Total Serum Bilirubin Values Research Articles

Transcutaneous bilirubin measurement: does it work in the real world?

In their study of the routine use of transcutaneous bilirubin (TcB) measurements in 27 well infant nurseries, Taylor et al1 found that 2.2% of TcB measurements underestimated the clinical laboratory measurement of total serum bilirubin (TSB) by ≥3.0 mg/dL, and the tendency for TcB to underestimate TSB increased with advancing newborn age (presumably up to the length of stay of a normal newborn). They nevertheless conclude that TcB measurements “provide reasonably accurate estimates of TSB values” and work well enough as a method for identifying significant hyperbilirubinemia. Because many nurseries now follow the recommendation to screen all infants with a TSB or TcB before discharge,2 it is important to know whether we can rely on the TcB as a screening measurement. Although some 30 years of worldwide experience with this technique have been largely rewarding,3 most of the published data come from research studies where attention is given to detail and quality control. The importance of quality control is illustrated in a report by Wainer et al,4 who noted that 25% of the TcB devices they studied “did not perform within allowable limits of our quality control procedures ….” Both of the instruments currently … Address correspondence to M. Jeffrey Maisels, MB, BCh, DSc, Division of Newborn Medicine, Beaumont Children’s Hospital, 3601 W 13 Mile Rd, Royal Oak, MI 48073. E-mail: jmaisels{at}beaumont.edu

Incidence, etiology, and outcomes of hazardous hyperbilirubinemia in newborns.

Total serum bilirubin (TSB) levels ≥ 30 mg/dL are rare but potentially hazardous. A better understanding of their incidence, causes, and outcomes could help inform preventive efforts. We identified infants born ≥ 35 weeks' gestational age from 1995-2011 in Kaiser Permanente Northern California (n = 525409) and examined the medical records of infants with a TSB ≥ 30 mg/dL to determine etiology and the occurrence of acute bilirubin encephalopathy. We reviewed inpatient and outpatient encounters through 2013 for evidence of sensorineural hearing loss (SNHL) or cerebral palsy (CP). We identified 47 infants with TSB ≥ 30 mg/dL (8.6 per 100000 births). In 44 infants (94%), the hyperbilirubinemia occurred after the initial birth hospitalization. The etiology was not identified in 33 (70%). Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in only 25 (53%) of whom 10 (40%) were deficient. Four children had acute bilirubin encephalopathy of whom 2 developed both CP and SNHL, and 1 developed isolated SNHL. These 3 infants all had G6PD deficiency and TSB >40 mg/dL. One additional 35-week infant with TSB 38.2 mg/dL had SNHL. Hazardous (≥ 30 mg/dL) hyperbilirubinemia is a rare event. No etiology could be identified from the clinical record in most cases. G6PD deficiency was the leading cause of hazardous hyperbilirubinemia when an etiology was identified, but many were not tested. Chronic, bilirubin-induced neurotoxicity was uncommon and occurred only in the setting of additional risk factors and TSB values well over (>15 mg/dL) the American Academy of Pediatrics exchange transfusion thresholds.

Usefulness of serum bilirubin levels as a biomarker for long-term clinical outcomes after percutaneous coronary intervention.

The aim of this study was to evaluate the prognostic value of serum total bilirubin on the development of adverse outcomes after percutaneous coronary intervention (PCI) besides high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP). Serum total bilirubin, hs-cTnT, and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac death. There were 21 events of cardiac death during a mean of 25.8 months of follow-up. When the serum total bilirubin cut-off level (median value) was set to 0.58 mg/dL using the receiver operating characteristic curve, the sensitivity was 95.2 % and the specificity was 51.0 % for differentiating between the group with cardiac death and the group without cardiac death. Kaplan-Meier analysis revealed that the lower serum total bilirubin group (<0.58 mg/dL) had a significantly higher cardiac death rate than the higher serum total bilirubin group (≥0.58 mg/dL) (10.4 vs. 0.6 %, log-rank: P = 0.0001). In conclusion, low serum total bilirubin is a predictive marker for cardiac death after PCI.

Reproducability of non-invasive bilirubin measurements.

To determine the level of agreement between transcutaneous bilirubin (TcB) measurements when sequentially measured by one and two users. A method comparison study design was used to compare two sequential TcB measurements (JM103, Drager Medical Inc., Telford, PA) obtained by the same user and then by two different users. Users were blinded to each others' results. Differences (bias) and limits of agreement (±2 precision or SD) between sequential measurements with the TcB by a single user and two users were calculated and graphed using the Bland-Altman method. Acceptable levels for bias and precision were set a priori at bias ≤±1.5 mg/dL and/or precision ≤±3.0 mg/dL. A total of 34 newborn infants were studied, with total serum bilirubin (TSB) levels ranging from 2.7 to 8.1 mg/dL, averaging (±SD) 5.5 ± 1.8 mg/dL. Differences (bias) and the level of agreement (precision; SD) for two sequential noninvasive TcB measurements obtained by a single user and two different users (-0.2 ± 0.7 and -0.4 ± 0.7, respectively) were within the acceptable ranges. We found good agreement between TcB measurements obtained sequentially by a single user and by two different users of the device, as well as between laboratory TSB values in low-risk newborn infants with normal bilirubin levels. These findings support the use of a noninvasive bilirubin meter to screen for hyperbilirubinemia, which could reduce the amount of blood obtained invasively from newborns.

Transcutaneous bilirubinometry is not influenced by term or skin color in neonates

BackgroundThe utility of transcutaneous bilirubin measurements (TcB) in screening for hyperbilirubinemia in preterm infants (<34weeks) and in non-white infants remains a matter of debate. AimTo evaluate accuracy of TcB in preterm and term infants of different ethnic backgrounds, using a second generation bilirubinometer. Study designThe Draeger JM-103® device was used to measure TcB. Eighty five measurements of TcB and total serum bilirubin (TSB) were retrospectively compared. Neonates were stratified into groups according to gestational age: <34weeks (group 1, n=44) and >34weeks (group 2, n=41), and according to ethnic origin: Caucasians (group A, n=49) and non-Caucasians (group B, n=36).Statistical analysis, using Pearson's correlation coefficient (r) and Bland–Altman analysis were performed to evaluate correlation and agreement between TSB and TcB values. Multiple linear regression was used to control for confounders for TSB values. ResultsCorrelation between TSB and TcB was high. Pearson's correlation coefficients were over 0.9 in all groups (0.910, 0.908, 0.916 and 0.934, p<0.0001 in groups 1, 2, A, and B respectively). Bland–Altman plots showed acceptable and close limits of agreements (56.8/−57.7, 54.2/−67.2, 57.7/−55.8, and 51.3/−69.9μmol/L in groups 1, 2, A and B respectively) with a trend for TcB to overestimate TSB in groups 2 and B. Birth term and skin color were not identified as confounding factors for predicting TSB in multiple linear regression. ConclusionsTcB measurements using the Draeger JM-103® device correlate significantly with TSB, regardless of term and skin color. Transcutaneous bilirubinometry seems to be a safe and cost-effective screening method for severe hyperbilirubinemia in newborns of different terms and ethnic origins.

English

OBJECTIVE: 1. Comparing Cord Serum Albumin level (CSA) with Cord Serum Bilirubin (CSB) in predicting neonatal hyperbilirubinemia. 2. To know the sensitivity, specificity, Positive predictive value and negative predictive value of CSA and CSB in predicting neonatal jaundice in term neonates. METHOD: Prospective study was performed on 174 healthy term neonates. Relevant maternal history is collected. Cord blood was collected from the healthy term neonates at birth, CSA and CSB measured. Neonate was assessed clinically every day. Total Serum Bilirubin (TSB) and blood group were assessed in neonate during 72-96 hours of life. TSB value ≥17mg/dl is considered Neonatal Hyperbilirubinemia (NH) which requires intervention like phototherapy (PT) or Exchange transfusion (ExT). RESULT: Study cohort is grouped in Group 1, Group 2 and Group 3 based on Cord Serum Albumin level ≤2.8g/dl, 2.9-3.3g/dl and ≥3.4g/dl, respectively. Based on CSB, study cohort divided into neonates with CSB ≤ 2mg/dl and CSB ≥ 2.1mg/dl. Statistical analysis done for correlation of CSA and CSB with NH. Statistical significance is seen for both CSA and CSB. CONCLUSION: Both CSA and CSB are equally effective in predicting NH at birth. These study variables can be considered as neonatal screening tool for NH for term neonates.

Total serum bilirubin as a negative prognostic factor in idiopathic canine chronic hepatitis

Total serum bilirubin (TBIL) is used as a prognostic factor in chronic hepatitis (CH) in human beings. To date, the authors are unaware of any studies looking at the value of TBIL as a prognostic factor in idiopathic canine CH. The objective of the current study was to assess if TBIL is a negative prognostic factor in idiopathic canine CH, and to identify other prognostic factors. Thirty-nine dogs with histologically confirmed idiopathic CH admitted to 2 referral centers between 1999 and 2010 were included in the study. Patients with concurrent diseases that could affect TBIL or the survival time were excluded. Total serum bilirubin was measured prior to liver biopsy, and CH was diagnosed according to standardized histological criteria. Survival time was calculated from time of diagnosis to time of death or euthanasia. Cox proportional hazard analysis was performed to identify prognostic factors. The mean survival time for the 39 dogs included in the analysis was 197 days (1-2,677), and the mean total serum bilirubin was 11 μmol/l (2-265). Total serum bilirubin was statistically significantly associated with survival (odds ratio = 1.082, P = 0.047) as were weight (odds ratio = 1.028, P = 0.028) and the presence of ascites (odds ratio = 6.758, P = 0.013). The current study demonstrates that TBIL could be used as an additional prognostic factor in canine CH.

Plotting Transcutaneous Bilirubin Measurements on Specific Transcutaneous Nomogram Results in Better Prediction of Significant Hyperbilirubinemia in Healthy Term and Near-Term Newborns: A Pilot Study

Background: The American Academy of Pediatrics has recommended a systematic assessment before discharge for the risk of severe hyperbilirubinemia. Plotting total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) on a TSB hour-specific nomogram is proposed as a tool for laboratory evaluation. Objectives: The aim of this study was to compare the predictive characteristics, particularly the incidence of false negative rate (FNR), of the practice of plotting TcB values on the TSB hour-specific risk nomogram versus on transcutaneous nomogram. Methods: Paired TSB and TcB measurements were conducted on 141 newborns. Risk of developing significant hyperbilirubinemia was defined as infants with bilirubin level ≥75% on TSB or ≥95% on TcB nomogram. TSB values, plotted on the TSB nomogram of Bhutani et al. [Pediatrics 1999;103:6-14], were used as reference. TcB values were plotted on the TSB nomogram and on the transcutaneous nomograms of Maisels and Kring [Pediatrics 2006;117:1169-1173] and Fouzas et al. [Pediatrics 2010;125:e52-e57]. Results: Plotting TcB measurements on a TSB nomogram resulted in a trend towards a higher FNR when compared to Maisels' and Fouzas' nomograms (18.0/1,000 compared to 10.2/1,000 and 8.6/1,000 respectively). Although not statistically significant, plotting TcB on transcutaneous nomogram resulted in better predictive values with the Fouzas' nomogram, having the best sensitivity (90.0%) and specificity (87.79%) as well as the highest positive (35.97%) and negative (99.14%) predictive value. Conclusion: Plotting TcB on a TSB nomogram may result in increased rate of FNR and decreased predictive characteristics. The practice of plotting TcB on a TSB nomogram needs further evaluation.

Elevated C‐Reactive Protein and Spontaneous Bacterial Peritonitis in Children With Chronic Liver Disease and Ascites

The aims of this study were to compare laboratory indices of spontaneous bacterial peritonitis (SBP) and noninfected ascites in children with chronic liver disease and to determine the infectious agents involved in SBP. The medical records of 90 children with chronic liver disease and ascites studied between January 2005 and August 2011 were reviewed for laboratory data of diagnostic significance in SBP. Standard laboratory tests included blood cell count, coagulation indices, liver and renal function tests, C-reactive protein (CRP), serum sodium concentration, serum albumin, and serum cultures. Ascitic fluid obtained from 152 paracentesis procedures was assayed for cytology, Gram stains, neutrophil counts, and bacteriological cultures. The SBP group manifested significantly lower albumin levels and elevated CRP levels, prothrombin times, international normalized ratios, and leukocyte number (P<0.05 in each case). CRP was shown to be an independent variable in the prediction of SBP. Values of serum creatinine, sodium concentration, urea, total bilirubin and differential leukocyte shift were comparable in SBP and noninfected ascites. Streptococcus pneumoniae was the most prevalent infectious agent in the ascitic fluid (44%). CRP may be useful in early detection and monitoring of SBP in children with liver disease.

Clinical study on Yinzhi-huang combined with probiotics in the treatment of neonatal hyperbilirubinemia

Objective To investigate the therapeutic efficacy of Yinzhi-huang combined with probiotics in the treatment of neonatal hyperbilirubinemia.Methods 80 neonates of hyperbilirubinemia were recruited into a treatment group (40 cases) and a control group (40 cases).The control group was treated with the gap blue light irradiation,besides,patients with rapid increase or high level of bilirubin were additionally treated with acid-correcting agents,Liver enzyme inducer,and albumin infusion; while the treatment group was additionally treated with Yinzhi-huang and probiotics on the basis of the control group.The values of serum total bilirubin before the treatment Was determined in both groups.During treatment,the changes of daily bilirubin,were monitored with percutaneous bilirubin monitor,and the time for serum bilirubin values decreased to normal level was studied in both groups.Results The two groups showed no significant difference in examination of the serum bilirubin values before treatment(P＞0.05).The daily bilirubin decreased value of treatment group(53.07± 17.80) μmol/L showed statistically significant compared with the control group(30.56± 13.43)μmol/L(P＜0.05); the time for serum bilirubin values decreased to normal level in the treatment group (4.87± 2.06) d was significantly different compared with the control group (7.12± 2.33) d,(P＜ 0.05).The apparent effective rate in the treatment group 75％ (30/40) was higher than that in the control group 35％(14/40)with statistical significance(x2=5.89,P＜0.05).The total effective rate in the treatment group 92.5％ (37/40)was higher than the control group 75％ (30/40)with statistical significance (x2=4.50,P＜0.05).Conclusion Yinzhi-huang combined with probiotics has better effects than conventional treatment in decreasing the daily bilirubin values,restoring normal serum bilirubin time of neonatal hyperbilirubinemia and it is worthy of clinical application. Key words: Yinzhi-huang ; Probiotics ; Neonatal ; Hyperbilirubinemia ;

Can transcutaneous bilirubinometry safely guide phototherapy treatment of neonatal jaundice in Malawi?

Objectives:To assess the correlation between total serum bilirubin (TSB) and transcutaneous bilirubin (TcB) values in Malawian newborn infants, and to investigate whether TcB can be used safely to guide phototherapy treatment in the absence of TSB results.Methods:128 newborn jaundiced infants were studied in the neonatal nursery at Queen Elizabeth Central Hospital, Blantyre. Paired TSB and TcB measurements (from forehead and sternum) were compared using the linear regression and Bland–Altman methods. Clinical decisions based on TcB results were compared with those based on ‘gold standard’ TSB results.Results:For infants not under phototherapy, the lowest TcB reading (from forehead or sternum) gave the strongest correlation with TSB: r = 0·83 for term infants and r = 0·71 for premature infants. For infants undergoing phototherapy, the highest TcB reading gave the strongest correlation with TSB: r = 0·66 for term infants and r = 0·71 for premature infants. TcB values overestimated the degree of jaundice. For infants not under phototherapy, the mean (SD) bias and imprecision of TcB was 25 (72) μmol/L for term infants and 37 (73) μmol/L for premature infants. For infants under phototherapy, the mean bias and imprecision was 30 (79) μmol/L for term infants and 44 (77) μmol/L for premature infants. For infants not under phototherapy, using the lowest TcB reading to guide treatment decisions (n = 167) had good sensitivity (91%) and specificity (90%). For infants undergoing phototherapy, using the highest TcB reading to guide treatment decisions (n = 129) had good sensitivity (94%), but lower specificity (36%).Conclusions:TcB can be used to safely guide phototherapy treatment in a resource-poor setting.

Prediction of Hyperbilirubinemia in Preterm Newborns Admitted in a Tertiary Care Teaching Hospital

Introduction: Neonatal hyperbilirubinemia is a cause of major concern for the parents as well as the pediatricians due to chance of neurotoxicity. Early prediction of development of significant hyperbilirubinemia can reduce anxiety and duration of hospital stay. Objective: To find out the risk of development of significant hyperbilirubinemia among preterm newborn within first seven days of life. Methodology: This prospective study was carried out in Dhaka Shishu Hospital during the period of January to June, 2007. One hundred &amp; eleven preterm newborns of 30-37 weeks gestational age were enrolled in first day of their life and their serum total and indirect bilirubin were estimated on the 1st, 2nd, 5th &amp; 7th day. Neonates with evidence of hemolysis, direct hyperbilirubinemia, sepsis &amp; major congenital malformation were excluded. Their 1st and 2nd day serum total bilirubin values were analyzed statistically at different cut off points from which significant hyperbilirubinemia can develop on 5th &amp; 7th day of life. Results: The study included 111 premature neonates of 30-37 weeks gestation who were enrolled on first day of their life. Their mean gestational age was 33.7(±2) weeks and mean birth weight was 1754(±341) gm. Of them, 38 (34%) neonates developed significant hyperbilirubinemia within first seven days of life. Among the study population, 40 (36%) neonates had serum total bilirubin value of &lt;2 mg/dL on first day of life. None of them developed significant hyperbilirubinemia (100% negative predictive value). Again 65 (58.5%) neonates had serum total bilirubin value of &lt;5 mg/dL on second day of life. Among them only 7.6% developed significant hyperbilirubinemia (92.3% negative predictive value). Conclusion: The first and second day serum total bilirubin values can predict subsequent hyperbilirubinemia within seven days of life. First day serum total bilirubin value of 2 mg/dL can be taken as a safe limit from which chance of significant hyperbilirubinemia is less. DOI: http://dx.doi.org/10.3329/bjch.v37i2.17265 BANGLADESH J CHILD HEALTH 2013; VOL 37 (2) : 85-89

BiliCheck vs JM-103 in identifying neonates not at risk of hyperbilirubinaemia

BackgroundTranscutaneous bilirubinometry is widely used to predict hyperbilirubinemia by using several devices. The aim of this study was to compare the predictive ability of BiliCheck vs JM-103 in identifying neonates not at risk of significant hyperbilirubinemia, putting the data obtained with the two instruments on our transcutaneous bilirubin nomogram built with the BiliCheck.MethodsTranscutaneous bilirubin (TcB) measurement was performed when jaundice appeared in newborn babies and/or just before discharge from the hospital. It was performed at the forehead with the two instruments within 5 minutes by two experienced neonatologists, each one blind to the value obtained by the other. Blood samples were drawn to obtain total serum bilirubin (TSB) levels soon after TcB measurements.ResultsA total of 627 paired-sample measurements were obtained from 298 newborn babies. Out of the total population studied, 16 newborn babies (5.4%) showed significant hyperbilirubinemia defined as TSB value >17 mg/dL, or as need for phototherapy treatment according to the AAP guidelines. TcB measurements showed false negative results in the first 60 hours of life using both devices. After the 60th hour of life, TcB measurements using both devices successfully predicted newborn babies not at risk of significant hyperbilirubinemia, being the JM-103 more reliable than BC because of fewer false positive results.ConclusionsOur study shows that both BC and JM-103 can exclude subsequent significant hyperbilirubinemia when the measurements are performed after the 60th hour of life. Nevertheless, the transcutaneous pre-discharge screening should be considered only as the first step, and it has to be followed by a follow-up through the first days after discharge.

Beneficial effects of S-adenosyl-L-methionine on post-hepatectomy residual liver function: a prospective, randomized, controlled clinical trial.

Hepatectomy is associated with high rates of postoperative liver dysfunction in patients with cirrhosis. Since S-adenosyl-L-methionine (SAMe) can be used to treat liver disease, we performed a prospective clinical trial to investigate whether it could be used after hepatectomy to benefit residual liver function. We studied 79 hepatitis-related chronic patients who underwent resection of hepatocellular carcinoma; 39 patients were randomly assigned to receive postoperative intravenous SAMe treatment, and 40 were randomly assigned to a control group. The postoperative SAMe treatment consisted of SAMe 1,000mg given intravenously for seven days. The other treatment was standardized. At inclusion into the trial no significant differences were observed between the two groups with respect to gender, age, Child classification, preoperative liver function tests, blood loss, total time of hepatic pedicle occlusion and the extent of liver resection. The overall frequency of postoperative liver insufficiency decreased from 42% in the control group to 31% in the SAMe group, although not statistically significant (p=0.121). When the patients who underwent hepatic pedicle occlusion by Pringle’s maneuver over 15min were analyzed, the frequency of postoperative liver insufficiency (p=0.028), serum total bilirubin levels on days 5 (p=0.025) and 7 (p=0.032) preoperatively, and the maximum value of postoperative serum total bilirubin (p=0.040) were significantly greater in the control than in the SAMe group. The results indicate that the postoperative SAMe therapy can benefit residual liver function of the patients with cirrhosis, especially in those suffering greater ischemia reperfusion injury.

3:46 PM Abstract No. 105 - Modeling the rate of bilirubin decay after percutaneous drainage prior to chemotherapy

Purpose To evaluate the potential of two models of bilirubin decay to predict response to drainage in patients who underwent biliary drainage to lower serum bilirubin prior to chemotherapy. Materials and Methods IRB-approved retrospective review identified 77 patients with malignant biliary obstruction who underwent a single biliary drainage to decrease bilirubin prior to chemotherapy administration and who had at least four subsequent serum bilirubin determinations (regardless of value) at 7-10 day intervals for the first 4 weeks following the procedure. Data were analyzed in both mono-exponential (ME) (bilirubin level is described in terms of pure exponential decay) and mono-exponential-static (MS) (bilirubin level is described in terms of exponential decay followed by an inflection point where the bilirubin level levels off to a constant value) models. Responders were defined as patients who achieved total serum bilirubin levels Results Across all patients, the MS model had better fit with total serum bilirubin values after drainage than the ME model (R2 0.82 vs 0.62, respectively). When patients were stratified into responders and non-responders, the MS model similarly had better fit to patient data (responders: R2 0.91 v 0.71; non-responders R2 0.66 v 0.45). Parameters extracted from both models (ME and MS) suggest that both estimated pre-drainage bilirubin (10.4 and 10.7 mg/dL, respectively) and the exponential decay rate (0.14 and 0.22 mg/dL/day) of responders was significantly different from the estimated pre-drainage bilirubin (15.0 and 15.1 mg/dL) (P=0.0003 and P Conclusion Models of bilirubin response to percutaneous drainage may be useful to provide early clinical separation of responders from non-responders, prompting additional drainage or internalization of drainage when clinically appropriate.

Bilirubin nomogram: A prediction tool or natural history profile?

Bilirubin nomograms have dual functions: (a) to track an individual baby using an evidencebased predictive risk assessment tool; and, (b) to inform the public health perspective on adverse outcome reduction by altering the natural course of the disease through early intervention. The original report that demonstrated the predictive value of a routine predischarge total serum bilirubin (TSB), measured as a universal screen, was simplified for immediate applicability to plot on an hour-specific bilirubin nomogram described for a population of racially diverse, healthy, term and near-term newborns during the first postnatal week in a Philadelphia hospital [1]. Subsequent studies have validated this predictive ability and the usefulness of this nomogram in several regional and multi-national populations [2]. When used with combination of TSB and transcutaneous testing, other centers have effectively promoted universal bilirubin screening [3, 4]. The outcome measure is the likelihood (LR) of TSB >95th percentile for age in hours. Based on the prevalence of “disease”: TSB in the high-risk zone, >95th percentile post-discharge for any population is (present / (present + absent)). One out of 23 infants in this study evidenced “disease”. The LR may calculate a revised or posttest probability of disease: posttest odds = pretest odds × LR where odds = probability ÷ (1 – probability). Because LR is prevalence independent, it can be used to calculate the posttest probability at any site in the world. Alternatively, the revised probability may be obtained for any site by dividing the absent component of the present : absent ratio for the total population by the LR to calculate the revised present : absent ratio for each risk zone (legend for Table 3 in reference 1). The clinical goal for any predictive test is defined by its outcome. We selected an identification of a higher-risk population to ensure a safety margin because of known imprecision of clinical diagnostic tests. Biological risk factors, accuracy as well as precision of bilirubin, pattern of clinical practice and access to healthcare markedly influence the predictive performance of the bilirubin tests. Gestational age, race and ethnicity are also singularly important [4, 5]. Subsequent consensus for TSB thresholds for use phototherapy governed by prematurity, hemolysis and clinical signs of neurotoxicity [2,4] have informed clinical practices similar to those in North America and Europe. However, geography and nationality are poor surrogates for biology, race, ethnicity and prematurity and have yet to be recognized as specific risk factors. Performance of a predictive test is also largely defined, in a research setting, with meticulous attention to study design, definitions, minimization of bias, subsequent validation in diverse cohorts and an anticipation of variable implementation in actual clinical practice. In this issue of Indian Pediatrics, Pathak, et al., [6] have attempted to replicate a predictive study without addressing a precise hypothesis and have expended immense effort without studying the vulnerability (if any) for their specific population cared for at their institution. Their data could be influenced by prevailing clinical practice pattern, race or ethnicity but not geography. Assessment of proven predictive tools for local institutional quality improvement should be benchmarked to best practice models and encouraged. On the other hand, novel questions impact nations with additional clinical or public health burden for bilirubin neurotoxicity that includes sepsis, small for dates, postnatal hypoalbuminemia, unrecognized hemolysis, insufficient breast milk intake or access to healthcare. Here, the risk of neurotoxicity can be altered by natural history of the disease itself. A national endeavor to define thresholds for interventions relevant to the diverse population is an achievable newborn health priority to reduce the prevalence of infants with TSB >95th percentile, use of exchange transfusion or possibly prevent kernicterus in India.

Predictive ability of first-day serum bilirubin and haptoglobin for subsequent significant hyperbilirubinemia in healthy-term and near-term newborn

Objective Predicting significant neonatal hyperbilirubinemia using cord blood haptoglobin and bilirubin on the first day of life. Background Neonatal jaundice is the result of an imbalance between the production and elimination of bilirubin. Bilirubin conjugation in newborns is significantly impaired in the first few days; even a small increase in the rate of production can contribute toward the development of hyperbilirubinemia. Hemolysis plays a significant role in bilirubin increase in newborns. When hemolysis takes place, a decrease in the haptoglobin blood level-binding hemoglobin in the environment occurs. Patients and methods A total of 61 healthy newborns of at least 35 weeks' gestation were followed in the first 5 days of life for the development of significant hyperbilirubinemia. All newborns were subjected to cord blood haptoglobin and bilirubin measurement soon after delivery. Total serum bilirubin (TSB) was measured on the fifth day of life. Only 46 newborns were brought in on the fifth day for follow-up. Results A total of 25/46 newborns (54.3%) developed significant hyperbilirubinemia (TSB on the fifth day≥17 mg/dl) and were considered as positive cases. A significant negative correlation was found between cord blood haptoglobin levels and the TSB values on the fifth day. A significant positive correlation was found between cord blood bilirubin levels and the TSB levels on the fifth day. A cut-off level of haptoglobin in cord blood of 7.5 mg/dl was determined to have the highest sensitivity (100%), specificity (81%), and positive predictive value (89%) in the prediction of occurrence of significant hyperbilirubinemia, whereas a cut-off level of cord blood TSB 2.73 mg/dl had the highest sensitivity (100%), specificity (90%), and positive predictive value (93%) in the prediction of significant neonatal hyperbilirubinemia. Conclusion The haptoglobin value and TSB value taken from the blood of the umbilical cord can be used as a guiding indicator to demonstrate the future occurrence of significant hyperbilirubinemia in newborns.

Bilirubin nomogram for prediction of significant hyperbilirubinemia in North Indian neonates

(i) To construct hour-specific serum total bilirubin (STB) nomogram in neonates born at =35 weeks of gestation; (ii)To evaluate efficacy of pre-discharge bilirubin measurement in predicting hyperbilirubinemia needing treatment. Diagnostic test performance in a prospective cohort study. Teaching hospital in Northern India. Healthy neonates with gestation =35 weeks or birth weight =2000 g. Serum total bilirubin was measured in all enrolled neonates at 24 ± 6, 72-96 and 96-144 h of postnatal age and when indicated clinically. Neonates were followed up during hospital stay and after discharge till completion of 7th postnatal day. Key outcome was significant hyperbilirubinemia (SHB) defined as need of phototherapy based on modified American Academy of Pediatrics (AAP) guidelines. In neonates born at 38 or more weeks of gestation middle line and in neonates born at 37 or less completed weeks of gestation, lower line of phototherapy thresholds were used to initiate phototherapy. For construction of nomogram, STB values were clubbed in six-hour epochs (age ± 3 hours) for postnatal age up to 48 h and twelve-hour epochs (age ± 6 hours) for age beyond 48 h. Predictive ability of the nomogram was assessed by calculating sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio, by plotting receiver-operating characteristics (ROC) curve and calculating c-statistic. 997 neonates (birth weight: 2627 ± 536 g, gestation: 37.8 ± 1.5 weeks) were enrolled, of which 931 completed followup. Among enrolled neonates 344 (34.5%) were low birth weight. Rate of exclusive breastfeeding during hospital stay was more than 80%. Bilirubin nomogram was constructed using 40th, 75th and 95th percentile values of hour-specific bilirubin. Pre-discharge STB of =95th percentile was assigned to be in high-risk zone, between 75th and 94th centile in upper-intermediate risk zone, between 40th and 74th centile in lower-intermediate risk zone and below 40th percentile in low-risk zone. Among 49 neonates with pre-discharge STB in high risk zone. 34 developed SHB (positive predictive value: 69.4%, sensitivity: 17.1%, positive likelihood ratio: 8.26). Among 342 neonates with pre-discharge STB in low risk zone, 32 developed PHB (negative predictive value: 90.6% and specificity: 42.5%, positive likelihood ratio: 0.37). Area under curve for this risk assessment strategy was 0.73. Hour-specific bilirubin nomogram and STB measurement can be used for predicting subsequent need of phototherapy. Further studies are needed to validate performance of risk demarcation zones defined in this hour-specific bilirubin nomogram.

1412 Transcutaneous Bilirubinometers Used Within a Structured Pathway Predicts High Serum Bilirubin Levels in Healthy Term Jaundiced Neonates Monitored at Home

BackgroundUK (NICE) guidelines recommend that bilirubin is monitored in all jaundiced babies. We implemented a home based integrated care pathway to monitor healthy term jaundiced neonates with transcutaneous bilirubinometers (TcB)....

Nasobiliary Drainage in an Episode of Intrahepatic Cholestasis in a Child With Mild ABCB11 Disease

Nasobiliary Drainage in an Episode of Intrahepatic Cholestasis in a Child With Mild <i>ABCB11</i> Disease