Neonatal jaundice 2333767 221792820 2008-06-26T03:21:44Z 130.216.244.60 {{Cleanup|date=January 2007}} {{DiseaseDisorder infobox | Name = Neonatal jaundice | Image = | Caption = | ICD10 = {{ICD10|P|58||p|50}}, {{ICD10|P|59||p|50}} | ICD9 = {{ICD9|773}}, {{ICD9|774}} | OMIM = | MedlinePlus = 001559 | eMedicineSubj = ped | eMedicineTopic = 1061 | DiseasesDB = 8881 | MeshID = 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. ==Causes== In neonates, benign jaundice tends to develop because of two factors - the breakdown of [[fetal hemoglobin]] as it is replaced with [[Hemoglobin|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: {{familytree/start}} {{familytree | | | | | | | | | | | | | A01 | | | | |A01=Neonatal jaundice}} {{familytree | | | | | | | | |,|-|-|-|-|^|-|-|-|-|.|}} {{familytree | | | | | | | | B01 | | | | | | | | B02|B01=[[Unconjugated bilirubin]]|B02=[[Conjugated bilirubin]]}} {{familytree | | | | | |,|-|-|^|-|-|.| | | |,|-|-|^|-|-|.| |}} {{familytree | | | | | C01 | | | | C02 | | C03 | | | | C04 | |C01=[[pathology|Pathologic]] |C02=[[Physiologic]] |C03=[[Hepatic]] |C04=Post-hepatic}} {{familytree | | |,|-|-|^|-|-|.| | | | | | | | | | | |}} {{familytree | | C01 | | | | C02 | | | | | | | | | | | |C01=[[hemolysis|Hemolytic]]|C02=Non-hemolytic}} {{familytree | | |)|-|-|-|-|-|.| | | | | | | | | | | |}} {{familytree | | C01 | | | | C02 | | | | | | | | | | | |C01=Intrinsic causes|C02=Extrinsic causes}} {{familytree/end}} ===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 **[[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]] **[[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. ===Non-hemolytic causes=== *[[Cephalohematoma]] *[[Polycythemia]] *[[Sepsis]] *[[Hypothyroidism]] *[[Gilbert's syndrome]] *[[Crigler-Najjar syndrome]] ===Hepatic causes=== *Infections **[[Sepsis]] **[[Hepatitis B]], [[TORCH syndrome|TORCH infections]] *Metabolic **[[Galactosemia]] **[[Alpha-1-antitrypsin deficiency]] **[[Cystic fibrosis]] *Drugs *[[Total parenteral nutrition]] *Idiopathic ===Post-hepatic=== *[[Biliary atresia]] *[[Bile duct]] obstruction ==Treatment== [[Image:Jaundice phototherapy.jpg|thumb|280px|right|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. <ref> 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.</ref> 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. <ref>Leung, C., Soong, WJ., Chen, SJ. (1992, July). Effect of light on total microbilirubin values in vitro. Chinese Medical Journal, 50(1), 41-45.</ref> 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. <ref> Stokowski, LA. (2006, December). Fundamentals of phototherapy for neonatal jaundice. Official Journal Of The National Association Of Neonatal Nurses, 6(6), 303-312.</ref> <ref>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</ref> 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 mm<sup>2</sup> to 5.3 mm<sup>2</sup>. 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) <ref> Pullmann, H., Theunissen, A., Galosi, A., Steigleder, GK. (1981). Effect of PUVA and SUP therapy on nevocellular nevi. Zeitschrift Für Hautkrankheiten.</ref> <ref>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. </ref> <ref> 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.</ref>. Increased feedings help move bilirubin through the neonate’s metabolic system <ref>Wood, S. (2007, March). Fact or fable?. Baby Talk, 72(2). </ref>. ==Non-organic causes== ===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. ===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. ==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. <ref>{{cite web |url=http://pediatrics.about.com/od/weeklyquestion/a/04_abo_incmplty.htm |title=ABO Incompatibility |accessdate=2007-06-30 |format= |work=}} at [[About.com]]</ref> ==Rare causes== Rarely, neonatal jaundice may be caused by a [[Genetics|genetic]] [[syndrome]] such as [[Crigler-Najjar syndrome]]. ==Complications== Prolonged hyperbilirubinemia (severe jaundice) can result into chronic bilirubin encephalopathy (kernicterus).<ref> Juetschke, L.J. (2005, Mar/Apr). Kernicterus: still a concern. Neonatal Network, 24(2), 7-19, 59-62</ref> <ref>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. </ref> Quick and accurate treatment of neonatal jaundice helps to reduce the risk of neonates developing kernicterus. <ref>Watchko, J.F. (2006, December). Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clinics In Perinatology, 33(4), 839-852.</ref> 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. <ref>Shah, Z., Chawla, A., Patkar, D., Pungaonkar, S. (2003, March). MRI in kernicterus. Australasian Radiology, 47(1), 55-57. </ref> 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. <ref> 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.</ref> 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. <ref>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. </ref> Exchange transfusions performed to lower high bilirubin levels are an aggressive treatment. <ref>Gómez, M. (2007, May/Jun). A graphical design- Theoretical model for neonatal jaundice. Medical Decision Making, 27(3), 250-265. </ref> <ref>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. </ref> ==See also== * [[Jaundice]] ==References== <references/> ==External links== *[http://bilitool.org BiliTool - Hyperbilirubinemia Risk Assessment for Newborns] *[http://www.childliverdisease.org/education/yellowalert Children's Liver Disease Foundation - information on jaundice in babies] *[http://edaff.siumed.edu/peds/Neonatal_Jaundice.pdf Neonatal jaundice] - [[Southern Illinois University School of Medicine]] *[http://www.paeds.co.uk/wiki/?title=Neonatal_Jaundice Neonatal Jaundice] at [http://www.Paeds.co.uk www.Paeds.co.uk] {{Certain conditions originating in the perinatal period}} [[Category:Pediatrics]] [[Category:Hepatology]] [[Category:Hematology]] [[de:Neugeborenengelbsucht]] [[es:Ictericia del recién nacido]] [[ja:新生児黄疸]] [[pl:Żółtaczka noworodków]] [[tr:Yenidoğan sarılığı]]