Gene Therapy in Patients with the Crigler-Najjar Syndrome.

BACKGROUND: Patients with the Crigler-Najjar syndrome lack the enzyme uridine diphosphoglucuronate glucuronosyltransferase 1A1 (UGT1A1), the absence of which leads to severe unconjugated hyperbilirubinemia that can cause irreversible neurologic injury and death. Prolonged, daily phototherapy partially controls the jaundice, but the only definitive cure is liver transplantation. METHODS: We report the results of the dose-escalation portion of a phase 1-2 study evaluating the safety and efficacy of a single intravenous infusion of an adeno-associated virus serotype 8 vector encoding UGT1A1 in patients with the Crigler-Najjar syndrome that was being treated with phototherapy. Five patients received a single infusion of the gene construct (GNT0003): two received 2×1012 vector genomes (vg) per kilogram of body weight, and three received 5×1012 vg per kilogram. The primary end points were measures of safety and efficacy; efficacy was defined as a serum bilirubin level of 300 µmol per liter or lower measured at 17 weeks, 1 week after discontinuation of phototherapy. RESULTS: No serious adverse events were reported. The most common adverse events were headache and alterations in liver-enzyme levels. Alanine aminotransferase increased to levels above the upper limit of the normal range in four patients, a finding potentially related to an immune response against the infused vector; these patients were treated with a course of glucocorticoids. By week 16, serum bilirubin levels in patients who received the lower dose of GNT0003 exceeded 300 µmol per liter. The patients who received the higher dose had bilirubin levels below 300 µmol per liter in the absence of phototherapy at the end of follow-up (mean [±SD] baseline bilirubin level, 351±56 µmol per liter; mean level at the final follow-up visit [week 78 in two patients and week 80 in the other], 149±33 µmol per liter). CONCLUSIONS: No serious adverse events were reported in patients treated with the gene-therapy vector GNT0003 in this small study. Patients who received the higher dose had a decrease in bilirubin levels and were not receiving phototherapy at least 78 weeks after vector administration. (Funded by Genethon and others; ClinicalTrials.gov number, NCT03466463.).

Risk factors for readmission for hyperbilirubinemia in neonates with ABO hemolytic disease: a single-center retrospective cohort study.

OBJECTIVE: ABO hemolytic disease of the newborn (ABO-HDN) is a major risk factor for severe hyperbilirubinemia, a common readmission reason for newborns. In this study, we aimed to assess the risk factors for readmission associated with hyperbilirubinemia in neonates with ABO-HDN. METHODS: A retrospective cohort study was conducted including newborns with gestational age ≥35 weeks and ABO-HDN in 2018. Among 291 newborns, 36 were readmitted for hyperbilirubinemia and defined as the readmission group. The remaining 255 cases were used as a control group. We then performed between-group comparisons of clinical conditions associated with hyperbilirubinemia. Logistic regression was used to select risk predictors of readmission associated with hyperbilirubinemia due to ABO-HDN. RESULTS: Baseline characteristics were similar between both groups (p > .05, respectively). However, total serum bilirubin (TSB) before initiating phototherapy was significantly higher in the readmission group when compared with that in the control group at 0-24 h, 24-48 h, and 48-72 h (183.70 µmol/L [interquartile range (IQR) 161.18-196.48] vs. 150.35 µmol/L [IQR 131.73-175.38], p = .005; 229.90 µmol/L [IQR 212.45-284.30] vs. 212.50 µmol/L [IQR 197.85-230.28], p = .026; 268.10 µmol/L [IQR 257.70-279.05] vs. 249.50 µmol/L [IQR 236.80-268.70], p = .045, respectively). The age of initiation of phototherapy in the readmission group was significantly lower than that in control group (30.0 h [IQR 18.0-49.00] vs. 42.0 h [IQR 23.0-61.0], p = .012). The rate of rebound hyperbilirubinemia after the first phototherapy treatment was significantly higher in the readmission group compared to that in the control group (9 [25%] vs. 13 [5.1%], p = .000), and the rate of positive direct antiglobulin testing was significantly higher than that in control group (17 [47.2%] vs. 74 [29.0%], p = .027). Logistic regression analysis showed that the age of initiation of photography, TSB level before the first phototherapy, and rebound hyperbilirubinemia after first phototherapy were independent risk factors for readmission in newborns with hyperbilirubinemia associated with ABO-HDN. CONCLUSIONS: Earlier age of phototherapy initiation, higher TSB levels at the time of initiating phototherapy and rebound hyperbilirubinemia after the first phototherapy treatment may increase the risk of readmission for hyperbilirubinemia in neonates with ABO-HDN. These factors should be considered in discharge planning and follow-up for newborns with ABO-HDN associated hyperbilirubinemia.

Decreasing Bilirubin Serum Tests in Healthy Newborns During Birth Hospitalization.

OBJECTIVES: Substantial variability exists in hyperbilirubinemia screening and monitoring leading to unnecessary total serum bilirubin (TSB) testing in healthy newborns. We aimed to assess the impact of value-care interventions to decrease the monthly TSB testing rate per 100 patient-days among healthy newborns in our Mother-Baby Unit by 30% by June 2022. METHODS: We formed a multidisciplinary team to review the current practice for ordering TSB among housestaff in our Mother-Baby Unit. We identified several themes: variation in clinical practice, fear of hyperbilirubinemia, and desire to act for high-intermediate risk bilirubin levels. The interventions consisted of obtaining faculty buy-in, redesigning the hyperbilirubinemia pathway, educating staff on high value-care, producing an instructional video, and prompting staff to incorporate a bilirubin risk assessment via smart phrases in our electronic health record. The primary outcome was the monthly TSB testing rate per 100 patient-days. Universal predischarge bilirubin screening, length of stay, phototherapy rates, and readmission rates were chosen as balancing measures. RESULTS: The monthly rate of TSB testing was reduced from 51 to 26.3 TSB per 100 patient-days, representing a 48% reduction. This improvement was sustained for 12 months. The percentage of infants with at least 1 TSB measurement during birth hospitalization decreased from 48% to 30%. Predischarge bilirubin screening, length of stay, and readmission rates were unchanged. CONCLUSIONS: Our quality improvement initiative led to a significant reduction in the monthly TSB testing per 100 patient-days in healthy newborns without evidence of harm.

Rates of phototherapy among ABO-incompatible newborns with a negative direct antiglobulin test.

OBJECTIVE: We analyze phototherapy rates after implementation of a Hyperbilirubinemia Clinical Pathway (HCP), which placed full-term ABOi DAT negative newborns on the low risk phototherapy nomogram, rather than medium risk, as previously done. STUDY DESIGN: A chart review was performed for ABOi newborns born ≥36 weeks gestation between January 2020 and October 2021. Primary outcome measures were rates of phototherapy across pre- and post-intervention groups and among DAT negative newborns. RESULTS: There was an increased proportion of newborns assigned to the low risk curve after the intervention. There were no significant differences in phototherapy rates among the intervention groups, although there was a non-significant decrease in phototherapy rates among DAT negative newborns after the intervention. There were no increases in adverse outcomes. CONCLUSIONS: Providers adhered to the guidelines after implementation of the HCP. ABOi DAT negative newborns can be viewed as low risk for hyperbilirubinemia requiring phototherapy.

Evaluation of thiol-disulfide homeostasis and oxidative stress parameters in newborns receiving phototherapy.

The aim of our study was to evaluate oxidative stress and thiol-disulfide homeostasis in term newborns receiving phototherapy. The study was planned as a single-blind, intervention study in a single center with level 3 neonatal intensive care unit to investigate the effect of phototherapy on the oxidative system in term newborns with hyperbilirubinemia. Neonates with hyperbilirubinemia were treated with total body exposure phototherapy technique for 18 h using a Novos® device. Blood samples of 28 term newborns were taken before and after phototherapy. Total and native thiol, total antioxidant status (TAS) and total oxidant status (TOS), and oxidative stress index (OSI) levels were measured. The 28 newborn patients included 15 (54%) males and 13 (46%) females with a mean birthweight of 3080.1 ± 366.5 g. Native and total thiol levels were found to be decreased in patients receiving phototherapy (p = 0.021, p = 0.010). Besides, significantly lower TAS and TOS levels were found after phototherapy (p < 0.001, p < 0.001). We found that decreased thiol levels were related to increased oxidative stress. We also determined significantly the lower bilirubin levels after phototherapy (p < 0.001). In conclusion, we found that phototherapy treatment induced decreased oxidative stress associated with hyperbilirubinemia in neonates. Thiol-disulfide homeostasis can be used as a marker of oxidative stress due to hyperbilirubinemia in the early period.

Investigation of EEG changes before and after phototherapy in infants with severe hyperbilirubinemia.

BACKGROUND: Despite the known effect of hyperbilirubinemia in neonates, the effect of phototherapy on electroencephalography (EEG) remains unknown. Therefore, we aimed to determine the alteration of electroencephalography in infants with hyperbilirubinemia before and after phototherapy. METHODS: This cross-sectional study was performed on infants of≥35 weeks of gestation with hyperbilirubinemia. Information including age, sex, birth weight, hemoglobin levels, and treatment measures was recorded. In all studied infants, an EEG was performed before (in the first eight hours of hospitalization) and after treatment (after phototherapy or blood transfusion). The required duration of phototherapy, hospitalization and adverse effects were assessed then EEG of the neonates was compared before and after treatment. RESULTS: A total of 52 infants (44% female and 56% male) were included in this study. Mean gestational age, weight, and bilirubin were 38.6±1.53 weeks, 3150±625 g, and 23.87±4.36 mg/dl, respectively. The most common findings before phototherapy were Frontal Theta (21 patients, 40.4 percent) and Delta Brush (14 patients, 26.9%), while the most common findings after phototherapy were Frontal Theta (20 patients, 38.5%) and Delta Brush (19 patients, 36.5%). Mean±SD of bilirubin in infants with and without Delta Brush was 21.30±1.67 mg/dl and 19.95±0.94 mg/dl, respectively. CONCLUSIONS: Hyperbilirubinemia in newborns may be linked to altered EEG findings. After phototherapy, the Frontal theta was reduced, but the Delta brush was intensified. Bilirubin levels were higher in infants with Delta Brush in their EEG compared to infants without this finding.

Validation of an instrument for the evaluation of exchange transfusion (INEXTUS) via an OSCE.

INTRODUCTION: Exchange transfusion is the treatment of choice for patients with severe hyperbilirubinemia who do not respond to phototherapy. This procedure is highly complex and requires substantial expertise to perform, however it´s not done frequently enough to guarantee adequate training. Traditional learning scenarios do not have a space reserved for teaching this procedure or an instrument that fully and objectively evaluates the skills that a professional must acquire.  OBJECTIVES: The purpose was to construct and evaluate the INEXTUS instrument´s validity evidence relevant to internal structure, in a simulated scenario through the performance of an objective structured clinical exam (OSCE).  MATERIALS AND METHODS: The Delphi consensus methodology was utilized to design the instrument; six experts participated through three rounds using the Google Forms platform. The categories and items previously obtained were subjected to validation by nine experts through a dichotomous survey. Prior to data collection, the evaluators were trained through a pilot test with 10 medical students. Subsequently, all residents of a paediatric programme were evaluated through the OSCE methodology in a simulated scenario, with 6 stations, of a clinical case of a new-born with an explicit need for exchange transfusion. During their participation in the scenario, the residents were first evaluated with the instrument developed. Additionally, audio and video filming of all students who participated was performed with the aim of conducting a second evaluation two weeks after the first four evaluators participated. RESULTS: The final INEXTUS instrument consists of 46 subitems grouped into 23 items divided into 6 categories, demonstrating an inter-rater intraclass correlation coefficient of 0.96 (95% CI 0.94, 0.98 p-value < 0.001). For the Fleiss Kappa of the 23 items evaluated, concordance was evaluated for 14 items but could not be determined for the 9 remaining items because all the ratings were equal, either because the items were not performed or they were all performed adequately. Of the 14 items, 9 good scores were obtained (95% CI 0.61 to 0.8; p value < 0.001), and 5 very good scores were obtained (95% CI 0.81 to 1; p value < 0.001). CONCLUSIONS: The INEXTUS instrument evaluates exchange transfusion skills in medical personnel in training in simulated scenarios using the OSCE methodology; it has high validity and reliability and is a high-impact educational tool.

Eosinophil count and tumor necrosis factor α in response to phototherapy treatment of neonatal hyperbilirubinemia: a cross sectional study.

BACKGROUND: Phototherapy (PT) is the most often utilized technique for treating and preventing severe hyperbilirubinemia in the term and preterm newborns. PT's proven benefit is that it decreases the requirement for exchange transfusions. To investigate the effect of PT on allergic response mediators in neonates with hyperbilirubinemia treated by PT, eosinophil counts and tumor necrosis factor alfa levels have been assessed. METHODS: This cross-sectional study included 100 full-term infants with indirect hyperbilirubinemia in the first two weeks of life who were indicated for PT. They were investigated by tumor necrosis factor α and eosinophil counts before and 72 h after starting PT. The used tests were paired with Student's t-test and Pearson coefficient. RESULTS: Relative and absolute eosinophil counts and tumor necrosis factor alfa were significantly higher after PT than before (p < 0.001). There was a significant positive correlation between total serum bilirubin and both tumor necrosis factor alfa and eosinophil % (r = 0.442 and r = 0.362, respectively, P < 0.001) before PT. There was a significant positive correlation between total serum bilirubin and both eosinophil count and eosinophil % (r = 0.281and r = 0.339), respectively (P < 0.001) after PT. There was a significant positive correlation between both tumor necrosis factor alfa and eosinophil % after PT (r = 0.545, P < 0.001). CONCLUSIONS: Serum tumor necrosis factor-alpha and eosinophilic count increased after treatment of neonatal hyperbilirubinemia by PT, which indicates an allergic response to PT in neonates.

A 12-Day-Old Female with Hypothermia, Hypoglycemia and Hyperbilirubinemia.

A 12-day-old, full-term female, born small for gestational age, presented to the emergency department with a 1-week history of worsening hyperbilirubinemia, intermittent hypoglycemia, and episodic hypothermia. The baby's emergency department evaluation revealed transaminitis, pneumatosis intestinalis, indirect hyperbilirubinemia, and hypoglycemia. She was admitted to the ICU and received intravenous glucose, bowel rest, and phototherapy. Thyroid-stimulating hormone, thyroxine, and cortisol levels were low, and growth hormone was undetectable. The patient was hospitalized for a total of 19 days and was discharged from the hospital.

Intravenous Fluid Supplementation for Preterm Infants With Hyperbilirubinemia: A Retrospective Cohort Study.

BACKGROUND: Hyperbilirubinemia is one of the most frequently occurring problems in the neonatal period, and phototherapy has remained the primary treatment of choice. Fluid supplementation has been proposed to reduce serum bilirubin levels. PURPOSE: To assess the risks and benefits of fluid supplementation compared with standard fluid management in preterm infants with unconjugated hyperbilirubinemia under conventional phototherapy. METHODS: A retrospective cohort study of preterm infants (gestational ages ≥28 to ≤32 weeks) admitted to the neonatal intensive care unit at the Maternity and Children Hospital in Jeddah, Saudi Arabia, from January 1, 2017, to December 31, 2017, and required the initiation of phototherapy in the first week of life. RESULTS: One hundred and fifteen infants were included; 51 received fluid supplementation, and 64 received standard fluid management. There were no significant differences in demographic characteristics between groups. The infants who received fluid supplementation had a significantly larger decline in the total serum bilirubin level per day and a shorter phototherapy duration ( P < .01). There were no significant differences in weight ( P = .14), or sodium ( P = .79) change per day or the need for exchange transfusion between groups. The prematurity-related inhospital morbidities were similar between groups. IMPLICATIONS FOR PRACTICE AND RESEARCH: Fluid supplementation in preterm infants receiving conventional phototherapy resulted in a faster decline in the bilirubin level and a shorter duration of phototherapy, without increasing prematurity-related morbidities. Future randomized controlled trials to assess the benefits and risks of fluid supplementation during conventional phototherapy in preterm infants are needed.

Stannsoporfin with phototherapy to treat hyperbilirubinemia in newborn hemolytic disease.

OBJECTIVE: To evaluate the efficacy and safety of tin mesoporphyrin (SnMP) in neonates with hyperbilirubinemia (HB) due to hemolysis. STUDY DESIGN: This multicenter, placebo-controlled phase 2b study (NCT01887327) randomized newborns (35-42 weeks) with hemolysis started on phototherapy (PT) to placebo (Ctrl), SnMP 3.0 mg/kg, or SnMP 4.5 mg/kg given once IM within 30 min of initiation of PT. RESULTS: In all, 91 patients were randomized (Ctrl: n = 30; 3 mg/kg SnMP: n = 30; 4.5 mg/kg SnMP: n = 31). At 48 h TSB significantly increased in Ctrl by 17.5% (95% CI 5.6-30.7; p = 0.004) and significantly decreased by -13% (95% CI -21.7 to -3.2; p = 0.013) in the 3.0 mg/kg and by -10.5% (95% CI -19.4 to -0.6; p = 0.041) in the 4.5 mg/kg group. Decreases in SnMP groups were significant (p < 0.0001) vs Ctrl. CONCLUSION: SnMP with PT significantly reduced TSB by 48 h. SnMP may be useful as a treatment for HB in neonates with hemolysis.

Treatment practices and implementation of guidelines for hyperbilirubinemia and rebound hyperbilirubinemia.

BACKGROUND: Hyperbilirubinemia (HB), defined as elevated total serum bilirubin (TSB) levels, commonly affects neonates and requires prompt treatment to prevent neurological complications. Up to 10%of neonates experience rebound hyperbilirubinemia (RHB), requiring re-initiation of treatment. Unfortunately, treatment guidelines lack practical recommendations surrounding subthreshold phototherapy, treatment termination, and RHB investigations. We examined local management practices for HB and RHB treatment in a well newborn nursery. As a secondary aim, we investigated the association between treatment practices and RHB rates. METHODS: Retrospective chart review identified neonates treated for hyperbilirubinemia between January 2015 and December 2019 during their birth hospitalization at a tertiary care centre. Standardized data collection sheets were used to record treatment parameters. RESULTS: Over the 5-year period, there were 9683 births and 305 (3.15%) neonates received phototherapy. Of the treated cases, 20-25%were subthreshold to practice guideline values. Upon treatment termination 25-55%of cases had TSB levels within 3 mg/dL, which may increase the risk of RHB. In our cohort, 20.3%of treated cases experienced one episode of RHB and 3.9%experienced two episodes of RHB. Although clinicians evaluated neonates for RHB 0-12 hours following treatment termination prior to discharge, many cases were identified in outpatient settings and required re-admission for phototherapy. CONCLUSION: When managing HB and RHB, treatment practices such as when to terminate treatment in relation to threshold values, and timing of RHB investigations, are largely inconsistent amongst clinicians. Future studies are required to better understand the landscape of hyperbilirubinemia treatment beyond initiation of phototherapy.

Effects of Placental Transfusion on Late Preterm Infants Admitted to a Mother-Baby Unit.

OBJECTIVE: Well-appearing late preterm infants admitted to a mother baby unit may benefit from either delayed cord clamping (DCC) or umbilical cord milking (UCM). However, there are concerns of adverse effects of increased blood volume such as polycythemia and hyperbilirubinemia. The purpose of this study is to examine the short-term effects of placental transfusion on late preterm infants born between 350/7 and 366/7 weeks of gestation. STUDY DESIGN: In this pre- and postimplementation retrospective cohort study, we compared late preterm infants who received placental transfusion (161 infants, DCC/UCM group) during a 2-year period after guideline implementation (postimplementation period: August 1, 2017, to July 31, 2019) to infants who had immediate cord clamping (118 infants, ICC group) born during a 2-year period before implementation (preimplementation period: August 1, 2015, to July 31, 2017). RESULTS: The mean hematocrit after birth was significantly higher in the DCC/UCM group. Fewer infants had a hematocrit <40% after birth in the DCC/UCM group compared with the ICC group. The incidence of hyperbilirubinemia needing phototherapy, neonatal intensive care unit (NICU) admissions, or readmissions to the hospital for phototherapy was similar between the groups. Fewer infants in the DCC/UCM group were admitted to the NICU primarily for respiratory distress. Symptomatic polycythemia did not occur in either group. Median hospital length of stay was 3 days for both groups. CONCLUSION: Placental transfusion (DCC or UCM) in late preterm infants admitted to a mother baby unit was not associated with increased incidence of hyperbilirubinemia needing phototherapy, symptomatic polycythemia, NICU admissions, or readmissions to the hospital for phototherapy. KEY POINTS: · Placental transfusion was feasible in late preterm infants.. · Placental transfusion resulted in higher mean hematocrit after birth.. · Placental transfusion did not increase the need for phototherapy.. · Fewer admissions to the NICU for respiratory distress were noted in the placental transfusion group..

Trends in hospitalizations of newborns with hyperbilirubinemia and kernicterus in United States: an epidemiological study.

BACKGROUND: Hyperbilirubinemia is one of the most common diagnosis in newborn nurseries in United States. Universal pre-discharge bilirubin screening decreased the incidence of extreme hyperbilirubinemia and risk of kernicterus. OBJECTIVES: We sought to assess temporal population trends of hyperbilirubinemia, kernicterus and usage of phototherapy, intravenous immunoglobulin (IVIG), and exchange transfusion. DESIGN/METHODS: Data from Healthcare Cost and Utilization Project (HCUP)-the Kids' Inpatient Database (KID) obtained for years 1997-2012. All neonatal discharges with ICD-9 codes for neonatal jaundice (774.2, 774.6), kernicterus (773.4, 774.7) and procedure codes for phototherapy (99.83), IVIG infusion (99.14), exchange transfusion (99.01) were extracted. We compared the trends of diagnosis of hyperbilirubinemia, kernicterus, use of phototherapy, IVIG, and exchange transfusion. RESULTS: During the study period, the proportion of infants diagnosed with hyperbilirubinemia increased by 65% (9.4% vs. 15.5%; p<.001) in term infants and 34.5% (33.5% vs. 45%; p<.001) in preterm infants, respectively. Rate of kernicterus discharges significantly reduced from 7 to 1.9 per 100,000 newborns. Overall, the number of exchange transfusions has decreased by 67% during study period while phototherapy and IVIG use increased by 83% and 170%, respectively. CONCLUSIONS: In last two decades, there was a significant decrease in neonatal discharges with a history of exchange transfusion or with a diagnosis of kernicterus. However, there was a significant increase in number of neonates discharged home with a history of phototherapy during birth hospitalization and decreased number of exchange transfusions were observed during the study period. Incremental implementation of universal predischarge bilirubin screening and treatments based on 2004 AAP recommended risk-based strategies might have contributed to timely interventions in infants with significant hyperbilirubinemia.

Medial olivary complex reflex in term newborns with hyperbilirubinemia.

OBJECTIVE: This study aimed to compare the integrity of the efferent auditory pathways of newborns that had high hyperbilirubinemia levels and required treatment due to these and healthy newborns. METHODS: Term-born (37 weeks or later) infants that were brought to the Newborn Polyclinic of the Baskent University Hospital were included in the study. The study included a total of 84 infants including healthy newborns (n = 42) and those that had jaundice and were receiving phototherapy (n = 42). After conducting a general otorhinolaryngology examination on all newborns included in the study, Transient Otoacoustic Emission (TEOAE) test was carried out in the absence and presence of contralateral noise. The obtained contralateral suppression values were compared between the two groups. RESULTS: In the TEOAE test, the responses obtained at 1 kHz in the newborns receiving phototherapy were found to be lower. The difference between the groups was significant (p = 0.038). The rates of suppression presence at 2 kHz, 2.8 kHz and total OAE were found significantly higher (p < 0.05) in the group not receiving phototherapy. Among the phototherapy-receiving infants, the hyperbilirubinemia levels of the infants in whom suppression was obtained in the contralateral suppression test did not show a statistically significant difference in comparison to those in whom suppression was not obtained (p > 0.05). CONCLUSION: Based on the obtained data, hyperbilirubinemia may have a disruptive effect on the efferent auditory system in newborns. Consequently, we are of the opinion that, in addition to hearing screening in risky newborn infants, a MOC suppression test would be useful.

Successful Treatment of Hyperbilirubinemia by Monitoring Serum Unbound Bilirubin in an Extremely Preterm Infant with Bacterial Infection.

BACKGROUND: Bacterial infections and some antibiotics show displacer effects on bilirubin-albumin binding and increase unbound bilirubin (UB) but not total bilirubin (TB) in serum. METHODS: A case study was conducted to show a successful treatment of hyperbilirubinemia by monitoring UB. RESULTS: In an extremely preterm infant with bloodstream bacterial infection caused by methicillin-resistant coagulase-negative staphylococci, 2 days after high-dose ampicillin and regular-dose amikacin were initiated, UB markedly increased, but TB did not. After vancomycin was substituted, UB decreased immediately with phototherapy and intravenous albumin infusion. CONCLUSIONS: When using antibiotics, the clinicians should be mindful regarding the displacer effect on bilirubin-albumin binding.