High levels of unbound bilirubin are associated with acute bilirubin encephalopathy in post-exchange transfusion neonates

Background Although it is known that unbound bilirubin can enter the brain, there is little evidence of its association with the development of acute bilirubin encephalopathy. Here, we investigated this potential relationship in neonates who had undergone exchange transfusion. Methods Data from 46 newborns who underwent exchange transfusion between 2016 and 1-1 to 2018-12-31 at the First People’s Hospital of Changde City in China were analyzed. The unbound bilirubin level was taken as the independent variable and the development of the acute bilirubin encephalopathy as the dependent variable. The covariates were age, birth weight, sex, red blood cell count, blood glucose, hemolytic disease, and whether the infant had received phototherapy. Results The mean age and gestational age of the neonates were 146.5 ± 86.9 h and 38.6 ± 1.3 weeks [38.7(34.6–41.1) weeks] old, respectively; 52.17% were male. Binary logistic regression analysis after adjustment for covariates showed a positive association between the levels of unbound bilirubin and the development of acute bilirubin encephalopathy (odds ratio = 1.41, 95% confidence intervals 1.05–1.91, P = < 0.05). Conclusion There is a significant association between unbound bilirubin levels and the development of acute bilirubin encephalopathy in neonates. Further investigations are required to explore the mechanisms.

Neonatal Jaundice in Preterm Infants with Bilirubin Encephalopathy

Introduction: The aim of this study is to clarify bilirubin parameters and its treatment in preterm infants with bilirubin encephalopathy (pBE). Methods: We asked the responders to an earlier nationwide Japanese survey on pBE to provide additional information. pBE was diagnosed based on the criteria used in the nationwide survey. We collected data on serum total bilirubin (TB), direct bilirubin (DB), albumin, and unbound bilirubin (UB) levels during the first 8 weeks of life, and on phototherapy and exchange transfusion treatments. Results: We obtained clinical data from 75 patients with pBE from 58 hospitals (response rate of 59%), who were born between 2002 and 2016. The average peak TB level was 12.6 mg/dL (215 μmol/L), and the average age at peak attainment was 19.7 days after birth. Albumin level was <2.5 g/dL in 44 patients, and the peak DB level was ≥2 mg/dL (34.2 μmol/L) in 20 patients. The average peak bilirubin/albumin (B/A) (mg/g) ratio was 3.8 (molar ratio of 0.475), and the average age at peak attainment was 18.6 days. The average peak UB level was 0.67 μg/dL (11.5 nmol/L). The median duration of phototherapy was 6 days, and the median day of the last session was 12. The peak TB level occurred after the last day of phototherapy in 30 of the 61 patients available for comparison. Conclusions: Most patients with pBE lacked marked elevations in serum TB levels and the B/A ratio, the peaks of which were sometimes delayed to >4 weeks after birth.

Relationship Between Unbound Bilirubin Levels and Acute Bilirubin Encephalopathy in Exchange Transfusion Neonates

BACKGROUND: Evidence regarding the relationship between unbound bilirubin levels and acute bilirubin encephalopathy was limited. Therefore, this study set out to investigate whether the unbound bilirubin level was independently related to acute bilirubin encephalopathy in children who underwent exchange transfusion after adjusting for other covariates. METHODS: A total of 46 neonates who underwent exchange transfusion were involved in The First People's Hospital Of Changde City in China from 2016-1-1 to 2018-12-31. The target independent variable and the dependent variable were unbound bilirubin levels measured at baseline and acute bilirubin encephalopathy respectively. Covariates involved in this study included sex, age, birth weight, blood glucose, red blood cell, hemolysis, receive phototherapy before exchange transfusion. RESULTS: The average gestational age of 46 selected participants was 38.6 ± 1.3 weeks old, the average age was 146.5 ± 86.9 hours old, 52.17% of them were male. Result of fully-adjusted binary logistic regression showed unbound bilirubin levels were positively associated with risk of acute bilirubin encephalopathy after adjusting confounders (Odds ratio = 1.41, 95% confidence intervals 1.05-1.91, P value <0.05). CONCLUSION: Unbound bilirubin levels are associated with neonatal acute bilirubin encephalopathy. The mechanism of unbound bilirubin levels leading to neonatal acute bilirubin encephalopathy needs to be further explored.

A Novel Method for Measuring Serum Unbound Bilirubin Levels Using Glucose Oxidase–Peroxidase and Bilirubin-Inducible Fluorescent Protein (UnaG): No Influence of Direct Bilirubin

The glucose oxidase–peroxidase (GOD–POD) method used to measure serum unbound bilirubin (UB) suffers from direct bilirubin (DB) interference. Using a bilirubin-inducible fluorescent protein from eel muscle (UnaG), a novel GOD–POD–UnaG method for measuring UB was developed. Newborn sera with an indirect bilirubin/albumin (iDB/A) molar ratio of <0.5 were classified into four groups of DB/total serum bilirubin (TB) ratios (<5%, 5–10%, 10–20%, and ≥20%), and the correlation between the UB levels and iDB/A ratio was examined. Linear regression analysis was performed to compare UB values from both methods with the iDB/A ratio from 38 sera samples with DB/TB ratio <5% and 11 samples with DB/TB ratio ≥5%. The correlation coefficient (r) between UB values and the iDB/A ratio for the GOD–POD method was 0.8096 (DB/TB ratio <5%, n = 239), 0.7265 (5–10%, n = 29), 0.7165 (10–20%, n = 17), and 0.4816 (≥20%, n = 16). UB values using the GOD–POD–UnaG method highly correlated with the iDB/A ratio in both <5% and ≥5% DB/TB ratio sera (r = 0.887 and 0.806, respectively), whereas a low correlation (r = 0.428) occurred for ≥5% DB/TB ratio sera using the GOD–POD method. Our GOD–POD–UnaG method can measure UB levels regardless of the presence of DB.