Venous Bilirubin Research Articles

Point-of-Care Capillary Compared to Venous Bilirubin Measurement in Neonates

AbstractWe aimed to evaluate the agreement between the point-of-care (POC) capillary bilirubin measurement with POC venous samples and the reference laboratory measurement. We conducted a prospective comparative study, including neonates ≥ 34 weeks of gestational age, and ≥ 72 h of age. The agreement between POC (Calmark Neo-Bilirubin, Sommargatan, Karlstad, Sweden) capillary, POC venous, and laboratory venous bilirubin was examined with the Bland–Altman plot and the Passing-Bablok regression analyses. The mean bilirubin was 13.54 (2.79) mg/dL in the POC capillary samples, 13.45 (2.69) mg/dL in the POC venous samples, and 12.68 (2.33) mg/dL in reference samples. Bland–Altman plots showed optimal agreement between the POC capillary and venous methods, and with the reference venous method. The bias between the POC capillary and venous methods was 0.094 [levels of agreement (− 3.118)− 3.306], between the POC capillary and the reference venous methods 0.865 [levels of agreement (− 2.283)− 4.014], and between the POC venous and the reference venous methods 0.771 [levels of agreement (− 1.814)− 3.357]. The POC capillary and venous bilirubin levels were in optimal agreement with each other, and with the reference venous measurements, supporting the POC Calmark Neo-Bilirubin capillary measurement as an alternative for a less-invasive, more rapid evaluation of bilirubin.

Benefits of Measuring the Transcutaneous Bilirubin in Neonates: Its Role in Preserving the Quality of Examination, Manipulation and Cost Effectiveness

Introduction: Hyperbilirubinemia is one of the most common diagnoses of neonatal period affecting about 60% of babies born around term 1,8 . The clinical evaluation of jaundice only through inspection is insufficient. The most accurate way of assessing it is measuring the value of venous bilirubin (VB), which is an invasive method. A simpler way is to measure transcutaneous bilirubin (TB), a spectrometric method that evaluates the bilirubin based on skin color 1,2 . Objectives: This study aims to test the effectiveness of the TB measurements in newborns, the impact on the frequency of manipulations and the cost-effectiveness of this procedure in the neonatology discipline in our country. Materials and methods: This retrospective study was conducted with a sample of neonatal population of a total of 1044 individuals, at the American Hospital 3, Tirana. With regard to the patients data collected from March-August 2017, 505 neonates were part of the study, 22 of which were excluded when the decision to take VB or from them was left at the doctor’s judgment. With respect to the patients data collected from March-August 2018, there were 539 neonates part of our study, 8 of which were excluded when the decision to take VB or not depended on the TB values. The exclusions criteria were: neonatal weight < 2000 gr, gestational age < 34 weeks, other pathologies that required NICU care, blood sample taken after the 14th day of life, and when data were incomplete. The quantitative and qualitative data of the total sample in the two years of the respective study were evaluated and analyzed according to the relevant protocols for the scientific study, using SSPI 2019. Results: It turned out from the evaluated and analyzed data of the population of the study, from 1044 subjects - neonates, out of whom, 505 belonged to 2017 and 539 belonged to 2018, that in the period March – August 2017, there were 483 neonates included in the study, of whom, 249 males and 234 females, 18 less than 2500 gr, 77 less than 3000 gr, 283 between 3000-4000 gr, 105 over 4000 gr. In terms of gestational age, 18 were less 37 weeks and 465 over 37 weeks. As regards the 2018 period, the study included 531 neonates, of whom, 272 males and 259 females, 16 less than 2500 gr, 95 less than 3000 gr, 381 were among 3000 - 4000 gr, 39 were over 4000 gr; 28 of them were less than 37 weeks, 513 were over 37 weeks. It was observed also that during 2018, the neonatal manipulations have been decreased from 39.8% to 24.2%, consequently, it corresponds integrally to reduced costs. Conclusions: At the end of the study it was found that the use of transcutaneous bilirubin significantly reduces the number of manipulations in infants. Keywords: Bilirubin, jaundice, neonate, transcutaneous DOI: 10.7176/ALST/92-03 Publication date: February 28 th 2022

Most Proper Timing of Transcutaneous Bilirubin Measurement After Phototherapy Treatment in the Newborn Period

Background: There are limited data about the proper transcutaneous bilirubin measuring time to detect levels that are close to serum bilirubin levels after ending the phototherapy treatment. Objectives: To compare the transcutaneous bilirubin and total serum bilirubin levels, and to evaluate the reliability of transcutaneous bilirubin measurements after phototherapy treatment of newborns because of hyperbilirubinemia. Methods: The study included 105 late preterm and term newborns consisting of 56 females (53.3%) and 49 males (46.6%), with gestational age 350/7 - 416/7 weeks who were treated with phototherapy. A Bilicheck (M&B-MBJ20) device was used for transcutaneous bilirubin measurements. The average of three measurements on the skin in the mid-sternal area were obtained. Correlations between transcutaneous bilirubin and venous bilirubin levels were evaluated 6 and 12 hours after phototherapy. Transcutaneous bilirubin measurements were performed simultaneously with blood collection or within a maximum ± 15 minutes time difference for total serum bilirubin. Results: The average phototherapy time was 10 ± 2 (range, 8 - 12) hours. The average difference between transcutaneous bilirubin and venous bilirubin levels post phototherapy was 2.61 mg/dL after 6 hours and 0.8 mg/dL after 12 hours. The hematocrit levels of the patients ranged between 40 - 66% with an average of 53% ± 4.8, the median level was 51%. Correlation coefficients according to hours after treatment were high for the 6th hour (r = 0.76) and very high for the 12th hour. Conclusions: Jaundice scanning with transcutaneous bilirubin measurements 6 - 12 hours after the end of phototherapy is reliable and may be helpful in preventing additional blood collection from the heel.

Drive-through transcutaneous bilirubin screening for neonatal jaundice: A safe and efficient system during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) cases was on an increasing trend, including in Malaysia. The Malaysian Ministry of Health had implemented a range of measures, such as the use of masks and social distancing, to reduce the risk of transmission. Traditionally, newborns are evaluated for neonatal jaundice using visual assessment, a capillary heel prick and serum bilirubin (SB) sampling in primary health-care clinics. This approach requires the physical presence of both parents and their newborns in the primary health-care clinics, causing crowding and increasing the risk of COVID-19 infections. To alleviate crowding, we implemented the transcutaneous bilirubin drive-through (DT) service, which is an established, non-invasive, painless and rapid method to determine the bilirubin levels. Throughout the screening, both parents and baby will be confined to their car. A total of 1842 babies were screened in our DT setting from April to July 2020. Of the total babies, 298 (16.1%) required venesection for SB measurement and 85 required admission for phototherapy. None with severe jaundice were missed since the implementation of this service. The average test duration per neonate was less than 5 min, while conventional venous bilirubin laboratory testing required an average of 1.5 h per neonate. The cost of the SB laboratory test and consumables was approximately USD 5 per test, with an estimated cost savings of USD 7720. DT screening may be introduced in health-care settings to reduce crowding and eliminate the need of painful blood sampling in newborns.

Transcutaneous bilirubinometry in neonates

In recent years, a new risk model for hyperbilirubinemia has emerged. There are several reasons for this. First, delivery of the health care system to the relatively healthy term or near-term infant and mother has changed, with earlier discharge and fewer routine tests (1). Second, physician awareness of the possibility of kernicterus in this population has changed, requiring increased vigilance (2). Third, the tendency toward demedicalization of the relatively healthy breastfed newborn has created the potential for development of severe hyperbilirubinemia (greater than 350 μmol/L). A recent study from Canada (2) concluded that severe hyperbilirubinemia continues to be observed in term and near-term neonates, with significant morbidity. Although jaundice occurs in the majority of newborns and most cases are benign, the newborn with severe jaundice must be identified, carefully followed and, if needed, treated appropriately because of the potential toxicity. Capillary collection of blood by heel puncture or blood collection from venous puncture has been the traditional method of screening and monitoring jaundice in neonates (3). This obviously causes pain and discomfort to infants and anxiety to parents. Transcutaneous bilirubin measurements using BiliChek (Respironics, USA) or other similar devices have been used sporadically in many countries, including the United States and Canada, for the screening of jaundiced infants. The clinical practice guideline that was recently published by the American Academy of Pediatrics (4) stated that there is an urgent need to improve the precision and accuracy of measurement of bilirubin in clinical laboratories. The Academy has called for additional studies on the cost-effectiveness and reproducibility of transcutaneous measurements of total serum bilirubin. Jaundice is first seen in the face of a newborn and generally progresses caudally to the body and the extremities. Visual estimation of jaundice will lead to errors; therefore, screening tools have been developed using noninvasive devices, such as BiliChek, to estimate bilirubin levels, and they have proven to be valid. Although studies are limited, they suggest a measurement within 34 μmol/L to 51 μmol/L when compared with serum bilirubin. A study by Jangaard et al (pages 79–83) evaluated the transcutaneous bilirubin device BiliChek by comparing transcutaneous bilirubin values with total serum bilirubin measurements in well term infants, ill term infants and preterm infants admitted to neonatal intensive care units, with and without phototherapy. The study consisted of two phases: in phase 1, 99 healthy, full-term infants who had not received phototherapy had transcutaneous bilirubin measurement performed simultaneously with heel puncture for serum bilirubin measurement. In phase 2, in 56 infants admitted to neonatal intensive care units, a total of 99 transcutaneous readings were performed at the time that serum bilirubin measurements were ordered for clinical reasons. The operators of the BiliChek device were blinded to the serum bilirubin levels. The authors found that transcutaneous bilirubin measurements were reasonably accurate for measuring bilirubin in term, jaundiced infants not undergoing phototherapy and in those receiving phototherapy if the area of skin was patched from the phototherapy. The BiliChek measurements were unreliable for preterm and ill infants. Jangaard et al should be congratulated for their work. Their study adds to the multiple other studies that are available comparing transcutaneous serum bilirubin measurements with capillary or venous bilirubin collection methods (5–7). Like others, they found that transcutaneous measurement has limitations. For instance, it becomes unreliable after initiation of phototherapy if the skin is not shielded from light because skin is bleached by the light. Their study did not address other important issues, such as varying degrees of skin thickness, skin colour and infants of different ethnic backgrounds, but the authors acknowledge these limitations. Future studies should include larger numbers of infants with larger numbers of measurements so that the reliability, specificity and sensitivity of such devices can be assessed. Infants in Canada are indeed from different ethnic backgrounds; therefore, variability, such as skin colour and thickness, becomes especially important in the Canadian population. Furthermore, it is crucial to investigate the cost-effectiveness of these instruments and the ability to use them for ongoing monitoring of jaundiced infants. If proven effective, these devices can be used to replace the traditional collection of serum from jaundiced infants for the measurement of bilirubin levels.

Human fetal bilirubin levels and fetal hemolytic disease

The development of secondary fetal anemia in association with maternal red blood cell alloimmunization requires hemolysis. In specimens obtained at the time of a clinically indicated cordocentesis, total and direct umbilical venous bilirubin was measured and the indirect umbilical venous bilirubin calculated in 43 antigen-positive and 30 control fetuses. Twenty-two (51%) of the antigen-positive fetuses had or subsequently developed severe anemia (hematocrit less than 30%). Umbilical venous total bilirubin (r = 0.47, p = 0.0008) and direct bilirubin (r = 0.520, p = 0.04) levels each rose with gestation. Indirect bilirubin did not vary significantly with gestation. Bilirubin was unrelated to hemoglobin. In contrast to the control fetuses, umbilical venous total bilirubin for antigen-positive fetuses was inversely related to hemoglobin (r = -0.57, p less than 0.0001) independent of gestational age (r = 0.53, p less than 0.0001) (multiple R of hemoglobin and gestational age for umbilical venous total bilirubin = 0.76, p less than 0.0001). Eighteen of 22 (82%) fetuses in whom anemia developed had an umbilical venous total bilirubin greater than or equal to 97.5 percentile compared with only eight of 21 (38%) fetuses in whom anemia did not develop (p = 0.009). In longitudinal study the umbilical venous total bilirubin frequently rose above normal weeks before the development of anemia. An umbilical venous total bilirubin greater than 3 mg/dl represented the warning line. Fifteen of 16 (94%) fetuses in whom either severe antenatal anemia or significant postnatal hyperbilirubinemia developed had an umbilical venous total bilirubin greater than 3 mg/dl. We conclude that the normal placental capacity for the transport of fetal bilirubin is exceeded in the face of enhanced fetal hemolysis. An elevated fetal bilirubin often precedes the development of antenatal anemia. The antigen-positive fetus with an elevated bilirubin is at high risk to develop anemia antenatally.

Human fetal bilirubin levels and fetal hemolytic disease

The development of secondary fetal anemia in association with maternal red blood cell alloimmunization requires hemolysis. In specimens obtained at the time of a clinically indicated cordocentesis, total and direct umbilical venous bilirubin was measured and the indirect umbilical venous bilirubin calculated in 43 antigen-positive and 30 control fetuses. Twenty-two (51%) of the antigen-positive fetuses had or subsequently developed severe anemia (hematocrit less than 30%). Umbilical venous total bilirubin (r = 0.47, p = 0.0008) and direct bilirubin (r = 0.520, p = 0.04) levels each rose with gestation. Indirect bilirubin did not vary significantly with gestation. Bilirubin was unrelated to hemoglobin. In contrast to the control fetuses, umbilical venous total bilirubin for antigen-positive fetuses was inversely related to hemoglobin (r = -0.57, p less than 0.0001) independent of gestational age (r = 0.53, p less than 0.0001) (multiple R of hemoglobin and gestational age for umbilical venous total bilirubin = 0.76, p less than 0.0001). Eighteen of 22 (82%) fetuses in whom anemia developed had an umbilical venous total bilirubin greater than or equal to 97.5 percentile compared with only eight of 21 (38%) fetuses in whom anemia did not develop (p = 0.009). In longitudinal study the umbilical venous total bilirubin frequently rose above normal weeks before the development of anemia. An umbilical venous total bilirubin greater than 3 mg/dl represented the warning line. Fifteen of 16 (94%) fetuses in whom either severe antenatal anemia or significant postnatal hyperbilirubinemia developed had an umbilical venous total bilirubin greater than 3 mg/dl. We conclude that the normal placental capacity for the transport of fetal bilirubin is exceeded in the face of enhanced fetal hemolysis. An elevated fetal bilirubin often precedes the development of antenatal anemia. The antigen-positive fetus with an elevated bilirubin is at high risk to develop anemia antenatally.

Capillary vs Venous Bilirubin Values

Sir .—I read with interest the response by Eidelman and Schimmel 1 to the article by Leslie et al 2 on the differences between capillary and venous bilirubin levels. It is always interesting when two studies reach the opposite conclusions. Leslie et al and co-workers found that venous bilirubin levels were generally higher than capillary whereas Eidelman and Schimmel found the opposite. Leslie and coworkers suggested that, because capillary levels appear to underestimate venous bilirubin levels, it is prudent to measure venous rather than capillary bilirubin levels when the total serum bilirubin level exceeds 170 μmol/L (10 mg/dL), whereas Eidelman and Schimmel opined that further studies are... needed... to ascertain the relationship of sample site and laboratory technique. Both of these statements require comment. The fact is that virtually every bilirubin level in the literature (on which we base current practice with regard to phototherapy and exchange transfusion for