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Journal ArticleDOI

The Neurological Sequelae of Neonatal Hyperbilirubinemia: Definitions, Diagnosis and Treatment of the Kernicterus Spectrum Disorders (KSDs).

TL;DR: Adopting a systematic nomenclature for the spectrum of clinical consequences of hyperbilirubinemia will help unify the field and promote more effective research in both prevention and treatment of KSDs.
Abstract: Background Despite its lengthy history, the study of jaundice, hyperbilirubinemia and kernicterus suffers from a lack of clarity and consistency in the key terms used to describe both the clinical and pathophysiological nature of these conditions. For example, the term Bilirubin-induced Neurological Dysfunction (BIND) has been used to refer to all neurological sequelae caused by exposure to high levels of bilirubin, to only mild neurological sequelae, or to scoring systems that quantitate the progressive stages of Acute Bilirubin Encephalopathy (ABE). Objective We seek to clarify and simplify terminology by introducing, defining, and proposing new terms and diagnostic criteria for kernicterus. Methods We propose a systematic nomenclature based on pathophysiological and clinical criteria, presenting a logical argument for each term. Acknowledging observations that kernicterus is symptomatically broad and diverse, we propose the use of the overarching term Kernicterus Spectrum Disorders (KSDs) to encompass all the neurological sequelae of bilirubin neurotoxicity including Acute Bilirubin Neurotoxicity (ABE). We further suggest subclassification of KSDs based on the principal disabling features of kernicterus (motor, auditory). Finally, we suggest the term subtle KSD to designate a child with a history of significant bilirubin neurotoxicity with mild or subtle developmental delays. Results and conclusion We conclude with a brief description of the limited treatments currently available for KSD, thereby underscoring the importance of further research. We believe that adopting a systematic nomenclature for the spectrum of clinical consequences of hyperbilirubinemia will help unify the field and promote more effective research in both prevention and treatment of KSDs.
Citations
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Journal ArticleDOI
TL;DR: Up-to-date evidence on the epidemiology of neonatal jaundice including its global burden based on estimates of its prevalence, and both fatal and non-fatal health outcomes is summarized.

134 citations

Journal ArticleDOI
TL;DR: The chemistry of the bilirubin molecule and its metabolism in the body is reviewed with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infants.
Abstract: Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.

41 citations

Journal ArticleDOI
07 Mar 2018
TL;DR: This work is distributed under the terms of the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/ 3.0/).
Abstract: php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Research and Reports in Neonatology 2018:8 33–44 Research and Reports in Neonatology Dovepress

36 citations


Cites background from "The Neurological Sequelae of Neonat..."

  • ...Deep brain stimulation may be beneficial in some cases.(15) Unfortunately, most of these options are priced out of the range of infants and children in LMICs....

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Journal ArticleDOI
02 Jan 2018
TL;DR: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control and suggests quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6 PD deficiency on umbilical cord blood.
Abstract: Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated.

33 citations

Journal ArticleDOI
TL;DR: The study stresses the importance of a systematic approach to neonatal jaundice and ongoing surveillance of extreme neonatal hyperbilirubinemia and KSD and concludes that blood type ABO isohemolytic disease was the most common explanatory etiology.
Abstract: To determine the incidence and etiology of extreme neonatal hyperbilirubinemia, defined as total serum bilirubin (TSB) ≥450 µmol/L, and kernicterus spectrum disorder (KSD) in Denmark between 2000 and 2015. We identified all infants born between 01.01.2000 and 31.12.2015 with TSB ≥450 µmol/L, ratio of conjugated to TSB <0.30, gestational age ≥35 weeks, and postnatal age ≤4 weeks, using Danish hospitals’ laboratory databases. We included 408 infants. The incidence of extreme neonatal hyperbilirubinemia among infants with gestational age ≥35 weeks was 42/100,000 during the study period with a seemingly decreasing incidence between 2005 and 2015. Twelve of the 408 infants developed KSD, (incidence 1.2/100,000) Blood type ABO isohemolytic disease was the most common explanatory etiology. Our study stresses the importance of a systematic approach to neonatal jaundice and ongoing surveillance of extreme neonatal hyperbilirubinemia and KSD.

32 citations


Cites background from "The Neurological Sequelae of Neonat..."

  • ...KSD is a spectrum of neurologic sequelae caused by excessive hyperbilirubinemia in form of auditory disturbances (deafness or hearing loss secondary to auditory neuropathy), dystonic or athetotic cerebral palsy, cognitive disability, gaze abnormalities, and dental enamel dysplasia of the deciduous teeth [4]....

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  • ...The term KSD [4] is applied to all infants with chronic bilirubin encephalopathy, both infants with only auditory problems—auditory KSD—and infants with auditory problems, cerebral palsy, and cognitive disability—classical KSD....

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  • ...The early phase is considered reversible, whereas the intermediate and advanced phases of ABE may be reversible [3] or result in kernicterus spectrum disorder (KSD) [4] or death....

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