Jaundice is the most common condition that requires medical attention in newborns. The yellow coloration of the skin and sclera in newborns with jaundice is the result of accumulation of unconjugated bilirubin. In most infants, unconjugated hyperbilirubinemia reflects a normal transitional phenomenon. However, in some infants, serum bilirubin levels may rise ecessively, which can be cause for concern because unconjugated bilirubin is neurotoic and can cause death in newborns and lifelong neurologic sequelae in infants who survive !kernicterus". #or these reasons, the presence of neonatal jaundice frequently results in diagnostic evaluation.$eonatal jaundice may have first been described in a %hinese tetbook &''' years ago. (edical theses, essays, and tetbooks from the &)th and &*th centuries contain discussions about the causes and treatment of neonatal jaundice. +everal of these tets also describe a lethal course in infants who probably had ,h isoimmuni-ation. In &)./, 0rth first described yellow staining of the brain, in a pattern later referred to by +chmorl as kernicterus.1athophysiology$eonatal physiologic jaundice results from simultaneous occurrence of the following two phenomena2&3 4 5ilirubin production is elevated because of increased breakdown of fetal erythrocytes. This is the resultof the shortened lifespan of fetal erythrocytes and the higher erythrocyte mass in neonates. Hepatic ecretory capacity is low both because of low concentrations of the binding protein ligandin in the hepatocytes and because of low activity of glucuronyl transferase, the en-yme responsible for binding bilirubin to glucuronic acid, thus making bilirubin water soluble !conjugation".5ilirubin is produced in the reticuloendothelial system as the end product of heme catabolism and is formed through oidation6reduction reactions. 7pproimately ./8 of bilirubin is derived from hemoglobin, but degradation of myoglobin, cytochromes, and catalase also contributes. In the first oidation step, biliverdin is formed from heme through the action of heme oygenase, the rate6limiting step in the process, releasing iron and carbon monoide. The iron is conserved for reuse, whereas carbon monoide is ecreted through the lungs and can be measured in the patient9s breath to quantify bilirubin production.$et, water6soluble biliverdin is reduced to bilirubin, which, because of the intramolecular hydrogen bonds, is almost insoluble in water in its most common isomeric form !bilirubin I:; @1AT". (onoconjugates are formed first and predominate in the newborn. @iconjugates appear to be formed at the cell membrane and may require the presence of the >@1AT tetramer.5ilirubin conjugation is biologically critical because it transforms a water6insoluble bilirubin molecule into a water6soluble molecule. =ater6solubility allows conjugated bilirubin to be ecreted into bile. >@1AT activity is low at birth but increases to adult values by age B6) weeks. In addition, certain drugs !phenobarbital, deamethasone, clofibrate" can be administered to increase >@1AT activity.Infants who have Ailbert syndrome or who are compound hetero-ygotes for the Ailbert promoter and structural mutations of the UDPGT1A1 coding region are at an increased risk of significant hyperbilirubinemia. Interactions between the Ailbert genotype and hemolytic anemias such as glucose6C6phosphatase dehydrogenase !A6C61@" deficiency, hereditary spherocytosis, or 750 hemolytic disease also appear to increase the risk of severe neonatal jaundice.#urther, the observation of jaundice in some infants with hypertrophic pyloric stenosis may also be related to a Ailbert6type variant. Aenetic polymorphism for the organic anion transporter protein 07T16D correlates with a E6fold increased risk for developing marked neonatal jaundice. %ombination of the OATP-2 gene polymorphismwith a variant UDPGT1A1 gene further increases this risk to DD6fold.2D3 +tudies also suggest that polymorphisms in the gene for glutathione6+6transferase !ligandin" may contribute to higher levels of total serum bilirubin.Thus, some interindividual variations in the course and severity of neonatal jaundice may be eplained genetically. 7s the impact of these genetic variants is more fully understood, development of a genetic test panel for risk of severe andFor prolonged neonatal jaundice may become feasible.2E30nce ecreted into bile and transferred to the intestines, bilirubin is eventually reduced to colorless tetrapyrroles by microbes in the colon. However, some deconjugation occurs in the proimal small intestine through the action of 56glucuronidases located in the brush border. This unconjugated bilirubin can be reabsorbed into the circulation, increasing the total plasma bilirubin pool. This cycle of uptake, conjugation, ecretion, deconjugation, and reabsorption is termed 9enterohepatic circulation9. The process may be etensive in the neonate, partly because nutrient intake is limited in the first days of life, prolonging the intestinal transit time.In mother6infant dyads who are eperiencing difficulties with the establishment of breast feeding, inadequate fluid and nutrient intake often leads to significant postnatal weight loss in the infant. +uch infants have an increased risk of developing jaundice through increased enterohepatic circulation, as described above. This phenomenon is often referred to as breastfeeding jaundice and is different from the breast milk jaundice described below.%ertain factors present in the breast milk of some mothers may also contribute to increased enterohepatic circulation of bilirubin !breast milk jaundice". G6glucuronidase may play a role by uncoupling bilirubin from its binding to glucuronic acid, thus making it available for reabsorption. @ata suggest that the risk of breast milk jaundice is significantly increased in infants who have genetic polymorphisms in the coding sequences of the UDPGT1A1 or OATP2 genes. 7lthough the mechanism that causes this phenomenon is not yet agreed on, evidence suggests that supplementation with certain breast milk substitutes may reduce the degree of breast milk jaundice !see 0ther therapies".$eonatal jaundice, although a normal transitional phenomenon in most infants, can occasionally become more pronounced. 5lood group incompatibilities !eg, ,h, 750" may increase bilirubin production through increased hemolysis. Historically, ,h isoimmuni-ation was an important cause of severe jaundice, often resulting in the development of kernicterus. 7lthough this condition has become relatively rare in industriali-ed countries following the use of ,h prophylais in ,h6negative women, ,h isoimmuni-ation remains common in developingcountries.$onimmune hemolytic disorders !spherocytosis, A6C61@ deficiency" may also cause increased jaundice, and increased hemolysis appears to have been present in some of the infants reported to have developed kernicterus in the >nited +tates in the past &/6D' years. The possible interaction between such conditions and genetic variants of the Ailbert and UDPGT1A1 genes, as well as genetic variants of several other proteins and en-ymes involved in bilirubin metabolism, is discussed above.These discoveries also highlight the challenges involved in the common use of the terms physiologic jaundice and pathologic jaundice. 7lthough physiologic jaundice is a helpful concept from a didactic perspective, applying it to an actual neonate with jaundice is more difficult.%onsider the following metaphor4 Think of total serum bilirubin in neonatal jaundice as a mountain covered by aglacier. If a measurement of the height of the mountain is taken when standing on the summit, the amount of rock and the amount of ice that comprise this measurement is unclear. The same is true for many total serum bilirubin values obtained in neonatal jaundice. 7n underpinning of physiologic processes and pathological process !eg, ,hesus incompatibility" may clearly contribute to the measurement. However, how much of the measured total value comes from each of these components is unclear. 7lso, because genetic variants in bilirubin metabolism are only eceptionally pursued in the diagnostic work6up of infants with jaundice, their possible contribution to the measured total serum bilirubin is usually unknown.HpidemiologyFrequencyUnited States$eonatal hyperbilirubinemia is etremely common because almost every newborn develops an unconjugated serum bilirubin level of more than E' ImolF? !&.) mgFd?" during the first week of life. Incidence figures are difficult to compare because authors of different studies do not use the same definitions for significant neonatal hyperbilirubinemia or jaundice. In addition, identification of infants to be tested depends on visual recognition ofjaundice by health care providers, which varies widely and depends both on observer attention and on infant characteristics such as race and gestational age.2B3=ith the above caveats, epidemiologic studies provide a frame of reference for estimated incidence. In &*)C, (aisels and Aifford reported C.&8 of infants with serum bilirubin levels of more than DD' ImolF? !&D.* mgFd?".2/3 In a D''E study in the >nited +tates, B.E8 of B.,)'& infants had total serum bilirubin levels in a range in which phototherapy was recommended by the &**B 7merican 7cademy of 1ediatrics !771" guidelines, and D.*8 had values in a range in which the &**B 771 guidelines suggest considering phototherapy.2C3 In some developing countries, the incidence of severe neonatal jaundice may be as much as &'' times higher than in more developed countries.2.3InternationalIncidence varies with ethnicity and geography. Incidence is higher in Hast 7sians and 7merican Indians and lower in 7fricans. Areeks living in Areece have a higher incidence than those of Areek descent living outside ofAreece.Incidence is higher in populations living at high altitudes. In &*)B, (oore et al reported ED..8 of infants with serum bilirubin levels of more than D'/ ImolF? !&D mgFd?" at E&'' m of altitude.2)37 study from Turkey reported significant jaundice in &'./8 of term infants and in D/.E8 of near6term infants.2*3 +ignificant jaundice was defined according to gestational and postnatal age and leveled off at &B mgFd? !DB' ImolF?" at B days in preterm infants and &. mgFd? !D*' ImolF?" in the term infants. +evere neonatal jaundice is&''6fold more frequent in $igeria than in industriali-ed countries.2.3 In @enmark, DB in &''.''' infants met echange transfusion criteria, while * in &''.''' developed acute bilirubin encephalopathy.2&'3+tudies seem to suggest that some of the ethnic variability in the incidence and severity of neonatal jaundice may be related to differences in the distribution of the genetic variants in bilirubin metabolism discussed above.2&, D3Mortality/MorbidityJernicterus is a complication of neonatal jaundice.The incidence of kernicterus in $orth 7merica and Hurope ranges from '.B6D.. cases per &'',''' births.2&&3 @eath from physiologic neonatal jaundice per se should not occur. @eath from kernicterus may occur, particularly in countries with less developed medical care systems. In one small study from rural $igeria, E&8 of infants with clinical jaundice tested had A6C61@ deficiency, and EC8 of the infants with A6C61@ deficiency died with presumed kernicterus compared with only E8 of the infants with a normal A6C61@ screening test result.2&D31lease see the (edscape @rugs K @iseases article Jernicterus for more information.RaceThe incidence of neonatal jaundice is increased in infants of Hast 7sian, 7merican Indian, and Areek descent, although the latter appears to apply only to infants born in Areece and thus may be environmental rather than ethnic in origin. 7frican infants are affected less often than non67frican infants. #or this reason, significant jaundice in an 7frican infant merits a closer evaluation of possible causes, including A6C61@ deficiency. In &*)/, ?inn et al reported on a series in which B*8 of Hast 7sian, D'8 of white, and &D8 of black infants had serum bilirubin levels of more than &.' ImolF? !&' mgFd?".2&E3The possible impact of genetic polymorphisms on ethnic variation in incidence and severity should be recogni-ed. Thus, in a study of Taiwanese infants, Huang et al reported that neonates who carry the D&& and E)) variants in the UGT1A1 andOATP2 genes and who are breastfed are at particularly high risk for severe hyperbilirubinemia.2&3Sex,isk of developing significant neonatal jaundice is higher in male infants. This does not appear to be related to bilirubin production rates, which are similar to those in female infants.AgeThe risk of significant neonatal jaundice is inversely proportional to gestational ageHistoryPresentation and duration of neonatal jaundice$ote the following4 Typically, presentation is on the second or third day of life. Jaundice that is visible during the first DB hours of life is likely to be nonphysiologicL further evaluation is suggested. Infants who present with jaundice after E6B days of life may also require closer scrutiny and monitoring. In infants with severe jaundice or jaundice that continues beyond the first &6D weeks of life, the results of the newborn metabolic screen should be checked for galactosemia and congenital hypothyroidism, further family history should be eplored !see below", the infant9s weight curve should be evaluated, the mother9s impressions as far as adequacy of breastfeeding should be elicited, and the stool color should be assessed.Family history0btain the following information4 1revious sibling with jaundice in the neonatal period, particularly if the jaundice required treatment 0ther family members with jaundice or known family history of Ailbert syndrome 7nemia, splenectomy, or bile stones in family members or known heredity for hemolytic disorders ?iver disease in family membersistory of !regnancy and deli"ery7scertain the following information4 (aternal illness suggestive of viral or other infection (aternal drug intake @elayed cord clamping 5irth trauma with bruising andFor fractures.Postnatal history0btain details of the following4 ?oss of stool color 5reastfeeding Areater than average weight loss +ymptoms or signs of hypothyroidism +ymptoms or signs of metabolic disease !eg, galactosemia" Hposure to total parental nutrition1hysical$eonatal jaundice first becomes visible in the face and forehead. Identification is aided by pressure on the skin,since blanching reveals the underlying color. Jaundice then gradually becomes visible on the trunk and etremities. This cephalocaudal progression is well described, even in &*th6century medical tets. Jaundice disappears in the opposite direction. The eplanation for this phenomenon is not well understood, but both changes in bilirubin6albumin binding related to pH and differences in skin temperature and blood flow have been proposed.2&B, &/3 This phenomenon is claimed to be clinically useful because, independent of other factors, visible jaundice in the lower etremities strongly suggests the need to check the bilirubin level, either in the serum or noninvasively via transcutaneous bilirubinometry.,ecent work in the authorMs group !TNllNfsrud et al, unpublished data" was not able to confirm this so6called cephalocaudal progression of jaundice. Thus, when dermal jaundice was measured noninvasively on the forehead, sternum, and symphysis, no cephalocaudal trend was evident.In most infants, yellow color is the only finding on physical eamination. (ore intense jaundice may be associated with drowsiness. 5rainstem auditory6evoked potentials performed at this time may reveal prolongation of latencies, decreased amplitudes, or both.0vert neurologic findings, such as changes in muscle tone, sei-ures, or altered cry characteristics, in a significantly jaundiced infant are danger signs and require immediate attention to prevent kernicterus. In the presence of such symptoms or signs, effective phototherapy should commence immediately without waiting for the laboratory test results !see ?aboratory +tudies". The potential need for echange transfusion should not preclude the immediate initiation of phototherapy.2&C, &.3Hepatosplenomegaly, petechiae, and microcephaly may be associated withhemolytic anemia, sepsis, and congenital infections and should trigger a diagnostic evaluation directed towards these diagnoses. $eonatal jaundice may be eacerbated in these situations.%auses1hysiologic jaundice is caused by a combination of increased bilirubin production secondary to accelerated destruction of erythrocytes, decreased ecretory capacity secondary to low levels of ligandin in hepatocytes, and low activity of the bilirubin6conjugating en-yme uridine diphosphoglucuronyltransferase !>@1AT".1athologic neonatal jaundice occurs when additional factors accompany the basic mechanisms described above. Hamples include immune or nonimmune hemolytic anemia, polycythemia, and the presence of bruisingor other etravasation of blood.@ecreased clearance of bilirubin may play a role in breast feeding jaundice, breast milk jaundice, and in severalmetabolic and endocrine disorders.,isk factors include the following4 ,ace4 Incidence is higher in Hast 7sians and 7merican Indians and is lower in 7fricansF7frican 7mericans. Aeography4 Incidence is higher in populations living at high altitudes. Areeks living in Areece appear to have a higher incidence than those living outside of Areece. Aenetics and familial risk4 Incidence is higher in infants with siblings who had significant neonatal jaundice and particularly in infants whose older siblings were treated for neonatal jaundice. Incidence is also higher in infants with mutationsFpolymorphisms in the genes that code for en-ymes and proteins involved in bilirubin metabolism, and in infants with homo-ygous or hetero-ygous glucose6C6phosphatase dehydrogenase !A6C61@" deficiency and other hereditary hemolytic anemias. %ombinations of such genetic variants appear to eacerbate neonatal jaundice. 2&, D, &), &*3 $utrition4 Incidence is higher in infants who are breastfed or who receive inadequate nutrition. The mechanism for this phenomenon may not be fully understood. However, when inadequate feeding volume is involved, increased enterohepatic circulation of bilirubin probably contributes to prolonged jaundice. ,ecent data have shown that breast milk jaundice correlates with higher levels of epidermal growth factor, both in breast milk and in infants9 serum. 2D'3 @ata suggest that the difference between breastfed and formula6fed infants may be less pronounced with some modern formulas. However, formulas containing protein hydrolysates have been shown to promote bilirubin ecretion. (aternal factors4 Infants of mothers with diabetes have higher incidence. >se of some drugs may increase the incidence, whereas others decrease the incidence. 5irthweight and gestational age4 Incidence is higher in premature infants and in infants with low birthweight. %ongenital infection@iagnostic %onsiderationsImportant considerations%linicians should recogni-e the potential of significant jaundice to cause brain damage, even in the healthy full6term neonate.7ssess whether a Ohealthy full6term neonateO is both healthy and was really delivered at term.%linician should personally eamine an infant reported by parents or other caregivers to be significantly jaundiced.%onsider risk factors for significant jaundice when an infant is prepared for early discharge from the birth hospital and failure to factor such risk into the plan for follow6up of the baby.0ther conditions to be considered%ertain conditions may cause nonphysiologic jaundice. In these infants, a baseline physiologic jaundice most likely occurs, which is then eaggerated, for eample, by increased enterohepatic circulation in bowel atresia, bile stasis in choledochal cyst, or increased bilirubin production in hemolytic anemias. +uch conditions include the following4 5owel atresia Hypertrophic pyloric stenosis %holedochal cyst %onjugated hyperbilirubinemia %rigler6$ajjar syndrome 7rias syndrome Ailbert syndrome Immune hemolytic anemia $onimmune hemolytic anemia %ongenital infections with cytomegalovirus or tooplasmosis@ifferential @iagnoses 5reast (ilk Jaundice %holestasis @ubin6Johnson +yndrome Aalactose6&61hosphate >ridyltransferase @eficiency !Aalactosemia" Hemolytic @isease of $ewborn Hepatitis 5 1ediatric 5iliary 7tresia 1ediatric %ytomegalovirus Infection 1ediatric @uodenal 7tresia 1ediatric Hypothyroidism?aboratory +tudies5ilirubin measurement may include the following4 Transcutaneous bilirubinometry can be performed using handheld devices that incorporate sophisticated optical algorithms. >se of such devices has been shown to reduce the need for blood sampling in infants with jaundice. 2D&3However, they cannot be used to monitor the progress of phototherapy. 2DD3 Transcutaneous bilirubinometry performs better than visual assessment. The latter is not a reliable technique for estimating levels of bilirubin, 2DE3 but the complete absence of jaundice as judged by the eye in good lighting conditions has quite high accuracy as far as predicting which infants are unlikely to develop hightotal serum bilirubin levels. 2DB3 In infants with mild jaundice, transcutaneous bilirubinometry may be all that is needed to assure that total bilirubin levels are safely below those requiring intervention. In infants with moderate jaundice, transcutaneous bilirubinometry may be useful in selecting patients who require phlebotomy or capillary blood sampling for serum bilirubin measurement. In infants with etreme jaundice, transcutaneous bilirubinometry may be a useful tool to fast6track suchinfants to rapid and aggressive therapy. >sually, a total serum bilirubin level test is the only one required in an infant with moderate jaundice who presents on the typical second or third day of life without a history and physical findings suggestive of a pathologic process. (easurement of bilirubin fractions !conjugated vs unconjugated" in serum is not usually required in infants who present as described above. However, in infants who have hepatosplenomegaly, petechiae, thrombocytopenia, or other findings suggestive of hepatobiliary disease, metabolic disorder, or congenital infection, early measurement of bilirubin fractions is suggested. The same may apply to infants who remain jaundiced beyond the first .6&' days of life, and to infants whose total serum bilirubin levels repeatedly rebound following treatment.7dditional studies may be indicated in the following situations4 Infants who present with jaundice on the first or after the third day of life Infants who are anemic at birth Infants who otherwise appear ill Infants in whom serum bilirubin levels are elevated enough to trigger treatment Infants in whom significant jaundice persists beyond the first D weeks of life Infants in whom family, maternal, pregnancy, or case histories suggest the possibility of a pathologic process Infants in whom physical eamination reveals findings not eplained by simple physiologic hyperbilirubinemiaIn addition to total serum bilirubin levels, other suggested studies may include the following, particularly if the rate of rise or the absolute bilirubin concentration is approaching the need for phototherapy4 5lood type and ,h determination in mother and infant @irect antiglobulin test !@7T" in the infant !direct %oombs test" Hemoglobin and hematocrit values +erum albumin levels4 This appears to be a useful adjunct in evaluating risk of toicity levels because albumin binds bilirubin in a ratio of &4& at the primary high6affinity binding site. $omogram for hour6specific bilirubin values4 This is a useful tool for predicting, either before or at the time of hospital discharge, which infants are likely to develop high serum bilirubin values. Infants identified in this manner require close follow6up monitoring and repeated bilirubin measurements. The predictive ability has been shown both for bilirubin values measured in serum and for values measured transcutaneously. The nomogram has also been shown to work well for @7T6positive infants with 75' incompatibility. 2D/3 7 positive @7T test result did not add any value to the clinical management of these infants beyond that already obtained by an hour6specific bilirubin value plotted onto the nomogram. (easurement of end6tidal carbon monoide in breath4 Hnd6tidal carbon monoide in breath !HT%0" may be used as an inde of bilirubin production. (easurement of HT%0 may assist in identifying individuals with increased bilirubin production and, thus, at increased risk of developing high bilirubin levels. 7n apparatus has been developed that makes measuring HT%0 simple !%o+ense T( HT%0 (onitor, %apnia, 1alo 7lto, %7, >+7". 1eripheral blood film for erythrocyte morphology ,eticulocyte count %onjugated bilirubin levels4 (easuring bilirubin fractions may be indicated in the circumstances described above. $ote that direct bilirubin measurements are often inaccurate, are subject to significant interlaboratory and intralaboratory variation, and are generally not a sensitive tool for diagnosingcholestasis unless repeated measurements confirm the presence of an elevated conjugated bilirubin. ?iver function tests4 7spartate aminotransferase !7+7T or +A0T" andalanine aminotransferase !7?7T or +A1T" levels are elevated in hepatocellular disease. 7lkaline phosphatase and P6glutamyltransferase!AAT" levels are often elevated in cholestatic disease. 7 P6ATF7?7T ratio of more than & is strongly suggestive of biliary obstruction. However, it does not distinguish between intrahepatic and etrahepatic cholestasis. Tests for viral andFor parasitic infection4 These may be indicated in infants with hepatosplenomegaly, petechiae, thrombocytopenia, or other evidence of hepatocellular disease. ,educing substance in urine4 This is a useful screening test for galactosemia, provided the infant has received sufficient quantities of milk. 5lood gas measurements4 The risk of bilirubin %$+ toicity is increased in acidosis, particularly respiratory acidosis. 5ilirubin6binding tests4 7lthough they are interesting research tools, these tests have not found widespread use in clinical practice. 7lthough elevated levels of unbound !OfreeO" bilirubin are associated with an increased risk of bilirubin encephalopathy, unbound bilirubin is but one of several factors that mediateFmodulate bilirubin toicity. Thyroid function testsImaging +tudies>ltrasonography4 >ltrasonography of the liver and bile ducts is warranted in infants with laboratory or clinical signs of cholestatic disease.,adionuclide scanning4 7 radionuclide liver scan for uptake of hepatoiminodiacetic acid !HI@7" is indicated if etrahepatic biliary atresia is suspected. 7t the author9s institution, patients are pretreated with phenobarbital / mgFkgFd for E6B days before performing the scan.0ther Tests7uditory and visually evoked potentials are affected during ongoing significant jaundiceL however, no criteria have been established that allow etrapolation from evoked potential findings to the risk of kernicterus. @ata suggest that the probability of a bilateral OreferO on an automated auditory brainstem response !775," study increases with unbound bilirubin concentrations.2DC3 5ecause unbound bilirubin concentrations may be more closely correlated with bilirubin neurotoicity, a OreferO finding may indicate an increased risk of bilirubin neurotoicity. 7 OreferO 775, result obtained shortly after admission of an infant with significant jaundice seemsto argue for immediate and aggressive treatment.5rainstem auditory6evoked potentials should be obtained in the aftermath of severe neonatal jaundice to eclude sensorineural hearing loss. In physiologic jaundice, the auditory6evoked potential returns to normal with the resolution of hyperbilirubinemia. However, in patients with significant neonatal jaundice or kernicterus, the auditory6evoked potential and functional hearing may remain abnormal.The phonetic characteristics of the infant9s cry are changed in significant neonatal jaundiceL however, computeri-ed analyses of these phonetic characteristics are not used in clinical practice.Histologic #indings0rgans, including the brain, are yellow in any individual with significant jaundiceL however, the yellow color does not always indicate %$+ toicity. This distinction was not always clearly understood in older descriptions of so6called Olow6bilirubin kernicterus.O 7t present, this has contributed to confusion and uncertainty regarding therapeutic guidelines and intervention levels.+ee Jernicterus for a more detailed description.(edical %are1hototherapy, intravenous immune globulin !IQIA", and echange transfusion are the most widely used therapeutic modalities in infants with neonatal jaundice.Photothera!y1hototherapy is the primary treatment in neonates with unconjugated hyperbilirubinemia. This therapeutic principle was discovered rather serendipitously in Hngland in the &*/'s and is now arguably the most widespread therapy of any kind !ecluding prophylactic treatments" used in newborns.1hototherapy is effective because E reactions can occur when bilirubin is eposed to light, as follows4 Initially, photooidation was believed to be responsible for the beneficial effect of phototherapy. However, although bilirubin is bleached through the action of light, the process is slow and is now believed to contribute only minimally to the therapeutic effect of phototherapy. %onfigurational isomeri-ation is a very rapid process that changes some of the predominant Bs" worldwide.2EB3 The survey revealed a significant disparity in guidelines.The image below shows a bo6and6whisker plot of the range of serum bilirubin values that trigger phototherapy and echange transfusion, respectively, in these $I%>s. Hvidently, an infant might receive an echange transfusion in one $I%> for a serum bilirubin level that would not trigger phototherapy in many other $I%>s. This disparity illustrates how difficult it has been to translate clinical data into sensible treatment guidelines.The graph represents indications for phototherapy and echange transfusion in infants !with a birthweight of E/'' g" in &') neonatal I%>s. The left panel shows the range of indications for phototherapy, whereas the right panel shows the indications for echange transfusion. $umbers on the vertical aes are serum bilirubin concentrations in mgFd? !lateral" and mmolF? !middle". In the left panel, the solid line refers to the current recommendation of the 7merican 7cademy of 1ediatrics !771" for low6risk infants, the line consisting of long dashes !6 6 6 6 6" represents the level at which the 771 recommends phototherapy for infants at intermediate risk, and the line with short dashes !66666" represents the suggested intervention level for infants at high risk. In the right panel, the dotted line !......" represents the 771 suggested intervention level for echange transfusion in infants considered at low risk, the line consisting of dash6dot6dash !6.6.6.6." represents the suggested intervention level for echange transfusion in infants at intermediate risk, and the line consisting of dash6dot6dot6dash !6..6..6..6" represents the suggested intervention level for infants at high risk. Intensive phototherapy is always recommended while preparations for echange transfusion are in progress. The bo6and6whisker plots show the following values4 lower error bar T &'th percentileL lower bo margin T D/th percentileL line transecting bo T medianL upper bo margin T ./th percentileL upper error bar T *'th percentileL and lower and upper diamonds T /th and */th percentiles, respectively.In D''B, the 771 published new guidelines for the management of hyperbilirubinemia in healthy full6term newborns.2E/3 These guidelines have been plotted on the image above.The D''B 771 guidelines represent a significant change from the &**B guidelines.2E/3 Thus, the emphasis on preventive action and risk evaluation is much stronger. 7n algorithm aids in the assessment of risk and the decision about further management and follow6up !see the image below". The committee that wrote the guidelines has carefully assessed the strength of the scientific evidence on which the guidelines are based.7lgorithm for the management of jaundice in thenewborn nursery.1ractitioners in $orth 7merica are advised to follow the D''B 771 guidelines. 7lthough the D''B 771 guidelines do not provide guidance for treatment of jaundice in the smaller and more prematureFimmature infants, a group of >+ eperts recently published their suggestions for management of jaundice in preterm infants younger than E/ weeks9 gestation.2EC3%linicians in different ethnic or geographic regions should consider tailoring these guidelines as pertinent to their own populations and must consider factors that are unique to their medical practice settings. +uch factors may include racial characteristics, prevalence of congenital hemolytic disorders, prevalence of genetic variants,and environmental concerns. +uch adaptation of guidelines should also take into consideration how healthcare delivery systems are organi-ed, as this is likely affect both in6hospital delivery of care as well as follow6up. 7t present, the wisest course of action may be to apply local guidelines, assuming that these have been successful in the prevention of kernicterus..=ith this background and the clear understanding that this is meant only as an eample, the image below shows the chart currently in use in all pediatric departments in $orway. These guidelines are the result of a D''C consensus in the $eonatal +ubgroup of the $orwegian 1ediatric +ociety. The similarities between the $orwegian chart and the D''B 771 guidelines are apparent.Auidelines for management of neonatal jaundice currentlyin use in all pediatric departments in $orway. The guidelines were based on previously used charts and were created through a consensus process in the $eonatal +ubgroup of the $orwegian 1ediatric +ociety. These guidelines were adopted as national at the fall meeting of the $orwegian 1ediatric +ociety. The reverse side of the chart contains eplanatory notes tohelp the user implement the guidelines. 7 separate information leaflet for parents was also created.The $orwegian chart suggests intervention limits for prematureFimmature infants. #or infants of less than &''' gram birthweight, these guidelines propose starting phototherapy at &'' ImolF? !C mgFd?" at age DB hours, increasing gradually to &/' ImolF? !).) mgFd?" at age B days, and remaining steady thereafter at that level. This compares with a range of )/ ImolF? !/ mgFd?" to &.& ImolF? !&' mgFd?" used in a $eonatal ,esearch $etwork !$,$" phototherapy trial in infants of less than &''' gram birthweight. The intervention level depended on postnatal age and whether the infant was allocated to conservative or aggressive phototherapy.2E.3In a post hoc analysis of the $,$ data, which compared infants who had not received any phototherapy with those who had received such treatment, the subgroup of infants with birthweights of /'&6./' grams who had not received any phototherapy had a significantly higher rate of mental developmental inde of less than /'.2E)3 However, it should be noted that in the original trial analysis, mortality in the aggressive phototherapy group at /'&6 to ./'6g birthweight was / percentage points higher than in the conservative group, which, although notsignificant with the statistical approach chosen for analysis, appeared to offset the possible developmental gainin survivors.2E.3 ,ecently these data were reanaly-ed using 5ayesian statistics2E*3 and showed that aggressive phototherapy significantly increased the risk of death in the sickest !being on mechanical ventilation at DB h" and smallest infants !U./' g birthweight", while at the same time reducing impairmentFsevere impairment.Jey points in the practical eecution of phototherapy include maimi-ing energy delivery and the available surface area. 7lso consider the following4 The infant should be naked ecept for diapers !use these only if deemed absolutely necessary and cutthem to minimum workable si-e", and the eyes should be covered to reduce risk of retinal damage. %heck the distance between the infant9s skin and the light source. =ith fluorescent lamps, the distanceshould be no greater than /' cm !D' in". This distance may be reduced down to &'6D' cm !B6) in" if temperature homeostasis is monitored to reduce the risk of overheating. $ote that this does not apply to quart- lamps. %over the inside of the bassinet with reflecting materialL white linen works well. Hang a white curtain around the phototherapy unit and bassinet. These simple epedients can multiply energy delivery by several fold. =hen using spotlights, ensure that the infant is placed at the center of the circle of light, since photoenergy drops off towards the circle9s perimeter. 0bserve the infant closely to ensure that the infant doesn9t move away from the high6energy area. +potlights are probably more appropriate for small premature infants than for larger near6term infants. 0lder data suggested that phototherapy was associated with increased insensible water lossL therefore, many clinicians have routinely added a certain percentage to the infant9s estimated basic fluid requirements. $ewer data suggest that if temperature homeostasis is maintained, fluid loss is not significantlyincreased by phototherapy. 7t the author9s institution, routine fluid supplementation for infants under phototherapy has not been used for more than a decade and is not recommended in national guidelines. ,ather, the infant is monitored for weight loss, urine output, and urine specific gravity. #luid intake is adjusted accordingly. In infants who are orally fed, the preferred fluid is milk because it serves as a vehicle to transport bilirubin out of the gut. Timing of follow6up serum bilirubin testing must be individuali-ed. In infants admitted with etreme serum bilirubin values !V/'' ImolF? or E' mgFd?", monitoring should occur every hour or every other hour. ,eductions in serum bilirubin values of )/ ImolF?Fh !/ mgFd?Fh" have been documented under such circumstances. In infants with more moderate elevations of serum bilirubin, monitoring every C6&D hours is probably adequate. Hpectations regarding efficacy of phototherapy must be tailored to the circumstances. In infants in whom serum bilirubin concentrations are still rising, a significant reduction of the rate of increase may be satisfactory. In infants in whom serum bilirubin concentrations are close to their peak, phototherapy should result in measurable reductions in serum bilirubin levels within a few hours. In general, the higher the starting serum bilirubin concentration, the more dramatic the initial rate of decline. @iscontinuation of phototherapy is a matter of judgment, and individual circumstances must be taken into consideration. In practice, phototherapy is discontinued when serum bilirubin levels fall D/6/' ImolF? !&./6E mgFd?" below the level that triggered the initiation of phototherapy. +erum bilirubin levels may rebound after treatment has been discontinued, and follow6up tests should be obtained within C6&D hours after discontinuation. Indications for prophylactic phototherapy are debatable. 1hototherapy probably serves no purpose in an infant who is not clinically jaundiced. In general, the lower the serum bilirubin level, the less efficient the phototherapy. It seems more rational to apply truly effective phototherapy once serum !and skin" bilirubin has reached levels at which photons may do some good. =herever phototherapy is offered as a therapeutic modality, a device for measuring the irradiance delivered by the equipment used should be readily at hand. This assists in configuring the phototherapy set6up to deliver optimal efficiency. +ome recommend this routinely, every time phototherapy is initiated, and use this as a tool to focus staff attention on maimi-ing energy delivery.Aenerally, phototherapy is very safe and may have no serious long6term effects in neonatesL however, the following adverse effects and complications have been noted4 Insensible water loss may occur, but data suggest that this issue is not as important as previously believed. ,ather than instituting blanket increases of fluid supplements to all infants receiving phototherapy, the author recommends fluid supplementation tailored to the infant9s individual needs, as measured through evaluation of weight curves, urine output, urine specific gravity, and fecal water loss. 7s noted above, a reanalysis of the $,$ trial of WaggressiveW versus WconservativeW phototherapy in premature infants of less than &''' g birthweight showed that mortality was increased in the subgroup of sick/'&6 to ./'6g birthweight infants receiving aggressive9 phototherapy. 2E*3 In a recent recommendation for treatment of hyperbilirubinemia in premature infants younger than E/ weeksM gestation, the authors propose that initial irradiance should be reduced in the most vulnerable infants. 2EC3 However, as pointed out in an editorial to this paper, etant data seem to be more compatible with the interpretation that duration of phototherapy is more dangerous than irradiance levels. 2B'3 Thus, it may be argued that phototherapy should be short and efficient rather than less efficient and of longer duration. This question is still open to interpretation and discussion. 1hototherapy may be associated with loose stools. Increased fecal water loss may create a need for fluid supplementation. ,etinal damage has been observed in some animal models during intense phototherapy. In an $I%> environment, infants eposed to higher levels of ambient light were found to have an increased risk of retinopathy. Therefore, covering the eyes of infants undergoing phototherapy with eye patches is routine. %are must be taken lest the patches slip and leave the eyes uncovered or occlude one or both nares. The combination of hyperbilirubinemia and phototherapy can produce @$76strand breakage and othereffects on cellular genetic material. In vitro and animal data have not demonstrated any implication for treatment of human neonates. However, because most hospitals use !cut6down" diapers during phototherapy,the issue of gonad shielding may be moot. +kin blood flow is increased during phototherapy, but this effect is less pronounced in modern servocontrolled incubators. However, redistribution of blood flow may occur in small premature infants. 7n increased incidence ofpatent ductus arteriosus !1@7" has been reported in these circumstances. The appropriate treatment of 1@7 has been reviewed. 2B&3 Hypocalcemia appears to be more common in premature infants under phototherapy lights. This has been suggested to be mediated by altered melatonin metabolism. %oncentrations of certain amino acids in total parenteral nutrition solutions subjected to phototherapy may deteriorate. +hield total parenteral nutrition solutions from light as much as possible. ,egular maintenance of the equipment is required because accidents have been reported, including burns resulting from a failure to replace >Q filters.Intra"enous immune globulinIn recent years, IQIA has been used for numerous immunologically mediated conditions. In the presence of ,h,750, or other blood group incompatibilities that cause significant neonatal jaundice, IQIA has been shown to significantly reduce the need for echange transfusions. However, it must be recogni-ed that some studies have failed to show efficacy. The reasons for this discrepancy have not been eplained. 0ne can speculate thatdifferences in the origin and characteristics of the IQIA preparation could play a role. If one particular IQIA preparation appears not to work, it may be worthwhile to try IQIA from a different sourceFmanufacturer.The D''B 771 guidelines suggest a dose range for IQIA of /''6&''' mgFkg.2E/3The author routinely uses /'' mgFkg infused intravenously over a period of D hours for ,h or 750 incompatibility when the total serum bilirubin levels approach or surpass the echange transfusions limits. The author has, on occasion, repeated the dose D6E times. In most cases, when this is combined with intensive phototherapy, avoiding echange transfusion is possible. In the authors9 institution, with about ./' $I%> admissions per year, the use of echange transfusions has decreased to '6D per year following the implementation of IQIA therapy for ,h and 750 isoimmuni-ation.2EE3 The author does not use IQIA in the presence ofhydrops. 7necdotally, IQIA appears less likely to be successful when the infant is anemic !Hb X &' gFd?".#xchange transfusionHchange transfusion is indicated for avoiding bilirubin neurotoicity when other therapeutic modalities have failed or are not sufficient. In addition, the procedure may be indicated in infants with erythroblastosis who present with severe anemia, hydrops, or both, even in the absence of high serum bilirubin levels.Hchange transfusion was once a common procedure. 7 significant proportion was performed in infants with ,hisoimmuni-ation. Immunotherapy in ,h6negative women at risk for sensiti-ation has significantly reduced the incidence of severe ,h erythroblastosis. Therefore, the number of infants requiring echange transfusion is now much smaller, and even large $I%>s may perform only a few procedures per year. 750 incompatibility has become the most frequent cause of hemolytic disease in industriali-ed countries.Harly echange transfusion has usually been performed because of anemia !cord hemoglobin X && gFd?", elevated cord bilirubin level !V.' ImolF? or B./ mgFd?", or both. 7 rapid rate of increase in the serum bilirubin level !V&/6D' ImolF? Fh or & mgFd?Fh" was an indication for echange transfusion, as was a more moderate rateof increase !V)6&' ImolF?Fh or './ mgFd?Fh" in the presence of moderate anemia !&&6&E gFd?".The serum bilirubin level that triggered an echange transfusion in infants with hemolytic jaundice was E/' ImolF? !D' mgFd?" or a rate of increase that predicted this level or higher. +trict adherence to the level of D' mgFd? has been jocularly referred to as vigintiphobia !fear of D'".%urrently, most eperts encourage an individuali-ed approach, recogni-ing that echange transfusion is not a risk6free procedure, that effective phototherapy converts &/6D/8 of bilirubin to nontoic isomers, and that transfusion of a small volume of packed red cells may correct anemia. 7dministration of IQIA !/'' mgFkg" has been shown to reduce red cell destruction and to limit the rate of increase of serum bilirubin levels in infants with ,h and 750 isoimmuni-ation !see above".%urrent 771 guidelines distinguish between E risk categories4 low, intermediate, and high.2E/3 These correspond to E levels of suggested intervention, which increase from birth and plateau at age B days. $aturally, intervention levels associated with echange transfusion are higher than those for phototherapy. Intensive phototherapy is strongly recommended in preparation for an echange transfusion. In fact, intensive phototherapy should be performed on an emergency basis in any infant admitted for pronounced jaundiceL do not await laboratory test results in these cases. 1hototherapy has minimal side effects in this scenario, whereasthe waiting period for laboratory test results and blood for echange can take hours and could constitute the difference between intact survival and survival with kernicterus. If phototherapy does not significantly lower serum bilirubin levels, echange transfusion should be performed.(any believe that hemolytic jaundice represents a greater risk for neurotoicity than nonhemolytic jaundice, although the reasons for this belief are not intuitively obvious, assuming that total serum bilirubin levels are equal. In animal studies, bilirubin entry into or clearance from the brain was not affected by the presence of hemolytic anemia.The technique of echange transfusion, including adverse effects and complications, is discussed etensively elsewhere. #or more information, please consult Hemolytic @isease of $ewborn.Management of infants $ith extreme jaundice$umerous cases have been reported in which infants have been readmitted to hospitals with etreme jaundice.In some cases, significant delays have occurred between the time the infant was first seen by medical personnel and the actual commencement of effective therapy.2BD37ny infant who returns to the hospital with significant jaundice within the first &6D weeks of birth should be immediately triaged with measurement of transcutaneous bilirubin. High values should result in immediate initiation of treatment. If such a measuring device is not available, or if the infant presents with any kind of neurological symptoms, the infant should be put in maimally efficient phototherapy as an emergency procedure, preferably by fast6tracking the infant to a $I%>. =aiting for laboratory results is not necessary before instituting such therapy because no valid contraindications to phototherapy are possible in this scenario.1lans for an echange transfusion do not constitute an argument for delaying or not performing phototherapy. Immediate benefit may be obtained within minutes, as soon as conversion of bilirubin into water6soluble photoisomers is measurable !see discussion above".The need for intravenous hydration in such infants has been discussed. In the absence of clinical signs of dehydration, no evidence suggests that overhydration is helpful. If the infant is dehydrated, hydration should begiven as clinically indicated. However, if the infant is able to tolerate oral feeding, oral hydration with a breast milk substitute is likely to be superior to intravenous hydration because it reduces enterohepatic circulation of bilirubin and helps OwashO bilirubin out of the bowel.Hvery hospital in which babies are delivered, or which has an emergency department in which infants may be seen, should develop a protocol and triage algorithm for rapid evaluation and management of jaundiced infants.The objective of such a protocol should be rapid recognition of risk severity and reduction in the time to initiate appropriate treatment.Infants admitted with signs of intermediate to advanced acute bilirubin encephalopathy !75H" are in urgent need of treatment because reversibility may be possible, even in such cases. The term Ocrash6cart approachO has been used as a recommendation in such cases. The author, together with other Huropean colleagues, has published a series that included C patients with signs of 75H who were urgently managed and appear to have escaped neurologic sequelae.2BE3In a review of the Jernicterus ,egistry, full recovery was noted in ) of && cases treated with a crash6cart approach, which included effective phototherapy plus echange transfusionL full recovery was not noted in cases in which delays had occurred.2BD3 In the Jernicterus ,egistry, reversal was not observed in cases treated with only phototherapyL the authors strongly recommend that echange transfusion be performed in such cases.2BD3 In the Huropean study, reversal was also seen in D patients who did not receive echange transfusion.2BE3 In one of these cases, IQIA was used in lieu of echange transfusionL in the other case, intensive phototherapy and intravenous albumin were used.%ther thera!iesIn infants with breast milk jaundice, interruption of breastfeeding for DB6B) hours and feeding with breast milk substitutes often helps to reduce the bilirubin level. Hvidence suggests that the simple epedient of supplementing feeds of breast milk with / m? of a breast milk substitute reduces the level and duration of jaundice in breast milkYfed infants. 5ecause this latter intervention causes less interference with the establishment of the breastfeeding dyad, the author prefers to use this approach rather than complete interruption of breast feeding in most cases.0ral bilirubin oidase can reduce serum bilirubin levels, presumably by reducing enterohepatic circulationL however, its use has not gained wide popularity. The same may be said for agar or charcoal feeds, which act by binding bilirubin in the gut. 5ilirubin oidase is not available as a drug, and for this reason, its use outside anapproved research protocol probably is proscribed in many countries.1rophylactic treatment of ,h6negative women with ,h immunoglobulin has significantly decreased the incidence and severity of ,h6hemolytic disease.+urgical %are+urgical care is not indicated in infants with physiologic neonatal jaundice. +urgical therapy is indicated in infants in whom jaundice is caused by bowel or eternal bile duct atresia.%onsultations#or infants with physiologic neonatal jaundice, no consultation is required. Aastroenterologists and surgeons may be consulted regarding infants with jaundice resulting from hepatobiliary or bowel disease.@iet5reastfeeding concerns associated with neonatal jaundice are as follows4 Incidence and duration of jaundice have increased as breastfeeding has become more popular. The factors in breast milk that contribute to this phenomenon are unclear. In selected infants, interruption of breastfeeding and its replacement for DB6B) hours by a breast milk substitute may be indicated. This decision should always be discussed in person with the mother before implementation. The author9s practice is now to first perform a trial of / m? of a hydroly-ed formula given after each breast meal. The author typically tries thisfor at least &6D days, with follow6up of bilirubin values. 0nly if this is unsuccessful does the author occasionally attempt interruption of breast feeding. =ith increasing emphasis on breastfeeding, some new mothers may have difficulty admitting !even to themselves" to a lack of success in establishing lactation. 0ccasionally, infants of breastfeeding mothers are admitted to hospitals with severe jaundice. They typically weigh significantly less than their birthweight at a time when they should have regained and surpassed that weight. 1resumably, the process is one of increased enterohepatic circulation, as bilirubin is left longer in the proimal gut for lack of milk to bind it and carry it onward and out. The author refers to this condition as lack6of6breast6milk jaundice. These infants may respond dramatically to phototherapy plus oral feedings of milk ad libitum.(edication +ummary(edications are not usually administered in infants with physiologic neonatal jaundice. However, in certain instances, phenobarbital, an inducer of hepatic bilirubin metabolism, has been used to enhance bilirubin metabolism. +everal studies have shown that phenobarbital is effective in reducing mean serum bilirubin values during the first week of life. 1henobarbital may be administered prenatally in the mother or postnatally inthe infant.In populations in which the incidence of neonatal jaundice or kernicterus is high, this type of pharmacologic treatment may warrant consideration. However, concerns surround the long6term effects of phenobarbital on these children. Therefore, this treatment is probably not justified in populations with a low incidence of severe neonatal jaundice. 0ther drugs can induce bilirubin metabolism, but lack of adequate safety data prevents their use outside research protocols.Intravenous immunoglobulin !IQIA" at /'' mgFkg has been shown to significantly reduce the need for echangetransfusions in infants with isoimmune hemolytic disease.2EE3 The mechanism is unknown but may be related to the way the immune system handles red cells that have been coated by antibodies. 1ublished eperience is still somewhat limited, but administration of immunoglobulin does not appear to be likely associated with greater risks for the infant than an echange transfusion. 1ublished data regarding efficacy are varied, perhaps suggesting that the specific origin and characteristics of the IQIA preparation may play a role. 7lthough speculative, lack of efficacy of a specific IQIA product may warrant trial of one from a different manufacturer or batch.7 new therapy currently under development consists of inhibition of bilirubin production through blockage of heme oygenase. This can be achieved through the use of metal mesoporphyrins and protoporphyrins. 7pparently, heme can be directly ecreted through the bileL thus, inhibition of heme oygenase does not result in accumulation of unprocessed heme. This approach may virtually eliminate neonatal jaundice as a clinical problem. However, before the treatment can be applied on a wide scale, important questions regarding the long6term safety of the drugs must be answered. 7lso, in light of data suggesting that bilirubin may play an important role as a free radical quencher, a more complete understanding of this putative role for bilirubin is required before wholesale inhibition of its production is contemplated.#urther 0utpatient %areIn the era of early discharge, newborns released within the first B) hours of life need to be reassessed for jaundice within &6D days. The use of the hour6specific bilirubin nomogram may assist in selecting infants with a high likelihood of developing significant hyperbilirubinemia. The D''B 771 guidelines emphasi-e the importance of universal systematic assessment for the risk of severe hyperbilirubinemia.2E/3 Auidelines from the Huropean +ociety for 1ediatric ,esearch reiterate the same principles.2&C3$eonatal jaundice is one of the most common reasons why neonates are brought to an emergency departmentafter discharge from the birth hospital.2BB3$ear6term infants are at higher risk than term infants of developing significant jaundice and merit closer surveillance.2B/3The question of universal bilirubin screening has received attention and is the subject of debate. +ome data suggest that predischarge bilirubin screening reduces the number of infants with severe jaundice, as well as the rate of hospital readmissions.2BC, B.3 0thers have found that home nurse visiting was cost6effective and prevented readmissions for jaundice and dehydration.2B)3 However, the cost6effectiveness of preventing kernicterus by universal screening has been questioned.2B*3$evertheless, in an update to the D''B 771 jaundice guidelines (aisels et al give a clear recommendation in favor of predischarge bilirubin screening, either by transcutaneous measurement or by serum analysis.2/'3These authors also recommend a more structured approach to management and follow6up according to the predischarge total serum bilirubin and transcutaneous bilirubin !Tc5" levels, gestational age !see the Aestational 7ge from Hstimated @ate of @elivery calculator", and other risk factors for hyperbilirubinemia. These risk factors include the following42/'3 1redischarge total serum bilirubin or transcutaneous bilirubin level measurement in the high6risk or high6intermediateYrisk -one ?ower gestational age Hclusive breastfeeding, particularly if nursing is not going well and weight loss is ecessive Jaundice observed in the first DB hours Isoimmune or other hemolytic disease !eg, A6C61@ deficiency" 1revious sibling with jaundice %ephalohematoma or significant bruising Hast 7sian raceTelephone consultations are not recommended because parental reports cannot be appropriately gauged. ,ecently, numerous infants have developed kernicterus, resulting, at least in part, from inadequate communication between practitioners or their representatives and parents.The availability of new devices for transcutaneous measurement of bilirubin levels should facilitate follow6up evaluations of infants discharged before B) hours of life.Home phototherapy is used in an effort to limit the high cost of applying such therapy in hospitals. $ote the following4 Home treatment can avoid or limit parent6child separation. Home treatment should be used with caution, since prevention of neurotoicity is the goal. +ome argue that an infant at risk for neurologic damage should not be at home. =ith effective treatment strategies, the average duration of phototherapy in the regular neonatal nursery at the author9s institution is less than &. hours. =hether the effort and cost to set up home therapy is worthwhile is debatable. This assessment may be different in different socioeconomic and health financing circumstances.Infants who have been treated for hemolytic jaundice require follow6up observation for several weeks because hemoglobin levels may fall lower than seen in physiologic anemia. Hrythrocyte transfusions may be required if infants develop symptomatic anemia.#urther Inpatient %areInfants who have been treated for neonatal jaundice can be discharged when they are feeding adequately and have had D successive serum bilirubin levels demonstrating a trend towards lower values.If the hospital does not routinely screen newborns for auditory function, ordering such tests prior to discharge isadvisable in infants who have had severe jaundice.The D''B 771 guideline recommends a systematic risk assessment for hyperbilirubinemia risk in all infants before discharge.2E/3 1arents should be provided with verbal and written information about jaundice.Inpatient K 0utpatient (edications7lthough drugs that impact bilirubin metabolism have been used in studies, drugs are not ordinarily used in unconjugated neonatal hyperbilirubinemia.TransferInfants in need of echange transfusion born at or admitted to facilities not capable of performing this procedure should be transferred to the nearest facility with such capability. In addition to complete records, the infant should be accompanied by a sample of maternal blood because this is needed by the blood bank to match blood.However, in determining the best use of time before transfer, as well as the timing of the transfer, the following factors should be considered4 If the infant is in imminent danger of kernicterus, or is already ehibiting signs of neurological compromise, the most efficient phototherapy possible under the circumstances should be immediately initiated and should be continued until transfer commences. If fiberoptic or any other kind of phototherapy is technically feasible during transport, it should be continued throughout the duration of the transport. If the hyperbilirubinemia is due to blood group isoimmuni-ation, an infusion of intravenous immunoglobulin !IQIA" at /'' mgFkg should be immediately started and continued before and during transfer until completed !D h".Hven if the receiving hospital determines that an echange transfusion should be performed, continuing optimalphototherapy until the actual echange procedure can commence is important. If fiberoptic phototherapy is available, the infant may be left on a fiberoptic mattress while the echange is carried out. 0ral hydration with abreast milk substitute may aid the clearance of bilirubin from the gut, thus inhibiting enterohepatic circulation of bilirubin, and should be given unless clearly contraindicated by the clinical state of the infant. 7lthough none of these suggestions have been tested in randomi-ed controlled trials, case reports, bilirubin photobiology, and epert opinion suggest that they may be beneficial and, at the very least, are unlikely to be harmful.@eterrenceF1revention1revention of severe neonatal jaundice is best achieved through attention to the risk status of the infant prior to discharge from the birth hospital, through parent education, and through careful planning of postdischarge follow6up.2E/, &C37 predischarge bilirubin measurement, obtained by transcutaneous or serum measurement and plotted into an hour6specific nomogram, has been shown to be a useful tool in distinguishing infants with a low risk of subsequently developing high bilirubin values.%linical risk factors include gestational age of less than E) weeks, the use of oytocin or vacuum during delivery, eclusive breast feeding, an older sibling with neonatal jaundice that required phototherapy, a rise of Z C mgFd?Fd !Z &'' R molF?Fd" in total serum bilirubin levels, and hematomas or etensive bruising. 5irth weight isalso associated with risk of developing significant jaundiceL the higher the birthweight, the higher the risk.1rognosis1rognosis is ecellent if the patient receives treatment according to accepted guidelines.5rain damage due to kernicterus remains a true risk, and the apparent increased incidence of kernicterus in recent years may be due to the misconception that jaundice in the healthy full6term infant is not dangerous and can be disregarded.1atient Hducation1arents should be educated about neonatal jaundice and receive written information prior to discharge from thebirth hospital. The parent information leaflet should preferably be available in several languages.