Date Published: June 14, 2019
Publisher: Public Library of Science
Author(s): Christian V. Hulzebos, Deirdre E. Vader-van Imhoff, Arend F. Bos, Peter H. Dijk, Umberto Simeoni.
Our objective was to analyze the relationship between transcutaneous bilirubin (TcB) measured on an unexposed area of skin and total serum bilirubin (TSB) in preterm infants before, during, and after phototherapy (PT). For this purpose paired TSB and TcB levels were measured daily during the first ten days after birth in preterm infants of less than 32 weeks’ gestation. TcB was measured with a Dräger Jaundice Meter JM-103 on the covered hipbone. Agreement between TSB and TcB levels was assessed before, during, and after PT. True negative and corresponding false negative percentages were calculated using different TcB cut-off levels. Data are presented as mean (±SD). We obtained 856 paired TcB and TSB levels in 109 preterm infants (66 boys, gestational age 29.4 ± 1.6 weeks and birth weight 1282 g ± 316 g). We found that the difference between TSB and TcB before PT was significantly lower, 44 (±36) μmol/L, than the difference during and after PT, 61 (±29) μmol/L and 63 (±25) μmol/L, respectively; P < 0.01. Blood sampling could be reduced by 42%, with 2% false negatives, when 50 μmol/L was added to the TcB level at 70% of the PT threshold. Our conclusion is that phototherapy enhances underestimation of TSB by TcB in preterms, even if measured on unexposed skin. The use of specific TcB cut-off levels substantially reduces the need for TSB measurements.
Transcutaneous bilirubin (TcB) levels provide a quick estimate of TSB levels based on the spectrophotometric measurement of the yellow color of the skin and subcutaneous tissue. As early as 1980, Yamanouchi and colleagues predicted the potential screening value of TcB . Currently, TcB measurements are advocated for the purpose of screening unconjugated hyperbilirubinemia in infants with a gestational age (GA) of more than 35 weeks . This measure has also proven to be reliable in preterm infants of less than 35 weeks’ gestation  and specific TcB cut-off thresholds were published for infants between 28–34 + 6 weeks to “identify infants that require a total serum bilirubin (TSB) to confirm or exclude the need for phototherapy (PT)” .
Out of the 114 patients included in the BARTrial 109 infants were included in this analysis. TcB measurements were not performed in four infants (three for unknown reasons and one infant died on the first day after birth). For one infant the timing of the TcB measurements was not documented. The majority of the infants, ie, 96 (88%) were Caucasian and 66 (61%) were boys. The mean (±SD) GA was 29.4 ± 1.6 weeks and the mean (±SD) birth weight was 1282 g ± 316 g. A total of 98 infants (91%) received PT with a mean (SD) total duration of 68 (±52) hours. Eleven infants (9%) did not receive any PT during the study period. A total of 856 paired TSB and TcB levels were obtained, with a mean of 8, ranging from 1 to 14 paired measurements per patient. The postnatal course of TSB and TcB were comparable with peak levels around Day 3. Fig 1 shows the agreement and correlation between TSB and TcB levels for all 856 measurements.
In the present study we found that TcB levels measured on the covered hipbone showed a strong correlation and good agreement with TSB levels in preterm infants of less than 32 weeks’ GA before, during, and after PT. The data also showed that TcB persistently underestimated the TSB level and that PT did affect this underestimation: the underestimation increased from approximately 45 μmol/L to approximately 60 μmol/L and this effect remained for as long as 48 hours after PT was stopped. We present a formula to correct this underestimation and the large variation in differences between TSB and TcB levels. It is possible to reduce blood sampling by 40%, with a minimal risk of missing preterm infants of less than 32 weeks’ GA with significant hyperbilirubinemia, by applying the following formula: add 50 μmol/L to the measured TcB value and use 70% of the TSB PT treatment threshold.
PT enhances underestimation of TSB by TcB that lasts after PT is stopped when measured on the covered hip bone in preterm infants of 32 weeks’ GA or less. A reduction of approximately 40% of blood samples is feasible without a substantial risk of missing high TSB levels, using a TcB+50 μmol/L cut-off level at 70% of the PT treatment threshold.