan]] of the [[abdomen]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]], or [[cholestatic]] workup in the setting of conjugated [[hyperbilirubinemia]].
 
*A [[CT scan]] of the [[abdomen]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]], or [[cholestatic]] workup in the setting of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]].


===MRI===
===MRI===
*[[MRI]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]], or [[cholestatic]] workup in the setting of conjugated [[hyperbilirubinemia]].
 
*A [[MRI]] is used to [[screen]] for [[biliary atresia]], [[choledochal cysts]], or [[cholestatic]] workup in the setting of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]].


===Other Imaging Findings===
===Other Imaging Findings===
*Other imaging modalities used for [[screening]] for [[cholestatic]] workup include the following:
 
*Other [[Imaging studies|imaging modalities]] used for [[screening]] for [[cholestatic]] workup include the following:
**[[Magnetic resonance cholangiopancreatography]] ([[MRCP]])
**[[Magnetic resonance cholangiopancreatography]] ([[MRCP]])
**[[Endoscopic retrograde cholangiopancreatography]] ([[ERCP]])
**[[Endoscopic retrograde cholangiopancreatography]] ([[ERCP]])
**Hepatobiliary scintigraphy with technetium-labeled iminodiacetic acid analog (HIIDA)  
**Hepatobiliary scintigraphy with technetium-labeled iminodiacetic acid analog ([[HIDA scan|HIDA]])
**[[Percutaneous transhepatic cholangiography]] (PTC)
**[[Percutaneous transhepatic cholangiography]] ([[PTC]])


===Other Diagnostic Studies===
===Other Diagnostic Studies===
*[[Diagnostic]] [[laparoscopy]] with/without [[treatment]]  
 
*[[Diagnostic]] [[laparoscopy]] with/without [[treatment]]
*[[Liver biopsy]]
*[[Liver biopsy]]


==Treatment==
==Treatment==
===Medical Therapy===
===Medical Therapy===
*[[Treatment]] of [[Jaundice]] is usually tailored towards the underlying [[etiology]] whether it a [[hematologic]] [[disease]] or a [[hepatobiliary]] [[pathology]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
 
*[[Treatment]] of [[jaundice]] is usually tailored towards the underlying [[etiology]] whether it a [[hematologic]] [[disease]] or a [[Hepatobiliary disease|hepatobiliary]] [[pathology]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*[[Treatment]] options include the following:
*[[Treatment]] options include the following:
**[[Phototherapy]]: Usually first line in [[neonates]] with severe [[hyperbilirubinemia]] to prevent [[neurologic]] [[sequelae]].
**[[Phototherapy]]: Usually first line in [[neonates]] with severe [[hyperbilirubinemia]] to prevent [[neurologic]] [[sequelae]].
**[[Intravenous]] [[immunoglobulin]](IVIG): helpful in [[hemolytic]] [[diseases]] and can be used in place of [[phototherapy]] and/or [[exchange transfusion]].
**[[Intravenous]] [[immunoglobulin]] ([[IVIG]]): Helpful in [[hemolytic]] [[diseases]] and can be used in place of [[phototherapy]] and/or [[exchange transfusion]].
**[[Exchange transfusion]]: When the above options become inadequate to reduce levels of rising [[bilirubin]] or at the slightest clue of [[bilirubin]] [[encephalopathy]], an [[exchange transfusion]] is done usually in the [[NICU]]/[[PICU]] and should be closely followed up for [[complications]] like:<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
**[[Exchange transfusion]]: When the above options become inadequate to reduce the levels of rising [[bilirubin]] or at the slightest clue of [[bilirubin]] [[encephalopathy]], an [[exchange transfusion]] is done usually in the [[NICU]]/[[PICU]] and should be closely followed up for [[complications]] such as:<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
***[[Cardiac arrhythmias]]
***[[Cardiac arrhythmias]]
***[[Sepsis]]  
***[[Sepsis]]
***[[Hyperkalemia]]
***[[Hyperkalemia]]
***[[Hypocalcemia]]
***[[Hypocalcemia]]
Line 330: Line 377:
***[[Phenobarbitone]]
***[[Phenobarbitone]]
***[[Metalloporphyrins]]
***[[Metalloporphyrins]]
*[[Patients]] with [[pruritus]] especially older kids can be treated with warm baths or given [[antihistamines]]. [[Cholestyramine]] can be used in severe cases of [[pruritus]]. <ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*[[Patients]] with [[pruritus]] especially older kids can be treated with warm baths or given [[antihistamines]]. [[Cholestyramine]] can be used in severe cases of [[pruritus]].<ref name="pmid31334972">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=31334972 | doi= | pmc= | url= }} </ref>
*Appropriate [[antiviral]], [[antibacterial]] and [[antiparasitic]] [[therapy]] for [[jaundice]] of [[viral]], [[bacterial]] and [[parasitic]] [[etiology]] respectively.
*Appropriate [[antiviral]], [[antibacterial]], and [[antiparasitic]] [[therapy]] for [[jaundice]] of [[viral]], [[bacterial]] and [[parasitic]] [[etiology]] respectively.


===Surgery===
===Surgery===


*[[Surgery]] is the mainstay of therapy or the definitive [[treatment]] for most obstructive causes of conjugated [[hyperbilirubinemia]].  
*[[Surgery]] is the mainstay of [[therapy]] or the definitive [[treatment]] for most [[Obstructive jaundice|obstructive]] [[causes]] of [[Conjugated bilirubin|conjugated]] [[hyperbilirubinemia]].
*Examples of procedures for common [[disorders]] are: <ref>https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/pediatrics/conjugated-hyperbilirubinemia-cholestasis/</ref>
*Examples of [[Procedure|procedures]] for common [[disorders]] are:  
**[[Choledochoentersotomy]] for [[choledochal cyst]]
**[[Choledochoentersotomy]] for [[choledochal cyst]]
**[[Hepatoportoenterostomy]] or the [[Kasai procedure]] for [[biliary atresia]]
**[[Hepatoportoenterostomy]] or the [[Kasai procedure]] for [[biliary atresia]]<ref name="pmid17878208">{{cite journal| author=Kelly DA, Davenport M| title=Current management of biliary atresia. | journal=Arch Dis Child | year= 2007 | volume= 92 | issue= 12 | pages= 1132-5 | pmid=17878208 | doi=10.1136/adc.2006.101451 | pmc=2066090 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17878208  }} </ref>
**Irrigation of the [[biliary tract]] for [[inspissated bile]]
**Irrigation of the [[biliary tract]] for [[inspissated bile]]
**[[Surgical]] drainage for [[common bile duct]] [[perforation]]  
**[[Surgical]] drainage for [[common bile duct]] [[perforation]]
*Timing of [[procedure]] with regards to the age of the [[child]], [[nutritional]] support in the form of [[vitamins]], and caloric replacements are extremely essential for the success of the [[procedure]].
*Timing of [[procedure]] with regards to the [[age]] of [[child]], [[nutritional]] support in the form of [[vitamins]], and [[Calorie|caloric]] replacements are extremely essential for the success of the [[procedure]].
 
===Prevention===
===Prevention===


*Several etiologies may be generally difficult to [[prevent]] however the [[prevention]] of [[complications]] from [[jaundice]] is equally crucial.  
*Several [[etiologies]] may be generally difficult to [[prevent]], however, the [[prevention]] of [[complications]] from [[jaundice]] is equally crucial.
*[[Parents]] should be educated on how to recognize [[jaundice]] very early in a [[neonate]] so as to present promptly for management. Some phone apps and an icterometer are novel means of accurately detecting [[jaundice]].<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*[[Parents]] should be educated on how to recognize [[jaundice]] very early in a [[neonate]] so as to present promptly for the management. Some phone apps and an icterometer are novel means of accurately detecting [[jaundice]].<ref name="pmid30422525">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=30422525 | doi= | pmc= | url= }} </ref>
*Appropriate [[vaccinations]] should be received prior to international [[travels]].
*Appropriate [[vaccinations]] should be received prior to international [[travel]].
*[[Prescribed]] [[medications]] should be taken in recommended [[dosages]].
*[[Prescribed]] [[medications]] should be taken in recommended [[dosages]].
*[[Herbal]] [[medications]] should be avoided unless a [[physician]] clears it as safe.
*[[Herbal]] [[medications]] should be avoided unless a [[physician]] clears it.
*[[Smoking]], use of illicit [[drugs]], and excess [[alcohol]] intake should be avoided in [[children]] and [[pregnant]] women.
*[[Smoking]], use of illicit [[drugs]], and excess [[alcohol]] intake should be avoided in [[children]] and [[pregnant]] women.
*Proper [[hand washing]] for [[pregnant]] mothers.
*Proper [[hand washing]] for [[pregnant]] mothers.
Line 355: Line 402:
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
 
[[Category:Up-To-Date]]
[[Category:Primary care]]
[[Category:Pediatrics]]
[[Category:Pediatrics]]

Latest revision as of 21:00, 24 February 2021

Jaundice in children Microchapters

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differential Diagnosis

Epidemiology and Demographics

Risk factors

Natural History, Complications and Prognosis

Diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ifeoma Anaya, M.D.[2]

Synonyms and keywords: Jaundice in kids, hyperbilirubinemia

Overview

The word 'Jaundice' is derived from the French word for yellow, which is jaune. Jaundice may be classified into two broad categories based on its time of onset and cause such as physiologic and pathologic jaundice. Jaundice is caused by high concentrations of bilirubin in the bloodstream, a condition known as hyperbilirubinemia. Hyperbilirubinemia can result from abnormalities in the metabolism of bilirubin which could occur at any stage from its production, which is a result of the excessive breakdown of red blood cells, defects in its hepatic metabolism, and its post hepatic transport. Pathologic causes of jaundice can be classified into causes of conjugated and unconjugated hyperbilirubinemia. Differentials for jaundice are very limited however, some skin discolorations in healthy individuals can look like jaundice in certain circumstances. The prevalence of jaundice varies among patient populations. In infants born at term, 60% will develop jaundice in their first-week of life, which rises to 80% in preterms. Common risk factors in the development of jaundice in children are a family history of jaundice, family history of a child born with jaundice, hyperthyroidism in the mother, medication use by the mother, etc. It is essential for every clinician to note that jaundice is not always a benign condition therefore, extensive investigation of a child with jaundice is necessary to prevent severe complications. Symptoms of jaundice in children may include the yellowish discoloration of skin, sclera, and mucous membrane. A useful technique in assessing the severity of jaundice is by using the principle of skin discoloration progressing in a cephalo-caudal direction in newborns. Laboratory findings include measuring the serum bilirubin from a blood sample. The total and conjugated portions are measured and the unconjugated fraction is measured by subtracting the conjugated fraction from the total. Echocardiography can detect cardiac abnormalities in patients with Alagille syndrome and biliary atresia. Ultrasonography of the abdomen is used to screen for biliary atresia, choledochal cysts, or cholestatic workup in the setting of conjugated hyperbilirubinemia. Treatment options include phototherapy, intravenous immunoglobulin (IVIG), and exchange transfusion. Pharmacological options are also there. Surgery is the mainstay of therapy or the definitive treatment for most obstructive causes of conjugated hyperbilirubinemia. Several etiologies may be generally difficult to prevent however, the prevention of complications from jaundice is equally crucial. Parents should be educated on how to recognize jaundice very early in a neonate so as to present promptly for the management.

Historical Perspective

Classification

Classification of Jaundice
Type of Jaundice Details
Physiologic jaundice
Pathological jaundice[1]

Pathophysiology

Causes

 
 
 
 
 
 
Causes of jaundice in children
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physiologic
 
 
 
Pathologic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unconjugated hyperbilirubinemia
 
 
 
Conjugated hyperbilirubinemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemolytic
 
 
 
Non-hemolytic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•Rh incompatibility
•ABO incompatibility
•Hemoglobinopathies (Thalassemia)
•Hematomas
•Polycythemia
•Sepsis
 
 
 
•Crigler-Najjar syndrome I and II
•Gilbert syndrome
•Breast milk jaundice
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious
 
Obstructive
 
Drugs
 
Genetic/Metabolic
 
Storage disorders
 
Endocirnopathies
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•Viral
•Bacterial
•Parasitic
 
•Biliary atresia
•Choledochal cyst
•Inspissated bile syndrome
•Neonatal sclerosing cholangitis
•Congenital hepatic fibrosis
•Intrinsic/extrinsic mass
 
•Ceftriaxone
•Isoniazid
•Erythromycin
•Rifampin
•Sulfa drugs
•Parenteral nutrition
•Methotrexate
 
•Alpha 1 antitrypsin deficiency
•Alagille syndrome
•Cystic fibrosis
•Tyrosinemia
•Galactosemia
•Rotor syndrome
•Trisomy 18 and Trisomy 21
 
•Gaucher's Disease
•Niemann-pick Disease
•Glycogen storage diseases
•Mucolipidoses
 
•Hypopituitarism
•Hypothyroidism
•McCune Albright syndrome
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Differentiating jaundice in children from other diseases

Epidemiology and Demographics

Age

Gender

Race

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Prevention

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 "StatPearls". 2020. PMID 30422525.
  2. ↑ Mittendorf R, Williams MA (1991). "Rho(D) immunoglobulin (RhoGAM): how it came into being". Obstet Gynecol. 77 (2): 301–3. doi:10.1097/00006250-199102000-00029. PMID 1846439.
  3. ↑ Weiss EM, Zimmerman SS (2013). "A tale of two hospitals: the evolution of phototherapy treatment for neonatal jaundice". Pediatrics. 131 (6): 1032–4. doi:10.1542/peds.2012-3651. PMID 23650299.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 "StatPearls". 2020. PMID 31334972.
  5. ↑ Mishra S, Agarwal R, Deorari AK, Paul VK (2008). "Jaundice in the newborns". Indian J Pediatr. 75 (2): 157–63. doi:10.1007/s12098-008-0024-7. PMID 18334797.
  6. ↑ 6.0 6.1 6.2 Chee YY, Chung PH, Wong RM, Wong KK (2018). "Jaundice in infants and children: causes, diagnosis, and management". Hong Kong Med J. 24 (3): 285–292. doi:10.12809/hkmj187245. PMID 29807950.
  7. ↑ Mojtahedi SY, Izadi A, Seirafi G, Khedmat L, Tavakolizadeh R (2018). "Risk Factors Associated with Neonatal Jaundice: A Cross-Sectional Study from Iran". Open Access Maced J Med Sci. 6 (8): 1387–1393. doi:10.3889/oamjms.2018.319. PMC 6108787. PMID 30159062.
  8. ↑ Kelly DA, Davenport M (2007). "Current management of biliary atresia". Arch Dis Child. 92 (12): 1132–5. doi:10.1136/adc.2006.101451. PMC 2066090. PMID 17878208.
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