# Neonatal jaundice

$^{Neonataljaundicetypicallypresentsinthefirstweekofpostnatallife,orlifeafterbirth.Jaundiceinthenewbornperiodisoftenself-limitingandharmless,howevermoreseriouspathologiccausesofjaundicemustnotbemissed.}$
In most of cases there is no specific underlying physiologic disorder. In other cases it results from red blood cell breakdown, liver disease, infection, hypothyroidism, or metabolic disorders (pathologic). Concerns, in otherwise healthy babies, occur when 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. In those with concerning findings further investigations to determine the underlying cause are recommended.
The need for treatment depends on bilirubin levels, the age of the child, and the underlying cause. Treatments may include more frequent feeding, phototherapy, or exchange transfusions. In those who are born early more aggressive treatment tends to be required.

## Sign and symptoms
### Complications
#### Kernicterus

$^{Whenbilirubinlevelsreachextremeelevation,kernicteruscanoccur.}$

#### $^{PathophysiologyofNewbornJaundice}$

$^{Bilirubin}$
$^{Bilirubinbindingtoalbumincanbedecreasedinasickneonate.}$
$^{Overall,thisprocessisimportantbecauseitallowsthenewborntogetridofexcessbilirubin.}$

#### $^{FetalMetabolismofBilirubin}$

$^{Newbornsproduceanincreasedrateofbilirubinperkilogrambodyweightwhencomparedtoadults.}$ $^{Afterbirth,theexcretionthroughtheplacentaisnolongeravailabletothefetus.}$
$^{Enterohepaticcirculation}$

## Causes

In newborns, jaundice tends to develop because of two factors—the breakdown of fetal hemoglobin as it is replaced with 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.
$^{PhysiologicalJaundiceandPathologicJaundice}$
| | | | | | | | | | | | | | | | | | | | | | | Neonatal jaundice | Neonatal jaundice | Neonatal jaundice | Neonatal jaundice | | | | | | | | |
| | | | | | | | | | | | | Unconjugated bilirubin | Unconjugated bilirubin | Unconjugated bilirubin | Unconjugated bilirubin | Unconjugated bilirubin | Unconjugated bilirubin | | | | | | | | | | | | | Conjugated bilirubin | Conjugated bilirubin | Conjugated bilirubin | Conjugated bilirubin | Conjugated bilirubin | Conjugated bilirubin |
| | | | | | | Pathologic | Pathologic | Pathologic | Pathologic | Pathologic | Pathologic | | | | | | | Physiological jaundice of neonates | Physiological jaundice of neonates | Physiological jaundice of neonates | Physiological jaundice of neonates | Physiological jaundice of neonates | Physiological jaundice of neonates | Hepatic | Hepatic | Hepatic | Hepatic | Hepatic | Hepatic | | | | | | | Post-hepatic | Post-hepatic | Post-hepatic | Post-hepatic | Post-hepatic | Post-hepatic |
| Hemolytic | Hemolytic | Hemolytic | Hemolytic | Hemolytic | Hemolytic | | | | | | | Non-hemolytic | Non-hemolytic | Non-hemolytic | Non-hemolytic | Non-hemolytic | Non-hemolytic | | | | | | | | | | | | | | | | | | | | |
| Intrinsic causes | Intrinsic causes | Intrinsic causes | Intrinsic causes | Intrinsic causes | Intrinsic causes | | | | | | | Extrinsic causes | Extrinsic causes | Extrinsic causes | Extrinsic causes | Extrinsic causes | Extrinsic causes | | | | | | | | | | | | | | | | | | | | |

### Physiologic Jaundice:

$^{Allofthesefactorscancontributetotransientunconjugatedhyperbilirubinemiainthenewborn,astheytransitionoverthefirstfewdaysfromintrauterinetoextrauterinelife.}$
Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This is called physiological jaundice. This pattern of hyperbilirubinemia has been classified into two functionally distinct periods.
* Phase one
* Term infants - jaundice lasts for about 10 days with a rapid rise of serum bilirubin up to 204 μmol/L (12 mg/dL).
* Preterm infants - jaundice lasts for about two weeks, with a rapid rise of serum bilirubin up to 255 μmol/L (15 mg/dL).
* Phase two - bilirubin levels decline to about 34 μmol/L (2 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.
$^{Unconjugatedhyperbilirubinemiaisthemostcommonreasonforjaundiceinthenewbornperiod.Inthemajorityofcases,unconjugatedhyperbilirubinemiaoccursinhealthynewborninfantsandisself-limitingandphysiologic.Inmostcases,theunconjugatedhyperbilirubinemiaandjaundiceoftheinfantself-resolvesasthenewborns'bilirubinprocessingmethodsevolvewithinthefirstfewweeksofextrauterinelife.}$
$^{Althoughinthemajorityofcases,unconjugatedhyperbilirubinemiaisphysiologic,therearealsoinstanceswhereunconjugatedhyperbilirubinemiacanbepathologicintheneonate.}$

### $^{PathologicCausesofUnconjugatedHyperbilirubinemiaintheNeonatalPeriod}$

$^{Causesofpathologicunconjugatedhyperbilirubinemiaaredividedintodifferentcategoriesrelatedtotheprocessingofbilirubin.}$
Any of the following features suggests pathological jaundice:
* 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 μmol/L (0.5 mg/dL) per hour or (85 μmol/L) 5 mg/dL per 24 hours.
* Total bilirubin more than 331.5 μmol/L (19.5 mg/dL) (hyperbilirubinemia).
* Direct bilirubin more than 34 μmol/L (2.0 mg/dL).
$^{Thefollowingareexamplesofwhatcancauseincreasedbilirubinproductionleadingtopathologicunconjugatedhyperbilirubinemiainthenewborn:}$
$^{HemolyticCausesofUnconjugatedHyperbilirubinemia}$
Hemolytic Causes of Unconjugated Hyperbilirubinemia (Intrinsic and Extrinsic Hemolysis)
Intrinsic causes of hemolysis:
* $^{Redbloodcellmembranedefects}$
* $^{EnzymeConditions}$
* Globin synthesis defect
** Sickle cell disease
** Alpha-thalassemia, e.g. HbH disease
$^{Examplesofextrinsiccausesofhemolysisthatleadtounconjugatedhyperbilirubinemiainthenewbornare:}$

#### Extrinsic causes of hemolysis

* Systemic conditions
** Sepsis: Sepsis can occur for a multitude of reasons in the newborn. Sepsis can occur from infections the newborn gets during or shortly before delivery such as Group B Streptococcus if the mother is note treated during delivery.
** Arteriovenous malformation
* Alloimmunity (The neonatal or cord blood gives a positive direct Coombs test and the maternal blood gives a positive indirect Coombs test)
** Hemolytic disease of the newborn (ABO)- See below
** Rh disease-See below
** Hemolytic disease of the newborn (anti-Kell)-See below
** Hemolytic disease of the newborn (anti-Rhc)
** Other blood type mismatches causing hemolytic disease of the newborn
$^{Thisisbecausethemother’santibodiesbindtoanddestroyfetalredbloodcells,whichinturncauseearlyunconjugatedhyperbilirubinemia.}$

### Non-hemolytic causes of Unconjugated Hyperbilirubinema

* Breastfeeding jaundice: See below
* Breast milk jaundice: See below
* Cephalohematoma: Present after birth, a hemorrhage under the scalp. Typically self resolve within 4 weeks. Can cause jaundice in the newborn when they accumulated blood breaks down$^.$
* Polycythemia: Newborns that have elevated numbers of red blood cells can have increased red blood cell breakdown causing hyperbilirubinemia. One cause of this is if there is a chronic low oxygen state while in the uterus
* Urinary tract infection
* Sepsis
* Hypothyroidism: Can cause prolonged jaundice in the newborn
* Gilbert's syndrome: Most prevalent genetic cause of unconjugated hyperbilirubinemia
* Crigler–Najjar syndrome: A serious genetic condition that causes hyperbilirubinemia within the first few days of life. Severe elevations in bilirubin can lead to kernicterus
* High GI obstruction (Pyloric stenosis, Bowel obstruction)

#### $^{BreastFeedingJaundice}$

$^{Whentheintakeofbreastmilkisdecreased,thiscausesastateofdecreasedbowelmovements,dehydrationandincreasedenterohepaticcirculationofbilirubin.}$ $^{Exclusivelyformulafedinfantsdonotexperiencebreastfeedingjaundice.}$

#### $^{BreastMilkJaundice}$

$^{Thislate-onsetjaundicemaydevelopinuptoonethirdofhealthybreastfedinfants.Thefollowingreasonscancausebreastmilkjaundice:}$

## Conjugated (Direct) Hyperbilirubinemia

$^{Conjugatedhyperbilirubinemiaisalsocalleddirecthyperbilirubinemia.Elevatedconjugatedbilirubininaneonateisalwayssuggestiveofanunderlyingdisorder.Increasedlevelsofconjugatedbilirubincannotcausekernicterusthough,sincethisformofbilirubin}$
$^{Wheneveranewbornisbornwithconjugatedhyperbilirubinemia,neonatalliverdiseasemustbeconsidered.Thefollowingarecausesofconjugated(direct)hyperbilirubinemiainthenewborn:}$

### Liver causes

* Infections
** Sepsis
** Hepatitis A: A viral infection of the liver. The infection is spread by fecal-oral route or by sexual contact. Hepatitis A is typically not transmitted from mother to newborn during pregnancy.
** Hepatitis B: A viral infection of the liver. There is a higher risk of transmission to the newborn if the mother is HBeAg-positive. Hepatitis B cannot pass through the placenta, however at birth there is a high risk of hepatitis B transmission. To prevent transmission to the newborn at birth, it is important that the infant receive the Hepatitis B vaccine and Hepatitis B Immune Globulin within 12 hours of birth
** TORCH infections: Includes toxoplasmosis, syphilis, HIV, varicella, mumps, parvovirus, rubella, cytomegalovirus and herpes infections.
* Metabolic
** Galactosemia:An inherited disorder that causes a buildup of galactose, a carbohydrate. There are multiple types of galactosemia. It can cause liver damage and conjugated hyperbilirubinemia
** Alpha 1-antitrypsin deficiency, which is commonly missed, and must be considered in DDx. An inherited disorder in which both the lungs and liver are diseased due to decreased levels of a protein called alpha-1 antitrypsin.
** Cystic fibrosis: An inherited disease that leads to a faulty protein. This faulty protein leads to the accumulation of mucus and widespread organ dysfunction. This disease can cause an obstruction of the biliary tract which leads to conjugated hyperbilirubinemia .
** Dubin–Johnson syndrome: An inherited disease of liver cells I which the ABCC2 gene is mutated. This mutation decreases the ability of liver cells to release bilirubin into bile. This causes buildup of conjugated bilirubin
** Rotor syndrome: A genetic disorder that occurs when two genes in liver cells are mutated. The fault genes cause liver cells to have reduced storage of bilirubin and cause hyperbilirubinemia
* Drugs
* Total parenteral nutrition: Also known as "TPN", is a source of complete nutrition that newborns can receive by intravenous methods if they cannot meet their nutritional needs by using their gastrointestinal tract.
* Idiopathic

### Post-liver

* $^{Biliaryatresia}$
** $^{Alagillesyndrome}$$^-$
** $^{Choledochalcyst}$$^-$ $^{Alsocalledcholedochalmalformation.Birthdefectsthatinvolvethebileductstructure.Cancausejaundiceandotherliverissues}$

## Diagnosis

$^{MonitoringofHyperbilirubinemiaintheNewborn}$
$^{Howarebilirubinlevelsevaluatedinthenewborn?}$
$^{Rhstandsforrhesusfactorandisaproteinthatisfoundonredbloodcells.YoucanbeeitherRh+andhavetheprotein,orRh-andnothavetheprotein.}$
$^{Thesenewbornsmustbemonitoredmorecloselyafterbirthtoensureinterventionforhighbilirubinlevelsisnotneeded.}$
Diagnosis of hyperbilirubineia can be made by measuring the serum bilirubin level in the blood. In those who are born after 35 weeks and are more than a day old, a transcutaneous bilirubinometer may also be used. The use of an icterometer, a piece of transparent plastic painted in five transverse strips of graded yellow lines, is not recommended.
$^{Transcutaneousbilirubinometer:(TCB)}$ $^{Thisishandheld,portableandrechargeablebutexpensive.Whenpressureisappliedtothephotoprobe,axenontubegeneratesastrobelight,andthislightpassesthroughthesubcutaneoustissue.Thereflectedlightreturnsthroughthesecondfiberopticbundletothespectrophotometricmodule.Theintensityoftheyellowcolorinthislight,aftercorrectingforthehemoglobin,ismeasuredandinstantlydisplayedinarbitraryunits.BilirubinisnotdirectlymeasuredbutTCBprovidesagoodscreeningtestfornewborns.}$
$^{Howarebilirubinlevelsinterpreted?}$
$^{Oncethetranscutaneousbilirubinometerorlaboratorybilirubintestcomesback,itmustbeinterpretedtounderstandifthenewbornrequirestreatmentornot.Iftheinfanthasanyriskfactors,theirbilirubinlevelsneedtobemonitoredmorecloselyandfrequently.}$
$^{Tounderstandtheneedfortreatment,multiplefactorsareconsidered,}$ $^{including}$ $^{Afterthesefactorsarereviewed,}$
$^{Newbornsshouldalsofollowcloselywiththeirpediatriciantomonitorjaundice.}$
$^{Iftherearemultipletranscutaneousbilirubin(TcB)ortotalserumbilirubin(TSB)measurements,itisimportanttoconsidertherateofriseofbilirubinlevels.}$ $^{Inthefirstdayoflifeifbilirubinincreasesatarateof}$ $^{greater}$ $^{than}$ $^{orequalto0.3mg/dLperhour}$ $^{Thiscouldbeduetoahemolyticprocessinthenewborn,wheretheirredbloodcellsarebeingdestroyed.}$

## 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 mg/dL) should receive phototherapy.

### Phototherapy

$^{Homephototherapycanalsobeanoptioninsomesituations,butmanyfactorsmustbemonitored,includingthequalityofmachine,howcomfortablethefamilyis,andhowthebilirubinlevelscanbemonitored.}$
$^{IntravenousImmunoglobulin}$
$^{Itcanbeusedinadditiontophototherapy.}$
$^{ExchangeTransfusion}$
$^{Itisusedtopreventkernicterusinnewborns.}$

## External Links

* American Academy of Pediatrics has issued guidelines for managing this disease, which can be obtained for free.https://publications.aap.org/pediatrics/article/150/3/e2022058859/188726/Clinical-Practice-Guideline-Revision-Management-of
* National Institute for Health and Care Excellence (NICE) has issued guidelines for the recognition and treatment of neonatal jaundice in the United Kingdom.
* 1 2 3 4 5 6 7 8 "Neonatal Hyperbilirubinemia". Merck Manuals Professional Edition. August 2015. Retrieved 11 December 2017.
* ↑ "Jaundice in newborn babies under 28 days | Guidance and guidelines". NICE. October 2016. Retrieved 11 December 2017.
* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Ivanov, D.O., ed. (2023), Nelson Textbook of Pediatrics, vol. 3, GEOTAR-Media Publishing Group, pp. 1–1328, doi:10.33029/9704-6921-7-pbn-2023-1-1328, ISBN 978-5-9704-6921-7, retrieved 19 March 2025
* 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 "Neonatal Hyperbilirubinemia - Pediatrics". Merck Manual Professional Edition. Retrieved 19 March 2025.
* 1 2 Reddy, Dinesh K.; Pandey, Shivlal (2025), "Kernicterus", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32644546, retrieved 19 March 2025
* 1 2 3 4 5 6 7 8 Hansen, Thor Willy Ruud (1 June 2010). "Core Concepts: Bilirubin Metabolism". NeoReviews. 11 (6): e316 – e322. doi:10.1542/neo.11-6-e316. ISSN 1526-9906.
* 1 2 3 4 Kalakonda, Aditya; Jenkins, Bianca A.; John, Savio (2025), "Physiology, Bilirubin", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29261920, retrieved 19 March 2025
* 1 2 Singh, Anand; Koritala, Thoyaja; Jialal, Ishwarlal (2025), "Unconjugated Hyperbilirubinemia", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31747203, retrieved 19 March 2025
* ↑ Par, Emma J.; Hughes, Chase A.; DeRico, Pierce (May 2023). "Neonatal Hyperbilirubinemia: Evaluation and Treatment". American Family Physician. 107 (5): 525–534. ISSN 1532-0650. PMID 37192079.
* 1 2 3 4 5 6 7 Ansong-Assoku, Betty; Shah, Sanket D.; Adnan, Mohammad; Ankola, Pratibha A. (2025), "Neonatal Jaundice", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30422525, retrieved 19 March 2025
* 1 2 Coté, Charles J.; Lerman, Jerrold; Anderson, Brian J., eds. (2019). A practice of anesthesia for infants and children (Sixth ed.). Philadelphia, PA: Elsevier. ISBN 978-0-323-42974-0.
* ↑ Lauer, B. J.; Spector, N. D. (1 August 2011). "Hyperbilirubinemia in the Newborn". Pediatrics in Review. 32 (8): 341–349. doi:10.1542/pir.32-8-341. ISSN 0191-9601. PMID 21807875.
* ↑ Enegela, Ogboche A.; Anjum, Fatima (2025), "Pyruvate Kinase Deficiency", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32809416, retrieved 19 March 2025
* 1 2 Sarwar, Ayesha; Citla Sridhar, Divyaswathi (2025), "Rh Hemolytic Disease", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 32809323, retrieved 19 March 2025
* 1 2 Maheshwari, Ashish; Zubair, Muhammad; Maheshwari, Apoorva (2025), "Kell Blood Group System", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 39536149, retrieved 19 March 2025
* ↑ Raines, Deborah A.; Krawiec, Conrad; Weisbrod, Luke J.; Jain, Sameer (2025), "Cephalohematoma", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 29262234, retrieved 19 March 2025
* 1 2 3 Bratton, Stephanie; Cantu, Rebecca M.; Stern, Mitchell (2025), "Breast Milk Jaundice", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30726019, retrieved 19 March 2025
* 1 2 3 4 5 6 7 8 9 10 11 12 13 Kemper, Alex R.; Newman, Thomas B.; Slaughter, Jonathan L.; Maisels, M. Jeffrey; Watchko, Jon F.; Downs, Stephen M.; Grout, Randall W.; Bundy, David G.; Stark, Ann R.; Bogen, Debra L.; Holmes, Alison Volpe; Feldman-Winter, Lori B.; Bhutani, Vinod K.; Brown, Steven R.; Maradiaga Panayotti, Gabriela M. (5 August 2022). "Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation". Pediatrics. 150 (3): e2022058859. doi:10.1542/peds.2022-058859. ISSN 0031-4005. PMID 35927462.
* ↑ Kamani, Lubna (2025), "Viral hepatitis in pregnancy", Hepatology, Elsevier, pp. 971–1001, doi:10.1016/b978-0-443-26711-6.00035-4, ISBN 978-0-443-30052-3, retrieved 19 March 2025
* ↑ PMC, Europe. "Europe PMC". europepmc.org. Retrieved 19 March 2025.
* ↑ Lauer, B. J.; Spector, N. D. (1 August 2011). "Hyperbilirubinemia in the Newborn". Pediatrics in Review. 32 (8): 341–349. doi:10.1542/pir.32-8-341. ISSN 0191-9601. PMID 21807875.