Nonhemolytic Hyperbilirubinemia Research Articles

Effect of hyperbilirubinemia and phototherapy on apoptotic microparticle levels in neonates.

We aimed to evaluate the effect of hyperbilirubinemia and phototherapy on total apoptotic, platelet-derived, endothelial-derived, and tissue factor (TF)-positive apoptotic microparticle (MP) levels in neonates with nonhemolytic pathologic hyperbilirubinemia. Thirty-three term neonates with nonhemolytic pathologic hyperbilirubinemia and 25 healthy term neonates were included. MP levels were analyzed by flow cytometry using peripheral blood samples only once for the neonates in the control group and twice for the neonates in the study group (before and after phototherapy). Annexin V-positive MPs were defined as apoptotic MPs. Platelet-derived MPs were defined as those containing CD31. MPs containing CD144 were defined as endothelial-derived MPs, and MPs expressing TF were identified as those containing CD142. The rates of total apoptotic and endothelial-derived apoptotic MPs were significantly higher in the study group than the control group before phototherapy (P = 0.012 and P = 0.003, respectively) and after phototherapy (P = 0.046 and P = 0.001, respectively). Total apoptotic, platelet-derived, endothelial-derived, and TF-positive apoptotic MPs did not show any significant differences before and after phototherapy in the study group (P = 0.908, P = 0.823, P = 0.748, and P = 0.437, respectively). Our study demonstrated that total apoptotic and endothelial-derived apoptotic MPs are increased in cases of nonhemolytic pathologic hyperbilirubinemia. We showed that phototherapy does not have a significant effect on apoptotic MP levels. Further studies are needed to evaluate the risk of elevated apoptotic MPs on the development of thromboembolism in neonates with nonhemolytic pathologic hyperbilirubinemia.

End-tidal carbon monoxide concentrations measured within 48 hours of birth predict hemolytic hyperbilirubinemia.

To determine, among neonates at-risk for hyperbilirubinemia, whether measuring end-tidal carbon monoxide concentration (ETCOc) twice before 48 hours could identify those who would develop hyperbilirubinemia and differentiate hemolytic vs. non-hemolytic causes. Prospective study on neonates meeting criteria "at-risk for hyperbilirubinemia." Routine bilirubin measurements and 10-day follow-up were used to categorize neonates as; (1) normal (no hyperbilirubinemia, all bilirubins <95th percentile of Bhutani nomogram), (2) having hemolytic hyperbilirubinemia (bilirubin ≥95th percentile, DAT+, elevated retic, or G6PD+), or (3) having non-hemolytic hyperbilirubinemia. 386 neonates were enrolled. 321 (83%) did not develop hyperbilirubinemia and 65 (17%) did, of which 29 were judged hemolytic and 36 non-hemolytic. High ETCOc differentiated the hemolytic group (p < 0.001). First-day ETCOc correlated with bilirubin and with reticulocyte count (r = 0.896 and 0.878) and sensitivity and specificity for predicting hyperbilirubinemia were excellent (83% and 95%). ETCO measurement in the first 48 hours after birth predicts hemolytic hyperbilirubinemia.

Analysis of the maternal and fetal adverse outcomes of 154 pregnant women with cesarean section in the second stage of labor

Objective: To investigate the perinatal maternal and fetal adverse outcomes of cesarean section in the different duration of the second stage of labor. Methods: A retrospective cohort study was conducted on the clinical data of 154 pregnant women with singleton head pregnancy who underwent cesarean section at different times of the second stage of labor due to maternal and fetal factors in the First Affiliated Hospital of Nanjing Medical University from January 1, 2019 to December 31, 2021. According to the duration of the second stage of labor, they were divided into <2 h group (54 cases), 2-<3 h group (61 cases), and ≥3 h group (39 cases). The general data of pregnant women and neonates, preoperative maternal and neonatal conditions related to labor stages, surgical indications, surgical procedures, and perioperative maternal and neonatal adverse outcomes were compared among the three groups. Results: (1) General Information: there were no significant differences in maternal age, gravidity and parity, proportion of primipara, gestational age at delivery, body mass index before delivery, pregnancy complications, labor analgesia rate and the duration of the first stage of labor among the three groups (all P>0.05). The differences of the gender composition, birth weight and incidence of macrosomia of the three groups were also not statistically significant (all P>0.05). (2) Maternal and fetal status and surgical indications: the incidence of intrapartum fever and type Ⅱ and Ⅲ fetal heart rate monitoring in the <2 h group were higher than those in the 2-<3 h group and the ≥3 h group, and the preoperative fetal head position in the ≥3 h group was lower than that in the 2-<3 h group, with statistically significant differences (all P<0.05). The proportion of cesarean section due to "fetal distress" was 40.7% (22/54) in the <2 h group, which was higher than that in the 2-<3 h group (4.9%, 3/61) and the ≥3 h group (2.6%, 1/39). The proportions of surgical indication of "relative cephalo-pelvic disproportion" were 98.4% (60/61) and 94.9% (37/39) in the 2-<3 h group and ≥3 h group, respectively, and the surgical indication of "fetal head descent arrest" were 41.0% (25/61) and 59.0% (23/39), respectively. Compared with <2 h group [63.0% (34/54), 13.0% (7/54)], the differences were statistically significant (all P<0.05). There were no significant difference in surgical indications between 2-<3 h group and ≥3 h group (all P>0.05). (3) Intraoperative conditions and perioperative complications of cesarean section: the puerperal morbidity rate of <2 h group was 37.0% (20/54), which was higher than those of 2-<3 h group (18.0%, 11/61) and ≥3 h group (7.7%, 3/39), the difference was statistically significant (P<0.05). There were no significant differences in operation time, intraoperative blood loss, incidence of fetal head inlay, uterine incision tear, modified B-Lynch suture for uterine atony, postpartum hemorrhage, perioperative blood transfusion, preoperative hemoglobin (Hb) level, perioperative Hb change, and postoperative hospital stay among the three groups (all P>0.05). (4) Adverse neonatal outcomes: non-hemolytic neonatal hyperbilirubinemia in ≥3 h group was 35.9% (14/39), which was significantly higher than that in <2 h group (13.0%, 7/54; P<0.05). Among the neonates admitted to neonatal intensive care unit (NICU) within 1 week after birth, the proportion of neonates admitted to NICU due to neonatal hyperbilirubinemia in ≥3 h group (15/19) was significantly higher than that in <2 h group (9/17) and 2-<3 h group (10/19), and the differences were statistically significant (all P<0.05). However, there was no significant difference between the <2 h group and the 2-<3 h group (P>0.05). There was no perinatal death in the three groups. Conclusions: The rate of puerperal morbidity is higher in patients who were transferred to cesarean section within 2 hours of the second stage of labor. In the early stage of the second stage of labor, the monitoring of fetal heart rate and amniotic fluid characteristics should be strengthened, especially the presence or absence of prenatal fever. In good maternal and neonatal conditions, conversion to cesarean section after 2 hours of the second stage of labor does not significantly increase the incidence of serious adverse maternal and neonatal outcomes. For the second stage of labor more than 3 hours before cesarean section, it is necessary to strengthen the monitoring of neonatal bilirubin.

Intermittent versus continuous phototherapy among term infants presenting with non-hemolytic moderate hyperbilirubinemia at a tertiary care hospital: a randomized controlled trial.

Objective: To compare the effectiveness of intermittent versus continuous phototherapy among term infants presenting with non-hemolytic moderate hyperbilirubinemia at a tertiary care hospital. Study Design: Single Center, Open Label, Prospective Randomized Controlled Trial. Setting: Department of Neonatology, Sir Sadiq Abbasi Hospital, Bahawalpur, Pakistan. Period: January 2022 to December 2022. Material &amp; Methods: A total of 38 neonates having maternal age between 18-35 years and gestational age at the time birth above or equal to 37 weeks presenting and admitted with non-haemolytic hyperbilirubinemia were included. These neonates (19 in each group) were randomized adopting lottery method to either continuous phototherapy group (CPT) or intermittent phototherapy group (IPT). At the time of enrollment, demographic characteristics like age (days), gender, birth weight (kg), mode of delivery, gestational age (weeks), maternal age (years), total serum bilirubin (mg/dl) in the neonates were noted. Total serum bilirubin levels were recorded after 24 hours of phototherapy. Results: In a total of 38 neonates, 20 (52.6%) were boys. The mean age was calculated to be 3.3±1.8 days. Mode of delivery was cesarean section in 24 (63.2%) neonates. The mean total serum bilirubin levels at baseline was recorded to be 15.5±1.7 mg/dl while comparison of baseline total serum bilirubin levels were not statistically significant different between both study groups (p=0.3715). The mean serum bilirubin levels after 24-hours were recorded to be 11.3±0.9 mg/dl in CPT group versus 11.0±1.1 mg/dl while the difference was noted to be statistically insignificant. (p=0.3637). Conclusion: The intermittent phototherapy yielded relatively similar reduction in total serum bilirubin when compared to continuous phototherapy among neonates with non-haemolytic moderate hyperbilirubinemia.

Liver Transplantation in a Patient with Crigler-Najjar Syndrome Type 1: A Case Report of Two Cases

Crigler Najjar syndrome(CNS); is a disease in which the diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme function, which plays a role in the glucuronidation of bilirubin, is deficient as a result of mutation in the uridine 5'-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene.1 As a result, non-hemolytic unconjugated hyperbilirubinemia is seen. Orthotopic liver transplantation (OLT) is seen as a curative treatment option in Crigler Najjar syndrome type 1 (CNS1). In this case report, we present our patients who were 11 months old and 8 years old with a diagnosis of CNS1, whose bilirubin levels were controlled by preoperative daily phototherapy and plasmapheresis, and who had OLT from their parents to two siblings. We wanted to show the importance of a close follow-up and multidisciplinary treatment approach in the early period before OLT in CNS1 patients and thus the benefit to the patient's prognosis in the postoperative period.

Isolated unconjugated hyperbilirubinemia in adults: the Gilbert’s versus Criggler Najar Syndrome Type 2 conundrum.

Gilbert’s syndrome is a genetic disorder characterised by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase-1, which conjugates bilirubin for excretion. Affected individuals are usually asymptomatic apart from a mild jaundice and investigations reveal a mild isolated indirect hyperbilirubinemia. This may be exacerbated in the face of environmental and physical stressors. It is very similar in presentation to Criggler-Najjar syndrome (CNS) type 2. There is a small risk of kernicterus in patients with CNS type 2 needing daily phenobarbitone therapy. This risk is miniscule in Gilbert’s syndrome. Genetic testing for polymorphisms of the UGT1A1 gene is the diagnostic clincher for Gilbert’s syndrome, but it can also be picked up by evaluating the response to phenobarbitone and fasting, particularly in resource poor settings. Due to limited availability, case reports documenting the genetic mutational analysis are sparse. We reported one such rare case with an unusually high indirect hyperbilirubinemia in Gilbert’s syndrome confirmed by both phenobarbitone response and genetic analysis.

Effect of ursodeoxycholic acid on indirect hyperbilirubinemia (nonhaemolytic and haemolytic) in neonates treated with phototherapy

Background Hyperbilirubinemia is a global problem in neonates. Classic management for indirect neonatal hyperbilirubinemia includes phototherapy and exchange transfusion. Phototherapy shows disadvantages, and exchange transfusion is related to significant morbidity. Aim To assess the added role of ursodeoxycholic acid (UDCA) in reducing unconjugated hyperbilirubinemia in neonates undergoing phototherapy. Patients and methods Our randomized controlled trial was performed on neonates with hyperbilirubinemia who needed phototherapy and were admitted to the neonatal care unit at Tanta University Hospital from May 2017 to March 2019. A total of 120 neonates were randomly divided into four groups: group A (n=30), which included neonates with nonhemolytic indirect hyperbilirubinemia who received UDCA 10 mg/kg/day beside the usual phototherapy; group B (n=30), which included neonates with isoimmune hemolytic indirect hyperbilirubinemia who received UDCA 10 mg/kg/day, besides the usual phototherapy; group C (n=30), which included neonates with nonhemolytic indirect hyperbilirubinemia who received phototherapy only; and group D (n=30), which included neonates with isoimmune hemolytic indirect hyperbilirubinemia who received phototherapy only. The total serum bilirubin (TSB) was determined every 24 h till being less than 10 mg/dl. Results TSB was significantly decreased in group A compared with group C (P&lt;0.05). However, TSB was comparable in groups B and D (P&gt;0.05). Duration of phototherapy was significantly shorter in groups A and B compared with groups C and D (P&lt;0.05). Conclusion UDCA shows a beneficial added role in the treatment of neonatal indirect hyperbilirubinemia, particularly in the nonhemolytic type.

Comparison of Intermittent vs. Continuous Phototherapy in the treatment of Non-Haemolytic Neonatal Hyperbilirubinemia

Introduction: Phototherapy is used in the treatment of hyperbilirubinemia in initial life-span of neonates. Our objective was the comparison of continuous vs intermittent phototherapy in the reduction of total serum bilirubin, bilirubin decrease rate, phototherapy time and hospital stay in non-haemolytic hyperbilirubinemia neonates. Place and Duration: The study was conducted at department of Pediatric medicine in Qazi Hussain Ahmad Medical Complex, Nowshera for the duration of six months from 16th January 2021 to 15th July 2021. Methods: The study involved 160 neonates with birth weight ≥2000 gm and age was above 34 weeks. They were randomly assigned to group A who were given continuous phototherapy for 3hrs and 50 mints and then rest for 45mints and group B who were given intermittent phototherapy for 3 hours and then rest for next 3 hours and so on. The levels of TSB were calculated in both groups and their comparison was made at every 12, 24 and 48 hrs after the start of phototherapy. Results: The mean of total serum bilirubin on admission was 16.01 ± 3.91 mg / dL for the continuous group and 15.21 ± 1.12 mg / dL for the intermittent group. The TSB mean after 12, 24 and 48 hrs. for continuous phototherapy was 13.30 ± 2.3 mg / dl, 11.1 ± 2.01 mg / dl, 9.26 ± 0.92 mg / dl and 13.1 ± 1.70 mg / dL, 9.54 ± 1.7 mg / dL, 8.9 ± 0.61 mg / dl (p &lt;0.05) for the intermittent group, respectively. The mean rate of decrease in serum concentration of bilirubin was 0.30 ± 0.14 mg / dl / h in group A and 0.19 ± 0.07 mg / dl / h in group B (p = 0.5). There was no big variance between the mean hospital stay in groups A and B (p = 0.550). Conclusions: Intermittent phototherapy is a better choice than continuous phototherapy in the treatment of non-haemolytic hyperbilirubinemia, with added benefits such as less frequent disruption of the mother-child relationship and reduced radiation therapy. Keywords: Intermittent phototherapy; Continuous phototherapy; Total serum bilirubin and Neonatal hyperbilirubinemia.

Levitt’s CO breath test in the differential diagnosis of chronic isolated hyperbilirubinemia

A key component of the differential diagnosis of isolated hyperbilirubinemia (HB) is distinguishing between hemolytic and non-hemolytic types. Routine hemolysis screening markers have unsatisfactory sensitivity and specificity. Erythrocyte (RBC) lifespan shortening, the gold standard marker of hemolysis, is seldomly measured due to the cumbersome and protracted nature of standard methods. A new Levitt’s CO breath test method may enable simple, rapid RBC lifespan measurement. In this pilot prospective diagnostic study, Levitt’s CO breath test was evaluated to discriminate hemolytic from non-hemolytic HB in adults. One hundred and thirty eligible non-smoking adult patients who were aged 18 or older, referred for chronic (>6 months) isolated HB or had a known diagnosis of isolated HB of a rare cause, were recruited, including 77 with non-hemolytic HB and 53 with hemolytic HB. ROC curve analysis was applied to determine the optimal cutoff for discriminating between hemolytic and non-hemolytic HB, and the performance was calculated. Results showed that the mean RBC lifespan in non-hemolytic HB (93 ± 26 d) was reduced (p = 0.001 vs. normal reference value of 126 d), but longer than that in hemolytic HB (36 ± 17 d; p = 0.001). RBC lifespans did not differ significantly between 26 patients with simple hemolytic HB (32 ± 14 d) and 27 patients with a Gilbert syndrome comorbidity (40 ± 18 d). ROC curve analysis revealed an optimal lifespan cutoff for discriminating between hemolytic and non-hemolytic HB of 60 d (AUC = 0.982), with a diagnostic accuracy of 95.4%, 94.3% sensitivity and 96.1% specificity respectively. These results indicate that Levitt’s CO breath test seems to be very sensitive and specific for detecting hemolysis in adult patients with chronic isolated HB, and could enable simple, rapid, and reliable differential diagnosis of isolated HB. A large-scale validation study of the method is warranted.

Periodic change of body position under phototherapy in term and preterm neonates with hyperbilirubinaemia.

Phototherapy is the mainstay of treatment of neonatal hyperbilirubinaemia. Periodic change in position of the neonate under phototherapy (from supine to prone or lateral positions) may improve the efficiency of phototherapy by hastening the access of phototherapy light to bilirubin deposited in different parts of the skin and subcutaneous tissue. To evaluate the effects of periodic change of body position during phototherapy as compared to no prescribed change in body position, on serum total bilirubin level and duration of treatment in neonates with unconjugated hyperbilirubinaemia during the first 28 days of life. Secondary objectives of the review included evaluation of the efficacy of periodic change of body position on the need for or number of exchange transfusions, incidence of bilirubin-induced neurological damage (BIND), side effects of phototherapy, and sudden infant death syndrome (SIDS). We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 3) in the Cochrane Library and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions on 5 March 2021. We also searched clinical trials databases and the reference lists of included studies and relevant reviews for randomised controlled trials (RCTs) and quasi-RCTs. We included RCTs and quasi-RCTs if they enrolled neonates (term and preterm) of either gender with unconjugated hyperbilirubinaemia requiring phototherapy and compared periodic change of the body position of the infant under phototherapy with no prescribed change in body position. Two review authors independently assessed trial quality and extracted data, consulting with a third review author in the case of disagreement. We used standard Cochrane methodological procedures, including assessing the risk of bias of included studies. We used the GRADE approach to assess the certainty of evidence. Primary outcomes were the duration of phototherapy and rate of fall of serum bilirubin at 24 hours. Secondary outcomes included the need for exchange transfusion, number of exchange transfusions, incidence of BIND, and SIDS. We included five studies (343 neonates) with an overall high risk of bias in the review. The body position under phototherapy was changed every two hours or every two-and-a-half hours in two studies each, and every three hours in one study. Three of the five studiesincluded healthy term neonates, whilst the other two studies also included preterm neonates (≥ 33 weeks' gestation); however, separate data about review outcomes in preterm neonates were not available. Periodic change in body position may lead tolittle or no difference in the duration of phototherapy (mean difference (MD) 1.71 hours, 95% confidence interval (CI) -3.17 to 6.59 hours; I² = 58%; 4 studies, 231 participants; low certainty evidence). Only one study reported the rate of fall of serum total bilirubin at 24 hours of starting the phototherapy. Periodic change in body position may lead tolittle or no difference in the rateof fall of serum total bilirubin at 24 hours(MD0.02 mg/dL/h, 95% CI -0.02 to 0.06 mg/dL/h; 1 study, 100 participants; low certainty evidence). We downgraded the certainty of evidence to low due to risk of bias and imprecision. None of the included studies reported the need for or number of exchange transfusions, incidence of BIND, or SIDS. Lack of separate data precluded subgroup analysis. The available evidence is insufficient to determine the effects of periodic change of body position compared with no prescribed change of body position under phototherapy. There is low certainty evidence that there may be little or no difference in the duration of phototherapy andrate of fall in bilirubin at 24 hours of starting phototherapy between periodic change in body position and no prescribed change of body position under phototherapy in term and preterm neonates. None of the included studies reported the effect of change of position on the need for or number of exchange transfusions, incidence of BIND, or SIDS. One study is awaitingclassification and could not be included in the review. Further studies are needed to evaluate theeffectof periodic change in body position under phototherapy, especially in neonates with haemolytic hyperbilirubinaemia and in very preterm neonates. The results of this systematic review apply mainly to neonates born at late-preterm or term gestation receiving phototherapy for non-haemolytic hyperbilirubinaemia.

Effect of Intravenous Fluid Adjuvant Therapy on Decreasing Serum Bilirubin during Intensive Phototherapy in Healthy Term Neonate with Severe Nonhemolytic Hyperbilirubinemia.

Phototherapy is the most common form of treatment and prevention of neonatal nonconjugated hyperbilirubinemia. It seems that intravenous fluid therapy as a complementary method of phototherapy can accelerate the healing process in affected infants. This study aimed at investigating intravenous fluid therapy's effect in decreasing serum bilirubin in healthy term neonates with nonhemolytic hyperbilirubinemia under intensive phototherapy. As many as 160 healthy term infants with severe nonhemolytic hyperbilirubinemia and without exclusion criteria were enrolled. Infants were randomized to the two treatment groups (phototherapy alone and combination with intravenous fluid therapy). Serum bilirubin at admission time, 6, 12, 24, and 48 h later were measured. We evaluated decreasing serum bilirubin levels and duration of hospitalization in both groups. In this study, the mean levels of serum bilirubin on admission time, 6, 12, 24, and 48 h after treatment gradually reduced in both groups; still, the decrease was not statistically significant between the two groups. Intravenous fluids therapy does not have a significant advantage in the process of phototherapy in healthy term neonates with severe nonhemolytic hyperbilirubinemia.

Single-surface Intensive Phototherapy or Double-Surface Intensive Phototherapy in Neonatal Non-Hemolytic Hyperbilirubinemia: A Comparison of Effectiveness and Complications.

Background: Severe indirect hyperbilirubinemia causes neurotoxicity, leading to potential permanent injuries to the neonatal nervous system. The present study intended to compare the effectiveness and complications of Single-Surface Intensive Phototherapy (SSIP) and Double-Surface Intensive Phototherapy (DSIP) in treating non-hemolytic hyperbilirubinemia in the neonatal ward of the Besat Hospital, Hamadan, Iran. Methods: In this prospective randomized clinical trial, 150 healthy full-term neonates born between 37-42 weeks gestation with ages <14 days old and birth weights ≥2500 gr who were affected by non-hemolytic hyperbilirubinemia with total serum bilirubin of 15-20 mg/dL were randomly allocated to two groups. Each group (n=75) underwent either SSIP or DSIP. Demographics, bilirubin level alterations, weight, platelet count, number of defecation per day, and body temperature of the patients were monitored and recorded in a specific questionnaire. Data analysis was performed using SPSS version 26.0 software, with the Chi-square and independent t-test. Results: The pre-intervention levels of indirect bilirubin were 17.07±1.46 mg/dL in the SSIP group and 17.10±1.54 mg/dL in the DSIP group (P-value = 0.853). After 24 and 48 hours of treatment, the mean indirect bilirubin level of the SSIP group reduced to 13.12±1.71 mg/dL and 9.69±1.68 mg/dL, respectively. In the DSIP group, the levels were 11.85±2.17 mg/dL and 8.43±1.56 mg/dL after 24 and 48 hours of treatment, respectively. The absolute reductions of indirect bilirubin were 7.76±3.28 mg/dL for the SSIP group and 8.96±4.49 mg/dL for the DSIP group (P-value = 0.458). Therefore, the indirect bilirubin levels were significantly different between the groups after 24 and 48 hours of treatment and at the time of discharge (P<0.05). There were no significant inter-group differences in weight, platelet count, and incidence of skin rash, while the number of defecation and body temperature were higher in the DSIP group (P <0.05). However, body temperature alterations had no clinical relevance. Conclusion: Compared to the SSIP, the DSIP showed faster effectiveness and led to a shorter hospital stay, while it did not entail higher levels of complications.

How dangerous Gilbert's syndrome is

Gilbert's syndrome is a benign (functional) hyperbilirubinemia, which is based on a hereditary disorder of bilirubin metabolism, as a result of which the concentration of unbound bilirubin can increase several times. Bilirubin, being a breakdown product of hemoglobin, circulates through the bloodstream, combining with albumin molecules. Such bilirubin is called indirect. In the endoplasmic reticulum, it is conjugated; the enzyme glucuronyltransferase is responsible for this process. In Gilbert's syndrome, as a result of insufficient production of this enzyme, the conjugation process is disrupted, and, as a result, the concentration of unconjugated bilirubin increases. According to statistics, this pathological condition is observed in about 5 % of Russians. This syndrome was first described in 1901 by the French physician Augustin Nicolas Gilbert, and was subsequently named after him. The literature also contains references to this syndrome, described as «constitutional hepatic dysfunction», «familial non-hemolytic hyperbilirubinemia», «idiopathic non-conjugated hyperbilirubinemia». Gilbert's syndrome is inherited in an autosomal recessive manner; men get ill 3–4 times more often than women. A number of scientists associate this with a possible inhibitory effect of testosterone on the enzyme UDP-GT1, which breaks down bilirubin. Clinically, Gilbert's syndrome is manifested by episodes of jaundice caused by an increase in the level of unconjugated bilirubin in the blood serum. Against the background of icterus of the sclera and skin, there is increased fatigue, the appearance of a feeling of bitterness in the mouth, loss of appetite, nausea, and sometimes vomiting. The association of Gilbert's syndrome with functional disorders of the biliary tract, in particular, with gallbladder dyskinesia, is often noted.

Clofibrate in the Treatment of the Non-hemolytic Hyperbilirubinemia in Preterm Neonates in Western Iran

Background: No studies, to the best of our knowledge, have been conducted on the effect of Clofibrate in reducing hyperbilirubinemia in preterm infants. Therefore, this study aimed at investigating the therapeutic effect of Clofibrate in treating hyperbilirubinemia of preterm neonates. Methods: This clinical trial was performed from April 4 to December 20, 2019, on neonates in Hamadan in western Iran. The allocation remained concealed to the researcher, neonates’ parents, and analyzer during the study. A dose of Clofibrate of 25 kg/mg was given on the first day of hospitalization. The neonates in the placebo group received the oral placebo 25 kg/mg in the same way as the oral Clofibrate. The data were analyzed using SPSS 16 with P-value < 0.05. Results: No statistically significant difference was observed in the baseline characteristics of the two groups based on the neonate’s age and gender, delivery method, and gestational age. The prescription of Clofibrate significantly reduced the duration of hospitalization (p= 0.002) and phototherapy (p= 0.001). Prescribing a single oral dose of Clofibrate (25 mg/Kg) along with phototherapy in preterm neonates significantly reduced total serum bilirubin levels at 24 and 48 hours after treatment compared with phototherapy alone (p= 0.001). However, this association was not significant in admission (p= 0.095). Conclusion: The findings of this study showed the effect of Clofibrate in treating hyperbilirubinemia of preterm neonates. In addition, prescribing Clofibrate significantly reduced the duration of hospitalization and phototherapy.

The Neurodevelopmental Outcome of Severe Neonatal Haemolytic and Non-hemolytic Hyperbilirubinemia

The Neurodevelopmental Outcome of Severe Neonatal Haemolytic and Non-hemolytic Hyperbilirubinemia

Maternal outcome of Crigler-Najjar syndrome type-2: Case report

Crigler-Najjar Syndrome type 2 [CN-2] is an uncommon inherited disorder characterized by non-hemolytic unconjugated hyperbilirubinemia. It is caused by mutations in one of the five exons of the UGT1A1 gene which codes for the enzyme hepatic uridine diphosphate glucoronosyl transferase-1, required for the conjugation and further excretion of bilirubin from the body via bile. Affected people are usually asymptomatic apart from jaundice and investigations reveal isolated indirect hyperbilirubinemia. It can be conveniently diagnosed by evaluating the response to phenobarbital in terms of reduction in bilirubin levels. Genetic testing confirms the finding of Crigler-Najjar syndrome. At least 20 different mutations of UGT1A1 have been associated with CN-2; all encode a bilirubin-uridine diphosphate glucuronosyl transferase-1 with markedly reduced but detectable enzymatic activity. Bilirubin concentrations are typically lower in CN-2, and plasma bilirubin levels can be reduced to 3 to 5 mg/dL by phenobarbital. Although uncommon in CN-2, bilirubin encephalopathy has occurred at all ages, typically associated with factors that temporarily elevation the plasma bilirubin concentration above baseline e.g. stress, prolonged fasting, an intercurrent illness like influenza. For this reason, phenobarbital therapy is often recommended. CN-2 is infrequent, and only a few pregnancies with this condition have been reported. The objective of the case study is to report a rare case of maternal CN-2 in the pregnancy and to evaluate whether pregnancy is safe in patients with the disease. A 29 years old mother with CN-2 had given birth to a baby girl by spontaneous vaginal delivery without complications. The newborn had mild unconjugated hyperbilirubinemia which was further treated by phototherapy and early morning sunlight. It can be concluded that that pregnancy need not be contraindicated in CN-2. Keywords: Hyperbilirubinemia, Phototherapy, UGT1A1 gene, Jaundice, Glucuronidation.

Continuous vs Intermittent Phototherapy in the Management of Non-Haemolytic Neonatal Hyperbilirubinemia - A Randomised Non - Inferiority Study

Introduction: Phototherapy is used to manage neonatal hyperbilirubinemia in early life. We aimed to compare between intermittent and continuous phototherapy in reducing TSB, rate of fall of bilirubin, duration of phototherapy and duration of hospitalisation in neonates with non-haemolytic hyperbilirubinemia. &#x0D; Methods: Total 190 neonates who were &gt; 34 weeks and birth weight ≥ 2000 gm were included. They were randomised into group A (continuous phototherapy) and group B (intermittent phototherapy). Group A received phototherapy for three hours and 45 minutes off and group B received phototherapy for three hours and then three hours off. TSB levels estimation were done in both groups and compared after each 12 hours, 24 hours, and 48 hours of commencing phototherapy. &#x0D; Results: The mean TSB at presentation was 15.64 ± 2.19 mg/dl for continuous and 15.03 ± 1.07 mg/dl for intermittent group. Mean TSB at 12, 24, 48 hours were 13.26 ± 2.4 mg/dl, 10.8 ± 1.72 mg/dl, 10.16 ± 0.95 mg/dl respectively for continuous and 12.6 ± 1.65 mg/dl, 10.04 ±1.8 mg/dl, 9.1 ± 0.66 mg/dl respectively for intermittent group (p &lt; 0.05). The mean rate of fall in serum bilirubin was 0.22 ± 0.12 mg/dl/hr for group A and 0.21 ± 0.08 mg/dl/hr for group B (p = 0.45). There was not much difference in mean duration of hospitalisation in both groups (p = 0.547). &#x0D; Conclusions: Intermittent phototherapy is a non-inferior option to continuous phototherapy, in the management of non-haemolytic hyperbilirubinemia with additional advantages of less interrupted mother infant bonding and decreased irradiance.

S2487 A Tale of Two Sydromes: A Unique Case of Crigler-Najjar in a Young Male

INTRODUCTION: Crigler-Najjar Syndrome (CNS) is an uncommon genetic disorder that is characterized by non-hemolytic unconjugated hyperbilirubinemia and is divided into types I and II. CNS II has much overlap with Gilbert's syndrome, another hereditary defect in bilirubin metabolism. Though these syndromes share similar presentations, diagnosis through careful history taking and performing early genetic analysis can aid in prompt diagnosis and reduce extraneous testing. Our case describes a young man who was diagnosed with CNS type II via genetic analysis after years of misdiagnosis. CASE DESCRIPTION/METHODS: An 18-year-old male presented to the hospital with jaundice. Labs revealed mild elevation of liver enzymes, total bilirubin of 19.7 mg/dL and direct bilirubin of 4.2 mg/dL. CT abdomen and pelvis showed mild hepatomegaly without biliary duct dilatation. Hemolysis labs including LDH and haptoglobin were normal. The patient underwent plasmapheresis and started on phenobarbital 60 mg three times a day. Repeat labs two weeks later showed improvement in bilirubin levels to 9.5 mg/dL. Further history revealed that the patient had a longstanding history of jaundice and elevated bilirubin levels since childhood. Due to persistently elevated bilirubin levels despite phenobarbital therapy, genetic testing was performed which revealed a homozygous mutation of the UGT1A1 gene which confirmed CNS type II. The patient continued to have monthly phototherapy treatments with an improvement in symptoms. DISCUSSION: CNS is a disorder in which there is a mutation in the UGT1A1 gene which is needed for bilirubin conjugation. CNS type I is fatal in infancy and CNS type II often presents with persistent jaundice. CNS type II is often confused with Gilbert's disease as both cause the same overlap of symptoms which are exacerbated by stress or illness. Our patient was initially diagnosed with Gilbert's as his symptoms occurred intermittently and bilirubin levels fell after previous treatments. A key difference is that in Gilbert's disease, total bilirubin levels rarely reach higher than 6 mg/dl and typically normalize after treatment. In contrast, in CNS type II, plasma exchange or phenobarbital cause bilirubin levels to drop by at least 25% however levels rarely normalize. In our patient, a key clinical indicator for CNS type II was the high bilirubin levels without drop to normal which should be used to differentiate between each syndrome.

Noninvasive Detection of Hemolysis with ETCOc Measurement in Neonates at Risk for Significant Hyperbilirubinemia

Background: Hemolytic hyperbilirubinemia due to blood group incompatibility or glucose-6-phosphate dehydrogenase deficiency (G6PD) is a common cause of significant hyperbilirubinemia. Hemolysis in a hyperbilirubinemic infant increases the risk of bilirubin neurotoxicity. A new portable device (CoSense) can rapidly detect breath end-tidal carbon monoxide corrected to ambient carbon monoxide (ETCOc). ETCOc levels are surrogate markers of hemoglobin breakdown and bilirubin production. Objective: The aim was to evaluate the association between ETCOc values and hemolysis and its relevance in neonates at risk for significant hyperbilirubinemia. Methods: A prospective study was conducted among newborn infants born at more than 35 weeks and with a birth weight greater than 2,000 g with a G6PD deficiency, blood group incompatibility, or clinical jaundice needing phototherapy during the first 7 days of life. The recruited infants had their breath ETCOc measured twice, first on the day of recruitment and then again on the following day. Results: Fifty infants completed this study. Their mean ETCOc was 1.61 (±0.56) ppm. There was a linear correlation (r = 0.89) between increasing ETCOc values and reticulocyte counts (RC). Sixteen newborns with ABO incompatibility had a significantly higher mean ETCOc of 1.98 ppm (±0.71) as compared to 1.43 (±0.38) ppm in the nonhemolytic hyperbilirubinemia (NHH) group (n = 25) (p = 0.002). This was suggestive of hemolysis as shown by the significantly higher RC of 6.90% (±3.38) compared to 4.68 (±1.26) in the NHH group (p <0.005). Neonates with an ETCOc level ≥1.8 ppm had a higher RC, a lower hemoglobin level, higher serum bilirubin levels, and a rapid rise in serum bilirubin and needed a longer duration of phototherapy. ETCOc values ≥1.8 ppm were suggestive of hemolysis (RC ≥6%), with a sensitivity of 90% and a specificity of 83%. Conclusion: Higher ETCOc values ≥1.8 ppm are suggestive of hemolysis and they are associated with significant hyperbilirubinemia.

The Effect of Phototherapy on Apaptosisin Hyperbilirubinemic Preterm Neonates

Objective: This study aimed to assess the impact of hyperbilirubinemia and Intensive phototherapy on apaptosis in peripheral blood of preterm infants. Patients and Method: The study was conducted on 18 preterm infants with non-hemolytic hyperbilirubinemia and 9 control healthy preterm infants. Apaptosismarkers (anti-apoptotic protein Bcl2, and pro-apoptotic protein BAX) was assessed using ELISA technique. Blood samples wereobtained at enrollment in all infants and after24 hours of exposure to intensive phototherapy in jaundiced infants. Result: Before phototherapy, no significant difference in the serum levels of bcl2 and Bax protein between jaundiced and non-jaundiced preterm infants (P = 0.570, p= 0.329 respectively), After phototherapy The serum levels of Bcl2 decrease while The serum levels of BAX increased significantly (P=0.003, p&lt;0.001 respectively). Conclusion: Hyperbilirubinemia does not influence apaptosis whereas intensive phototherapy do in preterm infants with hyperbilirubinemia.