Transcutaneous bilirubin estimation in extremely low birth weight infants receiving phototherapy: a prospective observational study.

BACKGROUND: Measurement of transcutaneous bilirubin (TcB) is a quick, reliable and painless method to guide management of hyperbilirubinemia. Studies in term and late preterm infants have found that TcB measurements from covered areas (TcB-C) during phototherapy (PHT) co-relate well with serum bilirubin levels. Limited data exists in extremely low birth weight (ELBW) infants. METHODS: In this prospective observational study, an opaque patch was placed on the back of an ELBW infant prior to initiation of PHT. TcB-C and TcB-E (TcB from exposed area) levels were measured at birth and at 24-h intervals for 5 days. Total serum bilirubin (TSB) levels were also measured within 30 min of obtaining TcB levels. A Wilcoxon signed rank test was used for data analysis. A mixed effect model was used to adjust for repeated measurements over time. The p value < 0.05 was considered significant. RESULTS: A total of 19 infants were enrolled in the study, with a mean gestational age of 26 ± 2 weeks and mean weight 827 ± 127 g. The difference between TcB-C and TSB was 2.68 ± 2.41 mg/dl (mean ± SD, p <  0.001). In contrast, the difference between TcB-E and TSB was - 0.51 ± 1.74 mg/dl (p = 0.02). TcB-C consistently overestimates TSB, while TcB-E consistently underestimates TSB. CONCLUSIONS: During PHT exposure, TcB-C does not correlate with TSB values in ELBW infants. TcB-C levels cannot be used as a surrogate for TSB measurement in ELBW infants.

The use of transcutaneous bilirubin nomograms for the prevention of bilirubin neurotoxicity in the neonates.

Purpose: Although neonatal jaundice is a ubiquitous and predominantly benign phenomenon, the risk of neurotoxicity exists in a number of infants with unconjugated hyperbilirubinemia. Plotting bilirubin values on nomograms enables clinicians to employ an anticipatory and individualized approach with the goal of avoiding excessive hyperbilirubinemia and preventing acute bilirubin encephalopathy and its progression to kernicterus. We aimed to construct nomograms for White term infants based on transcutaneous bilirubin (TcB) measurements using a JM-105 device. Methods: TcB measurements were taken in infants at ages ranging from 0 to 96 postnatal hours. We then constructed hour-specific TcB nomograms from forehead and sternum measurements in infants who did not require subsequent phototherapy. Results: We included 2,981 TcB measurements taken on the forehead and 2,977 measurements taken on the sternum in 301 White term newborn infants. We assessed the predictive abilities of the nomograms at six postnatal time intervals using receiver operating characteristic curves. The areas under the curves indicated reasonable prediction of hyperbilirubinemia requiring phototherapy, except for the forehead measurement taken within the first 12 h of life. Sensitivity tended to rise as postnatal age increased. Conclusion: The nomograms illustrate dermal bilirubin dynamics in White term neonates during the first 4 days of life. They may be useful tools to predict individualized risk of hyperbilirubinemia requiring treatment, and to plan optimal follow-up of infants at risk of bilirubin neurotoxicity.

Accuracy of enhanced transcutaneous bilirubinometry according to various measurement sites.

OBJECTIVE: The goal of the study was to provide missing data on the accuracy of enhanced transcutaneous bilirubinometry in a monoracial population of term neonates, considering three different measurement sites. MATERIAL AND METHODS: Transcutaneous bilirubin was measured using the JM-105 device on the forehead, chest, and abdomen. Blood sampling for total serum bilirubin concentration has been performed within 10 minutes of transcutaneous measurements. Paired transcutaneous bilirubin and total serum bilirubin measurements were statistically analyzed. RESULTS: The study group consisted of 102 healthy term Slovak infants. The correlation between total serum bilirubin and transcutaneous bilirubin was significant (coefficient of determination R2: 0.9045 forehead, 0.8808 sternum, 0.8467 abdomen). Transcutaneous measurements underestimated serum bilirubin levels significantly when total serum bilirubin values were higher than 15 mg/dL, irrespective of the site of transcutaneous measurements. The lowest mean difference between total serum bilirubin and transcutaneous bilirubin was identified on the sternum (median: -1.1 mg/dL). The area under the curve was >0.97 and >0.93 for detecting total serum bilirubin levels >10 mg/dL and >13 mg/dL, respectively, for all measurement sites. Transcutaneous measurements on the forehead and sternum provided very high sensitivity, with the best performance at the forehead. CONCLUSION: Transcutaneous bilirubinometry using an enhanced device is an accurate, sensitive, and convenient screening method in term Caucasian neonates. Transcutaneous bilirubin measurements on the forehead, sternum, and abdomen are reliable, with the best performance on the forehead. It is necessary to confirm higher transcutaneous bilirubin values with a total serum bilirubin measurement.

Cephalocaudal progression of neonatal jaundice assessed by transcutaneous bilirubin measurements.

OBJECTIVE: The cephalocaudal progression in neonatal jaundice is a well-known phenomenon. Since transcutaneous bilirubin measurements (TcB) are increasingly applied, for which different body site can be used, we aimed to quantify the cephalocaudal progression of neonatal jaundice through TcB and to assess the influence of gestational age, postnatal age and the degree of hyperbilirubinemia on this cephalocaudal progression. STUDY DESIGN: In jaundiced neonates ≥32 weeks of gestational age, TcB was measured on 5 sites: forehead, sternum, hipbone, proximal tibia and foot, during the first two weeks of life. RESULTS: 58 neonates were included. Mean ratios of TcB on the 5 sites compared to the forehead were: sternum 1,03 (SD 0,14), hipbone 0,80 (SD 0,16), proximal tibia 0,63 (SD 0,14) and foot 0,44 (SD 0,15). Gestational age, postnatal age nor the degree of hyperbilirubinemia were associated with the cephalocaudal progression (ANOVA p > 0,05). CONCLUSION: The cephalocaudal progression of neonatal jaundice is evident, with caudal levels of TcB being less than half of cephalic measurements. This implicates that TcB measurements caudal from the sternum are less reliable, and should be avoided. The degree of cephalocaudal progression is not associated with gestational or postnatal age, nor with height of bilirubin levels.

Noninvasive methods for bilirubin measurements in newborns: A report.

New technologies have become available for noninvasive assessments of neonatal hyperbilirubinemia. Our objective is to review the noninvasive methods for measuring bilirubin in the newborn. We searched relevant literature from 1966 to January 1, 2020, which included cross-sectional studies to define the accuracy of any noninvasive methods for measuring or estimating total serum/plasma bilirubin (TB) levels in newborns. We identified and included 83 relevant studies of direct visual assessment, icterometry, mobile phone applications, and transcutaneous bilirubinometry (TcB). Compared with laboratory TB measurements, visual assessment was the least accurate and least reliable (r: 0.37 to 074), while TcB was the most accurate, but not always near-equivalent (r: 0.45 to 0.99). The sensitivity and specificity of TcB cut-off values to detect significant hyperbilirubinemia (TB>95th percentile for age in hours) ranged from 74% to 100% and 18% to 89%, respectively.

Transcutaneous Bilirubin Levels and Risk of Significant Hyperbilirubinemia in Early-Term and Term Newborns.

OBJECTIVE: To compare the course of the transcutaneous bilirubin (TcB) values of early-term newborns with those of term newborns in the first month of life and to investigate whether early-term newborns have an increased risk of significant hyperbilirubinemia requiring treatment. DESIGN: A prospective, controlled cohort analysis. SETTING: A tertiary level mother-child birth and health care center. PARTICIPANTS: Four hundred early-term (37 0/7 to 38 6/7 weeks) and 320 term (39 0/7 to 41 6/7 weeks) newborns born during a 27-month period. METHODS: A total of six TcB measurements in a longitudinal manner were made in early-term and term newborns: the first two at 6 and 48 hours after birth and the next four on routine examination days (Days 4, 7, 15, and 30). Demographic characteristics, values of daily TcB measurements, number of newborns with significant hyperbilirubinemia, and risk of jaundice requiring treatment were compared between the two groups. RESULTS: All six TcB values were significantly greater in the early-term group than in the term group (p < .001 for each). Early-term newborns had a statistically significant increased risk of jaundice requiring treatment compared to term newborns (risk ratio = 1.91; 95% confidence interval [1.23-2.96]; p = .0046). Results of the repeated-measures analysis of variance and post hoc adjusted multiple comparison analysis showed that TcB levels increased to and peaked at 96 hours after birth and then gradually decreased to baseline (first measurement) levels at 30 days after birth in each group. CONCLUSIONS: Early-term newborns should not be treated as full-term newborns because they have significantly higher TcB levels. These newborns should be closely monitored for pathologic jaundice because they have increased risk for significant hyperbilirubinemia requiring phototherapy.

Predictability of transcutaneous bilirubinometry in late preterm and term infants at risk for pathological hyperbilirubinemia.

BACKGROUND: The aim was to assess the predictability of transcutaneous bilirubinometry in late preterm and term neonates at risk for pathological hyperbilirubinemia, and to identify the neonatal population in which transcutaneous bilirubin most accurately predicts serum bilirubin level (SB, mg/dl). METHODS: The correlations between transcutaneous bilirubin (TCB, mg/dl) and SB in different neonatal population subsets; and between ΔTSB (TCB-SB) and relevant neonatal variables and clinical groups were analyzed. RESULTS: TCB correlated with SB (r = 0.82, p < 0.05) in the cohort (n = 350) and in population subsets (r = 0.81-0.9, p < 0.001). Black infants with gestational age (GA) >35 weeks and chronological age (CA) >3 days recorded strongest correlation (r = 0.9, p < 0.001) followed by Blacks, and non-Black infants with CA >3 days and GA >35 weeks. ΔTSB was positive in Blacks, and in infants with CA <3 days, or with no phototherapy. ΔTSB was negative in non-Blacks, in infants with positive direct Coombs test (DC+) or those receiving phototherapy. Black race [beta (SE) = 1.3(0.33), p < 0.001] had positive, while CA [beta (SE) =-1.74 (0.36), p < 0.001], DC + status [beta (SE) =-0.72 (0.25), p = 0.004] and receipt of phototherapy [beta (SE) =-0.84 (0.21), p < 0.001] each had negative correlation with ΔTSB. ΔTSB for Blacks was >Whites, Hispanics and Asians. CONCLUSION: SB is best predicted by TCB in Black infants with CA over 3 days and GA over 35 weeks. Variability in SB estimation by TCB is race, CA and immune mediated hemolysis specific.

Prediction of the need for phototherapy during hospital stay in preterm infants by transcutaneous bilirubinometry.

BACKGROUND: Neonatal hyperbilirubinemia is a common condition that frequently requires treatment with phototherapy and less commonly by exchange transfusion, especially in preterm infants. It is important to identify and monitor infants at risk of severe unconjugated hyperbilirubinemia early in the postnatal period to instigate appropriate management plans. AIMS: To evaluate transcutaneous bilirubinometry (TCB) as a screening tool at 24 and 48 h of age to predict the need for phototherapy during hospital stay in preterm infants. STUDY DESIGN: A single centre prospective cohort study in a level III perinatal centre. SUBJECTS: Preterm infants (23+0 to 36+6 weeks of gestation) were eligible for enrolment. OUTCOME MEASURES: Primary outcome was to assess the predictive value of TCB at 24 and 48 h of age for the need of phototherapy during hospital stay. RESULTS: A total of 338 preterm infants were enrolled. The majority of infants (98.1%) born below 32 weeks of gestation required phototherapy. For infants born at >31 + 6 weeks of gestation, TCB at 24 h of age ≥81 µmol/l had sensitivity 83%, specificity 56%, positive predictive value (PPV) 54.7% and negative predictive value (NPV) 84%. TCB at 48 h of age ≥145 µmol/l had sensitivity 65%, specificity 62%, PPV 24% and NPV 90%. CONCLUSION: TCB performed poorly at 24 and 48 h of age as a predictor of phototherapy during hospital stay in preterm infants. The negative predictive value of the test at 48 h of age might be helpful for infants born after 31 + 6 weeks of gestation.

Validation of transcutaneous bilirubinometry during phototherapy for detection and monitoring of neonatal jaundice in a low-income setting.

Background: Severe neonatal jaundice (SNJ) and the associated long-term health sequelae are a significant problem in low-income countries (LIC) where measurement of total serum bilirubin (TSB) is often unavailable. Transcutaneous bilirubinometry (TcB) provides the opportunity for non-invasive, point-of-care monitoring. Few studies have evaluated its agreement with TSB levels during phototherapy in LIC.Aim: To determine agreement between TcB and TSB during phototherapy in a Haitian newborn population and to establish whether TcB can be safely used to guide treatment during phototherapy when TSB is unavailable.Methods: A single-centre prospective study (February to May 2017) in Cap Haïtien, northern Haiti was undertaken. Newborns <7 days of age with clinically detected jaundice were eligible for inclusion. A TcB device (JM-103) was used to screen for newborn jaundice along with a parallel TSB. A strip of black tape was placed across the sternum during phototherapy and uncovered for subsequent TcB measurements. Decisions about phototherapy treatment were based upon UK National Institute of Clinical Excellence (NICE) threshold criteria. Paired TSB and TcB measurements were compared using Bland-Altman methods.Results: The final analysis included 70 parallel TSB/TcB measurements from 35 infants within the first 5 days of life. Nineteen (54.3%) were male and 12 (34.3%) were <35 weeks. Thirty-two (91.4%) were receiving phototherapy. There was good agreement between TSB and TcB. Compared with TSB, TcB tended to over-estimate bilirubin (mean difference 11.1 µmol/L, 95% CI -10.2-32.5 µmol/L). However, at higher bilirubin levels (>250 µmol/L), TcB tended to under-estimate bilirubin compared with TSB and the difference increased.Conclusion: In an LIC setting in which serum bilirubin testing is not commonly available, TcB demonstrates good agreement with TSB and can be safely used to guide jaundice treatment during phototherapy but can lead to over-treatment at lower bilirubin levels and are more inaccurate at higher levels. For TcB levels >250 µmol, confirmation with serum bilirubin should be performed, if available, to avoid under-estimation.Abbreviations: LIC: low income countries; LMIC: low and middle income countries; TcB: transcutaneous bilirubinometry; TSB: transcutaneous serum biliubin.

Correlation between transcutaneous and serum bilirubin in preterm infants before, during, and after phototherapy.

BACKGROUND: Transcutaneous bilirubinometry (TcB) is routinely used to monitor jaundice in term and near-term infants. However, before 35 weeks gestation, the technique has not been widely adopted. AIM: The aim of this study is to study the correlation between TcB and total serum bilirubin (TsB) before, during, and after phototherapy in preterm infants born before 35 weeks' gestation. METHODS: Jaundice was monitored in infants born before 35 weeks' gestation by simultaneous measurements of TsB and TcB assessed by a Drager Jaundice Meter JM-103 (Draeger Medical, Inc., Telford, PA). RESULTS: About 588 pairs of measurements were recorded in 86 premature infants of 26-34 weeks, weighing 618-2400 grams. The overall correlation coefficient between TcB and TsB was 0.8 (p = .001). Subset analysis revealed lower correlation in infants born before 30 weeks. TcB was consistently estimated around 1 mg% lower than TsB. Neither the cause of the jaundice nor major neonatal morbidities significantly influenced the TcB-TsB correlation. CONCLUSIONS: TcB is a reliable measure of jaundice before 35 weeks' gestation with a mean under-estimation of ≈1 mg%. TcB use may reduce unnecessary invasive blood tests.

Comparison of the transcutaneous bilirubinometers BiliCare and Minolta JM-103 in late preterm and term neonates.

OBJECTIVES: To assess the agreement of transcutaneous bilirubin (TcB) measurement with the Bilicare™ System in comparison to TcB measured with JM-103™ and total serum bilirubin (TSB). METHODS: Caucasian infants with gestational age ≥35 weeks with non-hemolytic jaundice received TcB measurement with both Bilicare™ and JM-103™ devices. TSB was also obtained in infants at risk of phototherapy. RESULTS: We studied 458 infants measuring TcB with Bilicare™ and JM-103™, correlating the results and with TSB. The mean difference ± 2SD between Bilicare™ and JM-103™ TcB was 2.02 ± 4.46 mg/dL and decreased from 2.88 ± 3.17 to 1.20 ± 4.55, and to -0.95 ± 4.58 mg/dL at mild, moderate and high TcB values, respectively. CONCLUSIONS: Bilicare™ and JM-103™ TcB measurements are well correlated, but Bilicare™ over-estimates TcB for mild and moderate values and under-estimates it for high values compared to JM-103™. This could increase the prescription of TSB measurements for less serious cases and decrease them in the most worrisome.

Correlation of transcutaneous bilirubinometry (TcB) and total serum bilirubin (TsB) levels after phototherapy.

AIM: To investigate the correlation between transcutaneous bilirubinometry (TcB) and total serum bilirubin (TsB) in jaundiced infants before and after, but not during phototherapy. METHODS: This study prospectively investigated the correlation between TcB and TsB in term and near term infants before and after phototherapy. RESULTS: Overall 673 pairs of measurements (TcB and TsB) were performed on 371 infants of ≥35 weeks gestation and with birth weight above 2000 g. Of these 337 sets were from 200 infants who had not been treated with phototherapy (Group 1) and 336 measurements from 171 infants taken between 1 h and 5 d after phototherapy (Group 2). The correlation coefficient between TcB and TsB in the whole cohort was r = 0.72. The correlation was low during the first 8 h after phototherapy (r = 0.56), but thereafter the correlation returned to the range of 0.65-0.8. Using the Sobel test, no significant difference was found between the correlation coefficients at the different time periods, with the possible exception of the difference between 1 and 8 h and 9 and 16 h which was of borderline significance with a p value of 0.06. CONCLUSION: This study demonstrates good correlation between TcB and TsB by 8 h after phototherapy. This adds validity to community-based screening programs employing TcB measurements plotted on TsB nomograms. Such programs may contribute to prevention of tragic cases of bilirubin-induced neurologic damage.

Diagnostic usefulness of transcutaneous bilirubinometry in very preterm newborns.

BACKGROUND: This study was performed to find out whether transcutaneous bilirubinometry could be a valid screening method for hyperbilirubinemia in preterm infants, especially for those who needed mechanical ventilation. METHODS: We evaluated 63 preterm Iranian newborns who were managed in the neonatal intensive care unit of Shahidbeheshti University Hospital, Isfahan, Iran from April 2009 to April 2010. Transcutaneous bilirubin (TCB) measurements were obtained using BiliCheck(™) shortly before or 10 minutes after taking blood for determination of the plasma bilirubin level in premature newborns, who did not receive phototherapy. We assessed the correlation between the transcutaneous bilirubin and plasma bilirubin level by linear regression analysis. We also analyzed the gestational age, birth weight, postnatal age, sex, and hematocrit, for determination of their effect on transcutaneous bilirubin accuracy. RESULTS: The overall bilirubin concentration ranged from 5.4 to 17 mg/dL and from 4.8 to 17.3 mg/dl for total serum bilirubin (TSB) and transcutaneous bilirubin, respectively. The mean values obtained by transcutaneous bilirubinometry were slightly higher than the total TSB values. The correlation coefficient between TSB and TCB was r=0.82, P<0.001, and this was not influenced by gestational age, postnatal age or hematocrit, which were previously considered to be important. The correlation coefficient between TSB and TCB in mechanically ventilated preterm infants was r=0.75, P<0.001. CONCLUSION: Plasma bilirubin level can be accurately measured by BiliCheck(™) in premature newborns, even in newborns who need mechanical ventilation.