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'''For patient information, click [[Neonatal jaundice (patient information)|here]]'''
'''For patient information, click [[Neonatal jaundice (patient information)|here]]'''


{{DiseaseDisorder infobox |
{{Neonatal jaundice }}
  Name          = Neonatal jaundice |
{{CMG}} '''Assosciate Editor(s)-In-Chief:''' [[User: Prashanthsaddala|Prashanth Saddala M.B.B.S]], {{AEL}},  
  Image          = |
  Caption        = Infant undergoing home phototherapy for jaundice using a [[bili light|bili blanket]] |
  ICD10          = {{ICD10|P|58||p|50}}, {{ICD10|P|59||p|50}} |
  ICD9          = {{ICD9|773}}, {{ICD9|774}} |
  OMIM          = |
  MedlinePlus    = 001559 |
  eMedicineSubj  = |
  eMedicineTopic = |
  DiseasesDB    = 8881 |
}}
{{SI}}
{{CMG}}


==Overview==
'''''Synonyms and Keywords:''''' Jaundice of the newborn; Neonatal hyperbilirubinemia
'''Neonatal jaundice''' is a yellowing of the [[skin]] and other tissues of a newborn [[infant]] caused by increased levels of [[bilirubin]] in the [[blood]].


A [[bilirubin]] level of more than 85 umol/l (5 mg/dL) manifests clinical [[jaundice]] in [[neonates]] whereas in adults a level of 34 umol/l (2 mg/dL) would look [[icteric]]. In newborns jaundice is detected by blanching the skin with digital pressure so that it reveals underlying skin and subcutaneous tissue.  Jaundice newborns have an apparent icteric [[sclera]], and yellowing of the face, extending down onto the chest.
==[[Neonatal jaundice overview|Overview]]==


In neonates the dermal [[Icterus (medicine)|icterus]] is first noted in the face and as the bilirubin level rises proceeds caudal to the trunk and then to the extremities.<ref name="ReferenceA">Madlon-Kay, Diane J. Recognition of the Presence and Severity of Newborn Jaundice by Parents, Nurses, Physicians, and Icterometer Pediatrics 1997 100: e3</ref>
==[[Neonatal jaundice historical perspective|Historical Perspective]]==


Neonatal jaundice can be '''physiological''' or '''pathological'''. Neonatal physiological jaundice is usually harmless: this condition is often seen in [[infants]] around the second day after birth, lasting until day 8 in normal births, or to around day 14 in [[premature birth]]s. Serum [[bilirubin]] normally drops to a low level without any intervention required: the jaundice is presumably a consequence of metabolic and physiological adjustments after birth. In extreme cases, a brain-damaging condition known as [[kernicterus]] can occur; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. Neonatal jaundice is a risk factor for hearing loss.<ref>{{cite web|url=http://aapnews.aappublications.org/cgi/content/full/18/5/231 |title=Increased vigilance needed to prevent kernicterus in newborns --O�Keefe 18 (5): 231 -- AAP News |accessdate=2007-06-27 |format= |work=}}</ref>
==[[Neonatal jaundice classification|Classification]]==


All [[jaundice]] should be medically evaluated before treatment can be given.
==[[Neonatal jaundice pathophysiology|Pathophysiology]]==
==Epidemilogy and Demographics==
This condition is common in newborns affecting over half (50 -60%) of all babies in the first week of life.<ref>{{Cite conference
  | title = Neonatal Jaundice
  | booktitle = Intensive Care Nursery House Staff Manual
  | publisher = UCSF Children's Hospital
  | date = 2004
  | url = http://www.ucsfbenioffchildrens.org/pdf/manuals/41_Jaundice.pdf
  | accessdate = 26 July 2011}}</ref>
==Causes==


In neonates, benign 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 hepatic metabolic pathways which are unable to conjugate and so excrete bilirubin as fast as an adult.  This causes an accumulation of bilirubin in the body ([[hyperbilirubinemia]]), leading to the symptoms of jaundice.
==[[Neonatal jaundice causes|Causes]]==


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:
==[[Neonatal jaundice differential diagnosis|Differentiating Neonatal jaundice from other Diseases]]==


{{familytree/start}}
==[[Neonatal jaundice epidemiology and demographics|Epidemiology and Demographics]]==
{{familytree | | | | | | | | | | | | | A01 | | | | |A01=Neonatal jaundice}}
{{familytree | | | | | | | | |,|-|-|-|-|^|-|-|-|-|.|}}
{{familytree | | | | | | | | B01 | | | | | | | | B02|B01=[[Unconjugated bilirubin]]|B02=[[Conjugated bilirubin]]}}
{{familytree | | | | | |,|-|-|^|-|-|.| | | |,|-|-|^|-|-|.| |}}
{{familytree | | | | | C01 | | | | C02 | | C03 | | | | C04 | |C01=[[pathology|Pathologic]] |C02=[[Physiologic]] |C03=[[Hepatic]] |C04=Post-hepatic}}
{{familytree | | |,|-|-|^|-|-|.| | | | | | | | | | | |}}
{{familytree | | C01 | | | | C02 | | | | | | | | | | | |C01=[[hemolysis|Hemolytic]]|C02=Non-hemolytic}}
{{familytree | | |)|-|-|-|-|-|.| | | | | | | | | | | |}}
{{familytree | | C01 | | | | C02 | | | | | | | | | | | |C01=Intrinsic causes|C02=Extrinsic causes}}
{{familytree/end}}


===Intrinsic causes of hemolysis===
==[[Neonatal jaundice risk factors|Risk Factors]]==
*Membrane conditions
**[[Spherocytosis]]
**[[Hereditary elliptocytosis]]
*Systemic contitions
**[[Splenomegaly]]
**[[Sepsis]]
**[[Arteriovenous malformation]]
*Enzyme conditions
**[[Glucose-6-phosphate dehydrogenase deficiency]] (also called G6PD deficiency)
**[[Pyruvate kinase deficiency]]
*Globin synthesis defect
**[[Alpha-thalassemia]]


===Extrinsic causes of hemolysis===
==[[Neonatal jaundice screening|Screening]]==
*[[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)]]
**[[Rh disease]]
**[[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===
==[[Neonatal jaundice natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
*[[Cephalohematoma]]
*[[Polycythemia]]
*[[Sepsis]]
*[[Hypothyroidism]]
*[[Gilbert's syndrome]]
*[[Crigler-Najjar syndrome]]
 
===Hepatic causes===
*Infections
**[[Sepsis]]
**[[Hepatitis B]], [[TORCH syndrome|TORCH infections]]
*Metabolic
**[[Galactosemia]]
**[[Alpha-1-antitrypsin deficiency]]
**[[Cystic fibrosis]]
*Drugs
*[[Total parenteral nutrition]]
*Idiopathic
 
===Post-hepatic===
*[[Biliary atresia]]
*[[Bile duct]] obstruction
===Breast feeding jaundice===
"Breastfeeding jaundice" is caused by insufficient milk intake resulting in dehydration, and can be prevented by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.
 
===Breast milk jaundice===
Whereas breast ''feeding'' jaundice is a mechanical problem, breast ''milk'' jaundice is more of a biochemical problem. The term applies to jaundice in a newborn baby.
 
Very rarely, "breast milk jaundice" occurs during the second or third week of life.
 
* First, at birth, the gut is sterile, 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|coauthors=Ozkan H, Duman N, et al.|title=Breast milk jaundice correlates with high levels of epidermal growth factor|journal=Pediatr Res|year=2009|volume=66|pages=218–21}}</ref>
 
* Second, the breast-milk of some women contains a metabolite of progesterone called [[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|coauthors=Gartner LM, Seifter S, 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|pages=2037–47}}</ref>  {{Citation needed|date=July 2009}}. However, these results have not been supported by subsequent studies.<ref>{{cite journal|last=Murphy|first=J F|coauthors=Hughes I, Verrier Jones ER, Gaskell S, Pike AW.|title=Pregnanediols and breast-milk jaundice.|journal=Arch Dis Child|year=1981|volume=56|pages=474–76}}</ref>
 
* Third, 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|coauthors=Schultz GE, Gayatri G|title=High milk lipase activity associated with breastmilk jaundice.|journal=Pediatr Res|year=1980|volume=14|pages=1328–31}}</ref> {{Citation needed|date=July 2009}}.
 
Despite the advantages of breast feeding, there is a strong association of breast feeding with neonatal hyperbilirubinemia and thus risk of [[kernicterus]], though this is uncommon. Serum bilirubin levels may reach as high as 30&nbsp;mg/dL. Jaundice should be managed either with phototherapy or with exchange blood transfusion as is needed. Breast feeds however need not be discontinued. The child should be kept well hydrated and extra feeds given.
 
Neither condition is a reason to stop nursing, though caregivers may advise IV or other fluid administration to ensure the baby is not dehydrated.
 
==Natural history, Complications and Prognosis==
===Complications===
With high doses of bilirubin (severe hyperbilirubinemia) there can be a complication known as [[kernicterus]].  This is the chief condition that treatment of jaundice is aimed at preventing. The effects of kernicterus range from fever, seizures, and a high-pitched crying to mental retardation. This is due to a staining effect on the [[basal ganglia]] leading to neuronal damage. With aggressive treatment such as exchange transfusion to lower very high bilirubin levels, the neurological effects are almost always transient.


==Diagnosis==
==Diagnosis==
===Physical Examination===
[[Neonatal jaundice diagnostic study of choice|Diagnostic Study of Choice]] | [[Neonatal jaundice history and symptoms| History and Symptoms]] | [[Neonatal jaundice physical examination | Physical Examination]] | [[Neonatal jaundice laboratory findings|Laboratory Findings]] | [[Neonatal jaundice electrocardiogram|Electrocardiogram]] | [[Neonatal jaundice x ray|X Ray]] | [[Neonatal jaundice CT|CT]] | [[Neonatal jaundice MRI|MRI]] | [[Neonatal jaundice ultrasound|Echocardiography or Ultrasound]] | [[Neonatal jaundice other imaging findings|Other Imaging Findings]] | [[Neonatal jaundice other diagnostic studies|Other Diagnostic Studies]]
Notoriously inaccurate [[rules of thumb]] have been applied to the [[physical exam]] of the jaundiced infant. Some include estimation of serum [[bilirubin]] based on appearance.  One such rule of thumb includes infants whose jaundice is restricted to the face and part of the trunk above the [[Navel|umbilicus]], have the [[bilirubin]] less than 204&nbsp;umol/l (12&nbsp;mg/dL) (less dangerous level). Infants whose palms and soles are yellow, have serum bilirubin level over 255&nbsp;umol/l (15&nbsp;mg/dL) (more serious level)
===Non-invasive measurements of jaundice===
'''Ingram icterometer''': In this method a piece of transparent plastic known as '''Ingram icterometer''' is used. Ingram icterometer is painted in five transverse strips of graded yellow lines. The instrument is pressed against the nose and the yellow colour of the blanched skin is matched with the graded yellow lines and biluribin level is assigned.
 
'''Transcutaneous bilirubinometer''': This is hand held, portable and rechargeable but expensive and sophisticated. 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.


==Treatment==
==Treatment==
Infants with neonatal jaundice are often treated with [[bili light]]s, exposing them to high levels of colored light to break down the bilirubin. This works due to a photo oxidation process occurring on the bilirubin in the subcutaneous tissues of the neonate. Light energy creates isomerization of the bilirubin and consequently transformation into compounds that the new born can excrete via urine and stools.  Blue light is typically used for this purpose.  Green light is more effective at breaking down bilirubin, but is not commonly used because it makes the babies appear sickly, which is disturbing to observers.
[[Neonatal jaundice medical therapy|Medical Therapy]] | [[Neonatal jaundice surgery|Surgery]] | [[Neonatal jaundice primary prevention|Primary Prevention]] | [[Neonatal jaundice secondary prevention|Secondary Prevention]] | [[Neonatal jaundice cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Neonatal jaundice future or investigational therapies|Future or Investigational Therapies]]


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 umol/l ( 21&nbsp;mg/dL ) should receive phototherapy.<ref name =AAP2004>{{cite journal |author= |title=Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation |journal=Pediatrics |volume=114 |issue=1 |pages=297–316 |year=2004 |month=July |pmid=15231951 |doi= 10.1542/peds.114.1.297|url=http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=15231951 |author1= American Academy of Pediatrics Subcommittee on Hyperbilirubinemia}}</ref>
==Case Studies==
[[Neonatal jaundice case study one|Case#1]]


===Phototherapy===
==Related Chapters==
 
The use of phototherapy was first discovered, accidentally, at Rochford Hospital in Essex, England.  The ward sister (Charge Nurse) of the premature baby unit, firmly believed that the infants under her care benefited from fresh air and sunlight in the courtyard.  Although this led to the first noticing of jaundice being improved with sunlight, further studies only progressed when a vial of blood sent for bilirubin measurement sat on a windowsill in the lab for several hours.  The results indicated a much lower level of bilirubin than expected based on the patient's visible jaundice.  Further investigation lead to the determination that blue light, wavelength of 420-448&nbsp;nm, oxidized the bilirubin to biliverdin, a soluble product that does not contribute to kernicterus.  Although some pediatricians began using phototherapy in the United Kingdom following Dr. Cremer's publishing the above facts in the ''Lancet'' in 1958, most hospitals only began to regularly use phototherapy ten years later when an American group independently made the same discovery.<ref>{{Cite journal
| doi = 10.1136/adc.50.11.833
| issn = 0003-9888
| volume = 50
| issue = 11
| pages = 833–836
| last = Dobbs
| first = R H
| coauthors = R J Cremer
| title = Phototherapy.
| journal = Archives of Disease in Childhood
| date = 1975-11
| pmid = 1108807
| pmc = 1545706
}}</ref><ref>{{Cite journal
| doi = 10.1016/S0140-6736(58)91849-X
| issn = 0140-6736
| volume = 271
| issue = 7030
| pages = 1094–1097
| last = Cremer
| first = R. J.
| coauthors = P. W. Perryman, D. H. Richards
| title = INFLUENCE OF LIGHT ON THE HYPERBILIRUBINÆMIA OF INFANTS
| journal = The Lancet
| accessdate = 2010-08-01
| date = 1958-05-24
| url = http://www.sciencedirect.com.lrc1.usuhs.edu/science/article/B6T1B-497S8P6-7T/2/79532c4987c3e76cc9f804072c89252f
}}</ref>
[[Image:Jaundice phototherapy.jpg |thumb|left]]
Infants with neonatal jaundice are treated with colored light called phototherapy. Physicians randomly assigned 66 infants 35 weeks of gestation to receive phototherapy.  After 15±5 the levels of bilirubin, a yellowish bile pigment that in excessive amounts causes jaundice, were decreased down to 0.27±0.25&nbsp;mg/dl/h in the blue light.  This suggests that blue light therapy helps reduce high bilirubin levels that cause neonatal jaundice.<ref>{{cite journal |author=Amato M, Inaebnit D |title=Clinical usefulness of high intensity green light phototherapy in the treatment of neonatal jaundice |journal=Eur. J. Pediatr. |volume=150 |issue=4 |pages=274–6 |year=1991 |month=February |pmid=2029920 |doi= 10.1007/BF01955530|url=}}</ref> 
 
Exposing infants to high levels of colored light changes trans-bilirubin to the more water soluble cis-form which is excreted in the bile. Scientists studied 616 capillary blood samples from jaundiced newborn infants.  These samples were randomly divided into three groups.  One group contained 133 samples and would receive phototherapy with blue light.  Another group contained 202 samples would receive room light, or white light.  The final group contained 215 samples, and were left in a dark room. The total bilirubin levels were checked at 0, 2, 4, 6, 24, and 48 hours.  There was a significant decrease in bilirubin in the first group exposed to phototherapy after two hours, but no change occurred in the white light and dark room group.  After 6 hours, there was a significant change in bilirubin level in the white light group but not the dark room group.  It took 48 hours to record a change in the dark room group’s bilirubin level. Phototherapy is the most effective way of breaking down a neonate’s bilirubin.<ref>{{cite journal |author=Leung C, Soong WJ, Chen SJ |title=[Effect of light on total micro-bilirubin values in vitro] |language=Chinese |journal=Zhonghua Yi Xue Za Zhi (Taipei) |volume=50 |issue=1 |pages=41–5 |year=1992 |month=July |pmid=1326385 |doi= |url=}}</ref>
 
[[Phototherapy]] works through a process of isomerization that changes trans-bilirubin into the water-soluble cis-bilirubin isomer.<ref>{{cite journal |author=Stokowski LA |title=Fundamentals of phototherapy for neonatal jaundice |journal=Adv Neonatal Care |volume=6 |issue=6 |pages=303–12 |year=2006 |month=December |pmid=17208161 |doi=10.1016/j.adnc.2006.08.004 |url=}}</ref><ref>{{cite journal |author=Ennever JF, Sobel M, McDonagh AF, Speck WT |title=Phototherapy for neonatal jaundice: in vitro comparison of light sources |journal=Pediatr. Res. |volume=18 |issue=7 |pages=667–70 |year=1984 |month=July |pmid=6540860 |doi= 10.1203/00006450-198407000-00021|url=}}</ref>
 
In phototherapy, blue light is typically used because it is more effective at breaking down bilirubin (Amato, Inaebnit, 1991). Two matched groups of newborn infants with jaundice were exposed to intensive green or blue light phototherapy.  The efficiency of the treatment was measured by the rate of decline of serum bilirubin, which in excessive amounts causes jaundice, concentration after 6, 12 and 24 hours of light exposure.  A more rapid response was obtained using the blue lamps than the green lamps.  However, a shorter phototherapy recovery period was noticed in babies exposed to the green lamps(1). Green light is not commonly used because exposure time must be longer to see dramatic results(1).
 
Ultraviolet light therapy may increase the risk of or skin moles, in childhood. While an increased number of moles is related to an increased risk of skin cancer,<ref>{{cite journal |author=Pullmann H, Theunissen A, Galosi A, Steigleder GK |title=[Effect of PUVA and SUP therapy on nevocellular nevi (author's transl)] |language=German |journal=Z. Hautkr. |volume=56 |issue=21 |pages=1412–7 |year=1981 |month=November |pmid=7314762 |doi= |url=}}</ref><ref>{{cite journal |author=Titus-Ernstoff L, Perry AE, Spencer SK, Gibson JJ, Cole BF, Ernstoff MS |title=Pigmentary characteristics and moles in relation to melanoma risk |journal=Int. J. Cancer |volume=116 |issue=1 |pages=144–9 |year=2005 |month=August |pmid=15761869 |doi=10.1002/ijc.21001 |url=}}</ref><ref>{{cite journal |author=Randi G, Naldi L, Gallus S, Di Landro A, La Vecchia C |title=Number of nevi at a specific anatomical site and its relation to cutaneous malignant melanoma |journal=J. Invest. Dermatol. |volume=126 |issue=9 |pages=2106–10 |year=2006 |month=September |pmid=16645584 |doi=10.1038/sj.jid.5700334 |url=}}</ref> it is not ultraviolet light that is used for treating neonatal jaundice.  Rather, it is simply a specific frequency of blue light that does not carry these risks.
 
Increased feedings help move bilirubin through the neonate’s metabolic system.<ref>Wood, S. (2007, March). Fact or fable?. Baby Talk, 72(2).</ref>
 
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 baby's clothing close to its skin.
 
Brief exposure to '''indirect''' sunlight each day and increased feeding are also helpful. A newborn should not be exposed to direct [[sunlight]] because of the danger of [[sunburn]], which is much more harmful to a newborn's thin skin than that of an adult.
 
If the neonatal jaundice does not clear up with simple [[phototherapy]], other causes such as [[biliary atresia]], PFIC, bile duct paucity, Alagille's syndrome, alpha 1 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.
 
===Exchange transfusions===
Much like with phototherapy the level at which exchange transfusions 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 umol/l ( 25&nbsp;mg/dL ).<ref name=AAP2004/>
 
==See also==
* [[Jaundice]]
* [[Jaundice]]
==References==
{{reflist|2}}
{{Certain conditions originating in the perinatal period}}
{{SIB}}
[[de:Neugeborenengelbsucht]]
[[es:Ictericia del recién nacido]]


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Assosciate Editor(s)-In-Chief: Prashanth Saddala M.B.B.S, Ahmed Elsaiey, MBBCH [2],

Synonyms and Keywords: Jaundice of the newborn; Neonatal hyperbilirubinemia

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