This article may require cleanup to meet Wikipedia's quality standards. Please improve this article if you can. (January 2007)

This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (July 2009)

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. A bilirubin level of more than 85 umol/l (5 mg/dL) manifests clinical jaundice in neonates whereas in adults 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. This condition is common in upwards of 70% of newborns.

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].

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).

However, studies have shown that even trained examiners (physicians and nurses) make poor estimations based on physical appearance ^[1]

In infants jaundice can be measured using invasive or non-invasive methods. In non invasive method Ingram icterometer and Transcutaneous bilirubinometer are used.

Contents 1 Physiological jaundice 1.1 Causes 2 Pathological Jaundice of Neonates 2.1 Causes of Pathological Jaundice of Neonates 3 Differentiation between Physiological and Pathological jaundice 4 Causes of jaundice 4.1 Intrinsic causes of hemolysis 4.2 Extrinsic causes of hemolysis 4.3 Non-hemolytic causes 4.4 Hepatic causes 4.5 Post-hepatic 4.6 Non-organic causes 4.6.1 Breast feeding jaundice 4.6.2 Breast milk jaundice 4.6.3 Maternal diet and breast milk jaundice 5 Non-invasive measurement of jaundice 6 Treatment 6.1 Phototherapy 6.2 Exchange transfusions 7 Complications 8 Guidelines 9 References 10 External links

[edit] Physiological jaundice

Most infants develop visible jaundice due to elevation of unconjugated bilirubin concentration during their first week. This common condition is called physiological jaundice. This pattern of hyperbilirubinemia has been classified into two functionally distinct periods.

Phase one

1. Term infants - jaundice lasts for about 5 days with a rapid rise of serum bilirubin up to 204 umol/l (12 mg/dL).
2. Preterm infants: For preterm infants jaundice lasts for about a week, with a rapid rise of serum bilirubin up to 255 umol/l (15 mg/dL).

Phase two - bilirubin levels decline about 34 umol/l (2 mg/dL) for 2 weeks, eventually mimicking adult values.

1. Preterm infants - phase two can last more than 1 month.
2. In babies who receive exclusive breast feedings, phase two can last more than 1 month.

[edit] Causes

Possible mechanisms involved in physiological jaundice

Increase bilirubin load on liver cells

1. Increased red blood cell (RBC) volume
2. Increased labeled bilirubin
3. Increased circulation of bilirubin in the liver
4. Decreased RBC survival

Defective hepatic uptake of bilirubin from blood plasma

1. Decreased ligadin (Y protein)
2. Increased binding of Y proteins by other anions
3. Decreased liver uptake especially in phase two

Defective billirubin conjugation

1. Decreased UDPG activity

Defective bilirubin excretion

[edit] Pathological Jaundice of Neonates

(syn. Unconjugated pathological hyberbilirubinemia)

Any of the following features characterizes pathological jaundice:

1. Clinical jaundice appearing in the first 24 hours.
2. Increases in the level of total bilirubin by more than 8.5 umol/l (0.5 mg/dL) per hour or (85 umol/l) 5 mg/dL per 24 hours.
3. Total bilirubin more than 331.5 umol/l (19.5 mg/dL) (hyperbilirubinemia).
4. Direct bilirubin more than 34 umol/l (2.0 mg/dL).

[edit] Causes of Pathological Jaundice of Neonates

1. Increased production
   1. Fetomaternal blood group incompatibility: Rh, ABO
   2. Hereditary spherocytosis.
   3. Non-spherocytic hemolytic anemia: G-6-PD deficiency, a-thalassemia, Vitamin K3 induced hemolysis, pyruvate kinase deficiency.
   4. Sepsis.
   5. Increased enterohepatic circulation: Pyloric stenosis, or large bowel obstruction.
2. Decreased clearance
   1. Inborn errors of metabolism: Criggler-Najjar syndrome type I and II
   2. Drugs and Hormones: Hypothyroidism, breast milk jaundice.

[edit] Differentiation between Physiological and Pathological jaundice

The aim of clinical assessment is to distinguish physiological from pathological jaundice. The sign which helps to differentiate pathological jaundice of neonates from physiological jaundice of neonates are presence of intrauterine retardation, stigma of intrauterine infections (e.g. cataracts, microcephaly, hepatosplenomegaly etc), cephalhematoma, bruising, signs of intra ventricular hemorrhage etc. History of illness is noteworthy. Family history of jaundice and anemia, family history of neonatal or early infant death due to liver disease, maternal illness suggestive of viral infection (fever, rash or lymphadenopathy), Maternal drugs (e.g. Sulphonamides, anti-malarials causing hemolysis in G-6-PD deficiency) are suggestive of pathological jaundice in neonates.

[edit] Causes of jaundice

In neonates, 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

Physiological jaundice of Neonates

Hepatic

Post-hepatic

Hemolytic

Non-hemolytic

Intrinsic causes

Extrinsic causes

[edit] Intrinsic causes of hemolysis

• Membrane conditions
  • Spherocytosis
  • Hereditary elliptocytosis
• Systemic conditions
  • Splenomegaly
  • Sepsis
  • Arteriovenous malformation
• Enzyme conditions
  • Glucose-6-phosphate dehydrogenase deficiency (also called G6PD deficiency)
  • Pyruvate kinase deficiency
• Globin synthesis defect
  • sickle cell disease
  • Alpha-thalassemia

[edit] Extrinsic causes of hemolysis

• 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)^[2]

• • 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
  • Breast milk feeding.

[edit] Non-hemolytic causes

• Cephalohematoma
• Polycythemia
• Sepsis
• Hypothyroidism
• Gilbert's syndrome
• Crigler-Najjar syndrome

[edit] Hepatic causes

• Infections
  • Sepsis
  • Hepatitis B
  • TORCH infections
• Metabolic
  • Galactosemia
  • Alpha-1-antitrypsin deficiency
  • Cystic fibrosis
• Drugs
• Total parenteral nutrition
• Idiopathic

[edit] Post-hepatic

• Biliary atresia
• Bile duct obstruction

[edit] Non-organic causes

[edit] Breast feeding jaundice

"Breastfeeding 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 ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production. Passage of the baby through the vagina during birth helps stimulate milk production in the mother's body, so infants born by cesarean section are at higher risk for this condition.

[edit] 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 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.

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

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. Reduced conjugation of bilirubin leads to increased level of bilirubin in the blood^{[citation needed]}.

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^{[citation needed]}.

Breast-milk is now known to cause 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.

[edit] Maternal diet and breast milk jaundice

This section requires expansion.

[edit] Non-invasive measurement of jaundice

This method is more accurate and less subjective in estimating 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 rechargable 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.

[edit] 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 umol/l ( 21 mg/dL ) should receive phototherapy.^[3]

[edit] Phototherapy

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 mg/dl/h in the blue light. This shows that blue light therapy helps reduce high bilirubin levels that cause neonatal jaundice.^[4]

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.^[5]

Phototherapy works through a process of isomerization that changes the bilirubin into water-soluble isomers that can be passed without getting stuck in the liver.^[6][7]

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, which in turn also increased the risk of melanoma (skin cancer) ^[8][9][10].

Increased feedings help move bilirubin through the neonate’s metabolic system ^[11].

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.

[edit] 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 mg/dL ).^[3]

[edit] Complications

Prolonged hyperbilirubinemia (severe jaundice) can result into chronic bilirubin encephalopathy (kernicterus).^[12][13] Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus.^[14]

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.^[15]

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.^[16]

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.^[17]

Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment.^[18][19]

[edit] Guidelines

American Academy of Pediatrics has issued guidelines for managing this disease, which can be obtained for free ^[20].

[edit] References

1. ^ ^{a b} Madlon-Kay, Diane J. Recognition of the Presence and Severity of Newborn Jaundice by Parents, Nurses, Physicians, and Icterometer Pediatrics 1997 100: e3
2. ^ "ABO Incompatibility". http://pediatrics.about.com/od/weeklyquestion/a/04_abo_incmplty.htm. Retrieved 2007-06-30.  at About.com
3. ^ ^{a b} "Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation". Pediatrics 114 (1): 297–316. July 2004. doi:10.1542/peds.114.1.297. PMID 15231951. http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=15231951. 
4. ^ Amato M, Inaebnit D (February 1991). "Clinical usefulness of high intensity green light phototherapy in the treatment of neonatal jaundice". Eur. J. Pediatr. 150 (4): 274–6. doi:10.1007/BF01955530. PMID 2029920. 
5. ^ Leung C, Soong WJ, Chen SJ (July 1992). "[Effect of light on total micro-bilirubin values in vitro]" (in Chinese). Zhonghua Yi Xue Za Zhi (Taipei) 50 (1): 41–5. PMID 1326385. 
6. ^ Stokowski LA (December 2006). "Fundamentals of phototherapy for neonatal jaundice". Adv Neonatal Care 6 (6): 303–12. doi:10.1016/j.adnc.2006.08.004. PMID 17208161. 
7. ^ Ennever JF, Sobel M, McDonagh AF, Speck WT (July 1984). "Phototherapy for neonatal jaundice: in vitro comparison of light sources". Pediatr. Res. 18 (7): 667–70. doi:10.1203/00006450-198407000-00021. PMID 6540860. 
8. ^ Pullmann H, Theunissen A, Galosi A, Steigleder GK (November 1981). "[Effect of PUVA and SUP therapy on nevocellular nevi (author's transl)]" (in German). Z. Hautkr. 56 (21): 1412–7. PMID 7314762. 
9. ^ Titus-Ernstoff L, Perry AE, Spencer SK, Gibson JJ, Cole BF, Ernstoff MS (August 2005). "Pigmentary characteristics and moles in relation to melanoma risk". Int. J. Cancer 116 (1): 144–9. doi:10.1002/ijc.21001. PMID 15761869. 
10. ^ Randi G, Naldi L, Gallus S, Di Landro A, La Vecchia C (September 2006). "Number of nevi at a specific anatomical site and its relation to cutaneous malignant melanoma". J. Invest. Dermatol. 126 (9): 2106–10. doi:10.1038/sj.jid.5700334. PMID 16645584. 
11. ^ Wood, S. (2007, March). Fact or fable?. Baby Talk, 72(2).
12. ^ Juetschke, L.J. (2005, Mar/Apr). Kernicterus: still a concern. Neonatal Network, 24(2), 7-19, 59-62
13. ^ Colletti JE, Kothari S, Kothori S, Jackson DM, Kilgore KP, Barringer K (November 2007). "An emergency medicine approach to neonatal hyperbilirubinemia". Emerg. Med. Clin. North Am. 25 (4): 1117–35, vii. doi:10.1016/j.emc.2007.07.007. PMID 17950138. 
14. ^ Watchko JF (December 2006). "Hyperbilirubinemia and bilirubin toxicity in the late preterm infant". Clin Perinatol 33 (4): 839–52; abstract ix. doi:10.1016/j.clp.2006.09.002. PMID 17148008. 
15. ^ Shah Z, Chawla A, Patkar D, Pungaonkar S (March 2003). "MRI in kernicterus". Australas Radiol 47 (1): 55–7. doi:10.1046/j.1440-1673.2003.00973.x. PMID 12581055. 
16. ^ Malik BA, Butt MA, Shamoon M, Tehseen Z, Fatima A, Hashmat N (December 2005). "Seizures etiology in the newborn period". J Coll Physicians Surg Pak 15 (12): 786–90. doi:12.2005/JCPSP.786790. PMID 16398972. 
17. ^ Vohr BR, Lester B, Rapisardi G, et al. (August 1989). "Abnormal brain-stem function (brain-stem auditory evoked response) correlates with acoustic cry features in term infants with hyperbilirubinemia". J. Pediatr. 115 (2): 303–8. doi:10.1016/S0022-3476(89)80090-3. PMID 2754560. 
18. ^ Gómez M, Bielza C, Fernández del Pozo JA, Ríos-Insua S (2007). "A graphical decision-theoretic model for neonatal jaundice". Med Decis Making 27 (3): 250–65. doi:10.1177/0272989X07300605. PMID 17545496. 
19. ^ Rothberg AD, Thomson PD, Andronikou S, Cohen DF (July 1982). "Transient neonatal hyperammonaemia. A case report". S. Afr. Med. J. 62 (6): 175–6. PMID 7089816. 
20. ^ American Academy of Pediatrics. "AAP Issues New Guidelines for Identifying and Managing Newborn Jaundice". http://www.aap.org/family/jaundicefeature.htm. Retrieved 4 July 2009. 

[edit] External links

• BiliTool - Hyperbilirubinemia Risk Assessment for Newborns
• Children's Liver Disease Foundation - information on jaundice in babies
• Neonatal jaundice - Southern Illinois University School of Medicine
• Neonatal Jaundice at www.Paeds.co.uk

v • d • e Certain conditions originating in the perinatal period / fetal disease (P, 760-779) Maternal factors and complications placenta (Placenta praevia, Placental insufficiency) · Chorion/Amnion/Umbilical cord Chorioamnionitis  · Umbilical cord prolapse · Nuchal cord  · Twin-to-twin transfusion syndrome Length of gestation and fetal growth Small for gestational age · Large for gestational age · Preterm birth · Postmature birth Birth trauma Cephalhematoma · Brachial plexus lesion (Erb's palsy, Klumpke paralysis) By system Respiratory Intrauterine hypoxia · Infant respiratory distress syndrome · Transient tachypnea of the newborn · Meconium aspiration syndrome · pleural disease (Pneumothorax, Pneumomediastinum) · Wilson-Mikity syndrome · Bronchopulmonary dysplasia Cardiovascular Pneumopericardium · Persistent fetal circulation Haemorrhagic and haematological/ hematologic disease Vitamin K deficiency (Haemorrhagic disease of the newborn) · Hemolytic disease of the newborn (ABO HDN • Anti-Kell HDN • Rhesus c HDN • Rhesus D HDN • Rhesus E HDN) · Rh disease · Hydrops fetalis · Hyperbilirubinemia (Kernicterus, Neonatal jaundice) Velamentous cord insertion Digestive system Ileus · Necrotizing enterocolitis Integument and temperature regulation Erythema toxicum Nervous system Periventricular leukomalacia Musculoskeletal system Gray baby syndrome · muscle tone (Congenital hypertonia, Congenital hypotonia) Other disorders Perinatal infection (Congenital rubella syndrome, Neonatal herpes simplex) · Omphalitis Stillbirth/Perinatal mortality