Laboratory Studies
Bilirubin measurement may include the following:
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Transcutaneous bilirubinometry can be performed using handheld devices that incorporate sophisticated optical algorithms. Use of such devices has been shown to reduce the need for blood sampling in infants with jaundice. [26] However, they cannot be used to monitor the progress of phototherapy. [27]
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Transcutaneous bilirubinometry performs better than visual assessment. The latter is not a reliable technique for estimating levels of bilirubin, [28] 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 high total serum bilirubin levels. [29]
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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.
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In infants with moderate jaundice, transcutaneous bilirubinometry may be useful in selecting patients who require phlebotomy or capillary blood sampling for serum bilirubin measurement.
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In infants with extreme jaundice, transcutaneous bilirubinometry may be a useful tool to fast-track such infants to rapid and aggressive therapy.
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Usually, 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. Measurement 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 7-10 days of life, and to infants whose total serum bilirubin levels repeatedly rebound following treatment.
Additional studies may be indicated in the following situations:
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Infants who present with jaundice on the first or after the third day of life
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Infants who are anemic at birth
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Infants who otherwise appear ill
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Infants in whom serum bilirubin levels are elevated enough to trigger treatment
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Infants in whom significant jaundice persists beyond the first 2 weeks of life
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Infants in whom family, maternal, pregnancy, or case histories suggest the possibility of a pathologic process
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Infants in whom physical examination reveals findings not explained by simple physiologic hyperbilirubinemia
In 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 phototherapy:
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Blood type and Rh determination in mother and infant
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Direct antiglobulin test (DAT) in the infant (direct Coombs test)
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Hemoglobin and hematocrit values
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Serum albumin levels: This appears to be a useful adjunct in evaluating risk of toxicity levels because albumin binds bilirubin in a ratio of 1:1 at the primary high-affinity binding site.
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Nomogram for hour-specific bilirubin values: 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 follow-up 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 DAT-positive infants with AB0 incompatibility. [30] A positive DAT test result did not add any value to the clinical management of these infants beyond that already obtained by an hour-specific bilirubin value plotted onto the nomogram.
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Measurement of end-tidal carbon monoxide in breath: End-tidal carbon monoxide in breath (ETCO) may be used as an index of bilirubin production. Measurement of ETCO may assist in identifying individuals with increased bilirubin production and, thus, at increased risk of developing high bilirubin levels. An apparatus has been developed that makes measuring ETCO simple (CoSenseTM ETCO Monitor, Capnia, Palo Alto, CA, USA).
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Peripheral blood film for erythrocyte morphology
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Conjugated bilirubin levels: Measuring bilirubin fractions may be indicated in the circumstances described above. Note that direct bilirubin measurements are often inaccurate, are subject to significant interlaboratory and intralaboratory variation, and are generally not a sensitive tool for diagnosing cholestasis unless repeated measurements confirm the presence of an elevated conjugated bilirubin.
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Liver function tests: Aspartate aminotransferase (ASAT or SGOT) and alanine aminotransferase (ALAT or SGPT) levels are elevated in hepatocellular disease. Alkaline phosphatase and γ-glutamyltransferase (GGT) levels are often elevated in cholestatic disease. A γ-GT/ALAT ratio of more than 1 is strongly suggestive of biliary obstruction. However, it does not distinguish between intrahepatic and extrahepatic cholestasis.
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Tests for viral and/or parasitic infection: These may be indicated in infants with hepatosplenomegaly, petechiae, thrombocytopenia, or other evidence of hepatocellular disease.
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Reducing substance in urine: This is a useful screening test for galactosemia, provided the infant has received sufficient quantities of milk.
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Blood gas measurements: The risk of bilirubin CNS toxicity is increased in acidosis, particularly respiratory acidosis.
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Bilirubin-binding tests: Although they are interesting research tools, these tests have not found widespread use in clinical practice. Although elevated levels of unbound ("free") bilirubin are associated with an increased risk of bilirubin encephalopathy, unbound bilirubin is but one of several factors that mediate/modulate bilirubin toxicity.
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Thyroid function tests
Imaging Studies
Ultrasonography: Ultrasonography of the liver and bile ducts is warranted in infants with laboratory or clinical signs of cholestatic disease.
Radionuclide scanning: A radionuclide liver scan for uptake of hepatoiminodiacetic acid (HIDA) is indicated if extrahepatic biliary atresia is suspected. At the author's institution, patients are pretreated with phenobarbital 5 mg/kg/d for 3-4 days before performing the scan.
Other Tests
Auditory and visually evoked potentials are affected during ongoing significant jaundice; however, no criteria have been established that allow extrapolation from evoked potential findings to the risk of kernicterus. Data suggest that the probability of a bilateral "refer" on an automated auditory brainstem response (AABR) study increases with unbound bilirubin concentrations. [31] Because unbound bilirubin concentrations may be more closely correlated with bilirubin neurotoxicity, a "refer" finding may indicate an increased risk of bilirubin neurotoxicity. A "refer" AABR result obtained shortly after admission of an infant with significant jaundice seems to argue for immediate and aggressive treatment.
Brainstem auditory-evoked potentials should be obtained in the aftermath of severe neonatal jaundice to exclude sensorineural hearing loss. In physiologic jaundice, auditory-evoked potentials return to normal with the resolution of hyperbilirubinemia. However, in patients with significant neonatal jaundice or kernicterus, auditory-evoked potentials and functional hearing may remain abnormal.
The phonetic characteristics of the infant's cry are changed in significant neonatal jaundice; however, computerized analyses of these phonetic characteristics are not used in clinical practice.
Histologic Findings
Organs, including the brain, are yellow in any individual with significant jaundice; however, the yellow color does not always indicate CNS toxicity. This distinction was not always clearly understood in older descriptions of so-called "low-bilirubin kernicterus." At present, this has contributed to confusion and uncertainty regarding therapeutic guidelines and intervention levels.
See Kernicterus for a more detailed description.
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The graph represents indications for phototherapy and exchange transfusion in infants (with a birthweight of 3500 g) in 108 neonatal ICUs. The left panel shows the range of indications for phototherapy, whereas the right panel shows the indications for exchange transfusion. Numbers on the vertical axes are serum bilirubin concentrations in mg/dL (lateral) and mmol/L (middle). In the left panel, the solid line refers to the current recommendation of the American Academy of Pediatrics (AAP) for low-risk infants, the line consisting of long dashes (- - - - -) represents the level at which the AAP recommends phototherapy for infants at intermediate risk, and the line with short dashes (-----) represents the suggested intervention level for infants at high risk. In the right panel, the dotted line (......) represents the AAP suggested intervention level for exchange transfusion in infants considered at low risk, the line consisting of dash-dot-dash (-.-.-.-.) represents the suggested intervention level for exchange transfusion in infants at intermediate risk, and the line consisting of dash-dot-dot-dash (-..-..-..-) represents the suggested intervention level for infants at high risk. Intensive phototherapy is always recommended while preparations for exchange transfusion are in progress. The box-and-whisker plots show the following values: lower error bar = 10th percentile; lower box margin = 25th percentile; line transecting box = median; upper box margin = 75th percentile; upper error bar = 90th percentile; and lower and upper diamonds = 5th and 95th percentiles, respectively.
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Algorithm for the management of jaundice in the newborn nursery.
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Guidelines for management of neonatal jaundice currently in use in all pediatric departments in Norway. The guidelines were based on previously used charts and were created through a consensus process in the Neonatal Subgroup of the Norwegian Pediatric Society. These guidelines were adopted as national at the fall meeting of the Norwegian Pediatric Society. The reverse side of the chart contains explanatory notes to help the user implement the guidelines. A separate information leaflet for parents was also created.
