Hot Topic

Uses and Limitations of Transcutaneous Bilirubin Measurement



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Published: June 2009

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Dr. Karon and Dr. Cook provides an overview of the risk of hyperbilirubinemia in the newborn and discusses the American Academy of Pediatrics recommendations on identification and evaluation of newborn jaundice. They give an historic perspective on diagnosis and management, discuss the clinical picture, and discuss the uses and limitations of transcutaneous bilirubin. 

Presenters: Dr. Brad Karon

Presenters: Dr. Walter Cook

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Transcript

Introduction

Welcome to Mayo Medical Laboratories' Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice.

Our presenters for this program are Dr. Brad Karon, Assistant Professor of Laboratory Medicine and Pathology and Medical Director of the Hospital Clinical Laboratories and Point of Care Testing in the Division of Clinical Core Laboratory Services at Mayo Clinic and Dr. Walter Cook, from the Division of Community Pediatric and Adolescent Medicine in the Department of Pediatric and Adolescent Medicine. Dr. Karon and Dr. Cook will provide an overview of the risk of hyperbilirubinemia in the newborn and discuss the American Academy of Pediatrics recommendations on identification and evaluation of newborn jaundice.

They will give an historic perspective on diagnosis and management, discuss the clinical picture, and discuss the uses and limitations of transcutaneous bilirubin.

Outline

Today Dr. Karon and I would like to discuss the use of transcutaneous bilirubin monitors in the evaluation of newborn jaundice. In the upcoming slides we will review newborn jaundice, the American Academy of Pediatrics recommendations for evaluation of jaundice and describe our recent study using the Bilichek transcutaneous bilirubin monitor.

Introduction

We know that normal bilirubin levels increase during the first week of newborn life. Common reasons for this include: Shortened lifespan and increased fragility of the newborn’s RBCs; Immaturity of the liver conjugation system; Increased reabsorption of bilirubin via the enterohepatic circulatory system; and other factors. Bilirubin at low levels may be an antioxidant and protective but at extreme levels it can cause damage to the brain of the neonate.

Kernicterus

Kernicterus is defined as the chronic form of bilirubin encephalopathy and includes clinical signs of choreoathetoid cerebral palsy, sensory neural hearing loss, dental enamel dysplasia, and paralysis of upward gaze.

Historical Information

Prior to the late 1960s most kernicterus was due to Rh isoimmunization but due to the discovery of Rho Gam the reports of kernicterus in the 1970s to early 1980s were nonexistent in the North American and European literature. Thus in 1994 the AAP advised a kinder and gentler approach to newborn jaundice. However, with increasing reports of bilirubin encephalopathy the AAP revised the guidelines in 2004.

Focus of the Guideline

The AAP committee on newborn jaundice set up a program to decrease the frequency of severe hyperbilirubinemia with out increasing anxiety, decreasing breastfeeding, or accruing increased cost and unnecessary treatment.

Key Elements to the Recommendation

The key elements of the recommendations include providing breastfeeding support, develop nursery protocols for evaluation of newborn jaundice, recognize that visual inspection alone may lead to errors, and suggested that bilirubin levels need to be interpreted according to the baby’s age- which is a significant change from the 1994 recommendations.

The recommendations suggested the assessment risk of hyperbilirubinemia for every newborn baby prior to discharge from the hospital. Suggestions included a predischarge transcutaneous bilirubin or total serum bilirubin or evaluation of clinical risk factors. It is becoming clearer that every baby should have a bilirubin checked prior to discharge and then develop an appropriate follow up plan for this infant.

Mayo Study of TcB

Based on these recommendations and the lack of literature on this topic, we developed a study using the Bilichek transcutaneous bilirubin monitor to assess newborns and compared it with serum levels. Our feeling was that we could eliminate the number of blood draws of normal newborns while still screening every baby for jaundice.

Our study design called for us to enroll up to 200 infants who had a serum bilirubin level ordered by a physician because they suspected jaundice. For these infants, we performed a transcutaneous bilirubin reading within 30 minutes of a laboratory draw for serum bilirubin. We compared the BiliChek transcutaneous bilirubin value to serum bilirubin measured by two different methods--one that uses a classic diazo reaction and the Vitros method that measures conjugated and unconjugated bilirubin photometrically. We recorded gestational age, postnatal age in hours, and mother’s ethnicity for every infant enrolled in the study.

Mayo Study of TcB: TcB vs. diazo TsB

This is a Bland-Altmann plot showing the difference between transcutaneous and diazo serum bilirubin, on the y-axis, vs. the mean of transcutaneous and serum bilirubin on the x-axis. On average transcutaneous bilirubin was significantly higher than diazo serum bilirubin, with a median bias of 2.0 mg/dL. The relationship between transcutaneous and serum bilirubin does not appear to change much over the range of bilirubin levels encountered--suggesting a relatively constant bias between transcutaneous and serum bilirubin.

Mayo Study of TcB: TcB vs Vitros TsB

This is a Bland-Altmann plot showing the difference between transcutaneous and Vitros serum bilirubin, on the y-axis, vs. the mean of transcutaneous and serum bilirubin on the x-axis. Again the relationship between transcutaneous and serum bilirubin is relatively constant across the range of bilirubin values encountered, but the median bias is significantly less at 1.3 mg/dL. We can see from this data that the particular laboratory bilirubin method used is a major determinant of the relationship between transcutaneous and serum bilirubin.

Mayo Study of TcB

The major question we wanted to answer was whether transcutaneous bilirubin, along with postnatal age in hours, could be used to predict the risk of potentially dangerous serum bilirubin values. To do this, we took each transcutaneous value, along with the infant’s postnatal age in hours, and plotted that in the conventional Bhutani nomogram used to interpret serum bilirubin values in our practice. That nomogram uses bilirubin value and postnatal age in hours to divide risk into four zones: low, low-intermediate risk, high-intermediate, and high risk. For the purposes of this talk, we will assume that both low and low-intermediate zones represent low-risk infants; and both high and high-intermediate zones represent high-risk infants. We then calculated the sensitivity and specificity of a high-risk transcutaneous value predicting a high-risk serum value from the same infant.

This two by two concordance table shows how well transcutaneous bilirubin was able to predict high-risk serum bilirubin values when both were plotted in the Bhutani nomogram according to postnatal age at the time of measurement. The second row shows all infants with high-risk serum bilirubin values by the diazo method. The transcutaneous measurement predicted high-risk serum values in 51 of 52 infants with a high risk serum bilirubin, for a sensitivity of 98%. The first row of the table shows all infants with low-risk serum bilirubin values by the diazo method. The transcutaneous method correctly predicted low risk in only 48 of 125 infants with low-risk serum values, for a specificity of only 38%.

This is a concordance table comparing transcutaneous to Vitros serum bilirubin. The second row shows all infants with high-risk serum bilirubin values by the Vitros method. The transcutaneous measurement predicted a high-risk value in 63 of 67 infants with a high-risk serum values, for a sensitivity of 94%. The first row of the table shows all infants with low-risk serum bilirubin values by Vitros method. The transcutaneous method correctly predicted low risk in 35 of 64 infants with low-risk serum values; for a specificity of 55%. We can see that overestimation of bilirubin by the transcutaneous method leads to sensitive, but not specific, prediction of the risk of potentially dangerous serum bilirubin values. For screening purposes sensitivity is relatively more important than specificity, because infants with high-risk transcutaneous values will have a serum bilirubin drawn to confirm that risk; whereas infants who are low risk may be discharged without serum measurement.

We also found that none of the clinical variables we collected: gestational age, postnatal age, or mother’s ethnicity, had any significant effect on the relationship between transcutaneous and serum bilirubin. Among the laboratory variables we studied, the type of collection tube for serum bilirubin, clear vs. amber, did impact the relationship between transcutaneous and serum bilirubin for at least one of the serum methods studied.

Conclusions

In conclusion we found that transcutaneous bilirubin systematically overestimates serum bilirubin as it is measured at Mayo. This finding is different from what has been described in previous studies. The relationship between transcutaneous and serum bilirubin will be different in each institution. We studied many clinical and laboratory variables that could have potentially affected the relationship between transcutaneous and serum bilirubin. We found that only laboratory variables such as serum bilirubin method and collection container had any impact. Because the relationship between transcutaneous and laboratory bilirubin will likely vary by institution, the utility of transcutaneous bilirubin screening will also vary by health care setting.

In our institution we found that transcutaneous bilirubin is safe and effective as a screening tool to identify infants with potentially dangerous serum bilirubin levels. Because we know that transcutaneous bilirubin overestimates serum values within our institution, we have developed a protocol to screen all infants prior to discharge with transcutaneous bilirubin. The transcutaneous value, after application of an offset designed to help improve correlation with serum levels, is plotted in the Bhutani nomogram. If the infant has a low risk transcutaneous value, they are often discharged without a serum bilirubin value, though appropriate clinical follow-up is still necessary. If the infant has a high risk transcutaneous value, a serum bilirubin is performed and clinical actions are based upon that serum value with appropriate follow-up.

References

The last slide shows a few references for further information, including our study published last year for those of you who would like the gory details.


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