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==Overview==
==Overview==
Neonatal jaundice is caused by hemolysis of the RBCs mainly due to either intravascular causes or extravascular causes. Other causes include nonhemolytic causes as cephalosporines induced jaundice, genetic mutaitons of the UGT enzyme, and hepatic causes.  
Neonatal jaundice is caused by [[hemolysis]] of the [[RBCs]] mainly due to either [[intravascular]] causes or extravascular causes. Other causes include non-hemolytic causes such as [[cephalosporin]] induced [[jaundice]], [[genetic mutations]] of the [[UGT1A1|UGT enzyme]], and [[Hepatic|hepatic causes]].  


==Causes==
==Causes==


===Intrinsic causes of hemolysis===
=== Common causes ===
*Membrane conditions
* Common causes of neonatal jaundice include the following:<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><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>
**[[Spherocytosis]]
** Increase bilirubin production due to hemolysis. Hemolytic causes include:
**[[Hereditary elliptocytosis]]
*** '''Intrinsic causes of hemolysis'''
*Systemic contitions
****[[Spherocytosis]]
**[[Splenomegaly]]
****[[Hereditary elliptocytosis]]
**[[Sepsis]]
***'''Systemic contitions'''
**[[Arteriovenous malformation]]
****[[Splenomegaly]]
*Enzyme conditions
****[[Sepsis]]
**[[Glucose-6-phosphate dehydrogenase deficiency]] (also called G6PD deficiency)
****[[Arteriovenous malformation]]
**[[Pyruvate kinase deficiency]]
***'''Enzyme conditions'''
*Globin synthesis defect
****[[Glucose-6-phosphate dehydrogenase deficiency]] (also called [[G6PD deficiency]])
**[[Alpha-thalassemia]]
****[[Pyruvate kinase deficiency]]
***'''Globin synthesis defect'''
****[[Alpha-thalassemia]]
***'''Extrinsic causes of hemolysis'''
****[[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]]


===Extrinsic causes of hemolysis===
=== Less common causes ===
*[[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]])
* Less common causes of neonatal jaundice include the following disorders:<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><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>
**[[Hemolytic disease of the newborn (ABO)]]
** '''Non-hemolytic causes'''
**[[Rh disease]]
***[[Cephalhematoma]]
**[[Hemolytic disease of the newborn (anti-Kell)]]
***[[Polycythemia]]
**[[Hemolytic disease of the newborn (anti-Rhc)]]
***[[Sepsis]]
**Other blood type mismatches causing [[hemolytic disease of the newborn]]
***[[Hypothyroidism]]
***[[Gilbert's syndrome]]
***[[Crigler-Najjar syndrome]]


===Non-hemolytic causes===
* '''Hepatic causes'''
*[[Cephalohematoma]]
**'''Infections'''
*[[Polycythemia]]
***[[Sepsis]]
*[[Sepsis]]
***[[Hepatitis B]]
*[[Hypothyroidism]]
***[[TORCH syndrome|TORCH infections]]
*[[Gilbert's syndrome]]
**'''Metabolic'''
*[[Crigler-Najjar syndrome]]
***[[Galactosemia]]
***[[Alpha-1-antitrypsin deficiency]]
***[[Cystic fibrosis]]
**Drugs:
***[[Losartan and Hydrochlorothiazide|Losartan]]  
***[[Losartan and Hydrochlorothiazide|Hydrochlorothiazide]]
**[[Total parenteral nutrition]]


===Hepatic causes===
* '''Post-hepatic'''
*Infections
**[[Biliary atresia]]
**[[Sepsis]]
**[[Hepatitis B]], [[TORCH syndrome|TORCH infections]]
*Metabolic
**[[Galactosemia]]
**[[Alpha-1-antitrypsin deficiency]]
**[[Cystic fibrosis]]
*Drugs- [[Losartan and Hydrochlorothiazide]]
*[[Total parenteral nutrition]]
*Idiopathic
 
===Post-hepatic===
*[[Biliary atresia]]
*[[Bile duct]] obstruction
*[[Bile duct]] obstruction
===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.
===Causes by Organ System===


* 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>
{| style="width:80%; height:100px" border="1"
| style="width:25%" bgcolor="LightSteelBlue" ; border="1" |'''Cardiovascular'''
| style="width:75%" bgcolor="Beige" ; border="1" | No underlying causes
|-
| bgcolor="LightSteelBlue" | '''Chemical/Poisoning'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Dermatologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Drug Side Effect'''
| bgcolor="Beige" | [[Losartan and Hydrochlorothiazide|Losartan]], [[Losartan and Hydrochlorothiazide|Hydrochlorothiazide]]
|-
|- bgcolor="LightSteelBlue"
| '''Ear Nose Throat'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Endocrine'''
| bgcolor="Beige" | [[Hypothyroidism]]
|-
|- bgcolor="LightSteelBlue"
| '''Environmental'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Gastroenterologic'''
| bgcolor="Beige" | [[Gilbert's syndrome]], [[Crigler-Najjar syndrome]], [[Alpha-1-antitrypsin deficiency]], [[Biliary atresia]], [[Bile duct]] obstruction
|-
|- bgcolor="LightSteelBlue"
| '''Genetic'''
| bgcolor="Beige" | [[Cystic fibrosis]], [[Alpha-1-antitrypsin deficiency]]
|-
|- bgcolor="LightSteelBlue"
| '''Hematologic'''
| bgcolor="Beige" | [[Cephalhematoma]], [[Polycythemia]]
|-
|- bgcolor="LightSteelBlue"
| '''Iatrogenic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Infectious Disease'''
| bgcolor="Beige" | [[Sepsis]], [[Hepatitis B]], [[TORCH syndrome|TORCH infections]]
|-
|- bgcolor="LightSteelBlue"
| '''Musculoskeletal/Orthopedic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Neurologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Nutritional/Metabolic'''
| bgcolor="Beige" | [[Galactosemia]], [[Total parenteral nutrition]]
|-
|- bgcolor="LightSteelBlue"
| '''Obstetric/Gynecologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Oncologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Ophthalmologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Overdose/Toxicity'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Psychiatric'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Pulmonary'''
| bgcolor="Beige" | [[Alpha-1-antitrypsin deficiency]]
|-
|- bgcolor="LightSteelBlue"
| '''Renal/Electrolyte'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Rheumatology/Immunology/Allergy'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Sexual'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Trauma'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Urologic'''
| bgcolor="Beige" | No underlying causes
|-
|- bgcolor="LightSteelBlue"
| '''Miscellaneous'''
| bgcolor="Beige" | No underlying causes
|-
|}


* 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>
===Causes in Alphabetical Order===
 
{{columns-list|
* 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}}.
* Alloimmunity
 
*Alpha-1-antitrypsin deficiency
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. Breastfeeds however need not be discontinued. The child should be kept well hydrated and extra feeds given.
*Alpha-thalassemia
 
*Arteriovenous malformation
Neither condition is a reason to stop nursing, though caregivers may advise IV or other fluid administration to ensure the baby is not dehydrated.
*Bile duct obstruction
*Biliary atresia
*Cephalhematoma
*Crigler-Najjar syndrome
*Cystic fibrosis
*Galactosemia
*Gilbert's syndrome
*Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency)
*Hemolytic disease of the newborn (ABO)
*Hepatitis B
*Hereditary elliptocytosis
*Hydrochlorothiazide
*Hypothyroidism
*Losartan
*Polycythemia
*Pyruvate kinase deficiency
*Rh disease
*Sepsis
*Spherocytosis
*Splenomegaly
*TORCH infections
*Total parenteral nutrition
}}


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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Latest revision as of 22:56, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]

Overview

Neonatal jaundice is caused by hemolysis of the RBCs mainly due to either intravascular causes or extravascular causes. Other causes include non-hemolytic causes such as cephalosporin induced jaundice, genetic mutations of the UGT enzyme, and hepatic causes.

Causes

Common causes

Less common causes

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning No underlying causes
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect Losartan, Hydrochlorothiazide
Ear Nose Throat No underlying causes
Endocrine Hypothyroidism
Environmental No underlying causes
Gastroenterologic Gilbert's syndrome, Crigler-Najjar syndrome, Alpha-1-antitrypsin deficiency, Biliary atresia, Bile duct obstruction
Genetic Cystic fibrosis, Alpha-1-antitrypsin deficiency
Hematologic Cephalhematoma, Polycythemia
Iatrogenic No underlying causes
Infectious Disease Sepsis, Hepatitis B, TORCH infections
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic Galactosemia, Total parenteral nutrition
Obstetric/Gynecologic No underlying causes
Oncologic No underlying causes
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary Alpha-1-antitrypsin deficiency
Renal/Electrolyte No underlying causes
Rheumatology/Immunology/Allergy No underlying causes
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

  • Alloimmunity
  • Alpha-1-antitrypsin deficiency
  • Alpha-thalassemia
  • Arteriovenous malformation
  • Bile duct obstruction
  • Biliary atresia
  • Cephalhematoma
  • Crigler-Najjar syndrome
  • Cystic fibrosis
  • Galactosemia
  • Gilbert's syndrome
  • Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency)
  • Hemolytic disease of the newborn (ABO)
  • Hepatitis B
  • Hereditary elliptocytosis
  • Hydrochlorothiazide
  • Hypothyroidism
  • Losartan
  • Polycythemia
  • Pyruvate kinase deficiency
  • Rh disease
  • Sepsis
  • Spherocytosis
  • Splenomegaly
  • TORCH infections
  • Total parenteral nutrition

References

  1. ↑ Poland, R L (1980). "High milk lipase activity associated with breastmilk jaundice". Pediatr Res. 14: 1328–31. Unknown parameter |coauthors= ignored (help)
  2. ↑ Murphy, J F (1981). "Pregnanediols and breast-milk jaundice". Arch Dis Child. 56: 474–76. Unknown parameter |coauthors= ignored (help)
  3. ↑ Kumral, A (2009). "Breast milk jaundice correlates with high levels of epidermal growth factor". Pediatr Res. 66: 218–21. Unknown parameter |coauthors= ignored (help)
  4. ↑ Arias, IM (1964). "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". J Clin Invest. 43: 2037–47. Unknown parameter |coauthors= ignored (help)

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