Effect of vitamin E supplementation on bilirubin levels in infants with hyperbilirubinemia: a double-blind randomized clinical trial.

BACKGROUND: The effect of vitamin E supplementation on bilirubin levels in infants was previously explored, but the results were inconclusive. PURPOSE: To examine the effect of vitamin E supplementation on bilirubin levels in term infants in the neonatal intensive care unit (NICU). METHODS: This interventional double-blind randomized clinical trial was conducted in the Sanandaj Besat Hospital NICU. Enrolled newborns were between 37 and 42 weeks and 6 days of gestation and required phototherapy according to American Academy of Pediatrics clinical guidelines. A total of 138 infants were randomly assigned to vitamin E (n=68) or placebo (n=70) groups. In addition to phototherapy, the vitamin E group received 0.5 mL (5 IU) of supplemental vitamin E daily, whereas the placebo group received 0.5 mL of oral dextrose daily. STATA 17 was used for the data analysis. RESULTS: Changes in bilirubin levels at 24 hours postintervention did not differ significantly from baseline in either group. Vitamin E supplementation did not significantly reduce total bilirubin levels at 24 hours postintervention (mean difference [MD], -0.18; P=0.204; 95% confidence interval [CI], -1.39 to 1.02). However, the vitamin E group exhibited lower total bilirubin levels than the placebo group at 48 hours postintervention (MD, 0.18; P=0.365; 95% CI, -0.89 to 1.27) and 72 hours (MD, 0.36; P=0.356; 95% CI, -2.34 to 1.61), although the differences were not statistically significant. A subgroup analysis revealed that female infants experienced a greater reduction in total bilirubin levels than male infants. CONCLUSION: Infants administered vitamin E versus placebo demonstrated similar reductions in bilirubin levels and hospital stays. Although the average bilirubin changes did not differ significantly between groups, the vitamin E group showed a more noticeable reduction over time, indicating a positive effect of vitamin E supplementation on serum bilirubin reduction. Trial registration: IRCT20220806055625N2 (registered December 26, 2022; http://irct.ir/trial/67135).

Factors associated with neonatal jaundice among neonates admitted at referral hospitals in northeast Ethiopia: a facility-based unmatched case-control study.

BACKGROUND: Neonatal jaundice is a significant contributor to illness and death in newborns, leading to frequent admissions to neonatal intensive care units. To better understand this issue, a study was conducted to identify the factors contributing to neonatal jaundice among newborns admitted to Dessie and Woldia comprehensive specialized hospitals in northeast Ethiopia. METHODS: The study took place from April 1 to May 30, 2022, using unmatched case-control design. A total of 320 neonates paired with their mothers were involved, including 64 cases and 256 controls. Data were collected through a structured interviewer-administered questionnaire and a review of medical records. The collected data were analyzed using SPSS Version 23, and a multivariate logistic regression model was employed to understand the relationship between independent factors and the occurrence of neonatal jaundice. Statistical significance was determined at a threshold of P value less than 0.05. RESULTS: The study findings revealed that maternal age over 35 years, residing in urban areas [adjusted odds ratio (AOR) = 2.4, 95% confidence interval (CI): 1.23, 4.82], male gender (AOR = 4.3, 95% CI: 1.90, 9.74), prematurity (AOR = 3.9, 95% CI: 1.88, 8.09), and ABO incompatibility (AOR = 2.6, 95% CI: 1.16, 5.96) were significant determinants of neonatal jaundice. Conversely, the study indicated that cesarean birth was associated with a 76% lower likelihood of infant jaundice compared to vaginal delivery (AOR = 0.24, 95% CI: 0.08, 0.72). CONCLUSION: To prevent, diagnose, and treat neonatal jaundice effectively, efforts should primarily focus on managing ABO incompatibility and early detection of prematurity. Additionally, special attention should be given to neonates born through vaginal delivery, those with mothers over 35 years old, and those residing in urban areas, as they are at higher risk of developing newborn jaundice. Close monitoring of high-risk mother-infant pairs during the antenatal and postnatal periods, along with early intervention, is crucial for reducing the severity of neonatal jaundice in this study setting.

The association between bilirubin levels, and the incidence of metabolic syndrome and diabetes mellitus: a systematic review and meta-analysis of cohort studies.

OBJECTIVES: The objective of this meta-analysis was to investigate the association between plasma bilirubin levels and the incidence of metabolic syndrome and diabetes mellitus across all populations. METHODS: Several databases were searched, including PubMed (Medline), Scopus, Web of Science, and Embase (Elsevier), to identify relevant cohort studies. All cohort studies that reported the risk ratio along with a 95% confidence interval were included. The association between bilirubin levels and metabolic syndrome or diabetes was reported as a pooled RR with a 95% CI in the forest plot. All analyses were conducted using STATA version 17, with a significance level of 0.05. RESULTS: Out of the 10 studies included in the analysis, four investigated the effect of hyperbilirubinemia on the incidence of type 2 diabetes. When these four studies were combined, the pooled RR was 0.78 (95% CI: 0.73, 0.83; I2: 88.61%; P heterogeneity <  0.001), indicating a significant association between hyperbilirubinemia and decreased risk of type 2 diabetes. Five of the 10 studies evaluated the effect of hyperbilirubinemia on the incidence of metabolic syndrome, and the pooled RR was 0.70 (95% CI: 0.67, 0.73; I2: 78.13%; P heterogeneity <  0.001), indicating a significant association between hyperbilirubinemia and decreased risk of metabolic syndrome. CONCLUSION: The findings suggest that elevated levels of bilirubin may have a significant protective effect against the development of diabetes mellitus and metabolic syndrome.

Correlation between Alkaline Phosphatase and Neonatal Jaundice.

Background: Hyperbilirubinemia is one of the most common neonatal disorders and one of the risk factors of neurological complications. So this study was conducted to evaluate the correlation between alkaline phosphatase (ALP) and pathological jaundice. Methods: A case-control was performed on term neonates with and without pathological jaundice who were referred to the Hazrat-e-Ali Asghar Hospital in 2017. In both groups, cases (neonates with pathological jaundice, n=153) and control (neonates with and without pathological jaundice, n=153) levels of alkaline-phosphatase and serum total bilirubin were evaluated with biochemical tests. Moreover, other data were also recorded from their history and clinical examinations. In addition, the severity of jaundice, duration of hospitalization, type of required treatment, and probable complications after the treatment were considered in follow-up. Data were collected by checklist and entered to SPSS v.20. ALP level and its relationship with serum total bilirubin compared between two groups. Results: Mean level of ALP was 411.3 ± 134.2 U/L in the case group and 338 ± 131.4 U/L in the control group. Serum total bilirubin level was 11.9 mg/dl in the case group and 6.2 mg/dl in the control group. ALP levels in the case group were significantly more than the control group (p=0.001). There was no correlation between ALP and serum total bilirubin level in neonates in the case group (p=0.532). There was no statistically significant relationship between alkaline phosphatase level and gender of neonates, but the relationship of ALP level with types of delivery was statistically significant (p=0.002). There was not a significant relationship between ALP level with hospitalization duration (p=0.371). Conclusion: The result of this study showed that there is no correlation between ALP levels and pathological jaundice in patients, although this issue needs to be approved by the other studies.

The Effect of Different Timings of Delayed Cord Clamping of Term Infants on Maternal and Newborn Outcomes in Normal Vaginal Deliveries.

Background and objective Delayed cord clamping (DCC) has proven to be an ideal approach to reduce iron deficiency anemia; however, different timings of DCC relative to the birth outcome lead to conflicting results. The present study was conducted to determine the effects of different timings of DCC on the maternal and neonatal outcomes in normal vaginal deliveries at term. Methods This was an interventional study on neonates born at term without complications to mothers with uneventful pregnancies in the labor unit of a district hospital in Odisha, India. A total of 147 women were randomized to three intervention groups: DCC at one minute, DCC at two minutes, and DCC at three minutes. Hemoglobin and bilirubin levels, maternal blood loss, the timing of the third stage of labor, oxytocin use, and birth weight of the neonates were measured as the outcomes of different timings of DCC. Results At 24-48 hours of age, hemoglobin and bilirubin levels of the neonates were significantly higher with DCC at three minutes compared to DCC at one and two minutes. However, there were no significant differences among the three groups in terms of the need for phototherapy. The duration of the third stage of labor was significantly longer with DCC at three minutes. Maternal blood loss, oxytocin use, and birth weight of the neonates were not significantly associated with the timing of DCC. Conclusion Based on our findings, waiting to clamp the umbilical cord until three minutes can effectively reduce the incidence of iron deficiency anemia in newborns.

OPTIMUM DURATION OF PERCUTANEOUS TRANSHEPATIC CHOLANGIODRAINAGE IN COMMON BILE DUCT DISEASES COMPLICATED BY OBSTRUCTIVE JAUNDICE.

OBJECTIVE: The aim: Is to determine the optimum duration of percutaneous transhepatic cholangiodrainage depending on the duration of obstructive jaundice and the baseline total bilirubin level in patients with benign and malignant common bile duct diseases complicated by obstructive jaundice. PATIENTS AND METHODS: Materials and methods: The experience of applying percutaneous transhepatic cholangiodrainage was combined for 88 patients with common bile duct diseases complicated by obstructive jaundice. The patients were divided into three groups: the Group 1 included 15 patients (17.1%) with benign common bile duct diseases, the Group 2 included 11 patients (12.5%) with resectable cholangiocarcinomas, and the Group 3 included 62 patients (70.4%) with unresectable cholangiocarcinomas. To determine optimal terms of biliary decompression using percutaneous transhepatic cholangiodrainage, the Poisson process was applied, and, to be more precise, the quasi-Poisson distribution. RESULTS: Results: It was found that the reduction of total bilirubin was the fastest in Group 3 patients. It took these patients an average of 7-8 days to reduce total bilirubin to 50 µmole/l. In Group 1 patients, the process is somewhat slower. The duration of biliary decompression in this category of patients averages 10-12 days. For Group 2 patients, biliary decompression requires at least 12 days. CONCLUSION: Conclusions: Using the Poisson process, or, to be more precise, the quasi-Poisson distribution, we managed to determine the optimum duration of biliary decompression using percutaneous transhepatic cholangiodrainage depending on the obstructive jaundice duration and the baseline total serum bilirubin.

Defining the optimal bilirubin level before hepatectomy for hilar cholangiocarcinoma.

BACKGROUND: In the management of operable hilar cholangiocarcinoma (HC) patients with hyperbilirubinemia, preoperative biliary drainage is a measure to bring down the bilirubin to a certain level so as to avoid adverse postoperative outcomes that would otherwise result from hyperbilirubinemia. A cutoff value of bilirubin level in this context is needed but has not been agreed upon without controversy. This retrospective study aimed to identify a cutoff of preoperative bilirubin level that would minimize postoperative morbidity and mortality. METHODS: Data of patients having hepatectomy with curative intent for HC were analyzed. Discriminative analysis was performed to identify the preoperative bilirubin level that would make a survival difference. The identified level was used as the cutoff to divide patients into two groups. The groups were compared. RESULTS: Ninety patients received hepatectomy with curative intent for HC. Their median preoperative bilirubin level was 23 µmol/L. A cutoff preoperative bilirubin level of 75 µmol/L was derived from Youden's index (sensitivity 0.333; specificity 0.949) and confirmed to be optimal by logistic regression (relative risk 9.250; 95% confidence interval 1.932-44.291; p = 0.005), with mortality shown to be statistically different at 90 days (p = 0.008). Patients were divided into Group A (≤75 µmol/L; n = 82) and Group B (> 75 µmol/L; n = 8). Group B had a higher preoperative bilirubin level (p < 0.001), more intraoperative blood loss (3.12 vs 1.4 L; p = 0.008), transfusion (100% vs 42.0%; p = 0.011) and replacement (2.45 vs 0.0 L; p < 0.001), more postoperative renal complications (p = 0.036), more in-hospital deaths (50% vs 8.5%; p = 0.004), and more 90-day deaths (50% vs 9.8%; p = 0.008). Group A had a longer follow-up period (p = 0.008). The groups were otherwise comparable. Disease-free survival was similar between groups (p = 0.142) but overall survival was better in Group A (5-year, 25.2% vs 0%; p < 0.001). On multivariate analysis, preoperative bilirubin level and intraoperative blood replacement were risk factors for 90-day mortality. CONCLUSION: A cutoff value of preoperative bilirubin level of 75 µmol/L is suggested, as the study showed that a preoperative bilirubin level ≤ 75 µmol/L resulted in significantly less blood replacement necessitated by blood loss during operation and significantly better patient survival after surgery.

Preoperative Bilirubin Level Predicts Overall Survival and Tumor Recurrence After Resection for Perihilar Cholangiocarcinoma Patients.

OBJECTIVE: Currently, the correlation between preoperative bilirubin level and overall survival (OS) remains poorly defined in respectable perihilar cholangiocarcinoma (CC). The objectives of the current study were to evaluate the outcomes of perihilar CC after resection and then to analyze factors influencing curative resection, tumor recurrence and OS. METHODS: 115 patients with perihilar CC underwent surgical resection were retrospectively analyzed based on clinic characteristics, operative details, tumor recurrence and long-term survival data. RESULTS: The 1-, 3-, and 5-year OS rates after resection were 75.9%, 36.5%, 21.7%, whereas the corresponding tumor recurrence rates were 29.6%, 70.8%, 85.3%, respectively. Preoperative bilirubin level combined with liver resection, resection margin, vascular invasion and perineural invasion, lymph node metastasis and TNM stage were found to be correlated with OS and tumor recurrence. Multivariate analysis showed that preoperative bilirubin level together with resection margin, perineural invasion, and TNM stage were independent predictors of OS and tumor recurrence. Furthermore, preoperative bilirubin level was related with R0 resection, lymph node metastasis, TNM stage and postoperative liver function recovery. CONCLUSION: Preoperative bilirubin level may effectively reflect the severity of perihilar CC and predict the OS and tumor recurrence after resection for perihilar CC patients.

The influence of massage on neonatal hyperbilirubinemia: a meta-analysis of randomized controlled trials.

Introduction: The efficacy of massage to treat neonatal hyperbilirubinemia remains controversial. We conducted a systematic review and meta-analysis to explore the influence of massage on the neonatal hyperbilirubinemia. Methods: We search PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases through November 2017 for randomized controlled trials (RCTs) assessing the effect of massage on neonatal hyperbilirubinemia. This meta-analysis is performed using the random-effect model. Results: Six RCTs involving 357 patients are included in the meta-analysis. Overall, compared with the control group in neonatal hyperbilirubinemia, massage therapy is associated with substantially reduced serum bilirubin level within 4 d (mean difference (MD) = -2.31; 95% CI = -2.92 to -1.70; p < .00001) and transcutaneous bilirubin level within 4 d for neonatal hyperbilirubinemia (MD = -1.97; 95% CI = -2.55 to -1.39; p < .00001), but results no remarkable impact on serum bilirubin level on 2 d (MD = -0.82; 95% CI = -2.16-0.52; p = .23), transcutaneous bilirubin level on 2 d (MD = -0.17; 95% CI = -1.34 to 1.00; p = .77), frequency of defecation daily on 2 d (MD = 0.57; 95% CI = -0.03 to 1.16; p = .06), and frequency of defecation daily within 4 d (MD = 0.83; 95% CI = -0.11 to 1.76; p = .08). Conclusions: Massage therapy can significantly reduce serum bilirubin level and transcutaneous bilirubin level within 4 d, but demonstrates no influence on serum bilirubin level and transcutaneous bilirubin level on 2 d, frequency of defecation daily on 2 and 4 d for neonatal hyperbilirubinemia.

Role of C-Reactive Protein, White Blood Cell Counts, Bilirubin Levels, and Imaging in the Diagnosis of Acute Appendicitis as a Cause of Right Iliac Fossa Pain.

Background Right iliac fossa (RIF) pain is one of the most common modalities of presentation to surgical emergency. It remains a challenge to the treating clinicians to accurately diagnose or to rule out appendicitis. Objective The aim of the study was to compare the efficacy of clinical impression, biochemical markers, and imaging in the diagnosis of RIF pain with special reference to appendicitis and their implication in reducing the negative appendicectomy rates. Methods All patients presenting to casualty with RIF pain were included in the study. Blood investigations including C-reactive protein (CRP), serum bilirubin, white blood cell counts (WBC), and ultrasound (USG) were done. Based on the clinical impression, patients were either posted for appendicectomy or observed in equivocal cases. Patients who had recurrent pain on follow-up underwent appendicectomy or underwent contrast-enhanced computed tomography (CECT) in equivocal cases. Patients who only had a single self-limiting episode with no other alternative diagnosis or had a normal CECT report were included in a non-specific RIF pain group. Results The negative appendicectomy rate was 8.2%. The mean value of WBC counts (9.57x109/L vs 7.88x109/L; p<0.05) and that of serum bilirubin (1.37 mg/dl vs 0.89mg/dl; p<0.05) in the appendicitis and non-appendicitis group, respectively, were statistically significant. The percentage of CRP positivity was higher in the appendicitis group (51.9% vs 15%; p<0.05). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for USG (84.2%, 77.17%, 85.4%, and 75.5%), for CRP (51.8%, 85%, 82%, and 57%), for WBC count (45.1%, 88%, 86.6%, and 48.3%), and for serum bilirubin (69.2%, 75%, 81.4%, and 60.5%) were statistically significant between the groups. Conclusion Imaging and biochemical investigations including bilirubin can act as useful adjuncts to the clinical diagnosis of appendicitis.

Bile Gastritis Following Laparoscopic Single Anastomosis Gastric Bypass: Pilot Study to Assess Significance of Bilirubin Level in Gastric Aspirate.

INTRODUCTION: Laparoscopic single anastomosis gastric bypass (SAGB) is increasingly performed for morbidly obese patients. AIM OF WORK: This pilot study aims primarily at evaluating the incidence of bile gastritis after SAGB. The occurrence of reflux oesophagitis and reflux symptoms were also assessed. PATIENTS AND METHODS: This study included 20 patients having no reflux symptoms. All patients underwent a SAGB as a primary bariatric procedure by a single surgeon. Patients included consented to have an upper GI endoscopy done at 6 months postoperatively. Gastric aspirate was sent for bilirubin level assessment. Gastric and esophageal biopsies were submitted for histopathology and campylobacter-like organism (CLO) test. RESULTS: In our study, the rate of bile gastritis was 30%. In 18 patients, the level of bilirubin in gastric aspirate seems to be related to the degree of mucosal inflammation. The remaining two patients had microscopic moderate to severe gastritis with normal aspirate bilirubin level. Two patients with bilirubin level in aspirate more than 20 mg/dl had severe oesophagitis, gastritis with erosions, and metaplasia. Relationship between bilirubin level and histopathological findings of gastric biopsy examination was statistically significant with a P value of 0.001. CONCLUSION: The incidence of bile gastritis in this cohort is higher than reported in the literature, and this may be worrying. The correlation between endoscopic findings and patients' symptoms is poor. Bilirubin level and pH in aspirate might be useful tools to confirm alkaline reflux. Its level might help to choose candidates for revision surgery after SAGB. This needs further validation with larger sample size.

The Association between Prolonged Jaundice and TATA Box Dinucleotide Repeats in Gilbert's Syndrome.

INTRODUCTION: Jaundice is a common condition during the neonatal period. Prolonged jaundice occurs in a large number of breastfed infants, considering the impact of genetic factors on the incidence of jaundice. AIM: To determine the association between prolonged jaundice and TATA box dinucleotide repeats in Gilbert's Syndrome (GS). MATERIALS AND METHODS: In this case-control study, the case group consisted of 51 neonates with jaundice, aged more than two weeks with indirect bilirubin level higher than 10 mg/dl. Acute diseases, mother's use of phenobarbital and other medications were the exclusion criteria. The control group consisted of 54 newborns without jaundice. The two groups were matched in terms of age and sex. TATA box polymorphisms in the promoter region of UGT1A1 gene were evaluated using Polymerase Chain Reaction (PCR) in order to determine TATA box dinucleotide repeats. RESULTS: Overall, 64.7% and 50% of subjects in the case and control groups were male, respectively (p=0.168). The mean age of neonates in the case and control groups was 20.1±7.1days and 18.8±4.1 days, respectively. The distribution of Gilbert genome was not significantly different between the two groups. In the case group, 13.7% of the subjects were homozygous, 37.3% were heterozygous and 49% were normal. In the control group, 7.4% of the participants were homozygous, 35.2% were heterozygous and 57.4% were normal. CONCLUSION: The results of this study showed an association between TATA box polymorphism and prolonged jaundice in neonates which revealed that TATA box polymorphism is an important risk to increase and extend icterus.

Effect of turning vs. supine position under phototherapy on neonates with hyperbilirubinemia: a systematic review.

AIMS AND OBJECTIVES: To determine the most effective position jaundiced neonates should assume during phototherapy from appraised randomised controlled trials. BACKGROUND: Many local hospitals still alternate positions of jaundiced neonates receiving phototherapy despite the safe infant sleeping protocol of placing them supine. DESIGN: A systematic review was conducted. METHODS: Databases that included Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, Embase and The Cochrane Library were used. Randomized controlled trials published in English language that evaluate the best position for healthy jaundiced neonates aged day 1 to 14 under phototherapy were searched. In addition, any positioning done every 2-3 hours during phototherapy with the outcome measures being bilirubin reduction and duration of phototherapy were also searched and included (n = 5). Physiotherapy Evidence Database scale was adopted for quality assessment. All processes were conducted by both reviewers independently. Discrepancies were resolved by a third reviewer. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guideline were utilised. Out of 20 papers, five were included for qualitative synthesis. Data extraction was based on the template (participants, study designs etcetera) agreed by both authors. RESULTS: All five studies possessed external validity. One paper scored 7, three scored 5 while one scored 3. Four of these studies reported no difference in bilirubin reduction and duration of phototherapy. Only one study reported a significant drop in serum bilirubin and shorter duration of phototherapy in the supine group. CONCLUSION: It has been proved that keeping the jaundiced newborns in the supine position throughout phototherapy is as effective as turning them periodically based on the appraised studies. RELEVANCE TO CLINICAL PRACTICE: It is unnecessary to alternate positions of the jaundiced neonates when conventional phototherapy is delivered to lighten nurses' workload.

Addition of Molecular Adsorbent Recirculating System (MARS(®)) Albumin Dialysis for the Preoperative Management of Jaundiced Patients with Hilar Cholangiocarcinoma.

The preoperative management of hilar cholangiocarcinoma (HC) with jaundice focuses on decreasing the total serum bilirubin level (SBL) by performing preoperative biliary drainage (PBD). However, it takes about 6-8 weeks for the SBL to fall at a sufficient extent. The objective of this preliminary study was to evaluate the impact of Molecular Adsorbent Recirculating System (MARS(®)) dialysis (in association with PBD) on SBL decrease. From January 2010 to January 2011, we prospectively selected all jaundiced patients admitted to our university hospital for resectable HC and requiring PBD prior to major hepatectomy. The PBD was followed by 3 sessions of MARS dialysis over a period of 72 h. A total of 10 patients with HC were screened and two of them were included (Bismuth-Corlette stage IIIa, gender ratio 1, median age 68 years). The initial SBL in the two patients was 328 and 242 µmol/l, respectively. After three MARS dialysis sessions, the SBL had fallen by 30 and 52%, respectively. After the end of each session, there was a SBL rebound of about 10 µmol/l. The MARS decreased the serum creatinine level, the platelet count and the prothrombin index, but did not modify the serum albumin level. Pruritus disappeared after one and two sessions, respectively. MARS-related morbidity included hypotension (n = 1), tachycardia (n = 1), thrombocytopenia (n = 2) and anaemia (n = 1). When combined with PBD, MARS dialysis appears to accelerate the decrease in SBL and thus may enable earlier surgery. This hypothesis must be validated in a larger study.