Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study.

Background: Neonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET). Methods: This retrospective cohort study was conducted at the Central Women's Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer's rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth. Results: Groups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8-67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively). Conclusion: The management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.

Bilirubin photoisomers in rhesus monkey serum.

As rhesus monkeys exhibit physiological jaundice during the neonatal period, we used rhesus monkey serum to examine changes in bilirubin photoisomers. Bilirubin-rhesus monkey serum solution was irradiated with blue light-emitting diode, and changes in the absorbance and bilirubin fraction were compared with those in bilirubin- human serum albumin (HSA) and bilirubin-rat albumin solutions. The λmax decreased with light irradiation. The mean production rate of cyclobilirubin IXα was 1.98, 199 and 0.76 × 10-2/min in rhesus monkey serum, HSA and rat albumin, respectively. There was no significant difference between rhesus monkey serum and HSA. The (ZE)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.33, 0.45, and 0.10, respectively, differing significantly among the groups. The (EZ)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.020, 0.010, and 0.062, respectively, with no significant difference between rhesus monkey serum and HSA. The production rate of (EZ)-cyclobilirubin XIIIα(= (ZE)-cyclobilirubin XIIIα) was 0.73, 1.60, and 0.51 × 10-2/min, respectively, with differing significantly among the groups. The (EZ)-bilirubin IIIα/(ZZ)-bilirubin IIIα ratio was significantly different among the groups at 0.20, 0.38, and 0.15, respectively. This is the first report demonstrating the photoisomerization of bilirubin in rhesus monkey serum and the animal with the same cyclobilirubin production rate as HSA.Rhesus monkeys may be used as an animal model for neonatal hyperbilirubinemia in humans to evaluate the efficacy of phototherapy.

Influence of bilirubin photoisomers on unbound bilirubin measurement in clinical settings.

BACKGROUND: Measured unbound bilirubin concentration is influenced by bilirubin photoisomers. Bilirubin photoisomers are produced even with only a slight light exposure, and clinical samples are inevitably exposed to light. The objective of the study was to evaluate the influence of bilirubin photoisomers on the measurement of unbound bilirubin using serum of jaundiced neonates during blue light phototherapy. METHODS: Five neonates treated with phototherapy for hyperbilirubinaemia were enrolled. The samples were taken 12 h after initiation of phototherapy. Samples were processed by irradiation with blue light, by indoor ceiling light, by both blue light and indoor ceiling light or shaded. Bilirubin subfractions, total bilirubin and unbound bilirubin were measured. RESULTS: Compared with the non-irradiated samples, the (EZ)-cyclobilirubin concentration and (ZE)-bilirubin/(ZZ)-bilirubin ratio significantly increased in the blue light-irradiated samples, the (ZE)-bilirubin/(ZZ)-bilirubin ratio significantly increased in the indoor ceiling light-irradiated samples, and the (EZ)-cyclobilirubin, (EZ)-bilirubin and (ZE)-bilirubin/(ZZ)-bilirubin ratio significantly increased in the samples irradiated with both lights. No change was noted in unbound bilirubin in any group. CONCLUSIONS: We consider that changes in bilirubin photoisomers induced by light exposure during clinical practice do not influence the measured unbound bilirubin concentration.

Management of phototherapy for neonatal hyperbilirubinemia: is a new radiometer applicable for all wavelengths and light source types?

BACKGROUND: To evaluate the clinical effects of phototherapy for neonatal hyperbilirubinemia, it is necessary to measure the rate of cyclobilirubin production, which represents the main photochemical pathway of bilirubin metabolism. Since the Atom Phototherapy Analyzer can be used to calculate the theoretical relative light energy of irradiance as a means of assessing the cyclobilirubin production rate for each wavelength spectrum, the clinical effect of phototherapy can be evaluated regardless of the light source type. Using the Atom Phototherapy Analyzer, the correlation between the irradiance of various light sources with different peak wavelengths and the rate of cyclobilirubin production was investigated in vitro. We also investigated the utility of green LED in vitro. METHODS: A bilirubin-albumin complex solution was prepared, poured into tubes, and irradiated using various light sources. All light sources used were bed-type phototherapy devices; that is, green and blue LED and green and blue fluorescence tubes. The concentrations of photoisomers were measured after irradiation and compared with the irradiance of the light sources. RESULTS: The irradiance measured by the Atom Phototherapy Analyzer decreased in the following order: blue fluorescence tube > green LED > blue LED > green fluorescence tube. The cyclobilirubin production rates and irradiance values of the light sources were significantly positively correlated (R(2) = 0.93, P < 0.05). CONCLUSION: Our data indicate that the Atom Phototherapy Analyzer can be used to objectively evaluate the effects of phototherapy using various light sources. Further, the effects of green LED were similar to those of other light sources in vitro.

In vitro production of bilirubin photoisomers by light irradiation using neoBLUE.

BACKGROUND: The light-emitting diode is used as one of the new light sources for phototherapy. NeoBLUE (Atom Medical, Tokyo, Japan) incorporates blue light-emitting diodes for the treatment of neonatal hyperbilirubinemia. The authors compared the in vitro efficacy of neoBLUE with conventional phototherapy devices. METHODS: The three light devices used included neoBLUE and two conventional phototherapy devices with six blue-white (BW) or six green (GR) fluorescent tubes. A bilirubin/human serum albumin solution (15 mg/dL) in 200 x 300 mm elliptical bag was irradiated with each three light device. The average light intensity of neoBLUE, BW and GR was 22.5, 10.2 and 2.6 microW/cm(2) per nm, respectively, for the irradiated area. Bilirubin photoisomers and native bilirubin were measured by high-performance liquid chromatography. RESULTS: In neoBLUE, BW and GR, the respective production rate of cyclobilirubin was 6.0, 3.7 and 3.9 x 10(-2) mg/dL/min, and the respective (4Z, 15E)-bilirubin/(4Z, 15Z)-bilirubin ratio after irradiation was 0.44, 0.33 and 0.12; the (4Z, 15Z)-bilirubin reduction rate at 20 min after irradiation was 60, 68 and 82%, respectively. The reduction rate of (4Z, 15Z)-bilirubin correlated with the (4Z, 15E)-bilirubin/(4Z, 15Z)-bilirubin ratio. CONCLUSION: Phototherapy using the neoBLUE under high level may be clinically more effective than therapy using the conventional light source from the results of the production rate of cyclobilirubin.

Developmental changes in serum half-life of (EZ)-cyclobilirubin.

BACKGROUND: Phototherapy has been a standard treatment for neonatal hyperbilirubinemia for more than 40 years, but it has remained sub-optimal. AIMS: To clarify the developmental changes in parameters of (4E, 15Z)-cyclobilirubin ((EZ)-C) elimination in order to obtain basic data for establishing optimal phototherapy. STUDY DESIGN: Blood samples were taken at regular intervals after stopping phototherapy, and bilirubin fractions were analyzed by high-performance liquid chromatography. SUBJECTS AND METHODS: The subjects were 46 infants with hyperbilirubinemia who underwent phototherapy. The gestational age and birth weight of the subjects ranged from 25.0 to 41.0 weeks and from 656 to 3810 g, respectively, and the age at cessation of phototherapy was a median of 5 days. A kinetic model of (EZ)-C elimination was established, and the serum half-life of (EZ)-C was calculated on the basis of the determined model. Relationships of the half-life of (EZ)-C with birth weight and gestational age were investigated. RESULTS: Serum (EZ)-C elimination followed a first-order kinetic model in 43 infants and a zero-order kinetic model in three extremely low birth weight infants. The half-life of (EZ)-C calculated on the basis of a first-order elimination model in serum ranged from 68 to 274 min and showed weak negative correlations with birth weight and gestational age. CONCLUSIONS: Serum (EZ)-C excretion followed a first-order kinetic model in most of the neonates. The half-life of (EZ)-C becomes more prolonged in the very low birth weight infant and early gestational age.

Change of bilirubin photoisomers in the urine and serum before and after phototherapy compared with light source.

BACKGROUND: The clinical effect of phototherapy for neonatal hyperbilirubinemia is based on the production and elimination of cyclobilirubin. Generally, the clinical effect of light sources is estimated by the reduction in the total serum bilirubin level. One procedure with less invasiveness than blood collecting is urine collection. Whether the effectiveness of light sources used for phototherapy could be assessed using measurements of bilirubin photoisomers in urine was studied. METHODS: This study was a retrospective analysis of 38 term infants with hyperbilirubinemia who underwent phototherapy. Bilirubin fractions in serum and urine before and 24 h after the phototherapy were measured by high-performance liquid chromatography. The light sources used for the phototherapy were blue-white light (n = 11), Biliblanket plus high output (n = 13) or green light (n = 14). The relationships between serum and urine bilirubin photoisomers after phototherapy and whether the levels of urine bilirubin photoisomer are affected by the light sources with different wavelength characteristic were analyzed. RESULTS: There was no correlation between serum (ZE)-bilirubin and urine configurational isomers, but a weak positive correlation between serum (EZ)-cyclobilirubin and urine structural isomers after phototherapy. Although serum (ZE)-bilirubin levels depended on the wavelength characteristic of each light source during phototherapy, the urine configurational isomer levels did not depend on it. The increase in serum (EZ)-cyclobilirubin levels and the urine structural isomer levels were mostly in agreement. CONCLUSIONS: The urine bilirubin structural isomers may be used to estimate the serum (EZ)-cyclobilirubin levels and to evaluate the clinical effects of light sources.