NACB - Scientific Shorts
NACB - Scientific Shorts (formerly NACB Blog)
By Stanley F. Lo, PhD, DABCC, FACB

Why do we measure bilirubin in neonates?  As most of you know, the natural physiological process of neonatal jaundice can be harmful to the newborn if the bilirubin concentration is too high.  In the case of neonatal hyperbilirubinemia, the increase is primarily due to an immature liver which is unable to conjugate bilirubin due to decreased glucuronyl transferase activity.  Consequently, if left untreated, infants can progress to severe bilirubin encephalopathy and kernicterus, a form of brain damage due to deposition of bilirubin in the basal ganglia and brainstem nuclei.  There are several other causes that also need to be considered for hyperbilirubinemia, specifically hemolytic disorders.  Practice guidelines have been created to assist with this clinical situation and have recommended that interpretation of serum total bilirubin measurements must consider the age of the infant in hours in addition to other risk factors such as gestational age.  Currently, our clinicians have been educated to carry a nomogram in their pocket for proper determination.  Perhaps in the future, if our LIS system can accommodate nomogram determinations, we will provide an interpretation with the result.


Several laboratory methods exist for measuring bilirubin.  Most automated assays determine total, direct and indirect (calculated) bilirubin.  Only the Vitros methods provide total, unconjugated, and conjugated bilirubin results.  Calibration of these methods is complicated by the use of bovine serum, instead of human serum, enriched with unconjugated bilirubin and ditauraobilirubin.  For diazo based methods, unconjugated bilirubin in bovine serum reacts incompletely and unpredictably.  Therefore it is virtually impossible to assign accurate bilirubin calibrators using bovine serum as a protein base!  To add to the problem, the reactivity of ditaurobilirubin can lead to underestimation of bilirubin concentrations.  For better or worse, my laboratory uses the Vitros methods and we offer both the total bilirubin and neonatal bilirubin assays.  In an ideal situation, I would prefer to only offer the neonatal bilirubin method to provide determinations on the unconjugated and conjugated bilirubin fractions.


Noninvasive or transcutaneous methods are also available for measuring bilirubin in newborns.  This method uses reflectance densitometry and is very appealing as no blood draw is required.  But how do they compare to serum measurements?  The literature has several examples in which method comparisons between transcutaneous and automated clinical methods and the results indicate that transcutaneous results can be higher AND lower depending on the study.  One study did link their lab analyzers results to the reference method procedure and showed that the transcutaneous method resulted in higher bilirubin results.  Can the observed differences be explained by the problems associated with calibrators?  Are the differences due to the operational use of the transcutaneous device?  Could the differences be a combination of both calibrators and device?  Maybe it’s something completely different.  Nevertheless, many laboratories have done this comparison and implemented the device with a cutoff, above which a confirmatory measurement using a serum total bilirubin is requested.  What has been your experience?


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Posted by
On 4/7/2011

We have tried the trancutaneous method in our Outpatient Pediatric Clinic with blood comparisons sent to the hospital lab and it appeared that once the serum bilirubin got above 12mg/dL, the transcutaneous method was inaccurate. The reason for this trial was that the hospital results took so long to get back and having the anxious parents waiting was sometimes unbearable. The trancutaneous method is very expensive since most of the newborns are on Medicaid so it was cost prohibitive. You mentioned the Vitros which we have in one of our clinic labs, so I am thinking this could be an alternative option, faster turn-around time, etc. Do you think a parallel study of 20 newborns between the Vitros and the hospital method to be appropriate? Martina Christie, MT (HHS) MLS (ASCP) Laboratory Compliance Coordinator Brody School of Medicine

Posted by
On 3/24/2011

Hi Patti, Our hospital does not use the transcutaneous bilirubinometers, nor has been any inquiry. We also have outpatient clinics associated with our health system and I have not been approached with this topic. Most of our community pediatricians continue to acquire heelstick samples from neonates for bilirubin measurements. I don't know if this is the same practice for pediatricians within other healthcare systems in the area. Stan

Posted by
On 3/23/2011

Hi Stan, Does your hopsital use the transcutaneous bilirubinometers? We don't, and I've always wondered whether they are more comonly found in pediatric hopsitals or in non-pediatric hopsitals with large labor and delivery departments and NICUs. Patti Jones, Children's Dallas

Posted by
On 3/17/2011

Stan, nice summary of bilirubin measurement in neonates. We have some data on transcutaneous measurmement (not yet published) that suggests its use on older infants (4-7 days) in the outpatient environment is not as reliable as when used on 2-3 day old infants in the nursery. We used the same meters and compared to the same lab serum method, and found mean bias between TcB and TSB was much lower for the older outpatient infants, and variability between TcB and TSB much greater compared to infants in the nursery. When we tried to use the TcB values for risk prediction in the outpatient population it did not work well, so we have restricted use to nursery inpatients. Just wondering if anyone else out there has encountered similar issues with use of transcutaneous devices in the outpatient setting?

About the Author
Stanley F. Lo, PhD, DABCC, FACB
Stanley F. Lo, PhD, DABCC, FACB 

IFCC Intl Congress Pediatrics May 13-15, 2011 Berlin, Germany


Lo SF: The Lab's Role in Diagnosis of Neonatal Hyperbilirubinemia. CLN 2010; 36.


Additional Reading


Lo SF, Jendrzejczak B, Doumas BT.  Bovine serum-based bilirubin calibrators are inappropriate for some diazo methods.  Clin Chem 2010;56:869-872.


American Academy of Pediatrics, Subcommittee on Hyperbilirubinemia.  Clinical practice guideline: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation.  Pediatrics  2004;114:297-316.


Canadian Paediatric Society, Fetus and newborn Committee.  Guidelines for detection, management and prevention of hyperbilirubinemia in term and late preterm newborn infants (35 or more weeks’ gestation).  Paediatr Child Health 2007;12 (5):1B-12B.


Karon BS, Wickremasinghe AC,  Lo SF,  Saenger AK,  Cook WJ.  BiliChek transcutaneous bilirubin meter overestimates serum bilirubin as measured by the Doumas reference method.  Clin Biochem 2010;43:1009-1012.