Rate of glucose-6-phosphate dehydrogenase deficiency in neonatal indirect hyperbilirubinemia at a private tertiary centre.

OBJECTIVES: To investigate the rate of hospitalized neonates with glucose-6-phosphate dehydrogenase (G6PD) deficiency presented with indirect hyperbilirubinemia at a private tertiary center in Al-Ahsa, Saudi Arabia, over 4 years and to compare the characteristics of G6PD-deficient and normal neonates admitted for indirect hyperbilirubinemia. METHODS: The retrospective case control study was carried out at Almoosa Specialist Hospital, Al-Ahsa, Saudi Arabia. Data were collected from Yassasi Medical System from 2018-2021 and finalized in 2024. The study included 2 groups: G6PD-normal and G6PD-deficient neonates with indirect hyperbilirubinemia not having recognizable triggers of hemolysis. The analysis focused on serum bilirubin levels, direct bilirubin levels, hematocrit levels, hemoglobin levels, reticulocyte percentage, G6PD levels, duration of phototherapy, and the need for exchange transfusion. RESULTS: The study enrolled 3200 neonates with hyperbilirubinemia, of whom 274 met inclusion criteria. A total of 103 (37.6%) neonates were G6PD-deficient, with 77 (74.8%) being male and 26 (25.2%) female. Glucose-6-phosphate dehydrogenase-deficient neonates exhibited significantly higher initial total bilirubin levels and earlier sampling times. There was no significant correlation between G6PD deficiency and hematocrit or hemoglobin levels in hyperbilirubinemic neonates, but 4 neonates required exchange transfusion, demonstrating statistical significance (p=0.009). CONCLUSION: High rate of G6PD deficiency in neonates with indirect hyperbilirubinemia, requiring close monitoring to prevent exchange transfusions, with no significant differences in hematocrit or hemoglobin levels.

A Method for Compensating Hemoglobin Interference in Total Serum Bilirubin Measurement Using a Simple Two-Wavelength Reflectance Photometer.

Neonatal hyperbilirubinemia (NH) is a common condition in newborns, with elevated bilirubin levels potentially causing neurological damage or death. Accurate and timely measurements of total serum bilirubin are essential to prevent these outcomes. Direct spectrophotometry, a reliable method for measuring bilirubin, is particularly useful in constrained settings due to its potential for portable low-cost instrumentation. However, this method is susceptible to interference from hemoglobin, often present due to hemolysis. Typically, this interference is reduced using complex optical filters, reagents, multiple wavelengths, or combinations thereof, which increase costs and complexity while reducing usability. This study presents a hemoglobin compensation algorithm applied to a simple, portable, two-wavelength (465 and 590 nm) reflectance photometer designed to receive 30 µL of plasma or whole blood samples and perform the measurement without any reagents. Testing across five bilirubin and hemoglobin levels (4.96 to 28 mg/dL and 0.06 to 0.99 g/dL, respectively) demonstrated that the algorithm effectively reduces hemoglobin interference and overestimation errors. The overall root mean square error was reduced from 4.86 to 1.45 mg/dL, while the measurement bias decreased from -4.46 to -0.10 mg/dL. This substantial reduction in overestimation errors supports future clinical trials with neonatal blood samples.

Non-invasive detection of bilirubin concentrations during the first week of life in a low-resource setting along the Thailand-Myanmar border.

BACKGROUND: Neonatal hyperbilirubinaemia (NH) is a common problem worldwide and is a cause of morbidity and mortality especially in low-resource settings. METHODS: A study was carried out at Shoklo Malaria Research Unit (SMRU) clinics along the Thailand-Myanmar border to evaluate a non-invasive test for diagnosis of NH in a low-resource setting. Performance of a transcutaneous bilirubinometer Dräger Jaundice Meter JM-105 was assessed against routine capillary serum bilirubin testing (with BR-501 microbilirubinometer) before phototherapy during neonatal care in the first week of life. Results were analysed by direct agreement and by various bilirubin thresholds used in clinical practice. Total serum bilirubin was also measured in cord blood at birth and tested for prediction of hyperbilirubinaemia requiring phototherapy in the first week of life. RESULTS: Between April 2020 and May 2023, 742 neonates born at SMRU facilities were included in the study. A total of 695 neonates provided one to nine capillary blood samples for analysis of serum bilirubin (total 1244 tests) during the first week of life. Performance of transcutaneous bilirubinometer was assessed in 307 neonates who provided 687 paired transcutaneous capillary blood tests. Bilirubin levels were also measured in 738 cord blood samples. Adjusted values of transcutaneous bilirubinometer showed excellent agreement with capillary serum bilirubin concentration (intraclass correlation coefficient=0.923) and high sensitivity (>98%) at all clinical thresholds analysed across 3 years of sampling and multiple users. Concentrations of bilirubin detected in cord blood were not useful in identifying neonates at risk of hyperbilirubinaemia requiring treatment. CONCLUSIONS: The transcutaneous bilirubinometer is a reliable tool to screen neonates and identify those needing confirmatory blood testing. Bilirubin concentrations in cord blood are not predictive of hyperbilirubinaemia in neonates.

Validity of transcutaneous bilirubin measurements during and after phototherapy in term and late preterm infants.

The purpose of the study was to investigate correlation and concordance between total serum bilirubin (TSB) and transcutaneous bilirubin measured at covered (TcBC) and uncovered (TcBU) skin during and after discontinuation of phototherapy. A cross-sectional study included ≥ 34 weeks gestation infants requiring phototherapy for neonatal hyperbilirubinemia. In-house, photo-opaque patches were placed on infants' sternums before phototherapy initiation. Simultaneous blood sampling for TSB, TcBC, and TcBU measurements were performed. Among 103 infants included in the final analysis, 70% were full-term. Covering skin during phototherapy resulted in strong TcBC-TSB correlation (r = 0.91, 95% CI 0.87-0.94, P < 0.001) compared to TcBU (r = 0.53, 95% CI 0.37-0.65, P < 0.001), persisting post-phototherapy (r = 0.88, 95% CI 0.82-0.91, P < 0.001). Bland-Altman analysis showed a higher mean difference and wider 95% limits of agreement for TcBU-TSB during phototherapy (-6.3 mg/dL and -11.1 to -1.6) vs TcBC-TSB (0.9 mg/dL and -1.2 to 2.9). Passing-Bablok regression analysis confirmed good agreement between TcBC and TSB. CONCLUSIONS: The application of in-house, photo-opaque patches enhanced the correlation and agreement between TcBC and TSB during and after discontinuation of phototherapy. This may prove particularly useful in resource-limited settings where commercial devices are unavailable. WHAT IS KNOWN: • Transcutaneous bilirubin measurement has been widely used as a screening method for neonatal hyperbilirubinemia. • The accuracy of transcutaneous bilirubin measurements during and after phototherapy in infants with hyperbilirubinemia has been debated. WHAT IS NEW: • Our study demonstrated that utilizing carefully designed photo-opaque patches enhanced the accuracy of transcutaneous bilirubin measurement during and after phototherapy. • Effective in-house alternatives are crucial in resource-limited settings where commercial opaque patches are not always accessible or affordable.

Hematological abnormality and associated factors in newborns with hyperbilirubinemia before and after phototherapy at University of Gondar Comprehensive Specialized Hospital.

This study aimed to assess the magnitude of hematological toxicity and associated factors in newborns with hyperbilirubinemia. A cross-sectional study was conducted from April to December 2023. A total of 247 newborns were included. The data were collected using questionnaires and a data extraction sheet. Four 4 ml of blood was collected. A Sysmex KX-21 analyzer was used for blood analysis, and a Mindray BS-240 analyzer was used for bilirubin measurement. The data were entered into Epi-data and analyzed by SPSS. The logistic regression was used. The P value was set at 0.05. Before phototherapy, the hematological toxicities, such as anemia, leucopenia, and thrombocytopenia, were 45.7%, 22.2%, and 6.1%, respectively, whereas after phototherapy, anemia and thrombocytopenia, significantly increased, but the leucopenia, significantly decreased. The risk of developing anemia increased, 3.5, 2.7, and 2.1-fold among newborns with bilirubin > 18 mg/dl, with Rh blood group incompatibility, and treated with intensive phototherapy, respectively. Both low birth weight and intensive phototherapy increased the incidence of thrombocytopenia by 2 and 3.4-fold, respectively. Hematological toxicity was found to be a severe public health issue in newborns. Thus, strict follow-up and early detection of toxicity by considering aggravation factors are necessary.

Clinical Analysis of Abnormal Brainstem Auditory Evoked Potential in Neonates with Hyperbilirubinemia.

BACKGROUND: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage. METHODS: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities. RESULTS: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia (p > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity (p = 0.001), gestational diabetes (p = 0.03), Premature rupture of membranes (p = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors. CONCLUSIONS: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.

Severe Hemolytic Disease of a Newborn with Bilirubin of 37.3 mg/dL and High anti-A Titer: Corrected with Reconstituted Whole Blood Exchange.

High neonatal bilirubin is a common phenomenon responding to phototherapy. We report a case of a newborn with a highly elevated bilirubin of 37.3 mg/dL due to ABO incompatibility between the mother (Group O) and the newborn (Group A) requiring whole blood exchange, a procedure performed rarely to treat newborn hyperbilirubinemia. The newborn (38.8 weeks of gestation) initially showed a total bilirubin of 8.4 mg/dL and was discharged after being stabilized by phototherapy. However, the baby returned to the hospital with highly elevated bilirubin and was admitted to the Neonatal Intensive Care Unit (NICU). Emergent reconstituted whole blood exchanger therapy was initiated due to refractoriness to phototherapy and IVIG. Markedly elevated anti-A titer was found in the mother's blood (1:512) and cord blood (1:128). The baby was stabilized and eventually discharged with a serum bilirubin of 13.8 mg/dL. This case demonstrates the possible predictive value of mother/cord blood anti-A titers in severe newborn hyperbilirubinemia, which may prevent premature discharge and trigger early initiation of lifesaving therapy.

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

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

Bilirubin measurements in neonates: uniform neonatal treatment can only be achieved by improved standardization.

Measurement of total bilirubin (TBil) concentration in serum is the gold standard approach for diagnosing neonatal unconjugated hyperbilirubinemia. It is of utmost importance that the measured TBil concentration is sufficiently accurate to prevent under treatment, unnecessary escalation of care, or overtreatment. However, it is widely recognized that TBil measurements urgently require improvement in neonatal clinical chemistry. External quality assessment (EQA) programs for TBil assess for differences between laboratories and provide supporting evidence of significant differences between various methods, manufacturers and measurement platforms. At the same time, many countries have adopted or only slightly adapted the neonatal hyperbilirubinemia management guidelines from the USA or UK, often without addressing differences in the methodology of TBil measurements. In this report, we provide an overview of the components of bilirubin that are measured by laboratory platforms, the availability of current reference measurement procedures and reference materials, and the role of EQA surveys in this context. Furthermore, the current status of agreement in neonatal bilirubin against clinical decision thresholds is reviewed. We advocate for enhancements in accuracy and comparability of neonatal TBil measurements, propose a path forward to accomplish this, and reflect on the position of the International Federation for Clinical Chemistry and Laboratory Medicine (IFCC) Working Group Neonatal Bilirubin (WG-NB) in this matter.

Considerations for applying emerging technologies in paediatric laboratory medicine.

Emerging technology in laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Paediatric laboratory medicine itself may be considered an emerging area of specialisation that is established relatively recently following increased appreciation and understanding of the unique physiology and healthcare needs of the children. Through four clinical (neonatal hypoglycaemia, neonatal hyperbilirubinaemia, sickle cell disorder, congenital adrenal hyperplasia) and six technological (microassays, noninvasive testing, alternative matrices, next generation sequencing, exosome analysis, machine learning) illustrations, key takeaways of application of emerging technology for each area are summarised. Additionally, nine key considerations when applying emerging technology in paediatric laboratory medicine setting are discussed.

Phototherapy Alters the Plasma Metabolite Profile in Infants Born Preterm with Hyperbilirubinemia.

OBJECTIVE: To investigate the effects of gestational age (GA) and phototherapy on the plasma metabolite profile of preterm infants with neonatal hyperbilirubinemia (NHB). STUDY DESIGN: From a cohort of prospectively enrolled infants born preterm (n = 92), plasma samples of very preterm (VPT; GA, 28 + 0 to 31 + 6 weeks, n = 27) and moderate/late preterm (M/LPT; GA, 32 + 0 to 35 + 6 weeks, n = 33) infants requiring phototherapy for NHB were collected prior to the initiation of phototherapy and 24 hours after starting phototherapy. An additional sample was collected 48 hours after starting phototherapy in a randomly selected subset (n = 30; VPT n = 15; M/LPT n = 15). Metabolite profiles were determined using ultraperformance liquid chromatography tandem mass spectroscopy. Two-way ANCOVA was used to identify metabolites that differed between GA groups and timepoints after adjusting for total serum bilirubin levels (false discovery rate q-value < 0.05). Top impacted pathways were identified using pathway over-representation analysis. RESULTS: Phototherapy was initiated at lower total serum bilirubin (mean ± SD mg/dL) levels in VPT compared with M/LPT infants (7.3 ± 1.4 vs 9.9 ± 1.9, P < .01). We identified 664 metabolites that were significant for a phototherapy effect, 191 metabolites significant for GA, and 46 metabolites significant for GA × phototherapy interaction (false discovery rate q-value < 0.05). Longer duration phototherapy had a larger mean effect size (24 hours postphototherapy: d = 0.36; 48 hours postphototherapy: d = 0.43). Top pathways affected by phototherapy included membrane lipid metabolism, one-carbon metabolism, creatine biosynthesis, and oligodendrocyte differentiation. CONCLUSION: Phototherapy alters the plasma metabolite profile more than GA in preterm infants with NHB, affecting pathways related to lipid and one-carbon metabolism, energy biosynthesis, and oligodendrocyte differentiation.

Comparative analysis of the quantitative point-of-care CareSTART™ total bilirubin with central laboratory total bilirubin assays in neonatal blood samples.

This study aimed to assess and compare the accuracy of point-of-care CareSTART™ S1 Total Bilirubin test with a central laboratory total bilirubin assay using neonatal samples. This study was conducted using 152 paired measurements obtained from 122 neonates admitted to the neonatal intensive care unit. Total serum bilirubin (TSB) levels assayed with the central laboratory assay, laboratory bilirubinomter, trancutaneous bliribubin (TcB) instrument and CareSTART were compared using Bland-Altman analysis. The mean difference between the CareSTART and TSB values was -1.43 mg/dL and the 95% limit of agreement (LoA) was -4.25 to 1.39 mg/dL. CareSTART tended to underestimate total bilirubin concentrations compared with TcB, however, the LoA was narrower due to the smaller SD of mean difference for CareSTART. The CareSTART Total Bilirubin test provides an accurate alternative to TcB for total serum bilirubin measurement. Given its low-cost, ease-of-use, and portability, the use of CareSTART is expected to provide point-of-care measurements, especially in low-resource settings.

Evaluating the relationship between aEEG findings and two-year prognosis in neonates with severe hyperbilirubinemia.

OBJECTIVE: Identifying factors that can better predict the prognosis of neonates with hyperbilirubinemia is important. In this study, we aimed to evaluate the relationship between electroencephalography (EEG) findings and two-year prognosis in neonates with severe hyperbilirubinemia. METHODS & MATERIALS: In a cohort prospective study, we studied neonates with a total serum bilirubin level of higher than 18 mg/dL, who were admitted to the neonatal intensive care unit (NICU) of Ghaem hospital, Mashhad, Iran. EEG was recorded upon admission, for all neonates. Patients' data, including demographic characteristics, admission information, and pregnancy and birth data were gathered by obtaining history from parents and studying case files. Also, the relationship between initial EEG findings and final developmental status was assessed. RESULTS: Mean and standard deviation age of patients were 5.46 ± 3.13 days and average serum total bilirubin level was 23.97 ± 4.34 mg/dL at admission. Our findings revealed a significant correlation between the presence of trace alternant on EEG and developmental delay (P = .001). Presence of trace alternant waves on initial EEG at admission was significantly associated with developmental delay in the two year (P = .005). CONCLUSION: These results indicate a relationship between developmental prognosis and the severity of hyper bilirubinemia in neonates. Also, our findings show that the presence of trace alternate waves on the initial EEG is significantly associated with developmental delay of the neonate in the future.

[Multicenter evaluation of the diagnostic efficacy of jaundice color card for neonatal hyperbilirubinemia].

Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).

Comparison of prognosis between hyperbilirubinemic infants with and without hypernatremia.

OBJECTIVES: Hypernatremia may facilitate the diffusion of bilirubin through the blood-brain barrier and increase the risk of bilirubin encephalopathy. This study was conducted to compare the prognosis of jaundice infants with those with jaundice and hypernatremia. METHODS: A total of 615 term infants with idiopathic jaundice with or without hypernatremia were enrolled in this cohort study with 24-months follow-up at Ghaem Hospital, Mashhad, Iran, between 2010 and 2022. An in-house questionnaire including the laboratory evaluation and neonatal characteristics was used as the data collection tool. The follow-up of neonatal development status was performed using the Denver test II at 6, 12, 18, and 24 months after discharging from hospital. RESULTS: Normal outcomes were seen in 555 (90.2%) out of 615 studied infants, while 60 cases (9.8%) showed abnormal outcomes. Serum levels of sodium (P = 0.017), bilirubin (P = 0.001), urea (P = 0.024), and creatinine (P = 0.011) as well as hyperthermia (P = 0.046) and unconsciousness (P = 0.005) showed significant differences between the two groups. Approximately 16% of the newborns with both jaundice and hypernatremia, and 9% of those with only jaundice had unfavorable prognoses. Also, bilirubin level had the most predictive power (91.3%). CONCLUSIONS: Our results suggest that hypernatremia or jaundice alone, may affect the prognosis of infants aged 2 years; but jaundice and hypernatremia together, will intensify the developmental problems in jaundice infants. However, the role of hyperbilirubinemia in the incidence of complications is more than hypernatremia.

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

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

Hyperbilirubinemia screening and treatment in neonates born prior to 35 weeks of gestation.

BACKGROUND: Guidelines on when to screen for neonatal hyperbilirubinemia apply to infants born at 35 weeks or later of gestation. It is unknown whether infants born earlier would benefit from similar guidelines. Our objective was to examine hyperbilirubinemia screening and phototherapy prescription among early preterm infants during the first 6 days of life. METHODS: We reviewed the charts of 193 infants born prior to 35 weeks of gestation who were admitted to a tertiary care NICU in Southeastern Ontario in 2018-2019. Information on total serum bilirubin (TSB) measurements over each 12-hour interval during the first six days of life and the treatment decision (no treatment, initiate, continue, or stop phototherapy) was extracted. We also examined what proportion of infants were prescribed phototherapy during each 12-hour interval. RESULTS: Of 1006 TSB measurements performed over the first 6 days of life, 605 were done to determine whether phototherapy should be initiated. Treatment was prescribed in 275 instances (45%). A higher proportion of infants born prior to 28 weeks of gestation required phototherapy in the first 12 hours of life (37%) compared to those born at 28-32 weeks (20%) and 33-34 weeks (5.7%). CONCLUSIONS: Our results suggest that TSB measurements are often poorly timed to detect treatment need in infants born prior to 35 weeks of gestation. This unnecessarily increases the risk of complications from phlebotomy and is an ineffective use of health care resources. There is a need to develop guidelines to optimize hyperbilirubinemia screening among early preterm infants.

Pre-phototherapy total serum bilirubin levels in extremely preterm infants.

BACKGROUND: Extremely preterm infants are prone to hyperbilirubinemia and its sequelae. Currently recommended thresholds for initiating phototherapy in these newborns are consensus-based (CB). METHODS: A multi-site retrospective cohort study of 642 infants born at 240/7 to 286/7 weeks' gestation, between January 2013 and June 2017, was conducted at three NICUs in Canada. Pre-phototherapy TSB percentile levels at 24 h of age were generated and contrasted with published CB thresholds. RESULTS: Among infants born 240/7 to 256/7 weeks' gestation, the differences between our TSB percentiles vs. the CB threshold of 85.0 µmol/L were 10.0 µmol/L (95% CI, 6.0-16.0) at the 75th percentile and 35.3 µmol/L (95% CI, 26.1-42.8) at the 95th percentile. Respectively, among infants born at 260/7 to 276/7 weeks, differences were 19.4 µmol/L (95% CI, 16.8-23.4) and 43.3 µmol/L (95% CI, 34.7-46.9). Born at 280/7 to 286/7 weeks' gestation, differences between our 75th and 95th TSB percentiles and the CB threshold of 103 µmol/L were 6.9 µmol/L (95% CI, 3.2-12.0) and 36.0 µmol/L (95% CI, 31.0-44.3), respectively. CONCLUSIONS: We provide statistically derived pre-phototherapy TSB levels that may clarify patterns of pre-phototherapy TSB levels in extremely preterm infants. IMPACT: We present statistically derived pre-phototherapy total serum bilirubin levels in a cohort of extremely preterm infants. Most of these preterm infants received phototherapy-some at below currently published thresholds. There are notable differences between our statistically derived pre-phototherapy TSB levels and currently published lower limit TSB thresholds for phototherapy. Our study results assist in the understanding of pre-phototherapy TSB levels in extremely preterm infants.

High levels of pathological jaundice in the first 24 hours and neonatal hyperbilirubinaemia in an epidemiological cohort study on the Thailand-Myanmar border.

Population risks for neonatal hyperbilirubinaemia (NH) vary. Knowledge of local risks permits interventions that may reduce the proportion becoming severe. Between January 2015 and May 2016, in a resource-limited setting on the Thailand-Myanmar border, neonates from 28 weeks' gestation were enrolled into a prospective birth cohort. Each neonate had total serum bilirubin measurements: scheduled (24, 48, 72 and 144 hours of life) and clinically indicated; and weekly follow up until 1 month of age. Risk factors for developing NH were evaluated using Cox proportional hazard mixed model. Of 1710 neonates, 22% (376) developed NH (83% preterm, 19% term). All neonates born <35 weeks, four in five born 35-37 weeks, and three in twenty born ≥38 weeks had NH, giving an overall incidence of 249 per 1000 livebirths [95%CI 225, 403]. Mortality from acute bilirubin encephalopathy was 10% (2/20) amongst the 5.3% (20/376) who reached the severe NH threshold. One-quarter (26.3%) of NH occurred within 24 hours. NH onset varied with gestational age: at a median [IQR] 24 hours [24, 30] for neonates born 37 weeks or prematurely vs 59 hours [48, 84] for neonates born ≥38 weeks. Risk factors for NH in the first week of life independent of gestational age were: neonatal G6PD deficiency, birth bruising, Sgaw Karen ethnicity, primigravidae, pre-eclampsia, and prolonged rupture of membranes. The genetic impact of G6PD deficiency on NH was partially interpreted by using the florescent spot test and further genotyping work is in progress. The risk of NH in Sgaw Karen refugees may be overlooked internationally as they are most likely regarded as Burmese in countries of resettlement. Given high levels of pathological jaundice in the first 24 hours and overall high NH burden, guidelines changes were implemented including preventive PT for all neonates <35 weeks and for those 35-37 weeks with risk factors.