View source for Neonatal jaundice

{{Use dmy dates|date=September 2023}}
{{Infobox medical condition (new)
| name            = Neonatal jaundice
| synonyms        = Neonatal hyperbilirubinemia, neonatal icterus, jaundice in newborns
| image           = Jaundice in newborn.jpg
| caption         = Jaundice in a newborn
| pronounce       =
| field           = [[Pediatrics]]
| symptoms        = [[jaundice|Yellowish discoloration]] of the [[Human skin|skin]] and [[sclera|white part of the eyes]]<ref name=Mer2015/>
| complications   = [[Seizure]]s, [[cerebral palsy]], [[kernicterus]]<ref name=Mer2015/>
| onset           = Newborns<ref name=Mer2015/>
| duration        =
| types           = Physiologic, pathologic<ref name=Mer2015/>
| causes          = [[hemolysis|Red blood cell breakdown]], [[liver disease]], infection, [[hypothyroidism]], [[metabolic disorders]]<ref name=NICE2016/><ref name=Mer2015/>
| risks           =
| diagnosis       = Based on symptoms, confirmed by [[bilirubin]]<ref name=Mer2015/>
| differential    =
| prevention      =
| treatment       = More frequent feeding, [[phototherapy]], [[exchange transfusions]]<ref name=Mer2015/>
| medication      =
| prognosis       =
| frequency       = >50% of babies<ref name=Mer2015/>
| deaths          =
}}
<!-- Definition and symptoms -->

'''Neonatal jaundice''' is a [[jaundice|yellowish discoloration]] of the [[sclera|white part of the eyes]] and [[Human skin|skin]] in a newborn baby due to high [[bilirubin]] levels.<ref name=Mer2015/> Other symptoms may include excess sleepiness or poor feeding.<ref name=Mer2015/> Complications may include [[seizure]]s, [[cerebral palsy]], or [[kernicterus]].<ref name=Mer2015/>

<!-- Cause and diagnosis -->
In most of cases there is no specific underlying physiologic disorder.<ref name=NICE2016/> In other cases it results from [[hemolysis|red blood cell breakdown]], [[liver disease]], infection, [[hypothyroidism]], or [[metabolic disorders]] (pathologic).<ref name=NICE2016/><ref name=Mer2015/> A bilirubin level more than 34&nbsp;μmol/L (2&nbsp;mg/dL) may be visible.<ref name=Mer2015/> Concerns, in otherwise healthy babies, occur when levels are greater than 308&nbsp;μmol/L (18&nbsp;mg/dL), jaundice is noticed in the first day of life, there is a rapid rise in levels, jaundice lasts more than two weeks, or the baby appears unwell.<ref name=Mer2015/> In those with concerning findings further investigations to determine the underlying cause are recommended.<ref name=Mer2015/>

<!-- Treatment and epidemiology -->
The need for treatment depends on bilirubin levels, the age of the child, and the underlying cause.<ref name=Mer2015/><ref name=NICE2016Rec>{{cite web|title=Jaundice in newborn babies under 28 days|url=https://www.nice.org.uk/guidance/cg98/chapter/Recommendations|website=NICE|access-date=11 December 2017|date=October 2016}}</ref> Treatments may include more frequent feeding, [[phototherapy]], or [[exchange transfusions]].<ref name=Mer2015/> In those who are [[preterm|born early]] more aggressive treatment tends to be required.<ref name=Mer2015/> Physiologic jaundice generally lasts less than seven days.<ref name=Mer2015/> The condition affects over half of babies in the first week of life.<ref name=Mer2015>{{cite web|title=Neonatal Hyperbilirubinemia|url=http://www.merckmanuals.com/en-ca/professional/pediatrics/metabolic,-electrolyte,-and-toxic-disorders-in-neonates/neonatal-hyperbilirubinemia|website=Merck Manuals Professional Edition|access-date=11 December 2017|language=en-CA|date=August 2015}}</ref> Of babies that are born early about 80% are affected.<ref name=NICE2016>{{cite web|title=Jaundice in newborn babies under 28 days {{!}} Guidance and guidelines|url=https://www.nice.org.uk/guidance/cg98/chapter/Context|website=NICE|access-date=11 December 2017|date=October 2016}}</ref> Globally over 100,000 [[Late preterm infant|late-preterm]] and term babies die each year as a result of jaundice.<ref name=GBD2016>{{cite journal |last1=Olusanya |first1=BO |last2=Teeple |first2=S |last3=Kassebaum |first3=NJ |title=The Contribution of Neonatal Jaundice to Global Child Mortality: Findings From the GBD 2016 Study. |journal=Pediatrics |date=February 2018 |volume=141 |issue=2 |pages=e20171471 |doi=10.1542/peds.2017-1471 |pmid=29305393|doi-access=free }}</ref>
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==Sign and symptoms==
The primary symptom is [[jaundice|yellowish discoloration]] of the [[sclera|white part of the eyes]] and [[Human skin|skin]] in a newborn baby.<ref name="Mer2015" /> Other symptoms may include excess sleepiness or poor feeding.<ref name="Mer2015" />

A bilirubin level more than 34&nbsp;μmol/L (2&nbsp;mg/dL) may result in visible discoloration of the skin.<ref name="Mer2015" /> For the feet to be affected with a visual pigment, the level generally must be over 255&nbsp;μmol/L (15&nbsp;mg/dL).<ref name="Mer2015" />

===Complications===
Prolonged hyperbilirubinemia (severe jaundice) can result in chronic bilirubin encephalopathy ([[kernicterus]]).<ref>Juetschke, L.J. (2005, Mar/Apr). Kernicterus: still a concern. Neonatal Network, 24(2), 7-19, 59-62</ref><ref>{{cite journal |last1=Colletti|first1= JE|last2= Kothari|first2= S|last3=Kothori|first3= S|last4= Jackson|first4= DM|last5= Kilgore|first5= KP|last6= Barringer|first6= K |title=An emergency medicine approach to neonatal hyperbilirubinemia |journal=Emerg. Med. Clin. North Am. |volume=25 |issue=4 |pages=1117–35, vii |date=November 2007 |pmid=17950138 |doi=10.1016/j.emc.2007.07.007}}</ref>  Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus.<ref>{{cite journal |last1=Watchko |first1=JF |title=Hyperbilirubinemia and bilirubin toxicity in the late preterm infant |journal=Clin Perinatol |volume=33 |issue=4 |pages=839–52; abstract ix |date=December 2006 |pmid=17148008 |doi=10.1016/j.clp.2006.09.002 |url=http://unmfm.pbworks.com/w/file/fetch/37751502/Hyperbilirubinemia%20and%20Bilirubin%20Toxicity%20in%20the%20Late%20Preterm%20Infant.pdf |access-date=2019-09-26 |archive-date=2017-08-08 |archive-url=https://web.archive.org/web/20170808143902/http://unmfm.pbworks.com/w/file/fetch/37751502/Hyperbilirubinemia%20and%20Bilirubin%20Toxicity%20in%20the%20Late%20Preterm%20Infant.pdf |url-status=dead }}</ref>

Infants with kernicterus may have a fever<ref>{{cite journal |last1=Shah|first1= Z|last2=Chawla|first2=A|last3=Patkar|first3=D|last4= Pungaonkar|first4=S |title=MRI in kernicterus |journal=Australasian Radiology |volume=47 |issue=1 |pages=55–7 |date=March 2003 |pmid=12581055 |doi=10.1046/j.1440-1673.2003.00973.x }}</ref> or seizures.<ref>{{cite journal |last1=Malik|first1= BA|last2= Butt|first2= MA|last3= Shamoon|first3= M|last4= Tehseen|first4= Z|last5= Fatima|first5=A|last6= Hashmat|first6=N|title=Seizures etiology in the newborn period |journal=Journal of the College of Physicians and Surgeons--Pakistan |volume=15 |issue=12 |pages=786–90 |date=December 2005 |pmid=16398972}}</ref> High pitched crying can also be a side effect of kernicterus.<ref>{{Cite web |date=2018-09-07 |title=Newborn jaundice - Kernicterus |url=https://www.nhs.uk/conditions/jaundice-newborn/complications/ |access-date=2025-04-17 |website=nhs.uk |language=en}}</ref>

Rarely, if phototherapy is done in the presence of hepatic dysfunction with elevated direct bilirubin levels, [[Bronze baby syndrome]] can develop, which is a harmless but cosmetically unappealing complication.

==Causes==
In newborns, jaundice tends to develop because of two factors—the breakdown of [[fetal hemoglobin]] as it is replaced with [[Hemoglobin|adult hemoglobin]] and the relatively immature metabolic pathways of the liver, which are unable to conjugate and so excrete bilirubin as quickly as an adult. This causes an accumulation of bilirubin in the blood ([[hyperbilirubinemia]]), leading to the symptoms of jaundice.{{citation needed|date=December 2020}}

If the neonatal jaundice is not resolved with simple [[phototherapy]], other causes such as [[biliary atresia]], [[Progressive familial intrahepatic cholestasis]], bile duct paucity, [[Alagille syndrome]], [[alpha 1-antitrypsin deficiency]], and other pediatric liver diseases should be considered. The evaluation for these will include blood work and a variety of diagnostic tests.  Prolonged neonatal jaundice is serious and should be followed up promptly.<ref>{{Cite journal|last=Gilmour|first=Susan M|date=December 2004|title=Prolonged neonatal jaundice: When to worry and what to do|journal=Paediatrics & Child Health|volume=9|issue=10|pages=700–704|doi=10.1093/pch/9.10.700|issn=1205-7088|pmc=2724143|pmid=19688078}}</ref>

Severe neonatal jaundice may indicate the presence of other conditions contributing to the elevated bilirubin levels, of which there are a large variety of possibilities (see below).  These should be detected or excluded as part of the differential diagnosis to prevent the development of complications.  They can be grouped into the following categories:{{Citation needed|date=April 2025}}

{{Tree chart/start}}
{{Tree chart | | | | | | | | | | | | | A01 | | | | |A01=Neonatal jaundice}}
{{Tree chart | | | | | | | | |,|-|-|-|-|^|-|-|-|-|.|}}
{{Tree chart | | | | | | | | B01 | | | | | | | | B02|B01=[[Unconjugated bilirubin]]|B02=[[Conjugated bilirubin]]}}
{{Tree chart | | | | | |,|-|-|^|-|-|.| | | |,|-|-|^|-|-|.| |}}
{{Tree chart | | | | | C01 | | | | C02 | | C03 | | | | C04 | |C01=[[pathology|Pathologic]] |C02=Physiological jaundice of neonates |C03=[[Hepatic]] |C04=Post-hepatic}}
{{Tree chart | | |,|-|-|^|-|-|.| | | | | | | | | | | |}}
{{Tree chart | | C01 | | | | C02 | | | | | | | | | | | |C01=[[hemolysis|Hemolytic]]|C02=Non-hemolytic}}
{{Tree chart | | |)|-|-|-|-|-|.| | | | | | | | | | | |}}
{{Tree chart | | C01 | | | | C02 | | | | | | | | | | | |C01=Intrinsic causes|C02=Extrinsic causes}}
{{Tree chart/end}}

===Unconjugated===

====Hemolytic====

=====Intrinsic causes of hemolysis=====
* Membrane conditions
** [[Spherocytosis]]
** [[Hereditary elliptocytosis]]
* Enzyme conditions
** [[Glucose-6-phosphate dehydrogenase deficiency]] (also called G6PD deficiency)
** [[Pyruvate kinase deficiency]]
** Congenital erythropoietic porphyria (CEP, also called Morbus Günther; Uroporphyrinogen III Synthase deficiency)
* Globin synthesis defect
** [[Sickle cell disease]]
** [[Alpha-thalassemia]], e.g. HbH disease

=====Extrinsic causes of hemolysis=====
* Systemic conditions
** [[Sepsis]]
** [[Arteriovenous malformation]]
* [[Alloimmunity]] (The neonatal or [[cord blood]] gives a positive [[Coombs test#Direct Coombs test|direct Coombs test]] and the maternal blood gives a positive [[Coombs test#Indirect Coombs est|indirect Coombs test]])
** [[Hemolytic disease of the newborn (ABO)]]<ref name="family" />
** [[Rh disease]]<ref name="family">{{cite journal|url=http://www.osteopathicfamilyphysician.org/article/S1877-573X(12)00187-6/abstract|archive-url=https://archive.today/20130415161902/http://www.osteopathicfamilyphysician.org/article/S1877-573X(12)00187-6/abstract|url-status=dead|archive-date=2013-04-15|title=An osteopathic approach to reduction of readmissions for neonatal jaundice|last1=Click|first1=R|last2=Dahl-Smith|first2=J|last3=Fowler|first3=L|last4=DuBose|first4=J|last5=Deneau-Saxton|first5=M|last6=Herbert|first6=J|journal=Osteopathic Family Physician|volume=5|issue=1|date=January 2013|doi=10.1016/j.osfp.2012.09.005|pages=17–23|url-access=subscription}}</ref>
** [[Hemolytic disease of the newborn (anti-Kell)]]
** [[Hemolytic disease of the newborn (anti-Rhc)]]
** Other blood type mismatches causing [[hemolytic disease of the newborn]]

====Non-hemolytic causes====
* [[Breastfeeding]] jaundice
* [[Neonatal jaundice#Breast milk jaundice|Breast milk jaundice]]
* [[Cephalohematoma]]
* [[Polycythemia]]
* [[Urinary tract infection]]
* [[Sepsis]]
* [[Hypothyroidism]]
* [[Gilbert's syndrome]]
* [[Crigler–Najjar syndrome]]
* High GI obstruction ([[Pyloric stenosis]], [[Neonatal bowel obstruction|Bowel obstruction]])

===Conjugated (Direct)===

====Liver causes====
* Infections
** [[Sepsis]]
** [[Hepatitis A]]
** [[Hepatitis B]]
** [[TORCH syndrome|TORCH infections]]
* Metabolic
** [[Galactosemia]]
** [[Alpha 1-antitrypsin deficiency]], which is commonly missed, and must be considered in DDx
** [[Cystic fibrosis]]
** [[Dubin–Johnson syndrome]]
** [[Rotor syndrome]]
* Drugs
* [[Total parenteral nutrition]]
* Idiopathic

====Post-liver====
* [[Biliary atresia]] or [[bile duct]] obstruction
** [[Alagille syndrome]]
** [[Choledochal cyst]]

===Non-organic causes===

====Breastfeeding jaundice====
"Breastfeeding jaundice" (or "lack of breastfeeding jaundice") is caused by insufficient breast milk intake,<ref name="GarfunkelKaczorowski2002">{{cite book|author1=Lynn C. Garfunkel|author2=Jeffrey |author3=Cynthia Christy|title=Mosby's pediatric clinical advisor: instant diagnosis and treatment|url=https://books.google.com/books?id=3m0JEvOQSlEC&pg=PA200|access-date=14 June 2010|year=2002|publisher=Elsevier Health Sciences|isbn=978-0-323-01049-8|pages=200–}}</ref> resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased [[enterohepatic circulation]], resulting in increased reabsorption of bilirubin from the intestines.<ref>{{Cite journal|last1=Leung|first1=A. K.|last2=Sauve|first2=R. S.|date=1989-12-01|title=Breastfeeding and breast milk jaundice|journal=Journal of the Royal Society of Health|volume=109|issue=6|pages=213–217|issn=0264-0325|pmid=2513410|doi=10.1177/146642408910900615|s2cid=38974909}}</ref> Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.<ref>{{Cite web|last=CDC|date=2020-11-13|title=Jaundice|url=https://www.cdc.gov/breastfeeding/breastfeeding-special-circumstances/maternal-or-infant-illnesses/jaundice.html|access-date=2021-07-12|website=Centers for Disease Control and Prevention|language=en-us}}</ref>

====Breast milk jaundice====
Whereas breastfeeding jaundice is a mechanical problem, breast milk jaundice is a biochemical occurrence and the higher bilirubin possibly acts as an antioxidant. Breast milk jaundice occurs later in the newborn period, with the bilirubin level usually peaking in the sixth to 14th days of life. This late-onset jaundice may develop in up to one third of healthy breastfed infants.<ref>{{Cite journal | url=http://www.aafp.org/afp/2002/0215/p599.html | title=Hyperbilirubinemia in the Term Newborn| journal=American Family Physician| volume=65| issue=4| pages=599–606| date=2002-02-15| last1=Dennis| first1=Maj Beth L.| last2=Porter| first2=Meredith L.| pmid=11871676}}</ref>
# The gut is sterile at birth and normal gut flora takes time to establish. The bacteria in the adult gut convert conjugated [[bilirubin]] to [[stercobilinogen]] which is then oxidized to [[stercobilin]] and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border β-glucuronidase and reabsorbed. This process of re-absorption is called [[enterohepatic circulation]]. It has been suggested that bilirubin uptake in the gut (enterohepatic circulation) is increased in breast fed babies, possibly as the result of increased levels of epidermal growth factor (EGF) in breast milk.<ref>{{cite journal|last=Kumral|first=A|author2=Ozkan H |author3=Duman N |display-authors=etal |title=Breast milk jaundice correlates with high levels of epidermal growth factor|journal=Pediatr Res|year=2009|volume=66|issue=2|pages=218–21|doi=10.1203/pdr.0b013e3181ac4a30|pmid=19617811|doi-access=free}}</ref>{{Non-primary source needed|date=April 2025}} Breast milk also contains glucoronidase which will increase deconjugation and enterohepatic recirculation of bilirubin.{{cn|date=March 2025}}
# The breast-milk of some women contains a metabolite of progesterone called [[pregnanediol|3-alpha-20-beta pregnanediol]]. This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid (UDPGA) [[glucuronyl transferase]] responsible for conjugation and subsequent excretion of bilirubin. In the newborn liver, activity of glucuronyl transferase is only at 0.1-1% of adult levels, so conjugation of bilirubin is already reduced. Further inhibition of bilirubin conjugation leads to increased levels of bilirubin in the blood.<ref>{{cite journal|last=Arias|first=IM|author2=Gartner LM |author3=Seifter S |author4=Furman M |title=Prolonged neonatal unconjugated hyperbilirubinemia associated with breast feeding and a steroid, pregnane-3(alpha), 20(beta)-diol in maternal milk that inhibits glucuronide formation in vitro|journal=J Clin Invest|year=1964|volume=43|issue=11|pages=2037–47|doi=10.1172/jci105078 |pmid=14228539 |pmc=441992}}</ref>{{Non-primary source needed|date=April 2025}} However, these results have not been supported by subsequent studies.<ref>{{cite journal|last=Murphy|first=J F|author2=Hughes I|author3=Verrier Jones ER|author4=Gaskell S|author5=Pike AW|title=Pregnanediols and breast-milk jaundice|journal=Arch Dis Child|year=1981|volume=56|issue=6|pages=474–76|doi=10.1136/adc.56.6.474|pmid=7259280|pmc=1627473}}</ref>{{Non-primary source needed|date=April 2025}}
# An enzyme in breast milk called [[lipoprotein lipase]] produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase, which again leads to decreased conjugation and subsequent excretion of bilirubin.<ref>{{cite journal|last=Poland|first=R L|author2=Schultz GE |author3=Gayatri G |title=High milk lipase activity associated with breastmilk jaundice|journal=Pediatr Res|year=1980|volume=14|issue=12|pages=1328–31|doi=10.1203/00006450-198012000-00011|pmid=6782543|doi-access=free}}</ref>{{Update needed|date=April 2025}}

===Physiological jaundice===
Most [[infant]]s develop visible jaundice due to elevation of [[Bilirubin#Unconjugated ("indirect")|unconjugated bilirubin]] concentration during their first week.{{Citation needed|date=April 2025}} This is called physiological jaundice. This pattern of [[hyperbilirubinemia]] has been classified into two functionally distinct periods.<ref>{{Cite journal|last1=Porter|first1=Meredith L.|last2=Dennis|first2=Maj Beth L.|date=2002-02-15|title=Hyperbilirubinemia in the Term Newborn|url=https://www.aafp.org/afp/2002/0215/p599.html|journal=American Family Physician|volume=65|issue=4|pages=599–606|pmid=11871676|issn=0002-838X}}</ref>
* Phase one
# Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204&nbsp;μmol/L (12&nbsp;mg/dL).
# Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to 255&nbsp;μmol/L (15&nbsp;mg/dL).
* Phase two - bilirubin levels decline to about 34&nbsp;μmol/L (2&nbsp;mg/dL) for two weeks, eventually mimicking adult values.
# Preterm infants - phase two can last more than one month.
# Exclusively breastfed infants - phase two can last more than one month.

Mechanisms involved in physiological jaundice include:
* Relatively low activity of the enzyme [[glucuronosyltransferase]] which normally converts unconjugated bilirubin to conjugated bilirubin that can be excreted into the gastrointestinal tract.<ref name=jain2002/> Before birth, this enzyme is actively down-regulated, since bilirubin needs to remain unconjugated in order to cross the [[placenta]] to avoid being accumulated in the fetus.<ref>{{Cite journal | last1 = McDonagh | first1 = A. F. | s2cid = 21269991 | title = Movement of Bilirubin and Bilirubin Conjugates Across the Placenta | doi = 10.1542/peds.2006-3669 | journal = Pediatrics | volume = 119 | issue = 5 | pages = 1032–1033; author 1033 1033 | year = 2007 | pmid =  17473108}}</ref> After birth, it takes some time for this enzyme to gain function.
* Shorter life span of fetal red blood cells,<ref name=jain2002>[https://books.google.com/books?hl=en&lr=&id=ulR9AuVcJOIC&oi=fnd&pg=PA45 Page 45] in: Obstetrics & Gynaecology, by B. Jain, 2002. {{ISBN|8180562107}}, 9788180562105</ref> being approximately 80 to 90 days in a full term infant,<ref>{{Cite journal | last1 = Harrison | first1 = K. L. | title = Fetal Erythrocyte Lifespan | doi = 10.1111/j.1440-1754.1979.tb01197.x | journal = Journal of Paediatrics and Child Health | volume = 15 | issue = 2 | pages = 96–97 | year = 1979 | pmid =  485998| s2cid = 5370064 }}</ref> compared to 100 to 120 days in adults.
* Relatively low conversion of bilirubin to [[urobilinogen]] by the [[intestinal flora]], resulting in relatively high absorption of bilirubin back into the circulation.<ref name=jain2002/>

==Diagnosis==
Diagnosis is often by measuring the serum bilirubin level in the blood.<ref name=NICE2016Rec/> In those who are born after 35 weeks and are more than a day old transcutaneous bilirubinometer may also be used.<ref name=NICE2016Rec/> The use of an icterometer, a piece of transparent plastic painted in five transverse strips of graded yellow lines, is not recommended.<ref name=NICE2016Rec/>

===Transcutaneous bilirubinometer===
This is hand held, portable and rechargeable but expensive. When pressure is applied to the photoprobe, a xenon tube generates a strobe light, and this light passes through the subcutaneous tissue. The reflected light returns through the second fiber optic bundle to the spectrophotometric module. The intensity of the yellow color in this light, after correcting for the hemoglobin, is measured and instantly displayed in arbitrary units.{{citation needed|date=July 2020}}

===Pathological jaundice===
Any of the following features suggests pathological jaundice:{{citation needed|date=November 2021}}
# Clinical jaundice appearing in the first 24 hours or greater than 14 days of life.
# Increases in the level of total bilirubin by more than 8.5&nbsp;μmol/L (0.5&nbsp;mg/dL) per hour or (85&nbsp;μmol/L) 5&nbsp;mg/dL per 24 hours.
# Total bilirubin more than 331.5&nbsp;μmol/L (19.5&nbsp;mg/dL) ([[hyperbilirubinemia]]).
# Direct bilirubin more than 34&nbsp;μmol/L (2.0&nbsp;mg/dL).

The signs which help detect pathological jaundice are the presence of [[intrauterine growth restriction]], stigma of intrauterine infections (e.g. [[cataracts]], [[microcephaly|small head]], and [[hepatosplenomegaly|enlargement of the liver and spleen]]), [[cephalohematoma]], bruising, signs of bleeding in the brain's ventricles. History of illness is noteworthy. Family history of jaundice and anemia, family history of neonatal or early infant death due to liver disease, maternal illness suggestive of viral infection (fever, rash or [[lymphadenopathy]]), maternal drugs (e.g. [[sulphonamide (medicine)|sulphonamides]], anti-malarials causing [[hemolysis|red blood cell destruction]] in [[G6PD deficiency]]) are suggestive of pathological jaundice in neonates.{{Citation needed|date=November 2019}}

==Treatment==
The bilirubin levels for initiative of phototherapy varies depends on the age and health status of the newborn.  However, any newborn with a total serum bilirubin greater than 359 μmol/L ( 21&nbsp;mg/dL) should receive phototherapy.<ref name =AAP2004>{{cite journal |title=Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation |journal=Pediatrics |volume=114 |issue=1 |pages=297–316 |date=July 2004 |pmid=15231951 |doi= 10.1542/peds.114.1.297|author1= American Academy of Pediatrics Subcommittee on Hyperbilirubinemia|doi-access=free }}</ref> Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment.<ref>{{cite journal |last1=Gómez |first1=M |last2=Bielza |first2=C |last3=Fernández del Pozo |first3=JA |last4=Ríos-Insua |first4=S |year=2007 |title=A graphical decision-theoretic model for neonatal jaundice |journal=Med Decis Making |volume=27 |issue=3 |pages=250–65 |doi=10.1177/0272989X07300605 |pmid=17545496 |s2cid=14514900}}</ref>

===Phototherapy===
[[File:Phototherapy1.jpg|thumb|Phototherapy is the main treatment of neonatal jaundice]]
Babies with neonatal jaundice may be treated with colored light called [[phototherapy]], which works by changing trans-bilirubin into the water-soluble cis-bilirubin isomer.<ref>{{cite journal |author=Stokowski LA |s2cid=31233601 |title=Fundamentals of phototherapy for neonatal jaundice |journal=Adv Neonatal Care |volume=6 |issue=6 |pages=303–12 |date=December 2006 |pmid=17208161 |doi=10.1016/j.adnc.2006.08.004 }}</ref><ref name=SBM>{{cite journal|last1=Jones|first1=Clay|title=Separating Fact from Fiction in the Not-So-Normal Newborn Nursery: Newborn Jaundice|journal=Science-Based Medicine|date=9 May 2014|url=https://sciencebasedmedicine.org/separating-fact-from-fiction-in-the-not-so-normal-newborn-nursery-newborn-jaundice/}}</ref><ref name=Harrisons18>{{cite book|editor1-last=Longo|editor1-first=Dan L.|editor2-last=Kasper|editor2-first=Dennis L.|title=Harrison's principles of internal medicine.|date=2012|publisher=McGraw-Hill|location=New York|isbn=978-0071748896|edition=18th|chapter=Chapter 303: The Hyperbilirubinemias|last=Wolkoff|first=Allan W.}}</ref>{{rp|2533}}

The phototherapy involved is not ultraviolet light therapy but rather a specific frequency of blue light. The light can be applied with overhead lamps, which means that the baby's eyes need to be covered, or with a device called a [[biliblanket]], which sits under the [[Infant clothing|baby's clothing]] close to its skin.<ref name=SBM/>

The use of phototherapy was first discovered, accidentally, at Rochford Hospital in Essex, England, when a nurse, Sister [[Jean Ward]], noticed that babies exposed to sunlight had reduced jaundice, and a pathologist, Dr. Perryman, who noticed that a vial of blood left in the sun had turned green. Drs Cremer, Richards and Dobbs put together these observations,<ref>{{cite journal |last1=CREMER |first1=RJ |last2=PERRYMAN |first2=PW |last3=RICHARDS |first3=DH |title=Influence of light on the hyperbilirubinaemia of infants. |journal=Lancet |date=24 May 1958 |volume=1 |issue=7030 |pages=1094–7 |doi=10.1016/s0140-6736(58)91849-x |pmid=13550936}}</ref> leading to a landmark randomized clinical trial which was published in ''Pediatrics'' in 1968; it took another ten years for the practice to become established.<ref name=SBM/><ref>{{cite journal|last1=Lucey|first1=J|last2=Ferriero|first2=M|last3=Hewitt|first3=J|title=Prevention of hyperbilirubinemia of prematurity by phototherapy.|journal=Pediatrics|date=June 1968|volume=41|issue=6|pages=1047–54|doi=10.1542/peds.41.6.1047|pmid=5652916|s2cid=41816888}}</ref>
Massage therapy could be useful in addition to phototherapy in order to reduce the phototherapy duration. However, it does not appear to reduce the requirement for phototherapy in the treatment of neonatal jaundice.<ref>{{cite journal |last1=Abdellatif |first1=Mohammed |title=Massage therapy for the treatment of neonatal jaundice: A systematic review and network meta-analysis |journal=Journal of Neonatal Nursing |date=February 2020 |volume=26 |issue=1 |pages=17–24 |doi=10.1016/j.jnn.2019.09.002 |doi-access=free }}</ref>

Recent studies from several countries show that phototherapy can safely and effectively be performed in the family's home, and since 2022 home phototherapy is recommended as an alternative to readmission to hospital in the American national guidelines.<ref>{{Cite journal |last1=Anderson |first1=Candice Megan |last2=Kandasamy |first2=Yogavijayan |last3=Kilcullen |first3=Meegan |date=August 2021 |title=The efficacy of home phototherapy for physiological and non-physiological neonatal jaundice: A systematic review |url=https://linkinghub.elsevier.com/retrieve/pii/S1355184121001381 |journal=Journal of Neonatal Nursing |volume=28 |issue=5 |language=en |pages=312–326 |doi=10.1016/j.jnn.2021.08.010|s2cid=238646014 |url-access=subscription }}</ref><ref>{{Cite journal |last1=Pettersson |first1=M. |last2=Eriksson |first2=M. |last3=Albinsson |first3=E. |last4=Ohlin |first4=A. |date=2021-05-01 |title=Home phototherapy for hyperbilirubinemia in term neonates—an unblinded multicentre randomized controlled trial |url=https://doi.org/10.1007/s00431-021-03932-4 |journal=European Journal of Pediatrics |language=en |volume=180 |issue=5 |pages=1603–1610 |doi=10.1007/s00431-021-03932-4 |issn=1432-1076 |pmc=8032579 |pmid=33469713}}</ref><ref>{{Cite journal |title=Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation |doi=10.1542/peds.2022-058859|doi-access=free |journal=Pediatrics|date=2022 |pmid=35927462 |last1=Kemper |first1=A. R. |last2=Newman |first2=T. B. |last3=Slaughter |first3=J. L. |last4=Maisels |first4=M. J. |last5=Watchko |first5=J. F. |last6=Downs |first6=S. M. |last7=Grout |first7=R. W. |last8=Bundy |first8=D. G. |last9=Stark |first9=A. R. |last10=Bogen |first10=D. L. |last11=Holmes |first11=A. V. |last12=Feldman-Winter |first12=L. B. |last13=Bhutani |first13=V. K. |last14=Brown |first14=S. R. |last15=Maradiaga Panayotti |first15=G. M. |last16=Okechukwu |first16=K. |last17=Rappo |first17=P. D. |last18=Russell |first18=T. L. |volume=150 |issue=3 }}</ref>
However, there have been several reports about the possible relationship between neonatal phototherapy and the increased risk of future cancer. A recent systematic review has found that there may be a statistically significant association between phototherapy and various hematopoietic cancers (especially myeloid leukemia).<ref>Abdellatif, Mohammed, et al. "Association between neonatal phototherapy and future cancer: an updated systematic review and meta-analysis." European Journal of Pediatrics (2022): 1-13</ref>

===Exchange transfusions===
Much like with phototherapy the level at which [[exchange transfusion]] should occur depends on the health status and age of the newborn.  It should however be used for any newborn with a total serum bilirubin of greater than 428 μmol/L ( 25&nbsp;mg/dL ).<ref name=AAP2004/><ref name=Harrisons18/>{{rp|2533}}

==Research==
[[Penicillamine]] was studied in the 1970s in [[hyperbilirubinemia]] due to ABO [[hemolytic disease]].<ref name=Man2017>{{cite journal |last1=Mancuso |first1=Cesare |s2cid=21001248 |title=Bilirubin and brain: A pharmacological approach |journal=Neuropharmacology |date=May 15, 2017 |volume=118 |pages=113–123 |doi=10.1016/j.neuropharm.2017.03.013 |pmid=28315352 }}</ref> While tin mesoporphyrin IX may decrease bilirubin such use is not recommended in babies.<ref name=Man2017/> Preclinical studies have looked at [[minocycline]] to help prevent [[neurotoxicity]].<ref name=Man2017/> [[Clofibrate]] may decrease the duration of phototherapy.<ref name=Man2017/> Evidence as of 2012 however is insufficient to recommend its use.<ref>{{cite journal |last1=Gholitabar |first1=M |last2=McGuire |first2=H |last3=Rennie |first3=J |last4=Manning |first4=D |last5=Lai |first5=R |title=Clofibrate in combination with phototherapy for unconjugated neonatal hyperbilirubinaemia. |journal=The Cochrane Database of Systematic Reviews |date=12 December 2012 |volume=12 |issue=3 |pages=CD009017 |doi=10.1002/14651858.CD009017.pub2 |pmid=23235669|pmc=6426433 }}</ref>

==References==
{{Reflist}}

== External links ==
* [[American Academy of Pediatrics]] has issued guidelines for managing this disease, which can be obtained for free.
* [[National Institute for Health and Care Excellence]] (NICE) has issued guidelines for the recognition and treatment of neonatal jaundice in the [[United Kingdom]].
{{Medical resources
|  ICD10          = {{ICD10|P|58||p|50}}, {{ICD10|P|59||p|50}}
|  ICD9           = {{ICD9|773}}, {{ICD9|774}}
|  OMIM           =
|  MedlinePlus    = 001559
|  eMedicineSubj  = ped
|  eMedicineTopic = 1061
|  DiseasesDB     = 8881
|  MeshID         = D007567
}}
{{Certain conditions originating in the perinatal period}}

{{DEFAULTSORT:Neonatal Jaundice}}
[[Category:Neonatology]]
[[Category:Hepatology]]
[[Category:Haemorrhagic and haematological disorders of fetus and newborn]]
[[Category:Wikipedia medicine articles ready to translate]]