Neonatal jaundice

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Neonatal jaundice
Classification and external resources
ICD-10 P58., P59.
ICD-9 773, 774
DiseasesDB 8881
MedlinePlus 001559
eMedicine ped/1061 
MeSH D007567

Neonatal jaundice is a yellowing of the skin and other tissues of a newborn infant caused by the accumulation of indirect unconjugated bilirubin in the skin due to an overall increase in the total bilirubin in the blood. Neonatal jaundice is of two types: physiological or non-physiological, which is considered pathological. Physiological jaundice, which is usually harmless, is often seen in infants around the second day after birth. This usually lasts until day 8 in normal birth; in premature birth, it could last until day 14. In physiological jaundice serum bilirubin normally drops to a low level without intervention; this type of jaundice is presumably due to the lack of sufficient glucuronyl transferase, the enzyme responsible for conjugation of bilirubin prior to excretion, and it's resolved once the enzyme has been produced in sufficient quantities to allow conjugation and excretion of bilirubin as bile salts. Jaundice that appears on the first day of life is always pathologic, with bilirubin usually higher than 15mg/dL, and it's not resolved on its own.

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

Contents

[edit] 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 quickly as an adult. This causes an accumulation of bilirubin in the blood (hyperbilirubinemia), leading to the symptoms of jaundice.

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.

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
 
 
 
 
 
 
 
 
 
 
 

[edit] Intrinsic causes of hemolysis

[edit] Extrinsic causes of hemolysis

[edit] Non-hemolytic causes

[edit] Hepatic causes

[edit] Post-hepatic


[edit] Treatment

newborn infant undergoing (white-light) phototherapy to treat neonatal jaundice
newborn infant undergoing (white-light) phototherapy to treat neonatal jaundice

Infants with neonatal jaundice are treated with colored light called phototherapy. Scientists 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 mg/dl/h in the blue light. This shows that blue light therapy helps reduce high bilirubin levels that cause neonatal jaundice. [1]

Exposing infants to high levels of colored light breaks down the bilirubin. 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. [2]

Phototherapy works through a process of isomerization (same molecule but with a different arrangement of the atoms) that changes the bilirubin into water-soluble isomers that can be passed without getting stuck in the liver. [3] [4]

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).

Light therapy may increase the risk of nevi, or skin moles, in childhood. Randomly 36 nevi, or moles, received ultraviolet phototherapy. After exposure, the moles average size increased from 4.7 mm2 to 5.3 mm2. This was observed in 28 of the 36 moles. Going further, an autoradiograph proved that each mole had an increase in melanocytes, keratinocytes and dermal cells (all skin cells) in comparison with the unexposed nevi. [5] Which in turn also increases the risk of melanoma. (skin cancer)[6] [7]

Increased feedings help move bilirubin through the neonate’s metabolic system [8]

[edit] Non-organic causes

[edit] Breast feeding jaundice

"Breastfeeding jaundice," perhaps more appropriately called "starvation jaundice," or "lack of breastfeeding jaundice," is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This can usually be prevented by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production. Infants born by cesarian section are at higher risk for this condition because they lack passage of the newborn through the vagina. Passage through the vagina helps to stimulate milk production.

[edit] Breast milk jaundice

The term breast-milk jaundice refers to jaundice in a newborn baby who is exclusively breastfed and in whom other causes of jaundice have been ruled out. The jaundice appears at the end of the first week of life and hence overlaps physiological jaundice. It can last for up to two months. Several factors are thought to be responsible for this condition.

In exclusively breastfed babies the establishment of normal gut flora is delayed. The bacteria in the 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 and reabsorbed. This process of re-absorption is called entero-hepatic circulation.

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. Reduced conjugation of bilirubin leads to increased level of bilirubin in the blood.

Lipoprotein lipase an enzyme present in breast-milk produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase which again leads to decreased conjugation and subsequent excretion of bilirubin.

Breast-milk jaundice does not usually cause any complication like kernicterus if the baby is otherwise healthy. The serum bilirubin level rarely goes above 20 mg /dL. It is usually not necessary to discontinue breast-feeding as the condition resolves spontaneously. Adequate hydration should be maintained by giving extra fluids if necessary.

[edit] Non-physiologic causes

A small percentage of infants will have "hemolytic jaundice". The infant's red blood cells will be broken down quicker because antibodies that attack the infant's red blood cells are transferred from the mother to the baby's bloodstream. The antibodies may be due to ABO (blood group) incompatibility or Rhesus factor differences. [9]

[edit] Rare causes

Rarely, neonatal jaundice may be caused by a genetic syndrome such as Crigler-Najjar syndrome.

[edit] Complications

Prolonged hyperbilirubinemia (severe jaundice) can result into chronic bilirubin encephalopathy (kernicterus).[10] [11] Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus. [12]

An effect of kernicterus is a fever. A male full term neonate had hyperbilirubinemia (kernicterus) and jaundice at the age of 4 days old. He displayed symptoms of increased lethargy, refusal to eat, and had a fever. The neonate who was diagnosed with kernicterus displayed symptoms of a fever. [13]

Another effect of kernicterus is seizures. The Neonatal Unit at Allied Hospital Faisalabad studied 200 neonates of either gender who presented seizures during their hospital stay from April 2003 to June 2004. The seizures were evaluated and one cause of the seizures was kernicterus. 4.5%, or 9 neonates, displayed seizures caused by kernicterus. [14]

High pitched crying is an effect of kernicterus. Scientists used a computer to record and measure cranial nerves 8, 9 and 12 in 50 infants who were divided into two groups equally depending upon bilirubin concentrations. Of the 50 infants, 43 had tracings of high pitched crying. [15]

A more severe effect of kernicterus is mental retardation. A case report revealed a seemingly healthy Caucasian boy born at 37 weeks in 1997 was diagnosed with kernicterus. Upon discharge at 22 hours, problems were noted and he was readmitted the next day. The pediatrician recommended 15 minutes of sun exposure a day. Throughout the next 4 days, the infant developed poor breastfeeding and lethargy. On day 6, blood samples were taken and found that his bilirubin level was excessively high at 27mg/dl and later his levels peaked at 33.4 mg/dl. In the next four months the boy developed athetoid cerebral palsy, a type of mental retardation. Kernicterus was diagnosed at 4 months of age.(8)

These effects are due to a yellow staining effect on the basal ganglia (area on bottom of the brain that controls motor abilities) leading to neuronal damage. (11)

Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment. [16] [17]

[edit] See also

[edit] References

  1. ^ Amato, M., Inaebnit, D. (1991, February). Clinical usefulness of high intensity green light phototherapy in the treatment of neonatal jaundice. European Journal Of Pediatrics, 150(4), 274-276.
  2. ^ Leung, C., Soong, WJ., Chen, SJ. (1992, July). Effect of light on total microbilirubin values in vitro. Chinese Medical Journal, 50(1), 41-45.
  3. ^ Stokowski, LA. (2006, December). Fundamentals of phototherapy for neonatal jaundice. Official Journal Of The National Association Of Neonatal Nurses, 6(6), 303-312.
  4. ^ Ennever, J.F., Sobel, M., McDonagh, A.F., Speck, W.F. (1984, July). Phototherapy for neonatal jaundice: in vitro comparison of light sources. Pediatric Research, 18(7), 667-670
  5. ^ Pullmann, H., Theunissen, A., Galosi, A., Steigleder, GK. (1981). Effect of PUVA and SUP therapy on nevocellular nevi. Zeitschrift Für Hautkrankheiten.
  6. ^ Titus-Ernstoff, L., Perry, A.E., Spencer, S.K., Gibson, J.J., Cole, B.F., Ernstoff, M.S. (2005, August). Pigmentary characteristics and moles in relation to melanoma risk. International Journal Of Cancer, 116(1), 144-149.
  7. ^ Randi, G., Naldi, L., Gallus, S., Di Landron, A., La Vecchia, C. (2006, April). Number of nevi at a specific anatomical site and its relation to cutaneous malignant melanoma. The Journal Of Investigative Dermatology, 129(9), 2106-2110.
  8. ^ Wood, S. (2007, March). Fact or fable?. Baby Talk, 72(2).
  9. ^ ABO Incompatibility. Retrieved on 2007-06-30. at About.com
  10. ^ Juetschke, L.J. (2005, Mar/Apr). Kernicterus: still a concern. Neonatal Network, 24(2), 7-19, 59-62
  11. ^ Colletti, J.E., Kothori, S., Jackson, D.M., Kilgore, K.P., Barringer,K. (2007, November). An emergency medicine approach to neonatal hyperbilirubinemia. Emergency Medicine Clinics Of North America, 25(4), 1117-1135.
  12. ^ Watchko, J.F. (2006, December). Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clinics In Perinatology, 33(4), 839-852.
  13. ^ Shah, Z., Chawla, A., Patkar, D., Pungaonkar, S. (2003, March). MRI in kernicterus. Australasian Radiology, 47(1), 55-57.
  14. ^ Malik, B.A., Butt, M.A., Shamoon, M., Tehseen, Z., Fatima, A., Hashmat, N. (2005, December). Seizures etiology in the newborn period. Journal Of The College Of Physicians And Surgeons—Pakistan, 15(12), 786-790.
  15. ^ Vohr, B.R., Lester, B., Rapisardi, G., O’Dea, C., Brown, L., Peucker, M., Cashore, W., Oh, W. (1989, August). Abnormal brain-stem function (brain-stem auditory evoked response) correlates with acoustic cry features in term infants with hyperbilirubinemia. The Journal Of Pediatrics, 115(2), 303-308.
  16. ^ Gómez, M. (2007, May/Jun). A graphical design- Theoretical model for neonatal jaundice. Medical Decision Making, 27(3), 250-265.
  17. ^ Rotheberg, A.D., Thomson, P.D., Andronikou, S., Cohen, D.F. (1982, July). Transient neonatal hyperammonaemia. A case report. South African Medical Journal, 62(6), 175-176.


[edit] External links

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Certain conditions originating in the perinatal period (P, 760-779)
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