Susceptibility weighted imaging can be a sensitive sequence to detect brain damage in neonates with kernicterus: a case report.

BACKGROUND: Kernicterus in the acute phase is difficult to diagnose. It depends on a high signal on T1 at the globus pallidum and subthalamic nucleus level. Unfortunately, these areas also show a relatively high signal on T1 in neonates as an expression of early myelination. Therefore, a less myelin-dependent sequence, like SWI, may be more sensitive to detecting damage in the globus pallidum area. CASE PRESENTATION: A term baby developed jaundice on day three following an uncomplicated pregnancy and delivery. Total bilirubin peaked at 542 µmol/L on day four. Phototherapy was started, and an exchange transfusion was performed. ABR showed absent responses on day 10. MRI on day eight demonstrated abnormal high signal globus pallidus on T1w, isointense on T2w, without diffusion restriction, and high signal on SWI at globus pallidal and subthalamus level and phase image at globus pallidal level. These findings were consistent with the challenging diagnosis of kernicterus. On follow-up, the infant presented with sensorineural hearing loss and had a work-up for cochlear implant surgery. At 3 months of age, the follow-up MR shows normalization of the T1 and SWI signals and a high signal on T2. CONCLUSIONS: SWI seems more sensitive to injury than the T1w and lacks the disadvantage of the T1w sequence, where early myelin confers a high signal.

[Interpretation of the 2022 American Academy of Pediatrics guidelines for the management of hyperbilirubinemia in newborn infants]. / 2022ç‰ˆç¾Žå›½å„¿ç§‘å­¦ä¼šæ–°ç”Ÿå„¿é«˜èƒ†çº¢ç´ è¡€ç—‡ç®¡ç†æŒ‡å—è§£è¯».

The American Academy of Pediatrics updated the guidelines for the management of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks in September 2022. Based on the evidence over the past 18 years, the guidelines are updated from the aspects of the prevention, risk assessment, intervention, and follow-up of hyperbilirubinemia in the newborn infants with a gestational age of ≥35 weeks. This article gives an interpretation of the key points in the guidelines, so as to safely reduce the risk of bilirubin encephalopathy and unnecessary intervention.

Technical Report: Diagnosis and Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.

CONTEXT: Severe hyperbilirubinemia is associated with kernicterus. Informed guidance on hyperbilirubinemia management, including preventive treatment thresholds, is essential to safely minimize neurodevelopmental risk. OBJECTIVE: To update the evidence base necessary to develop the 2022 American Academy of Pediatrics clinical practice guideline for management of hyperbilirubinemia in the newborn infant ≥35 weeks' gestation. DATA SOURCE: PubMed. STUDY SELECTION: English language randomized controlled trials and observational studies. Excluded: case reports or series, nonsystematic reviews, and investigations focused on <35-weeks' gestation infants. DATA EXTRACTION: Topics addressed in the previous clinical practice guideline (2004) and follow-up commentary (2009) were updated with new evidence published through March 2022. Evidence reviews were conducted for previously unaddressed topics (phototherapy-associated adverse effects and effectiveness of intravenous immune globulin [IVIG] to prevent exchange transfusion). RESULTS: New evidence indicates that neurotoxicity does not occur until bilirubin concentrations are well above the 2004 exchange transfusion thresholds. Systematic review of phototherapy-associated adverse effects found limited and/or inconsistent evidence of late adverse effects, including cancer and epilepsy. IVIG has unclear benefit for preventing exchange transfusion in infants with isoimmune hemolytic disease, with a possible risk of harm due to necrotizing enterocolitis. LIMITATIONS: The search was limited to 1 database and English language studies. CONCLUSIONS: Accumulated evidence justified narrowly raising phototherapy treatment thresholds in the updated clinical practice guideline. Limited evidence for effectiveness with some evidence of risk of harm support the revised recommendations to limit IVIG use.

Neonatal Hyperbilirubinemia.

Neonatal hyperbilirubinemia (NH) is a common phenomenon. In most cases, NH is benign and transient. However, in severe NH cases, neonates can develop encephalopathy and kernicterus. With appropriate screening and treatment, these adverse sequelae can be prevented. This article aims to provide the reader with an in-depth understanding of (1) bilirubin metabolism, (2) risk factors for severe NH, (3) NH screening and treatment, (4) various etiologies of severe NH, and (5) consequences of severe, untreated NH. [Pediatr Ann. 2022;51(6):e219-e227.].

Trends and Resource Use for Kernicterus Hospitalizations in the United States.

OBJECTIVE: To evaluate the trends in hospitalization for kernicterus in the United States from 2006 through 2016. METHOD: Repeated, cross-sectional analysis of the 2006 to 2016 editions of the Kids' Inpatient Database. All neonatal hospitalizations with an International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification code for kernicterus and admitted at age ≤28 days were included. RESULTS: Among 16 094 653 neonatal hospitalizations from 2006 to 2016, 20.5% were diagnosed with jaundice with overall incidence of kernicterus 0.5 per 100 000. The rate of kernicterus (per 100 000) was higher among males (0.59), Asian or Pacific Islanders (1.04), and urban teaching hospitals (0.72). Between 2006 and 2016, the incidence of kernicterus decreased from 0.7 to 0.2 per 100 000 (P-trend = .03). The overall median length of stay for kernicterus was 5 days (interquartile range [IQR], 3-8 days). The overall median inflation-adjusted cost of hospitalization was $5470 (IQR, $1609-$19 989). CONCLUSIONS: Although the incidence of kernicterus decreased between 2006 and 2016, its continued occurrence at a higher rate among Asian or Pacific Islander and Black race or ethnicity in the United States require further probing. Multipronged approach including designating kernicterus as a reportable event, strengthening newborn hyperbilirubinemia care practices and bilirubin surveillance, parental empowerment, and removing barriers to care can potentially decrease the rate of kernicterus further.

MGE-Like Neural Progenitor Cell Survival and Expression of Parvalbumin and Proenkephalin in a Jaundiced Rat Model of Kernicterus.

Kernicterus is a permanent condition caused by brain damage from bilirubin toxicity. Dystonia is one of the most debilitating symptoms of kernicterus and results from damage to the globus pallidus (GP). One potential therapeutic strategy to treat dystonia in kernicterus is to replace lost GP neurons and restore basal ganglia circuits through stem cell transplantation. Toward this end, we differentiated human embryonic stem cells (hESCs) into medial ganglion eminence (MGE; the embryological origin of most of the GP neurons)-like neural precursor cells (NPCs). We determined neurochemical phenotype in cell culture and after transplanting into the GP of jaundiced Gunn rats. We also determined grafted cell survival as well as migration, distribution, and morphology after transplantation. As in the GP, most cultured MGE-like NPCs expressed γ-aminobutyric acid (GABA), with some co-expressing markers for parvalbumin (PV) and others expressing markers for pro-enkephalin (PENK). MGE-like NPCs survived in brains at least 7 weeks after transplantation, with most aggregating near the injection site. Grafted cells expressed GABA and PV or PENK as in the normal GP. Although survival was low and the maturity of grafted cells varied, many cells produced neurite outgrowth. While promising, our results suggest the need to further optimize the differentiation protocol for MGE-like NPC for potential use in treating dystonia in kernicterus.

Bilirubin Encephalopathy.

PURPOSE OF REVIEW: Hyperbilirubinemia is commonly seen in neonates. Though hyperbilirubinemia is typically asymptomatic, severe elevation of bilirubin levels can lead to acute bilirubin encephalopathy and progress to kernicterus spectrum disorder, a chronic condition characterized by hearing loss, extrapyramidal dysfunction, ophthalmoplegia, and enamel hypoplasia. Epidemiological data show that the implementation of universal pre-discharge bilirubin screening programs has reduced the rates of hyperbilirubinemia-associated complications. However, acute bilirubin encephalopathy and kernicterus spectrum disorder are still particularly common in low- and middle-income countries. RECENT FINDINGS: The understanding of the genetic and biochemical processes that increase the susceptibility of defined anatomical areas of the central nervous system to the deleterious effects of bilirubin may facilitate the development of effective treatments for acute bilirubin encephalopathy and kernicterus spectrum disorder. Scoring systems are available for the diagnosis and severity grading of these conditions. The treatment of hyperbilirubinemia in newborns relies on the use of phototherapy and exchange transfusion. However, novel therapeutic options including deep brain stimulation, brain-computer interface, and stem cell transplantation may alleviate the heavy disease burden associated with kernicterus spectrum disorder. Despite improved screening and treatment options, the prevalence of acute bilirubin encephalopathy and kernicterus spectrum disorder remains elevated in low- and middle-income countries. The continued presence and associated long-term disability of these conditions warrant further research to improve their prevention and management.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study.

BACKGROUND: Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. METHODS: This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. RESULTS: A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. CONCLUSIONS: In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Outcome Analysis of Severe Hyperbilirubinemia in Neonates Undergoing Exchange Transfusion.

OBJECTIVE: Severe neonatal hyperbilirubinemia can cause neurological disability or mortality if not effectively managed. Exchange transfusion (ET) is an efficient treatment to prevent bilirubin neurotoxicity. The purpose of this study was to evaluate outcomes in severe neonatal hyperbilirubinemia with ET and to identify the potential risk factors for poor outcomes. METHODS: Newborns of ≥28 weeks of gestational age with severe hyperbilirubinemia who underwent ET from January 2015 to August 2019 were included. Demographic data were recorded and analyzed according to follow-up outcomes at 12 months of corrected age. Poor outcomes were defined as death due to bilirubin encephalopathy or survival with at least one of the following complications: cerebral palsy, psychomotor retardation (psychomotor developmental index < 70), mental retardation (mental developmental index < 70), or hearing impairment. RESULTS: A total of 524 infants were eligible for recruitment to the study, and 62 infants were lost to follow-up. The outcome data from 462 infants were used for grouping analysis, of which 398 cases (86.1%) had normal outcomes and 64 cases (13.9%) suffered poor outcomes. Bivariate logistic regression analysis showed that peak total serum bilirubin (TSB) (odds ratio [OR] = 1.011, 95% confidence interval [CI] = 1.008-1.015, p = 0.000) and sepsis (OR = 4.352, 95% CI = 2.013-9.409, p < 0.001) were associated with poor outcomes of hyperbilirubinemia. Receiver operator characteristic curve analysis showed that peak TSB ≥452.9 µmol/L could predict poor outcomes of severe hyperbilirubinemia. CONCLUSION: Peak TSB and sepsis were associated with poor outcomes in infants with severe hyperbilirubinemia, and peak TSB ≥452.9 µmol/L could predict poor outcomes.

Detecting acute bilirubin encephalopathy in neonates based on multimodal MRI with deep learning.

BACKGROUND: Differentiating acute bilirubin encephalopathy (ABE) from non-ABE in neonates with hyperbilirubinemia (HB) from routine magnetic resonance imaging (MRI) is extremely challenging since both conditions demonstrate similar T1 hyperintensities. To this end, we investigated whether the integration of multimodal MRI from routine clinical scans with deep-learning approaches could improve diagnostic performance. METHODS: A total of 75 neonates with ABE and 75 neonates with HB (non-ABE) were included in the study. Each patient had three types of multimodal images taken, i.e., a T1-weighted image (T1WI), a T2-weighted image (T2WI), and an apparent diffusion coefficient (ADC) map. The three types of MRI contrasts and their combination were fed into two deep convolutional neural networks (CNNs), i.e., ResNet18 and DenseNet201. The performance of CNNs was compared with a traditional statistical method named logistic regression. RESULTS: We demonstrated that diagnostic methods with the multimodal data were better than any of the single-modal data. Both CNN models outperformed the logistic regression method. The best performance was achieved by DenseNet201 with the combination of three modalities of T1WI, T2WI, and ADC, with an accuracy of 0.929 ± 0.042 and an area under the curve (AUC) of 0.991 ± 0.007. CONCLUSIONS: Our study demonstrated that CNN models with multimodal MRI significantly improve the accuracy of diagnosing ABE. IMPACT: We proposed an efficient strategy of detecting ABE in neonates based on multimodal MRI with deep learning, which achieved an accuracy of 0.929 ± 0.042 and an AUC of 0.991 ± 0.007. We demonstrated the advantage of integrating multimodal MRI in detecting ABE in neonates with HB, using deep-learning models. Our strategy of diagnosing ABE using deep-learning techniques with multimodal MRI from routine clinical scans is potentially applicable to clinical practice.

Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US Database.

OBJECTIVE: The objective of this study was to assess the prevalence and trends for neonatal hyperbilirubinemia, and the development of bilirubin neurotoxicity in the USA. STUDY DESIGN: We used a de-identified national dataset for the years 2002-2017. The study included all newborn inpatients with postnatal age ≤28 days. Cochran-Armitage trend test was used for trend analyses. Regression analyses were performed and adjusted odds ratios (aOR) were reported. RESULTS: The study included 57,989,476 infants; of them 53,259,758 (91.8%) were term infants and 4,725,178 (8.2%) were preterm infants. Bilirubin neurotoxicity decreased over the years in term infants (Z = 0.36, p = 0.03) without change in preterm infants (Z = 42.5, p = 0.12). Black neonates were less likely to be diagnosed with hyperbilirubinemia than White neonates (aOR = 0.77, 95% confidence interval (CI): 0.77-0.78, p < 0.001) and more likely to develop bilirubin neurotoxicity than White neonates (aOR = 3.0.5, 95% CI: 2.13-4.36, p < 0.001). Bilirubin neurotoxicity rate in the overall population was 2.4 per 100,000 live births. CONCLUSIONS: Bilirubin neurotoxicity has significantly decreased in term infants and did not change in preterm infants. Despite the less diagnosis of hyperbilirubinemia in Black newborns, they are disproportionately at increased risk of developing bilirubin neurotoxicity when compared to White newborns. IMPACT: In this article, we analyzed the National Inpatient Database. This is the largest study of its kind using data on 57,989,476 neonates. The article has multiple novel findings: (1) it demonstrated that utilization of phototherapy has increased significantly over the years, (2) the rate of kernicterus for neonates decreased in term infants and did not change in preterm babies, (3) kernicterus was mostly encountered in infants without isoimmunization jaundice, and (4) there is a clear racial disparity in neonatal jaundice; although Black newborns have less neonatal jaundice, they are at increased risk of developing kernicterus.

Neuroglobin expression and function in the temporal cortex of bilirubin encephalopathy rats.

Bilirubin encephalopathy (BE) is a neurological syndrome in newborns, mainly caused by neuronal injury due to excessive oxidative stress produced by unconjugated bilirubin (UCB). Neuroglobin (NGB) can protect the brain by removing oxidative stress species, but its expression and significance in BE are not clear. To address this question, the neonatal BE model was established by injecting UCB into the cerebellomedullary cistern of 7-day-old SD rats. Rats were divided into a sham and BE 6 hr group, BE 12 hr group, BE 24 hr group, and BE 7 d group according to UCB action times. Hematoxylin/eosin and Nissl staining, and electron microscopy were employed to observe the pathological and ultrastructural changes of nerve cells in each group. Immunofluorescence staining was used to detect NGB expression sites and cell types. Western blotting and quantitative PCR served to detect NGB expression and test the mitochondrial apoptosis signal pathway. The results confirm that UCB can lead to pathological damage and ultrastructural changes in rats' temporal cortex, increasing the expression of apoptosis-related proteins Bax, Bcl-2, Cyt c, Caspase-3, and neuronal NGB. UCB promotes NGB expression with an increase in action time and reach a peak at 12 hr. In summary, brain damage induced by UCB will cause an increase in NGB expression, the increasing NGB can inhibit neuron apoptosis in early BE phases. Therefore, promoting the expression of endogenous NGB, to act as a neuroprotective agent may be a potential treatment strategy for BE.

Kernicterus Spectrum Disorders Diagnostic Toolkit: validation using retrospective chart review.

BACKGROUND: Kernicterus Spectrum Disorders (KSDs) result from hyperbilirubinemia-induced brain injury. We developed a Toolkit (KSD-TK) to predict the likelihood of KSDs. This study aims to validate the KSD-TK by comparing it to clinical diagnoses made by the Kernicterus Clinic in the Division of Neurology. METHODS: Through retrospective chart review, we completed a KSD-TK for 37 patients evaluated between 2011 and 2019 using highest bilirubin, newborn risk factors, neonatal exam, follow-up exam, auditory testing, tooth enamel, and MRI brain results. KSD-TK results were compared to the clinical diagnoses given by a kernicterus expert (SS). RESULTS: Of 37 patients, 29 were clinically diagnosed with kernicterus, including 14/14 with KSD-TK scored as "definite", 14/15 "probable", and 1/2 with "possible" kernicterus. None of 6 patients with KSD-TK "not kernicterus" were clinically diagnosed with kernicterus. Combining KSD-TK "definite" and "probable", the KSD-TK has 96.6% sensitivity and 87.5% specificity. Each KSD-TK component had high sensitivity, but only three had specificity ≥0.75: auditory neuropathy spectrum disorder, abnormal movements and/or tone on follow-up exam, and abnormal globus pallidus and/or subthalamic nucleus on MRI. CONCLUSION: The KSD-TK is a promising screening tool for patients at risk for kernicterus. IMPACT: This study provides validation of a Kernicterus Spectrum Disorders (KSDs) Toolkit. The toolkit provides screening criteria for predicting KSD diagnosis. Scores of definite or probable have high sensitivity and specificity for KSDs. Abnormal auditory processing, exam, and MRI were most specific for KSDs.

Trends in hospitalizations of newborns with hyperbilirubinemia and kernicterus in United States: an epidemiological study.

BACKGROUND: Hyperbilirubinemia is one of the most common diagnosis in newborn nurseries in United States. Universal pre-discharge bilirubin screening decreased the incidence of extreme hyperbilirubinemia and risk of kernicterus. OBJECTIVES: We sought to assess temporal population trends of hyperbilirubinemia, kernicterus and usage of phototherapy, intravenous immunoglobulin (IVIG), and exchange transfusion. DESIGN/METHODS: Data from Healthcare Cost and Utilization Project (HCUP)-the Kids' Inpatient Database (KID) obtained for years 1997-2012. All neonatal discharges with ICD-9 codes for neonatal jaundice (774.2, 774.6), kernicterus (773.4, 774.7) and procedure codes for phototherapy (99.83), IVIG infusion (99.14), exchange transfusion (99.01) were extracted. We compared the trends of diagnosis of hyperbilirubinemia, kernicterus, use of phototherapy, IVIG, and exchange transfusion. RESULTS: During the study period, the proportion of infants diagnosed with hyperbilirubinemia increased by 65% (9.4% vs. 15.5%; p<.001) in term infants and 34.5% (33.5% vs. 45%; p<.001) in preterm infants, respectively. Rate of kernicterus discharges significantly reduced from 7 to 1.9 per 100,000 newborns. Overall, the number of exchange transfusions has decreased by 67% during study period while phototherapy and IVIG use increased by 83% and 170%, respectively. CONCLUSIONS: In last two decades, there was a significant decrease in neonatal discharges with a history of exchange transfusion or with a diagnosis of kernicterus. However, there was a significant increase in number of neonates discharged home with a history of phototherapy during birth hospitalization and decreased number of exchange transfusions were observed during the study period. Incremental implementation of universal predischarge bilirubin screening and treatments based on 2004 AAP recommended risk-based strategies might have contributed to timely interventions in infants with significant hyperbilirubinemia.

Economic evaluation of point of care universal newborn screening for glucose-6-Phosphate dehydrogenase deficiency in United States.

BACKGROUND AND OBJECTIVES: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is frequent inherited enzymopathy that poses potentially preventable risk for extreme hyperbilirubinemia (EHB) which can, rarely, lead to acute bilirubin encephalopathy, childhood kernicterus and death. We aimed to estimate quality adjusted life years (QALY) lost due to G6PD deficiency associated with EHB and economic costs to best estimate value of universal pre-discharge screening. METHODS: We did a cost utility analysis for US birth cohort utilizing pre-discharge screening decision tree model to estimate population burden and EHB outcomes, based on literature search and expert opinions. Employing human capital approach, we measured health benefits in terms of QALYs and economic losses. QALYs and costs were discounted at 3%; one-way sensitivity analysis was used for decision variables. RESULTS: We determined for USA live births of 3.86 million in 2017, 1464 cases of EHB were estimated to be due to G6PD deficiency (CI 95%; range: 1270-1656) and contributed 2 deaths (CI 95%; range 1.3-3.2) and 14 (CI 95%; range: 9.1-21.5) cases of kernicterus. Over lifetime horizon, the model predicted undiscounted and discounted gains of 165 (102-252) life years; 241 (183-433) QALYs and 16 (9.9-24.5) life years; 89 (67.9-160.5) QALYs, respectively. Assuming 50% effectiveness, benefit cost ratios ranged from 0.19 to 3.42 for diverse operational settings. The cost to prevent a single case of kernicterus was $2.7 to 6.8 million per annum with cost per QALY gained at $35,946 to $89,159. CONCLUSION: At incremental cost-effective threshold of $100,000/life year, pre-discharge screening would be expected to prove cost effective in preventing EHB related morbidities and mortality attributed to G6PD deficiency.

Normalizing hyperactivity of the Gunn rat with bilirubin-induced neurological disorders via ketanserin.

BACKGROUND: Severe neonatal hyperbilirubinemia has been known to cause the clinical syndrome of kernicterus and a milder one the syndrome of bilirubin-induced neurologic dysfunction (BIND). BIND clinically manifests itself after the neonatal period as developmental delay, cognitive impairment, and related behavioral and psychiatric disorders. The complete picture of BIND is not clear. METHODS: The Gunn rat is a mutant strain of the Wistar rat with the BIND phenotype, and it demonstrates abnormal behavior. We investigated serotonergic dysfunction in Gunn rats by pharmacological analyses and ex vivo neurochemical analyses. RESULTS: Ketanserin, the 5-HT2AR antagonist, normalizes hyperlocomotion of Gunn rats. Both serotonin and its metabolites in the frontal cortex of Gunn rats were higher in concentrations than in control Wistar rats. The 5-HT2AR mRNA expression was downregulated without alteration of the protein abundance in the Gunn rat frontal cortex. The TPH2 protein level in the Gunn rat raphe region was significantly higher than that in the Wistar rat. CONCLUSIONS: It would be of value to be able to postulate that a therapeutic strategy for BIND disorders would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after onset of BIND manifestations. IMPACT: We demonstrated serotonergic dysregulation underlying hyperlocomotion in Gunn rats. This finding suggests that a therapeutic strategy for bilirubin-induced neurologic dysfunction (BIND) would be the restoration of brain regions affected by the serotonergic dysfunction to normal operation to prevent before or to normalize after the onset of the BIND manifestations. Ketanserin normalizes hyperlocomotion of Gunn rats. To our knowledge, this is the first study to demonstrate a hyperlocomotion link to serotonergic dysregulation in Gunn rats.

POCT management of neonatal bilirubinemia ­ guidelines for an optimization of kernicterus monitoring / Intérêt de la bilirubinémie en néonatalogie : recommandations pour une utilisation coordonnée par le LBM de la biologie délocalisée et des tests rapides d'orientation diagnostique

In pediatrics, accurate measurement of total serum bilirubin (TSB) is of major importance for reliable diagnosis and appropriate management of neonatal jaundice. However, several studies evidenced poor comparability of results obtained with the different available methods either in central lab or in POCT, on serum, capillary blood or transcutaneous. This situation is partly due to the lack of Reference Materials, especially for high bilirubin concentrations but also on poor communication between central lab and neonatology unit. To progress on these issues, we have compiled some data from CNRHP to propose guidelines for choice, use and management of POCT devices and to help clinical laboratories to achieve a better answer to clinical needs with specific local constraints. The results from several CNRHP studies are presented: traceability to International System of Units, inter-laboratories comparability, POCT vs central labs comparisons with POCT CO-oximeter or photometer, integration of transcutaneous bilirubinometer. We propose, based on an analysis of devices advantages and issues, guidelines to help labs either to improve neonates monitoring in their local context; we distinguished the choices inside laboratory for a better harmonization of results compared to published thresholds and outside lab contexts, to organize a coordinated chain with POCT devices, with capillary and/or transcutaneous approaches.

En néonatalogie, la mesure précise de la bilirubinémie est essentielle pour le diagnostic et le suivi de l'ictère, en regard de seuils consensuels internationaux. Toutefois, une faible comparabilité des résultats est observée entre les laboratoires de biologie médicale (LBM) et avec les dispositifs délocalisés ou transcutanés. Cette situation est en partie due à des défauts de standardisation des méthodes, mais aussi à une coordination insuffisante entre les laboratoires et les unités de soins. L'objectif de ce travail est de progresser dans l'optimisation de la prise en charge des nouveau-nés en proposant des critères de choix et d'articulation des différentes réponses biologiques, EBM, EBMD et TROD, en fonction des besoins cliniques locaux et des moyens disponibles. Les résultats de plusieurs études ciblées sur la bilirubinémie néonatale sont présentés : raccordement au système international, harmonisation interlaboratoires, comparabilité EBMD-CNRHP d'un CO-oxymètre délocalisé en maternité, comparabilité EBMD-CNRHP d'un photomètre délocalisé en maternité, intégration d'un bilirubinomètre transcutané. Nous proposons ensuite, sur la base d'une analyse critique des différents types de dispositifs, des recommandations pour aider les LBM à améliorer la prise en charge des nouveau-nés dans leur contexte local, d'une part sur la mesure de la bilirubinémie néonatale au sein du LBM et d'autre part sur l'organisation d'une chaîne coordonnée EBM ­ EBMD ­ TROD en concertation avec les unités de soins.

Intensive phototherapy vs. exchange transfusion for the treatment of neonatal hyperbilirubinemia: a multicenter retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.@*METHODS@#This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.@*RESULTS@#A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.@*CONCLUSIONS@#In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.