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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 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 and duration, 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 appears 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==
==Causes==
*Causes of jaundice in children can be classified as follows:


{{Family tree/start}}
*[[Causes]] of [[jaundice]] in [[children]] can be [[Classification|classified]] as follows:
{{Family tree | | | | | | | | A01 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |A01=Causes of jaundice in children}}
{{familytree/start}}
{{Family tree | | | | | |,|-|-|^|-|-|.| | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | A01 | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |A01=[[Causes]] of [[jaundice]] in [[children]]}}
{{Family tree | | | | | B01 | | | | B02 | | | | | | | | | | | | | | | | | | | | | | | | | | |B01=Physiologic|B02=Pathologic}}
{{familytree| | | | |,|-|-|^|-|-|.| | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | B01 | | | | B02 | | | | | | | | | | | | | | | | | | | | | | | | | | |B01=[[Physiologic]]|B02=[[Pathologic]]}}
{{Family tree | | | | | | | | |,|-|-|^|-|-|.| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | C01 | | | | C02 | | | | | | | | | | | | | | | | | | | | | | | |C01=Unconjugated hyperbilirubinemia|C02=Conjugated hyperbilirubinemia}}
{{familytree| | | | | | | |,|-|-|^|-|-|.| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | C01 | | | | C02 | | | | | | | | | | | | | | | | | | | | | | | |C01=Unconjugated [[hyperbilirubinemia]]|C02=Conjugated [[hyperbilirubinemia]]}}
{{Family tree | | | | | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | |,|-|-|^|-|-|.| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | |!| | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | D01 | | | | D02 | |!| | | | | | | | | | | | | | | | | | | | | | | | |D01=Hemolytic|D02=Non-hemolytic}}
{{familytree| | | | |,|-|-|^|-|-|.| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | |!| | | | | |!| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | D01 | | | | D02 | |!| | | | | | | | | | | | | | | | | | | | | | | | |D01=[[Hemolytic]]|D02=Non-[[hemolytic]]}}
{{Family tree | | | | | |!| | | | | |!| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree| | | | |!| | | | | |!| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | 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| | | | |!| | | | | |!| | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{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]]}}
{{Family tree | | |,|-|-|-|v|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| | | | | | | | | | | | | | | | |}}
{{familytree| | | | | | | | | | | | | |!| | | | | | | | | | | | | | | | | | | | | | | | |}}
{{Family tree | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | | | | | | | | | | | | | | |}}
{{familytree| |,|-|-|-|v|-|-|-|v|-|-|-|+|-|-|-|v|-|-|-|.| | | | | | | | | | | | | | | | |}}
{{Family tree | | F01 | | F02 | | F03 | | F04 | | F05 | | F06 | | | | | | | | | | | | | | | |F01=Infectious|F02=Obstructive|F03=Drugs|F04=Genetic/Metabolic|F05=Storage disorders|F06=Endocirnopathies}}
{{familytree| |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | | | | | | | | | | | | | | |}}
{{Family tree | | |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | | | | | | | | | | | | | | |}}
{{familytree| F01 | | F02 | | F03 | | F04 | | F05 | | F06 | | | | | | | | | | | | | | | |F01=[[Infectious]]|F02=Obstructive|F03=[[Drugs]]|F04=[[Genetic]]/[[Metabolic]]|F05=Storage disorders|F06=Endocirnopathies}}
{{Family tree | | 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>•Trisomies 18 and 21|G05=•Gaucher's disease<br>•Niemann-pick disease<br>•Glycogen storage diseases<br>•Mucolipidoses|G06=•Hypopituitarism<br>•Hypothyroidism<br>•McCune Albright syndrome}}
{{familytree| |!| | | |!| | | |!| | | |!| | | |!| | | |!| | | | | | | | | | | | | | | | |}}
{{Family tree | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{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}}
{{Family tree/end}}
{{familytree| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |}}
{{familytree/end}}


==Differentiating Jaundice in children from other Diseases==
==Differentiating jaundice in children from other diseases==


*Differentials for jaundice are very limited however some skin discolorations in healthy individuals can look like jaundice in certain circumstances.
*Alternative [[Diagnosis|diagnoses]] for [[jaundice]] are limited however, some [[Skin discoloration|skin discolorations]] in [[healthy]] individuals can resemble [[jaundice]] in certain circumstances.
*Use of the antimalarial and antihelminthic drug, Quinacrine can cause yellowish discoloration of the skin of individuals who take it.
*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.
*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 spares the mucus 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>
*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.
 
*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>
*The [[prevalence]] of [[jaundice]] varies among [[patient]] [[populations]].
*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>  
*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>
*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.
*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>
*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>
*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 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]]
**Splenomegaly
**[[Splenomegaly]]
**Ascites
**[[Ascites]]


===Laboratory Findings===
===Laboratory Findings===


*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:
**Cystic fibrosis
**[[Cystic fibrosis]]
**Tyrosinemia
**[[Tyrosinemia]]
**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]]
**AST
**[[AST]]
**ALT
**[[ALT]]
**ALP
**[[ALP]]
**GGT
**[[GGT]]
*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]]
**HDV
**[[HDV]]
**HEV
**[[HEV]]
**HIV
**[[HIV]]
**CMV
**[[CMV]]
**EBV
**[[EBV]]
**Parvovirus-B19
**[[Parvovirus B19]]
*Serum ammonia  
*[[Serum]] [[ammonia]]
*Blood cultures
*[[Blood cultures]]
*Urinalysis
*[[Urinalysis]]
*Urine microscopy, culture, and sensitivity
*[[Urine]] [[microscopy]], [[culture]], and [[sensitivity]]
*Stool microscopy, culture, and sensitivity
*[[Stool]] [[microscopy]], [[culture]], and [[sensitivity]]
*TORCH screening
*[[TORCH]] [[screening]]
*Serum ferritin
*[[Serum]] [[ferritin]]
*Serum ceruloplasmin
*[[Serum]] [[ceruloplasmin]]
*Autoimmune antibodies
*[[Autoimmune]] [[antibodies]]


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


===Other Diagnostic Studies===
===Other Diagnostic Studies===
*Diagnostic laparoscopy with/without treatment  
 
*Liver biopsy
*[[Diagnostic]] [[laparoscopy]] with/without [[treatment]]
*[[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 options include the following:
*[[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>
**Phototherapy: Usually first line in neonates with severe hyperbilirubinemia to prevent neurologic sequelae.
*[[Treatment]] options include the following:
**Intravenous immunoglobulin(IVIG): helpful in hemolytic diseases and can be used in place of phototherapy and/or exchange transfusion.
**[[Phototherapy]]: Usually first line in [[neonates]] with severe [[hyperbilirubinemia]] to prevent [[neurologic]] [[sequelae]].
**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>
**[[Intravenous]] [[immunoglobulin]] ([[IVIG]]): Helpful in [[hemolytic]] [[diseases]] and can be used in place of [[phototherapy]] and/or [[exchange transfusion]].
***Cardiac arrhythmias
**[[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>
***Sepsis  
***[[Cardiac arrhythmias]]
***Hyperkalemia
***[[Sepsis]]
***Hypocalcemia
***[[Hyperkalemia]]
***Necrotising enterocolitis
***[[Hypocalcemia]]
***Exchange transfusion also removes hemolytic antibodies from Rh isoimmunization and ABO incompatibility.
***[[Necrotising enterocolitis]]
**Pharmacologic remedies such as:  
***[[Exchange transfusion]] also removes [[hemolytic]] [[antibodies]] from Rh [[isoimmunization]] and [[ABO]] incompatibility.
***Phenobarbitone
**[[Pharmacologic]] remedies such as:  
***Metalloporphyrins
***[[Phenobarbitone]]
*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>
***[[Metalloporphyrins]]
*Appropriate antiviral therapy for jaundice of viral etiology.
*[[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.


===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.
*[[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.


==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

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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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