Neonatal jaundice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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.

In neonates the dermal icterus is first noted in the face and as the bilirubin level rises proceeds caudal to the trunk and then to the extremities.[1]

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 births. 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.[2]

All jaundice should be medically evaluated before treatment can be given.

Epidemilogy and Demographics

This condition is common in newborns affecting over half (50 -60%) of all babies in the first week of life.[3]

Causes

In neonates, benign jaundice tends to develop because of two factors - the breakdown of fetal hemoglobin as it is replaced with 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.

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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unconjugated bilirubin
 
 
 
 
 
 
 
Conjugated bilirubin
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pathologic
 
 
 
Physiologic
 
Hepatic
 
 
 
Post-hepatic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hemolytic
 
 
 
Non-hemolytic
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intrinsic causes
 
 
 
Extrinsic causes
 
 
 
 
 
 
 
 
 
 
 

Intrinsic causes of hemolysis

Extrinsic causes of hemolysis

Non-hemolytic causes

Hepatic causes

Post-hepatic

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.[4]
  • 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 [5][citation needed]. However, these results have not been supported by subsequent studies.[6]
  • 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 [7][citation needed].

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 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

Physical Examination

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 umbilicus, have the bilirubin less than 204 umol/l (12 mg/dL) (less dangerous level). Infants whose palms and soles are yellow, have serum bilirubin level over 255 umol/l (15 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

Infants with neonatal jaundice are often treated with bili lights, 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. A recent study has shown that light therapy may increase the risk of skin moles (or "nevi") in childhood which in turn also increases the risk of melanoma (skin cancer).[8][9]

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.

See also

References

  1. Madlon-Kay, Diane J. Recognition of the Presence and Severity of Newborn Jaundice by Parents, Nurses, Physicians, and Icterometer Pediatrics 1997 100: e3
  2. [http://aapnews.aappublications.org/cgi/content/full/18/5/231 "Increased vigilance needed to prevent kernicterus in newborns --O�Keefe 18 (5): 231 -- AAP News"]. Retrieved 2007-06-27. replacement character in |title= at position 66 (help)
  3. "Neonatal Jaundice" (PDF). Intensive Care Nursery House Staff Manual. UCSF Children's Hospital. 2004. Retrieved 26 July 2011.
  4. Kumral, A (2009). "Breast milk jaundice correlates with high levels of epidermal growth factor". Pediatr Res. 66: 218–21. Unknown parameter |coauthors= ignored (help)
  5. 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)
  6. Murphy, J F (1981). "Pregnanediols and breast-milk jaundice". Arch Dis Child. 56: 474–76. Unknown parameter |coauthors= ignored (help)
  7. Poland, R L (1980). "High milk lipase activity associated with breastmilk jaundice". Pediatr Res. 14: 1328–31. Unknown parameter |coauthors= ignored (help)
  8. [http://www.medpagetoday.com/HematologyOncology/SkinCancer/tb/4730 "Childhood Moles Linked to Neonatal Jaundice Treatment - CME Teaching Brief� - MedPage Today"]. Retrieved 2007-06-30. replacement character in |title= at position 75 (help)
  9. "Infant Jaundice Treatment May Encourage Moles - Skin diseases, conditions and procedures on MedicineNet.com". Retrieved 2007-06-30.

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