Peak Serum Bilirubin Research Articles

Revisiting the Malignant Masquerade at the Liver Hilum: Have We Made Progress?

Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection. Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26months (range 0-281months). Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80U/mL (range 1-5779) and 21U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant). Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.

Association between adverse outcomes of hepatitis A and acetaminophen use: A population-based cohort study.

Acetaminophen (APAP) may cause acute liver injury with therapeutic doses in high-risk conditions such as chronic alcohol consumption or malnutrition. In acute hepatitis A (AHA), however, the safety of APAP has not been fully established. This study examined the potential association between APAP use and clinical outcomes of AHA in a nationwide and hospital-based cohort. Adult patients with AHA were identified from claims data of South Korean national healthcare insurance between 2008 and 2016 (n=43,500). Logistic regression models were used to compare the risk of adverse outcomes (renal replacement therapy, hepatic encephalopathy and/or brain edema, mechanical ventilation, and liver transplantation) in patients exposed to APAP against control and patients exposed to NSAIDs. A propensity score (PS)-matched hospital-based AHA cohort (n=146) was assessed for biochemical profiles after exposure to APAP or NSAIDs. AHA patients were exposed to APAP or NSAIDs in 26.4% and 11.5% of cases, respectively. Compared to NSAID treatment, APAP exposure was associated with a higher incidence of hospitalization (98.8% vs. 92.4%; p<0.0001). APAP exposure was independently associated with increased adverse outcomes (odds ratio [OR]=5.66, p<0.0001 against control; OR =1.67, p=0.0015 against NSAIDs). PS-matched hospital cohort showed higher peak serum bilirubin levels (7.0vs. 5.3mg/dL; p=0.03) and a longer time to recovery of jaundice after APAP use than with NSAID use. APAP exposure was associated with increased adverse outcomes in a nationwide AHA cohort.

Umbilical Cord Milking in Nonvigorous Infants: A Cluster-Randomized Crossover Trial

ABSTRACT Approximately 6 million infants each year require resuscitation at birth. Requiring this intervention is associated with higher risk of hypoxic-ischemic encephalopathy (HIE), cerebral palsy, attention-deficit or hyperactive disorder, autism, neonatal stroke, and death. In infants needing resuscitation, optimal cord management is essential to enhance placental transfusion. Delayed cord clamping (DCC) is used to enable placental transfusion in vigorous infants, but in nonvigorous infants—those who are limp, pale, or have minimal or no breathing—early cord clamping (ECC) is recommended. Another intervention for nonvigorous infants requiring resuscitation is umbilical cord milking (UCM). UCM can improve heart rate, blood pressure, urine output, cerebral oxygenation, and hemoglobin levels, and prevent anemia. In addition, it can achieve placental transfusion without delaying resuscitation as with DCC and can be completed as quickly as ECC. No harm has been observed in studies involving UCM. Despite these benefits, studies are lacking on optimal cord management strategies in nonvigorous infants requiring resuscitation. The aim of this study was to examine whether UCM reduces admission to the neonatal intensive care unit (NICU) versus ECC in nonvigorous newborns. This was a pragmatic, cluster-randomized, crossover trial conducted at 10 hospitals in the United States, Canada, and Poland. Included were viable infants delivered between January 2019 and May 2021 who were between 35 and 42 weeks of gestation and nonvigorous at birth. Nonvigorous was defined as poor tone, pallor, or lack of breathing in the first 15 seconds after birth. Excluded were infants with major congenital or chromosomal anomalies, cardiac defects except small ventricular septal defects, complete placental abruption or cutting through the placenta at delivery, monochorionic multiples, cord anomalies, and the presence of nonreducible nuchal cord. Hospitals were randomized 1:1 to UCM or ECC in period 1 from January 2019 to January 2020, then crossed over to the other intervention during period 2 from February 2020 to May 2021. The primary outcome was NICU admission related to the intervention in the first 24 hours of life. The safety outcome was HIE. A total of 1730 infants were included in the analysis with 872 in the UCM group and 858 in the ECC group. The difference in the frequency of NICU admission was not statistically significant, with 23% in the UCM group and 28% in the ECC group (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.41–1.14). In comparison to the ECC group, UCM was associated with lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%; crude OR, 0.72; 95% CI, 0.56–0.92), receipt of cardiorespiratory support in the delivery room (61% vs 71%; modeled OR, 0.57; 95% CI, 0.33–0.99), and therapeutic hypothermia (3% vs 4%; crude OR, 0.58; 95% CI, 0.33–0.99). In addition, there was no significant difference in any grade of HIE, although moderate-to-severe HIE was less common in the UCM group (1% vs 3%; crude OR, 0.48; 95% CI, 0.24–0.96). The UCM group also had increased hemoglobin (modeled mean difference, 0.68 g/dL; 95% CI, 0.31–1.05) and peak serum bilirubin (modeled mean difference, 1.4 mg/dL; 95% CI, 0.5–2.2). In nonvigorous newborns needing resuscitation, UCM was not associated with a reduction in NICU admissions compared with ECC. UCM was associated with a decrease in cardiorespiratory support in the delivery room, fewer cases of moderate-to-severe HIE, lower use of therapeutic hypothermia, and higher hemoglobin.

Novel radiological technique to recognize acute liver failure caused by yellow phosphorous containing rodenticides.

Yellow phosphorous rodenticide (YPR) poisoning is the commonest cause for acute liver failure (ALF) in southern and western India. Due to medicolegal issues, history of YPR ingestion may not be available. As early recognition of YPR poisoning is important and there are no specific biochemical assays, other early predictors to identify this entity is necessary. We evaluated the diagnostic role of plain computed tomography (CT) in identifying YPR-induced ALF. All patients admitted to the liver unit with a diagnosis of ALF underwent a plain CT scan abdomen. Demographic details, clinical history, laboratory parameters, liver attenuation index (LAI) calculated on CT scan, treatment details, need for liver transplantation and clinical outcome were analyzed. Parameters for YPR-induced ALF (ALF-YPR) and other causes (ALF-OTH) were compared. Ability of LAI to distinguish ALF-YPR and ALF-OTH was analyzed using receiver operating characteristic (ROC) curve analysis. Twenty-four patients (15 female [62.5%]) were included in the study. Thirteen patients (54%) had YPR poisoning, while the rest formed the ALF-OTH group (11,46%). ALF-YPR patients had higher transaminase levels, lower peak serum bilirubin levels. ALF-YPR livers had significantly lower LAI as compared to ALF-OTH (- 30 vs. - 8, p = 0.001). On ROC curve analysis, an LAI greater than - 18 ruled out YPR as the cause for ALF with 91% sensitivity and 85% specificity. On regression analysis, LAI was the only independent factor predicting ALF-YPR (odds ratio - 0.86, [0.76, 0.96] p = 0.008). Our data shows that LAI on plain abdominal CT scan can be used to quickly recognize ALF-YPR in unclear cases so that necessary treatment protocol can be activated, or patient transfer arranged. Our analysis shows that an LAI greater than - 18 can reliably rule out YPR ingestion as the cause for ALF.

Correlation Between Peak Serum Bilirubin During 1st Week of Life and Future Neurodevelopmental Outcome in Healthy Term Babies

Study was done to look for the future neurodevelopmental outcome of the babies with extremely high serum bilirubin level at 1st week of life. Fifty one term and near term babies were enrolled with features of acute bilirubin encephalopathy (ABE), with bilirubin level more than20mg/dl. They were followed up at 3rd and 6th month to observe their neurodevelopment. Neurological outcome was measured with Denver Development Screening Test (DDST-II) and brainstem evoked response audiometry (BERA). The mean peak total serum bilirubin (TSB) was 25.3±2.35(mg/dl). Abnormal developmental was found in 23.5% babies (12 out of 51) and abnormalities were more in the babies whose TSB was beyond 28mg/dl. Abnormal BERA was found among 13.7% babies. TSB value below 25 mg/dl can be considered as safe cut off value for reversibility of bilirubin induced acute brain damage.

Impact of Umbilical Cord Milking on Hematological Parameters in Preterm Neonates With Placental Insufficiency.

BackgroundData is still lacking about the expediency of umbilical cord milking (UCM) in preterm neonates born to mothers with placental insufficiency (PI).ObjectiveTo study the effect of UCM in preterm neonates who had ante-natal evidence of placental insufficiency on peripheral blood cluster of differentiation 34 (CD34) percentage, hematological indices, and clinical outcomes.MethodsPreterm neonates, <34 weeks' gestation, born to mothers with evidence of placental insufficiency that underwent UCM (PI+UCM group) were compared with historical controls whose umbilical stumps were immediately clamped [PI+ICC (immediate cord clamping) group] in a case-control study. Peripheral blood CD34 percentage as a measure of hematopoietic stem cell transfusion was the primary outcome. Early and late-onset anemia; polycythemia; frequency of packed red blood cells (PRBCs) transfusion during NICU stay; peak total serum bilirubin (TSB); incidence of phototherapy, admission rectal temperature; first 24 h hypothermia and hypoglycemia; episodes of hypotension and need for volume expander boluses and inotropic support during the first 24 h of age; duration of oxygen therapy; bronchopulmonary dysplasia (BPD); severe intra-ventricular hemorrhage (IVH); necrotizing enterocolitis (NEC); culture-proven late-onset sepsis; length of hospital stay; and in-hospital mortality were secondary outcomes.ResultsIn preterm infants with placental insufficiency, umbilical cord milking was associated with greater peripheral blood CD34 percentage, hemoglobin levels initially and at postnatal age of 2 months, alongside significantly shorter duration of oxygen therapy compared with ICC group. Frequency of packed RBCs transfusion during hospital stay was comparable. Neonates in UCM group had a greater peak TSB level during admission with significantly higher need for phototherapy initiation compared with ICC. Logistic regression, adjusted for gestational age, revealed that UCM resulted in greater CD34 percentage, higher initial hemoglobin level, higher peak serum bilirubin, significant increase of phototherapy initiation, and higher hemoglobin level at 2 months.ConclusionsUCM in preterm neonates born to mothers with placental insufficiency was feasible and resulted in greater CD34 percentage, higher initial hemoglobin level, higher peak serum bilirubin, significant increase of phototherapy initiation, and higher hemoglobin level at 2 months.

Is perinatal asphyxia associated with an increase in serum bilirubin in neonates? A case-control study.

Perinatal asphyxia affects different organs of body depending upon the severity of hypoxemia and ischemia. This study was carried out to evaluate severity of hyperbilirubinemia in relation to severity of asphyxia. A case-control study. Asphyxiated newborns with Apgar score ≤7 at 1 min. and categorized as severe birth asphyxia according to the WHO classification of diseases (ICD10) were matched with controls without birth asphyxia. All babies were examined twice daily for dermal icterus until start of phototherapy. Babies with congenital heart disease, sepsis, cephalohematoma, blood group incompatibility were excluded. Arterial blood gas analysis was done along with serial TSB measurement as per standard guidelines. 50 cases and 50 matched controls were enrolled. The average birth weight and gestation in cases was 2427 ± 30.05 g and 35.9 ± 2.5 weeks and among control it was 2633 ± 378.62 g and 37.76 ± 0.116 weeks. Among cases, onset of jaundice was 56.64 ± 20.43 h compared to 63.36 ± 23 h in control group. In the cases, the average pH was 7.31 ± 0.06, CO2 was 41.52 ± 84, O2 was 94.98 ± 14.83, and HCO3 was 18.56 ± 2.04. The rise and peak of serum bilirubin differed between the case and control groups; in the cases, the peak occurred at the 22nd h of life, then plateaued from the 40th to the 78th hour of life, and ultimately fell at the 96th hour of life. In comparison, the rise and peak of serum bilirubin occurred comparatively late in the control group. The rise and peak in the control group occurred at the 80th and 96th h of life, respectively. The multiple linear regression analysis showed CRP, Apgar at 5 min. below 7 and male gender significantly affects the rise of serum bilirubin (P < 0.05). The peak serum bilirubin in asphyxiated newborns occurs earlier, and plateau for longer duration compared to normal newborns. Low Apgar at 5 min. has significant correlation to earlier rise of bilirubin.

Delayed cord clamping in small for gestational age preterm infants

Infants with restricted growth for age are frequently exposed to insufficient placental circulation and are more likely to develop postnatal complications. Delayed cord clamping at birth for these infants requires further exploration. This study aimed to compare the short-term neonatal outcomes of delayed cord clamping with that of early cord clamping in small for gestational age preterm infants and to explore whether the effects of delayed cord clamping in small for gestational age preterm infants are different from that in non-small for gestational age preterm infants. We conducted a national retrospective cohort study, including infants born at <33 weeks' gestation and admitted to the Canadian Neonatal Network units between January 2015 and December 2017. Small for gestational age infants (birthweight of <10th percentile for gestational age and sex) who received delayed cord clamping ≥30 seconds were compared with those who received early cord clamping. In addition, non-small for gestational age infants who received delayed cord clamping were compared with those who received early cord clamping. The main study outcomes included composite outcome of mortality or major morbidity, neonatal morbidity rate, mortality rate, peak serum bilirubin, and number of blood transfusions. Multivariable logistic and linear regression models with a generalized estimation equation approach were used to account for the clustering of infants within centers. Overall, 9722 infants met the inclusion criteria. Of those infants, 1027 (10.6%) were small for gestational age. The median (interquartile range) gestational age was 31 weeks (range, 28-32 weeks). After adjusting for potential confounders, delayed cord clamping in small for gestational age infants was associated with a reduction in the composite outcome of mortality or major morbidity (adjusted odds ratio, 0.60; 95% confidence interval, 0.42-0.86) compared with early cord clamping. There was no difference between the 2 groups in peak serum bilirubin. Many associated benefits of delayed cord clamping in small for gestational age infants were similar to those in non-small for gestational age infants. Delayed cord clamping in small for gestational age preterm infants was associated with decreased odds of mortality or major morbidity. Many of the benefits of delayed cord clamping in the small for gestational age preterm infants were similar to those identified in the non-small for gestational age preterm infants.

Cyclophosphamide Followed By Intravenous Busulfan (Cy-Bu) As Myeloablative Conditioning: Impact on Venoocclusive Disease and Transplant Outcomes, Real World Experience

Background: Busulfan (BU) followed by Cyclophosphamide (BU-CY)is one of the most commonly used myeloablative conditioning(MAC) regimens in allogenic Hematopoietic Stem Cell Transplant (HSCT).BU is not inherently hepatotoxic but decreases the levels of glutathione which is critical in the metabolism of toxic CY metabolites.This has been implicated in the higher rates of Sinusoidal Obstruction Syndrome (SOS) with this protocol due to increased sinusoidal endothelial cell injury. Reversal of the protocol i.e cyclophosphamide followed by Busulfan (CY-BU) has been shown to reduce the rates of SOS, especially in myelofibrosis patients.Aim: We retrospectively analysed 25 patients who were given CY-BU as MAC from Jan 2015 to June 2017 for effect on SOS and overall D100 mortality and morbidity in these patients.Patients and methods: Since Jan 2015 we adopted protocol of CY-BU conditioning for all matched sbling donor (MSD) myeloablative transplants at our bone marrow transplant (BMT)center, which included patients of thalassemia major. Briefly CY-BUprotocol consists of CY 60mg/kg on days -7 and -6 followed by intravenous BU 3.2 mg/kg on days -5 to -2 (total 04 days). In patients of thalassemia anti thymocyte globulin (ATG) was administered on day-1 as part of conditioning. All patients received cyclosporine and methotrexate as graft versus host disease (GVHD) prophylaxis. All patients were monitored daily from D-7 to D+30 post HSCT for development of SOS. SOS was defined as per Baltimore criteria and patients meeting criteria for SOS were classified as mild, moderate or severe SOS. All patients were monitored every week after D+30 for presence of GVHD or any other complications till D +100.Results:Twenty five patients underwent HSCT with a CY-BU myeloablative conditioning protocol from Jan 2015 to June 2017. They were compared with 56 controls that underwent HSCT with BU-CY as the conditioning protocol during the period immediately before we switched to CY-BU. The median (IQR) age of patients was 17.5 (6.75 - 35.25) years for BU-CY and 14.00 (6.00 - 27.00) years for CY-BU. There were 38 (68%) males in BU-CY and 16 (64%) males in CY-BU group. The diagnosis in both the groups combined were 13 (16%) ALL, 23 (28%) AML, 14 (17%) CML and 31 (38%) Thalassemia and others. The median peak serum bilirubin in the CY-BU cohort was 1.4mg/dl as compared to 2.45mg/dl in the BU-CY cohort (p = 0.006) (Fig-1) and there was also a trend towards lesser transaminitis in the CY-BU group. 12% patients in the CY-BU group developed mild SOS in comparison to 25% in the BU-CY cohort. The incidence of severe SOS was 20% in the BU-CY group as compared to 4% in the CY-BU group. Overall 72% in the CY-BU cohort did not develop SOS as compared to 45% in the BU-CY cohort. The p value for chi square test for overall difference in VOD between both the groups was 0.082. There was no difference in occurrence of GVHD or other regimen related toxicity like hemorrhagic cystitis in the two groups. There was no difference in the D+100 mortality in the two groups (14% (BU-CY) vs 8% (CY-BU), p = 0.517). CY-BU conditioning appears to reduce the rates of SOS in all transplants including Thalassemia patients, in comparision to BU-CY. A larger study in Thalassemia patients is required to confirm our findings.Conclusions: Reversing the order of administration to cyclophosphamide followed by busulfan (CY-BU) is well tolerated MAC regimen and is associated with significantly less hepatotoxicity. This study limited by smaller number of patients, shows trend towards significantly less incidence of severe SOS and mortality due to SOS with CY-BU regimen. We are aware that our limited number of patients could have effected statistical analysis as far as GVHD and other transplant related mortality issues are concerned. However significant less hepatotoxicity as shown by our study is very important for patients of thalassemia major who due to hepatic iron overload have higher incidence of SOS. There is a need for prospectively studying CY-BU in a larger cohort of patients and comparing with other novel MAC regimens like treosulfan and thiotepa to develop a more effective and safe conditioning regimen.Figure 1: Box-plot comparing maximum serum bilirubin (max_bil) in peritransplant period in two groups (see text) [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Evaluation of the ISGLS Criteria for Post-hepatectomy Liver Failure: Insights from Consideration of the Comprehensive Complication Index as a Measure of Morbidity

Purpose: We aimed to evaluate the International Study Group of Liver Surgery (ISGLS) definition and grading system for post-hepatectomy liver failure (PHLF) using the Comprehensive Complication Index (CCI), a standardized morbidity measure. Methods: Adult patients who underwent major hepatic resection between 2010-2020 were included from twelve international centers. We identified patients who met criteria for PHLF based on three definitions: 1) ISGLS, 2) INR >1.7 and serum bilirubin >3 mg/dL (Balzan), or 3) peak serum bilirubin >7 mg/dL (Mullen). We compared the 90-day mortality and major morbidity predicted by each definition. We then tabulated the distribution of CCI by ISGLS grade and used logistic regression to determine the odds of CCI>40 and 90-day mortality associated with ISGLS grade. Results: Among 1654 patients, 444 (26.8%) met ISGLS PHLF criteria. Of the three PHLF definitions, the ISGLS definition had the highest AUC (0.72) and sensitivity (69.4) for prediction of 90-day mortality. Patients with ISGLS PHLF grades B and C were at increased odds of CCI>40 (Grade B OR 3.7; 95% CI: 2.0-6.9; and Grade C OR 96.1; 95% CI: 45.8-201.3) and 90-day mortality (Grade B OR 2.8; 95% CI: 1.0-7.4; and Grade C OR 108.0; 95% CI: 53.3, 218.7). ISGLS grade A PHLF was not associated with CCI>40 or 90-day mortality (Table 1). Conclusions: In this diverse, international cohort of patients undergoing major hepatectomy, ISGLS grade A was not associated with significant morbidity or mortality, calling into question the current classification of patients in this group as having clinically significant PHLF.FP08.06_Table 1Comparison of Morbidity and Mortality by ISGLS Grade (n=1654)No ISGLS PHLF n=1210ISGLS A n=287ISGLS B n=103ISGLS C n=54CCI, median (IQR)0 (0-20.9)8.7 (0-26.2)27.6 (20.9-35.9)100 (44.9-100)P<0.001 CCI: 0672 (55.5)138 (48.1)0 (0)0 (0) CCI: 1-20110 (9.1)21 (7.3)12 (11.7)0 (0) CCI: 20-40375 (31.0)111 (38.7)76 (73.8)10 (18.5) CCI: 40-6032 (2.6)9 (3.1)14 (13.6)9 (16.7) CCI: 60-802 (0.2)0 (0)0 (0)1 (1.9) CCI: 80-10019 (1.6)8 (2.8)1 (0.97)34 (63.0)OR for CCI>40 (95% CI)-1.37 (0.78-2.41)3.72 (2.02-6.87)96.05 (45.84-201.27)AUC=0.72OR for 90-day mortality (95% CI)-1.75 (0.80-3.83)2.76 (1.02-7.43)108.00 (53.33-218.72)AUC=0.78 Open table in a new tab

Predictors of 90-Day Mortality following Hepatic Resection for Hepatocellular Carcinoma

Background/Purpose: 90-day mortality is a key performance indicator for short-term perioperative outcome of hepatic resection (HR). Although many preoperative, intraoperative, and postoperative variables predict 90-day mortality following elective HR, only few are specific to hepatocellular carcinoma (HCC). This study aims to determine the predictors of 90-day mortality following elective HR for HCC. Methods: We report a retrospective analysis of patients who underwent elective HR between January 1, 2007, and December 31, 2017. Health status, perioperative variables, and the presence of post-hepatectomy liver failure (PHLF) were studied. Cox’s regression evaluated factors predicting 90-day mortality. Results: Two hundred and forty-four patients diagnosed with HCC underwent HR; 102 (41.8%) underwent a major HR. The postoperative 90-day mortality rate was 5.3%. Multivariate analysis demonstrated that Child-Pugh score (p < 0.001), intraoperative blood loss (p = 0.013), the 50-50 criteria for PHLF (p < 0.001) on postoperative day 5, and peak serum bilirubin >119 µmol/L (p = 0.007) on postoperative day 3 predict 90-day mortality. Conclusion: In patients with HCC undergoing HR, Child-Pugh score, intraoperative blood loss, the 50-50 criteria for PHLF on postoperative day 5, and peak serum bilirubin >119 µmol/L on postoperative day 3 predict 90-day mortality following elective HR for HCC.

Comparison of Efficacy of Prophylactic versus Therapeutic Phototherapy in Preterm Neonates

Background: Jaundice neonatorum may predisposes preterm to develop bilirubin induced neurologic dysfunction even at lower total serum bilirubin level than term infant. Prophylactic phototherapy helps to maintain a lower serum bilirubin level may reduce the need for exchange transfusion in order to prevent kernicterus. Objective: To compare the efficacy of prophylactic versus therapeutic phototherapy among preterm neonates in reducing the frequency of exchange transfusion. Study Design: Randomized Controlled Trial. Settings: Neonatal Unit of Pediatrics department, Sir Ganga Ram Hospital Lahore-Pakistan. Duration: September 2018 to June 2019. Methodology: Two hundred preterm admitted in neonatal unit were enrolled and divided into 2 groups (A and B) using random numbers. Prophylactic phototherapy was initiated in Group A neonates within first 6 hours of life while it was applied when the serum bilirubin has reached to a pre-specified level in Group B. Daily total serum bilirubin level (also direct and indirect) was measured. Efficacy was measured in terms of preventing exchange transfusion. Data was entered and analyzed with SPSS version 21. Chi square was applied to compare efficacy between two groups with p ˂ 0.05 as significant. Results: Mean gestational age was 35.4 0.9 weeks in group A and 35.6 0.7 weeks in group B. There were 54% males and 46% females in group A while 51% males and 49% females in group B. The peak mean serum bilirubin level was observed on 3rd and 4th days in groups A and B respectively. Jaundiced neonates who received exchange transfusion in group A and B were 3% and 8% respectively (p=0.1209). Prophylactic phototherapy found efficacious in 97% preterm although, they received it for longer duration (147 34.25 vs 98 27.10 hours) (p 0.00001). Conclusion: Neonates received prophylactic phototherapy required less exchange transfusions compared to therapeutic group.

A Comparison of Strategies for Managing the Umbilical Cord at Birth in Preterm Infants

To evaluate the rates of practice, and the associations between different cord management strategies at birth (delayed cord clamping [DCC], umbilical cord milking [UCM], and early cord clamping [ECC]) and mortality or major morbidity, rates of blood transfusion, and peak serum bilirubin in a large national cohort of very preterm infants. We retrospectively studied preterm infants <33weeks of gestation admitted to the Canadian Neonatal Network between January 2015 and December 2017. Patients who received ECC (<30seconds), UCM, or DCC (≥30seconds) were compared. Multiple generalized linear/quantile logistic regression models were used. Of 12 749 admitted infants, 9729 were included; 4916 (50.5%) received ECC, 394 (4.1%) UCM, and 4419 (45.4%) DCC. After adjustment for potential confounders identified between groups in univariate analyses, the odds of mortality or major morbidity were higher in the ECC group when compared with UCM group (aOR, 1.18; 95% CI, 1.03-1.35). Mortality and intraventricular hemorrhage were associated with ECC as compared with DCC (aOR, 1.6 [95% CI, 1.22-2.1] and aOR, 1.29 [95% CI, 1.19-1.41], respectively). The odds of severe intraventricular hemorrhage were higher with UCM compared with DCC (aOR, 1.38; 95% CI, 1.05-1.81). Rates of blood transfusion were higher with ECC compared with UCM and DCC (aOR, 1.67 [95% CI, 1.31-2.14] and aOR, 1.68 [95% CI, 1.35-2.09], respectively), although peak serum bilirubin levels were not significantly different. Both DCC and UCM were associated with better short-term outcomes than ECC; however, the odds of severe intraventricular hemorrhage were higher with UCM compared with DCC.

Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants

Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g). To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants. This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018. Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT). Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power. Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, -39; 95% CI, -45 to -32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, -0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of -4.5% (95% CI, -10.9 to 2.0). Morbidities did not differ between groups. Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants. ClinicalTrials.gov Identifier: NCT01944696.

The relationship between hyperbilirubinemia and the promoter region and first exon of UGT1A1 gene polymorphisms in Vietnamese newborns.

To investigate the relationship between unexplained indirect hyperbilirubinemia of Vietnamese newborns and the polymorphism of the promoter TATA box and exon 1 of bilirubin uridine diphosphate glucuronosyltransferase (UGT1A1) gene. A total of 149 neonates were divided into the hyperbilirubinemia group (n = 99) and control group (n = 50). The gene polymorphisms of UGT1A1 gene in the two groups were detected by PCR and direct sequencing, which revealed the relationship between UGT1A1 polymorphism with neonatal hyperbilirubinemia of neonates. The types of UGT1A1 polymorphism in the hyperbilirubinemia group and the peak total serum bilirubin (PSB) levels with different genotypes were observed. (1) (TA)7 insertion mutation, 211G>A, 189C>T, 190G>A, 378C>T and 686C>A were detected. (2) The allele frequency of 211G>A allele mutation was significantly different between the two groups (p < 0.05). (3) Logistic regression analysis showed that homozygosity and heterozygosity of 211G>A were both significantly associated with neonatal hyperbilirubinemia. (4) In the hyperbilirubinemia group, the peak total serum bilirubin level of 211G>A homozygous neonates was higher than that of the wild-type neonates (p < 0.05). We noted that there was an association between neonates with unexplained indirect hyperbilirubinemia in Vietnam and the polymorphism of UGT1A1c.211G>A. In addition, the homozygous 211G>A polymorphism was related to the degree of hyperbilirubinemia. Our article provided data on UGT1A1 polymorphism distribution in the Vietnamese population, which have not been reported yet. Our findings revealed that mutations in UGT1A1 gene are risk factors for unexplained hyperbilirubinemia in Vietnamese neonates. Our article will strengthen the cognition of neonatal jaundice at the genetic level in the pediatric field in Vietnam.

Neurodevelopmental outcome at 6 months of age in full-term healthy newborns with neonatal hyperbilirubinemia

Background: Neonatal hyperbilirubinemia (NNH) is an important cause of preventable brain damage among infants. Neurodevelopmental assessment and Brainstem-Evoked Response Audiometry (BERA) may help in the early identification and management of neurodevelopmental sequelae. Objectives: The objectives of this study were to find the association between neonatal peak serum bilirubin levels and the neurodevelopmental outcomes at 6 months in term infants with NNH and to assess the changes in BERA of these neonates. Methodology: A prospective cohort study was conducted in the Department of Pediatrics, Gandhi Medical College, Bhopal. All healthy, full-term, appropriate-for-date neonates, admitted from December 2014 to June 2015 with hyperbilirubinemia and serum bilirubin >12 mg/dL, were included in the study and were followed up till 6 months of age. The neurodevelopmental assessment was done using the Denver Developmental Screening Test II and BERA was done at an average age of 69 ± 6 days. Results: A total of 77 newborns were enrolled, and 73 completed the study. Of these 77 neonates, 40 (51.65%) had abnormal BERA results, whereas 3 (3.9%) had neurodevelopmental abnormalities. BERA and neurodevelopmental abnormalities were associated with a mean serum bilirubin of 22.58 mg/dL and 31.33 mg/dL, respectively. The cutoff value of serum bilirubin was 16.3 mg/dL and 23.8 mg/dL, respectively, to detect BERA and neurodevelopmental abnormalities, respectively. All patients (11) who received exchange transfusion had BERA abnormalities, and 3/11 (27.3%) had neurodevelopmental abnormalities. The association of ABO incompatibility was significant (P

Profiling of UGT1A1*6, UGT1A1*60, UGT1A1*93, and UGT1A1*28 Polymorphisms in Indonesian Neonates With Hyperbilirubinemia Using Multiplex PCR Sequencing.

Background: Single nucleotide polymorphism (SNP) variants of the uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) gene have been studied as an important factor in neonatal hyperbilirubinemia (jaundice) severity. Specific ethnicities, including Asians, have certain SNPs that appear more frequently than others.Aim: To identify the most common SNPs in Indonesian neonates and their association with the severity of neonatal hyperbilirubinemia.Methods: Eighty-eight inborn and outborn jaundiced infants from three different hospitals (Bengkulu, Jakarta, Biak Papua) across Indonesia were enrolled in this cross-sectional study and their peak total serum bilirubin (TSB) levels assessed. SNP variant analyses of the TATAA box, promoter, and exon 1 regions of UGT1A1 gene from 78 of the 88 infants were carried out using the SNaPshotR Multiplex Polymerase Chain Reaction (PCR) System followed by DNA sequencing.Results: We detected SNP variants UGT1A1*28, UGT1A1*60, UGT1A1*93, and UGT1A1*6 in our population. Mean total serum bilirubin (TSB) was 14.59 ± 5.57 mg/dL. Bivariate analyses using delivery location, gestational age, birth weight, mother's age, and ethnicity were shown to be associated with moderate-to-severe hyperbilirubinemia (p < 0.05). None of the four SNPs appeared to be associated with moderate-to-severe hyperbilirubinemia. In multivariate analysis, however, only the “other ethnic group” (e.g., Chinese, Bengkulu, Papua, Bima) category showed an association with moderate-to-severe hyperbilirubinemia, with an odds ratio of 6.49 (95% CI 1.01–41.67; p < 0.05).Conclusions: We found that the UGT1A1*60 is the most common SNP detected in neonates with hyperbilirubinemia in the Indonesian population. Interestingly, in Indonesia, UGT1A1 polymorphisms do not appear to be associated with differences in the severity of hyperbilirubinemia.

Potential protective effects of bilirubin following the treatment of neonatal hypoxic-ischemic encephalopathy with hypothermia therapy.

Background: Therapeutic hypothermia (TH) is the standard therapy for hypoxic-ischemic encephalopathy (HIE) and is associated with a wide range of physiological changes. Objective: We re-evaluated the effects of HIE and TH on bilirubin measurements following HIE in a center involved in the China cooling randomized controlled trial (RCT). Methods: Serial serum bilirubin concentrations measured during the first week of life were compared among the HIE + NT (normothermia) group, HIE + TH treatment group and control group (without HIE). Survivors of HIE were followed and assessed at approximately 2 years of age, and the results were correlated with peak bilirubin levels during the first week of life. Results: One hundred and thirty-eight infants were available for analysis. Significantly lower bilirubin levels were recorded in the HIE + NT group than in the controls (P<0.05). Significant differences were not observed among the patients in the HIE + NT group (mild to severe) or between the HIE + TH group and the HIE + NT group at any time point (P>0.05). The peak serum bilirubin concentrations recorded at 96 h of age showed a good correlation with the results of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III) (P=0.02). Conclusion: Bilirubin potentially exerts a neuroprotective effect during the first week of life, and low temperature does not affect the possible antioxidant function of bilirubin during TH following HIE.

Learning from claims: hyperbilirubinaemia and kernicterus

We examined claims made against the National Health Service (NHS) involving neonatal jaundice in order to determine whether there were lessons that could be learnt from common themes.This was a...

Cord bilirubin as a Predictor of Neonatal Hyper bilirubinemia in healthy term babies

Objectives: To assess the value of cord blood bilirubin in identifying term healthy babies who develop significant hyperbilirubinemia. Methodology: This Prospective cohort study, conducted from May 2016 to September 2016 in a tertiary care hospital included 100 term healthy breastfed babies without Rh incompatibility or significant illness. Cord bilirubin was estimated in all babies. Neonates were followed up daily for 5 days for hyperbilirubinemia. Serum bilirubin levels were estimated on day 5 in all babies. Significant hyperbilirubinemia was defined as bilirubin > 15 mg/dl after 72 hours. Results: Mean cord bilirubin was 2.8 +2.4 mg /dl in those who developed hyperbilirubinemia and 2.5+2.91 mg/dl in those who did not. Clinically detectable jaundice was present in 72%.Twenty-two percent babies developed hyperbilirubinemia. Peak serum bilirubin of babies who developed significant hyperbilirubinemia was 23+ 2.8mg/dl at 120 hours. Cord bilirubin of > 2mg /dl was present in 64 babies and 19 (29%) developed hyper bilirubinemia. Cord bilirubin 2mg/dl. ABO incompatibility was significantly associated with hyperbilirubinemia (p=0.0006). Conclusion: Cord bilirubin can be a good predictor of hyperbilirubinemia. Neonates with cord bilirubin 2 mg/dl need close follow up.