Original Research Published on May 9, 2021

 

Comparison of Serum Bilirubin to Transcutaneous Bilirubin During and After Phototherapy

Swetha K Thappaa, Anand M Ra, Preetha Remeshb, Divia Nathb,Vishnu Mohanb

 

a. Department of Paediatrics, Aster MIMS Hospital, Calicut, Kerala;

b. Department of Neonatology, Aster MIMS Hospital, Calicut, Kerala

 

 

Abstract

Objective: To compare transcutaneous bilirubin with total serum bilirubin in neonates during and after phototherapy

Study design: A prospective observational study for one year

Participants: 799 neonates >35 weeks of gestation, developing jaundice within 10 days of life.

Intervention: A photo-occlusive patch was applied over the sternum. TcB assessment with Drager JM 103 multi wavelength handheld transcutaneous bilirubinometer was done in this area paired with a concurrent serum sample during and 24 hours after stopping phototherapy.

Outcome: In our study the mean TCB during phototherapy was 13.26 ± 2.42 mg/dl with minimum value of 4.50 mg/dL and maximum value of 18.40 mg/dL in the study population (95% CI 13.09 to 13.43 mg/dL). The mean TSB during phototherapy was 13.06 ± 2.52 mg/dl with minimum value of 4.30 mg/dL and maximum value of 18.70 mg/dl in the study population (95% CI 12.88 to 13.23 mg/dL). The mean TCB 24 hours after stopping phototherapy was 10.37 ± 2 mg/dL with minimum value of 4.20 mg/dL and maximum value of 16.10 mg/dL in the study population (95% CI 10.33 to 10.61 mg/dL). The mean TSB 24 hours after stopping phototherapy was 10.47 ± 2.02 mg/dL, minimum value of 4.80 mg/dl and maximum value of 15.30 mg/dL in the study population (95% CI 10.33 to 10.61).

Results: Transcutaneous bilirubin has a good correlation with total serum bilirubin during phototherapy. (r=0.881, P<0.001). Transcutaneous bilirubin has a significant correlation with total serum bilirubin after phototherapy. (r=0.912, P<0.001).

Conclusion: In our study transcutaneous bilirubin correlated significantly with total serum bilirubin at the patched sternal site during and 24 hours after stopping phototherapy, supporting previous studies.

 

Introduction

Icterus neonatorum or neonatal jaundice affects up to 60% of term & 80% of preterm newborns and is the most common cause of hospital readmission in the initial neonatal period. Severe hyperbilirubinemia occurs in less than 2% of term infants and can lead to bilirubin encephalopathy (kernicterus) and permanent neurodevelopmental delay.1

The crux of hyperbilirubinemia and bilirubin-induced neurotoxicity risk evaluation remains the measurement of total serum bilirubin and the mainstays of intervention are phototherapy and exchange transfusion.2 Prevention of kernicterus in the term or late preterm neonate is one of the primary focus of newborn care.3  In order to properly assess the risk of significant hyper bilirubinaemia, the American Academy of Paediatrics recommends to measure either the serum bilirubin with a spectrophotometric method (TSB) or the transcutaneous bilirubin (TcB)4

Methods

The study was conducted in a level III NICU for a period of one year (from June 2018- June 2019) at Aster Malabar Institute of Medical Sciences, Calicut, Kerala. The study was approved by the Institutional Ethics Committee and was done under institutional protocols. A written informed consent was obtained from either of the parents or guardian prior to enrollment in the study.

Neonates >35 weeks gestation with clinical jaundice detected within first 10 days of birth were included and neonates with conjugated hyperbilirubinemia, birth defects were excluded.

A patch of skin measuring approximately 2cm x 2 cm over sternum was photo protected using a patch made out from IBIS eye protector material (Eye protector we use during routine phototherapy) and placed after first TcB measurement and concurrent serum bilirubin sent before phototherapy is initiated.

Phototherapy was instituted if the TSB fulfilled the American Academy of Paediatrics bilirubin nomograms.5

Phototherapy was given using newer light emitting diode units with appropriate irradiance.

Transcutaneous bilirubin was measured from the photo shielded area over sternum, with Drager JM-103 hand held transbilirubinometer. The device was calibrated before usage according to the manufacturer’s recommendations6

A concurrent serum bilirubin sample was also taken which was estimated using diazo method in the hospital lab. A sample before, during and 24 hours after phototherapy was paired with TcB values.

Statistical Analysis:

Sample size was calculated for a co-relation coefficient r=0.1 taken from previous studies and was calculated as 783. Association between quantitative explanatory and outcome variables was assessed by calculating Pearson correlation coefficient and the data was represented in a scatter diagram. Liner regression analysis was done. Regression coefficient, along with its 95% CI and p values are presented.

Bland Altman plot was done to evaluate the agreement among two measurement techniques.

P value < 0.05 was considered statistically significant.

IBM SPSS version 22.0 was used for statistical analysis7

Results

Among the 799 study population, gestational age was distributed as 76 (9.51%) between 35-36W+6D, 130 (16.27%) between 37W-37W+6D, 326 (40.80) between 38W-38W+6D, 219 (27.14%) between 39W-39W+6D and 48 (6.01%) were >40W.

The baseline characteristics are shown in Table 1 and the clinical characteristics are shown in Table 2.

TcB estimated at sternum correlated significantly with TSB during phototherapy (r=0.912, P<0.001) and after phototherapy (r=0.912, P<0.001) over the patched sternal area (Figure 1).

The mean TCB during phototherapy was 13.26 ± 2.42, minimum level was 4.50 and maximum level was 18.40 (95% CI 13.09 to 13.43) and the mean TSB during phototherapy was 13.06 ± 2.52, minimum level was 4.30 and maximum level was 18.70 in the study population (95% CI 12.88 to 13.23).

The mean TCB 24 hours after stopping phototherapy was 10.37 ± 2.0, minimum level was 4.20 and maximum level was 16.10 (95% CI 10.33 to 10.61) and the mean TSB 24 hours after stopping phototherapy was 10.47 ± 2.02 in the study population, minimum level was 4.80 and maximum level was 15.30 in the study population (95% CI 10.33 to 10.61).

Bland Altman analysis showed 90% of the data points in the 95% confidence interval which are the limits of agreement (Figure 2).


Figure 1. Scatter Plot


Figure 2. Bland Altman Plot

 

Discussion

The present study was done to compare transcutaneous bilirubin to serum bilirubin during and after phototherapy. Literature review has less number of studies done in relation with phototherapy, while transcutaneous bilirubin assessment has been more or less replacing conventional serum bilirubin assessment before phototherapy. Our study aimed to establish comparison between the two modalities of bilirubin estimation in relation with phototherapy ie; during and after phototherapy.

Our study showed a strong correlation between TcB as measured from a shielded photo protected area at the sternum and TSB measurements in a cohort of jaundiced late preterm and term newborns during and after phototherapy. The correlations of TcB and TSB before, during and after phototherapy were high and comparable. There was no significant difference between TSB and TcB from covered area of the skin.

Other parameters analysed were the neonatal and maternal risk factors including Rh incompatibility, ABO incompatibility, mode of delivery, neonatal and maternal hypothyroidism, maternal diabetes, cephalhematoma and subgaleal bleed.  TcB estimated at sternum correlated significantly with TSB prior to initiation of phototherapy (r=0.881), during phototherapy (r=0.912) and after phototherapy (r=0.912). Using the Bland Altman analysis , 90% of the data points were in the 95% confidence interval which are the limits of agreement.

Few other studies have demonstrated a good agreement between TSB and patched TcB during phototherapy in preterm neonates.8,9 Study by Pendse etal showed a strong correlation between transcutaneous bilirubin and serum bilirubin in neonates 30 weeks to 37 weeks.10

Study by Panburana etal showed TcB and TSB values had linear correlation with significant correlation coefficient (r 0.81, p < 0.001) before, during and after phototherapy. TcB levels tended be higher than TSB with mean difference of 0.44 mg/dL (95% CI: 0.7433-0.1323 mg/dL) and SD:1.64. TSB confirmation was recommended when TcB cutoff values greater than 9, 12, 13, 15 mg/dL at 24 (TSB:8 mg/dL), 36 (TSB: 10 mg/dL), 48 (TSB: 12 mg/dL) and 72 (TSB: 15 mg/dL) hours postnatal age, respectively.11

While most studies provided correlation coefficients, only few studies provided data for the Bland-Altman difference plots. Unfortunately, the translation into clinical practice of a strong correlation coefficient noted between TcB and TSB tests is difficult, as it does not provide acceptable information in terms of the expected difference between these measurements for a single subject. Contrarily, data presented as Bland-Altman difference plots (in terms of bias and precision estimates) could allow a reasonable prediction of the range of the TSB values likely for a given TcB reading, which is thus much more helpful in clinical practice and decision-making.

Strength of the Study:

TcB measurement in jaundiced, healthy otherwise normal neonates under phototherapy from properly shielded area of the skin is relatively accurate and can be performed to monitor bilirubin levels. It will lead to a decrease in the frequency of painful blood sampling.

The strength of our study includes a prospective study with a relatively good sample size, its methodology, and stringent measures taken to downplay inter-observer variation with an aim to establish the role of TcB as a surrogate marker of TSB.

Limitations of the Study:

Transcutaneous bilirubinometers have an upper limit, above which the device will not generate the bilirubin value. Our device Drager JM-103 has an upper limit value of 20mg/dL, above which the machine shows error. Hence subjects were not included in the study whose transcutaneous measurement was >20 mg/dL.

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