Predischarge Total Serum Bilirubin Research Articles

Predischarge Transcutaneous Bilirubin and Total Serum Bilirubin in Predicting Readmission Due to Significant Hyperbilirubinemia in Near-Term and Term Neonates

Background: Prevention of bilirubin encephalopathy in healthy near-term and term neonates is the primary focus of newborn care. This study aims to assess the predictive accuracy of transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) measured before discharge for subsequent readmission because of significant hyperbilirubinemia in near-term and term neonates during the first postnatal week and to analyze the risk factors associated with readmission because of significant hyperbilirubinemia. Methods: TcB with BiliChek device and TSB measurements with bilirubinometer were obtained prior to discharge in all healthy near-term and term neonates delivered and admitted in the postnatal wards during the study period. Postnatal age (in hours) was recorded during bilirubin measurement. Results: The predictive ability of predischarge TcB measurement for the optimum cutoff of 104 µmol/L derived from the area under the receiver operating characteristic curve has a negative predictive value of 99.3% with a negative likelihood ratio (LR) of 0.15 and sensitivity of 91.7%, whereas the predictive ability of predischarge TSB measurement for the optimum cutoff of 109 µmol/L derived from the area under the receiver operating characteristic curve has 100% sensitivity and 100% negative predictive value with a negative LR of 0.0 for no readmission because of significant hyperbilirubinemia. The predischarge TSB level of those readmitted neonates had a very high odds for high-risk zone [OR (95% CI) 358.4 (96.39, 1332.59)] and 7.8 folds higher odds for intermediate-risk zone compared to those neonates who did not require readmission in Bhutani’s predischarge nomogram. Conclusion: The result of our study showed that both TcB obtained by using BiliChek device and TSB measurements obtained by bilirubinometer for the optimum cutoffs of 104 µmol/L and 109 µmol/L, respectively, and with negative LR of 0.15 and 0.0, respectively, can be used as a safe predischarge tool for no readmission because of significant hyperbilirubinemia after 24 h of postnatal age. The existing Bhutani’s predischarge nomogram for predicting significant hyperbilirubinemia should be an additional screening tool to reduce the rate of subsequent readmission because of hyperbilirubinemia.

Simplifying Hyperbilirubinemia Risk Estimation.

Jaundice impacts more than half of term and late preterm newborns in the first week of life. Although in most cases, jaundice is benign, the consequences of severe hyperbilirubinemia are debilitating; thus, identification of newborns likely to exceed bilirubin treatment thresholds is needed. The American Academy of Pediatrics (AAP) recommends stratification of predischarge total serum bilirubin (TSB) levels by using the Bhutani Nomogram to help determine the appropriate timing of newborn follow-up. A separate nomogram is then used to determine if an infant meets criteria for phototherapy.1Kuzniewicz et al2 aim to simplify the process and more precisely determine when a newborn requires outpatient follow-up for jaundice with a simple equation. Starting with a retrospective cohort study of a diverse sample of 148 162 newborns born at ≥35 weeks’ gestation at 11 Kaiser Permanente Northern California facilities from 2012 to 2017, the researchers identified newborns whose TSB measurements did not exceed phototherapy levels and did not receive phototherapy during the birth hospitalization. Using the newborn’s last TSB value before hospital discharge (predischarge TSB), the authors calculated the difference between the predischarge total serum bilirubin and the corresponding American Academy of Pediatrics phototherapy threshold (in milligrams/deciliter) (Δ-TSB). Newborns who required phototherapy after discharge were identified. The authors compared the ability of the Δ-TSB model to predict postdischarge TSB above phototherapy thresholds to the Bhutani Nomogram. Examining additional variables, they also compared a more complicated Δ-TSB-Plus model. Although all 3 models performed well for those at highest and lowest risk of subsequent severe hyperbilirubinemia, both Δ-TSB and Δ-TSB-Plus models differentiated newborns in the intermediate zones better than the Bhutani Nomogram. Forty-four percent of newborns in Bhutani’s high-intermediate risk zone (who would have follow-up recommended within 48 hours) had a Δ-TSB between −4 and −5 mg/dL. In these newborns, the risk of ever having a subsequent TSB measurement greater than the AAP threshold was only 1.6%, suggesting follow-up within 48 hours might not be indicated.The Δ-TSB measurements used in this study relied on clinician discretion in follow-up; therefore, the predictive accuracy of the Δ-TSB models may be inflated because of differential verification bias as the authors mention. Only TSB measurements were included, but many hospitals and clinics use transcutaneous bilirubinometry.3 Although one can extrapolate the Δ-TSB for low bilirubin levels, the additional uncertainty involved when transcutaneous bilirubin measurements are used to approximate TSB levels has the potential to impact effective implementation of the Δ-TSB risk prediction approach.4 The 2004 AAP bilirubin thresholds were used in this study, but some clinicians caring for the patients studied may have followed other recommendations. For example, if the Northern California Neonatal Consortium criteria were used,5 some newborns may not have received a TSB assessment. Because nearly half of treated newborns were provided home phototherapy, we suspect their bilirubin levels were close to AAP thresholds. Clinicians may want to understand which newborns returned with bilirubin levels nearing or exceeding exchange thresholds and if they were predictable6; these data were not provided. Given the wide range of gestational ages in the AAP phototherapy risk strata (35–38 weeks; >38 weeks), a more delineated approach by gestational age and sex would be helpful because we know lower gestational age and male sex contribute to a higher risk of hyperbilirubinemia.7,8 An implementation study across different health systems will improve the generalizability of the Δ-TSB strategy.Despite any limitations, this study could have significant impact on the experience of care for new families and curb health care overuse. Currently, the AAP Bright Futures Guidelines recommend timing the initial newborn posthospitalization continuing care visit within 3 to 5 days after birth and 48 to 72 hours after discharge. This recommendation is based primarily on concern for jaundice and feeding problems leading to excessive weight loss.9 Implementation of a Δ-TSB approach has the potential to simplify postdischarge phototherapy risk estimation and might decrease unnecessary health care visits and extra hospital days for newborns previously stratified to the high-intermediate and low-intermediate risk zones on the Bhutani Nomogram. Select newborns could be discharged at 24 hours rather than 48 hours given this new evidence supporting an enhanced understanding of bilirubin trajectories. Some newborns with intermediate risk could safely defer in-person follow-up through weekends, holidays, and inclement weather days, whereas others may avoid daily outpatient bilirubin sampling with more optimally timed follow-up. This research also highlights, with large numbers, how truly low risk some newborns are for developing significant hyperbilirubinemia. With increasing adoption of telemedicine,10 those newborns who are also at low risk of feeding problems could be safely cared for in their homes.We thank Arthur Jaffe, MD, for reviewing and editing this commentary.

Accuracy of the Bilicare™ transcutaneous bilirubinometer as the predischarge screening tool for significant hyperbilirubinemia in healthy term and late preterm neonates

Background: The Bilicare™ is a new device that measures transcutaneous bilirubin (TcB) level at the ear pinna. There are only few studies which have evaluated its accuracy in clinical practice.Objective: This study aims to determine the accuracy of Bilicare™ as a predischarge screening tool in late preterm and term neonates and to define the optimal cutoff point for determining the need to measure total serum bilirubin (TSB).Methods: The 35 weeks’ gestation or more and healthy neonates who underwent predischarge TSB measurement were enrolled. Bilicare™ TcB was measured within 30 minutes of blood sampling. Paired TcB and TSB data were analyzed.Results: We collected 214 paired samples. Mean age (SD) at TcB measurement was 57.17 (7.47) hours. Mean TSB (SD) was 9.79 (2.83) mg/dL. TcB showed a significant correlation with TSB (r = 0.84, r2 = 0.7). The mean difference (SD) between TcB and TSB was 0.7 (0.21) mg/dL (95%CI 0.49–0.91). TcB tended to overestimate TSB level at the TSB values of <12 mg/dL but underestimate at the higher TSB level. The accuracy of using TcB values to detect neonates who required phototherapy was 92.5%. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 78.3, 94.2, 62.1, and 97.3%, respectively. If TcB +3 mg/dL was applied as a cutoff point, the sensitivity, specificity, PPV, and NPV were 100, 53.9, 20.7, and 100%, respectively.Conclusions: Bilicare™ TcB and TSB measurements were well correlated. The TcB level +3 mg/dL could detect all neonates who had significant hyperbilirubinemia requiring phototherapy during their birth hospitalization.

Umbilical cord blood acid-base analysis and the development of significant hyperbilirubinemia in near-term and term newborns: a cohort study

BackgroundThe recognition, follow-up, and early treatment of neonatal jaundice has become more difficult, since the earlier discharge of newborns from hospitals has become common practice. Since intrapartum hypoxic stress has been pointed as predisposing factor for the occurrence of hyperbilirubinemia risk, we tested the association with the cord blood acid-base index tests.MethodsA cohort of healthy term and near-term newborns underwent umbilical cord hemogasanalysis at birth and capillary heel total serum bilirubin (TSB) pre-discharge, scheduled at 36 h of life, to define the risk of significant hyperbilirubinemia, defined as >9 mg/dL TSB level, ≥ 75th percentile on nomogram of Bhutani et al.ResultsIt was found that among 537 studied neonates, 133 (24.8%) had pre-discharge TSB levels of >9 mg/dL. When the cord blood gas analysis index tests were compared, their acidemia levels were significantly higher than those of neonates with normal TSB levels: HCO3− (20.71 ± 2.37 vs. 21.29 ± 2.25 mEq/L, p < 0.010), base deficit (−3.52 ± 3.188 vs. -2.68 ± 3.266 mEq/L, p < 0.010), and lactacidemia (3.84 ± 1.864 vs. 3.39 ± 1.737 mEq/L, p < 0.012), respectively. However, logistic regression analysis showed that base deficit was the strongest index of the pre-discharge hyperbilirubinemia risk (OR, 95% CI 0.593; 0.411–0.856), and the hyperbilirubinemia risk increased by 40% with the decrease of 1 mEq/L of base deficit.ConclusionsUmbilical cord blood acidemia and lactacidemia are significant indexes of adaptive mechanisms at birth. The base deficit provides the strongest association with future development of high bilirubin on an hour specific bilirubin nomogram generating risk stratification score in term and near-term neonates.

Identifying term breast-fed infants at risk of significant hyperbilirubinemia

The aim of this study was to establish a model to identify term breast-fed infants who are at risk of developing significant neonatal hyperbilirubinemia. A prospective study was designed to investigate the effects of birth weight, mode of delivery, cephalohematoma, glucose-6-phosphate dehydrogenase (G6PD) deficiency, predischarge total serum bilirubin, variant uridine 5'diphospho-glucuronosyltransferase 1A1 (UGT1A1) gene, and hepatic solute carrier organic anion transporter 1B1 (SLCO1B1) gene on significant hyperbilirubinemia in term breast-fed neonates. Significant hyperbilirubinemia was defined as a bilirubin level exceeding the hour-specific phototherapy treatment threshold recommended by the American Academy of Pediatrics in 2004. Of 240 exclusively breast-fed term neonates, 26 (10.8%) had significant hyperbilirubinemia. The predischarge total serum bilirubin on the third day (odds ratio (OR) = 2.63; 95% confidence interval (CI): 1.87-3.70; P < 0.001) and the variant UGT1A1 gene at nucleotide 211 (OR = 5.00; 95% CI: 1.08-23.03; P < 0.05) were significant risk factors. The area under the receiver operating characteristic (ROC) curve of the predictive probability was 0.964 (95% CI: 0.932-0.984; P < 0.0001). Combining the total serum bilirubin on the third day and the variant UGT1A1 gene at nucleotide 211 can predict hyperbilirubinemia well in term breast-fed infants.

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.

Rebound hyperbilirubinaemia in neonates admitted to Mofid Children’s Hospital, Tehran, Iran

Introduction and aim. Approximately 60% of term neonates and 80% of preterm neonates develop hyperbilirubinaemia in the first week of life. Rebound hyperbilirubinaemia may occur after cessation of phototherapy, especially when the Coombs test is positive, in premature infants, and in those treated with phototherapy for less than 72 hours. The main aim of this study was to evaluate the billirubin level 24 and 48 hours after cessation of phototherapy in neonates admitted to our hospital with jaundice. We also evaluated haemoglobin (Hb) levels and duration of phototherapy for a possible association with rebound hyperbilirubinaemia. Patients and methods. The study was a clinical trial in term neonates (gestational age ≥37 weeks) with hyperbilirubinaemia who were admitted to the Deptartment of Neonatology at Mofid Children’s Hospital, Tehran, Iran. Exclusion criteria were neonatal infection, glucose-6-phosphate dehydrogenase deficiency, a history of neonatal exchange transfusion, and parental refusal. Phototherapy was delivered via a Philips TL 45/20W at 15 - 20 cm distance from the skin. We discharged patients after cessation of phototherapy. Total serum bilirubin (TSB) was checked in the neonates 24 and 48 hours after cessation of phototherapy. We included patients in whom follow-up tests were completed at 24 and 48 hours after discharge. Chi-square and Student’s t-tests were used for data analysis using SPSS version 13.0 (SPSS Inc., Chicago, IL, USA). Results. Twenty-five girls and 37 boys were included in the study. The mean admission age was 5.4 (standard deviation (SD) 0.5) days for girls and 8.0 (SD 0.6) days for boys (p=0.041). The mean Hb values for the girls and the boys were 15.0 (SD 0.39) g/dl and 15.9 (SD 0.36) g/dl, respectively (p=0.108). The mean TSB levels for the girls and the boys were 322.6 (SD 9.4) µmol/l and 322.3 (SD 7.3) µmol/l, respectively (p>0.05). The mean admission and pre-discharge TSB levels of 322.3 (SD 5.6) µmol/l and 187.9 (SD 3.2) µmol/l were significantly different (p=0.0). The mean TSB levels 24 and 48 hours later were 197.8 (SD 4.6) and 195.1 (SD 5.3) µmol/l, respectively, with no significant difference between them (p>0.05). Conclusion. We found no significant differences between mean TSB levels at the time of termination of phototherapy and 24 and 48 hours later. We therefore do not recommend checking for rebound bilirubinaemia after phototherapy.

Normal distribution of pre-discharge total serum bilirubin in a culturally diverse cohort of healthy term newborn infants

Objective: To determine the percentile distribution of the pre-discharge total serum bilirubin (TSB) in a culturally diverse cohort of healthy term newborns. Study Design: Pre-discharge TSB values obtained during the first 96 hours of life in term newborn infants with birth weight 2,500 grams and no evidence of isoimmunization and hyperbilirubinemia (prior to and after discharge) were studied with respect to race/ethnic background and gender. The population's mean pre-discharge TSB levels and TSB percentile distribution (40th, 75th, and 95th) of the TSB values at 12-hour intervals were identified and compared with the American Academy of Pediatrics (AAP) recommended TSB nomogram. Descriptive, factorial ANOVA and multivariate regression statistics were used to analyze the results. Results: The study included 751 healthy newborns of which 215 (28.6%) were white, 91 (12.1%) were black, 303 (40.3%) were Hispanic, and 142 (18.9%) were Asian. We found that the pre-discharge TSB values in these term healthy newborns were significantly associated with the age at TSB testing, weight loss and exclusive breastfeeding but not race/ethnicity and gender. The TSB values were mainly in the 40th percentile zone. The numbers of TSBs in the 95th percentile zone varied from 3.2% to 6.4% at the different time points of measurement. After 48 hours of age, there was a discrepancy of 1 to 2 mg/dL as compared to the AAP recommended TSB nomogram. Conclusion: There is race/ethnicity and gender uniformity in the pre-discharge TSB levels of term healthy newborns. The observed discrepancy with the reference data suggests the need for determination of population-specific normal pre-discharge TSB values in each hospital setting for the effective post-discharge surveillance of all eligible infants.

Significant weight loss in breastfed term infants readmitted for hyperbilirubinemia

BackgroundWeight loss of greater than 7% from birth weight indicates possible feeding problems. Inadequate oral intake causes weight loss and increases the bilirubin enterohepatic circulation. The objective of this study was to describe the association between total serum bilirubin (TSB) levels and weight loss in healthy term infants readmitted for hyperbilirubinemia after birth hospitalization.MethodsWe reviewed medical records of breastfed term infants who received phototherapy according to TSB levels readmitted to Caja Petrolera de Salud Clinic in La Paz, Bolivia during January 2005 through October 2008.ResultsSeventy-nine infants were studied (64.6% were males). The hyperbilirubinemia readmission rate was 5% among breastfed infants. Term infants were readmitted at a median age of 4 days. Mean TSB level was 18.6 ± 3 mg/dL. Thirty (38%) had significant weight loss. A weak correlation between TSB levels and percent of weight loss was identified (r = 0.20; p < 0.05). The frequency of severe hyperbilirubinemia (> 20 mg/dL) was notably higher among infants with significant weight loss (46.7% vs. 18.4%; p < 0.05). The risk of having severe hyperbilirubinemia was approximately 4 times greater for infants with significant weight loss (OR: 3.9; 95% CI: 1.4-10.8; p < 0.05).ConclusionsSignificant weight loss could be a useful parameter to identify breastfed term infants at risk of severe hyperbilirubinemia either during birth hospitalization or outpatient follow-up visits in settings where routine pre-discharge TSB levels have not been implemented yet.

Preventing kernicterus: a wake-up call

Preventing kernicterus: a wake-up call

A Systems Approach for Neonatal Hyperbilirubinemia in Term and Near‐Term Newborns

To propose and implement a family-centered systems approach to manage newborn jaundice for safer outcomes. Observational study for known adverse outcomes. Semiprivate urban birthing hospital. 31,059 well babies discharged as healthy from a cohort of 41,961 live births (1990-2000). Incremental implementation of a systems approach that incorporated a hospital policy to (a) authorize nurses to obtain a bilirubin (total serum/transcutaneous) measurement for clinical jaundice, (b) universal predischarge total serum bilirubin (at routine metabolic screening), and (c) targeted follow-up, using the bilirubin nomogram (hour-specific, percentile-based total serum bilirubin/transcutaneous bilirubin). Known adverse outcomes assessed for early- and late-onset severe hyperbilirubinemia before, during, and after systems approach implementation. Adverse outcomes decreased for well babies: exchange transfusion, intensive phototherapy, and readmission. During the study period, there were no "never events" (total serum bilirubin greater than or equal to 30 mg/dl), while "close calls" (total serum bilirubin greater than or equal to 25 mg/dl) were 1 in 15,000 as compared to a reported incidence of 1 in 625. Reduced adverse events, significant reduction in close calls, and no never events met family expectations for safer experiences with this approach.

Identifying newborns at risk of significant hyperbilirubinaemia: a comparison of two recommended approaches

Aims: To compare the predictive performance of clinical risk factor assessment and pre-discharge bilirubin measurement as screening tools for identifying infants at risk of developing significant neonatal hyperbilirubinaemia (post-discharge total...

Functional organization of the central nervous system with respect to orientation in time.

<b>Aims:</b> To compare the predictive performance of clinical risk factor assessment and pre-discharge bilirubin measurement as screening tools for identifying infants at risk of developing significant neonatal hyperbilirubinaemia (post-discharge total serum bilirubin (TSB) &gt;95th centile). <b>Methods:</b> Retrospective cohort study of term and near term infants born in an urban community teaching hospital in Pennsylvania (1993–97). A clinical risk factor scoring system was developed and its predictive performance compared to a pre-discharge TSB expressed as a risk zone on a bilirubin nomogram. Main outcome measures were prediction model discrimination, range of predicted probabilities, and sensitivity, specificity, positive and negative predictive values, and likelihood ratios for various positivity criteria. <b>Results:</b> The clinical risk factor scoring system developed included birth weight, gestational age &lt;38 weeks, oxytocin use during delivery, vacuum extraction, breast feeding, and combination breast and bottle feeding. The pre-discharge bilirubin risk zone had better discrimination (c = 0.83; 95% CI 0.80 to 0.86) than the clinical risk factor score (c = 0.71; 95% CI 0.66 to 0.76) and predicted risk of significant hyperbilirubinaemia as high as 59% compared with a maximum of 44% for the clinical risk factor score. Neither the risk score nor the pre-discharge TSB risk zone predicted the outcome with ⩾0.98 sensitivity without significantly compromising specificity (0.13 and 0.21, respectively). Multi-level clinical risk factor scores and TSB risk zones produced likelihood ratios of 0.15–3.25 and 0.05–9.43, respectively. <b>Conclusions:</b> The pre-discharge bilirubin expressed as a risk zone on an hour specific bilirubin nomogram is more accurate and generates wider risk stratification than a clinical risk factor score.