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1.
Medicine (Baltimore) ; 99(9): e19364, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118780

RESUMO

To establish a clinical prediction rule for acute bilirubin encephalopathy (ABE) in term/near-term neonates with extreme hyperbilirubinemia.A retrospective cohort study was conducted between January 2015 and December 2018. Six hundred seventy-three out of 26,369 consecutive neonates with extreme hyperbilirubinemia were enrolled in this study. Data included demographic characteristics, total serum bilirubin (TSB), albumin, bilirubin/albumin ratio (B/A), direct antiglobulin test, glucose-6-phosphate deficiency, asphyxia, sepsis, acidosis. ABE was defined as a bilirubin induced neurological dysfunction score of 4 to 9. We used stepwise logistic regression to select predictors of ABE and devised a prediction score.Of the 673 eligible infants, 10.8% suffered from ABE. Our prediction score consisted of 3 variables: TSB (as a continuous variable; odds ratio [OR] 1.16; 95% confidence interval [CI], 1.02-1.31; logistic coefficient 0.15), B/A (as a continuous variable; OR 1.88; 95% CI, 1.19-2.97; logistic coefficient 0.67), and sepsis (OR 3.78; 95% CI, 1.40-10.21; logistic coefficient 1.19). Multiplying the logistic coefficients by 10 and subtracting 75, resulted in the following equation for the score: Score = 12 × (if sepsis) + 1.5 × (TSB) + 7 × (B/A) - 75. The model performed well with an area under the curve of 0.871.The risk of ABE can be quantified according to TSB, B/A, and sepsis in term/near-term neonates with extreme hyperbilirubinemia.


Assuntos
Hiperbilirrubinemia/complicações , Kernicterus/etiologia , Bilirrubina/análise , Bilirrubina/sangue , China/epidemiologia , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Hiperbilirrubinemia/diagnóstico , Hiperbilirrubinemia/epidemiologia , Recém-Nascido , Kernicterus/diagnóstico , Kernicterus/epidemiologia , Masculino , Estudos Retrospectivos
2.
Artigo em Chinês | MEDLINE | ID: mdl-31446717

RESUMO

SummaryNeonatal hyperbilirubinemia is the most common clinical symptom in neonates. When the concentration of free bilirubin in blood is too high, it crosses through the blood-brain barrier and selectively deposits in specific brain nuclei to cause neurotoxicity and bilirubin neurological dysfunction. The auditory nervous system is highly sensitive to bilirubin. Therefore, auditory neuropathy is the most important or even the only clinical symptom of bilirubin neurological dysfunction. Chronic bilirubin encephalopathy can be classified to three types as mild, moderate and severe,according to the audiological manifestations and other neurological sequelae. Early recognition and intervention of bilirubin-induced hearing impairment is of great significance to improve the speech recognition rate of the referred children. This article reviews the most important studies about the clinical characteristics, pathogenesis and treatment of bilirubin-induced hearing impairment.


Assuntos
Perda Auditiva/etiologia , Perda Auditiva/terapia , Hiperbilirrubinemia/complicações , Bilirrubina , Humanos , Kernicterus/complicações
3.
JAMA Netw Open ; 2(3): e190858, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30901042

RESUMO

Importance: Neonatal hyperbilirubinemia can cause lifelong neurodevelopmental impairment (kernicterus) even in high-resource settings. A better understanding of the incidence and processes leading to kernicterus may help in the design of preventive measures. Objectives: To determine incidence rates of hazardous hyperbilirubinemia and kernicterus among near-term to term newborns and to evaluate health care professional adherence to best practices. Design, Setting, and Participants: This population-based nationwide cohort study used prospectively collected data on the highest serum bilirubin level for all infants born alive at 35 weeks' gestation or longer and admitted to neonatal care at all 46 delivery and 37 neonatal units in Sweden from 2008 to 2016. Medical records for newborns with hazardous hyperbilirubinemia were evaluated for best neonatal practices and for a diagnosis of kernicterus up to 2 years of age. Data analyses were performed between September 2017 and February 2018. Exposures: Extreme (serum bilirubin levels, 25.0-29.9 mg/dL [425-509 µmol/L]) and hazardous (serum bilirubin levels, ≥30.0 mg/dL [≥510 µmol/L]) neonatal hyperbilirubinemia. Main Outcomes and Measures: The primary outcome was kernicterus, defined as hazardous neonatal hyperbilirubinemia followed by cerebral palsy, sensorineural hearing loss, gaze paralysis, or neurodevelopmental retardation. Secondary outcomes were health care professional adherence to national guidelines using a predefined protocol with 10 key performance indicators for diagnosis and treatment as well as assessment of whether bilirubin-associated brain damage might have been avoidable. Results: Among 992 378 live-born infants (958 051 term births and 34 327 near-term births), 494 (320 boys; mean [SD] birth weight, 3505 [527] g) developed extreme hyperbilirubinemia (50 per 100 000 infants), 6.8 per 100 000 infants developed hazardous hyperbilirubinemia, and 1.3 per 100 000 infants developed kernicterus. Among 13 children developing kernicterus, brain injury was assessed as potentially avoidable for 11 children based on the presence of 1 or several of the following possible causes: untimely or lack of predischarge bilirubin screening (n = 6), misinterpretation of bilirubin values (n = 2), untimely or delayed initiation of treatment with intensive phototherapy (n = 1), untimely or no treatment with exchange transfusion (n = 6), or lack of repeated exchange transfusions despite indication (n = 1). Conclusions and Relevance: Hazardous hyperbilirubinemia in near-term or term newborns still occurs in Sweden and was associated with disabling brain damage in 13 per million births. For most of these cases, health care professional noncompliance with best practices was identified, suggesting that a substantial proportion of these cases might have been avoided.


Assuntos
Hiperbilirrubinemia Neonatal , Kernicterus , Feminino , Fidelidade a Diretrizes , Humanos , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/epidemiologia , Hiperbilirrubinemia Neonatal/terapia , Recém-Nascido , Kernicterus/diagnóstico , Kernicterus/epidemiologia , Kernicterus/terapia , Masculino , Estudos Prospectivos , Suécia
4.
Autops. Case Rep ; 9(1): e2018057, Jan.-Mar. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-986740
5.
Neonatology ; 115(3): 242-246, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30669144

RESUMO

BACKGROUND: Acute bilirubin encephalopathy (ABE) is a potentially devastating condition that can lead to death or life-long neurodevelopmental handicaps. ABE is particularly tragic because it is, in theory, completely preventable. Progress toward its prevention has been hampered by the perception that the extreme hyperbilirubinemia giving rise to ABE typically has no clear causation, with the majority of previous cases being labeled as "idiopathic" neonatal jaundice. OBJECTIVES: This research briefing is intended to inform readers of a new prospective study aimed at clarifying the causes of ABE. This is accomplished by identifying qualifying patients with ABE anywhere in the USA and then documenting their clinical characteristics and the results of testing 28 specific genetic associations in a web-based, institutional review board-approved, REDCap (research electronic data capture) deidentified registry. METHODS: In this research briefing, we present an overview of ABE and discuss the problem that most patients in the past have been labeled as having "idiopathic" hyperbilirubinemia. We also present data supporting a new theory that most (perhaps all) ABE patients have mutations or polymorphisms in genes involved in bilirubin production or metabolism. We introduce a new registry seeking to enroll 100 neonates with ABE as a voluntary, deidentified database, with next generation sequencing of 28 genes involved in bilirubin production/metabolism provided to enrollees at no cost. RESULTS AND CONCLUSIONS: The Neonatal Acute Bilirubin Encephalopathy Registry (NABER) study will correlate deidentified clinical and genetic data in order to clarify the underlying causes of hyperbilirubinemia in current ABE patients. We maintain that the improved understanding this study produces will constitute a needed step toward devising new clinical pathways and strategies for preventing ABE in neonates.


Assuntos
Bilirrubina/genética , Kernicterus/genética , Sistema de Registros , Bilirrubina/análise , Humanos , Recém-Nascido , Kernicterus/etiologia , Estudos Prospectivos , Projetos de Pesquisa , Estados Unidos
6.
Arch Dis Child Fetal Neonatal Ed ; 104(2): F202-F204, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29802103

RESUMO

We examined claims made against the National Health Service (NHS) involving neonatal jaundice in order to determine whether there were lessons that could be learnt from common themes.This was a retrospective anonymised study using information from the NHS Resolution database for 2001-2011.Twenty cases (16 males) had sufficient information for analysis. Fifteen had confirmed cerebral palsy and two young children had damage to the globus pallidus without confirmed CP. In three cases, the outcome was uncertain. Two were extremely preterm, five were born at 34-36 weeks' gestation. Jaundice was typically present very early in life; in four cases, it was noted at less than 24hours of age, and in 14 cases, it was first noted on the second to third day. There was a lag between recognition and readmission, with a range of 26-102 hours. The peak serum bilirubin level was over 600 µmol/L in all the babies born at term. An underlying diagnosis was found in all but two; six had glucose-6-phosphatase deficiency (one also had Gilbert's syndrome); five were diagnosed with ABO incompatibility; three with Rh haemolytic disease; one with spherocytosis and three preterm. The total cost of these claims by August 2017 was almost £150.5 million. This figure is likely to rise.These data show that, in the group who litigate, babies who develop kernicterus generally have an underlying diagnosis. We recommend adherence to theNational Institute for Health and Care Excellence guideline that recommends measuring the bilirubin level within 6 hours in all babies who are visibly jaundiced.


Assuntos
Hiperbilirrubinemia/epidemiologia , Seguro Saúde/estatística & dados numéricos , Kernicterus/epidemiologia , Bilirrubina/sangue , Inglaterra/epidemiologia , Custos de Cuidados de Saúde , Humanos , Hiperbilirrubinemia/economia , Hiperbilirrubinemia/etiologia , Incidência , Recém-Nascido , Seguro Saúde/economia , Icterícia Neonatal/economia , Icterícia Neonatal/epidemiologia , Icterícia Neonatal/etiologia , Kernicterus/economia , Kernicterus/etiologia , Estudos Retrospectivos
7.
World J Pediatr ; 15(1): 42-48, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30406356

RESUMO

BACKGROUND: Acute bilirubin encephalopathy (ABE) still represents a significant cause of morbidity and mortality throughout the world, especially in developing countries. We aimed to determine the prevalence of ABE based on the Johnson bilirubin-induced neurologic dysfunction (BIND) score and to describe the discharge outcomes. METHODS: We prospectively studied all newborns ≥ 35 weeks with ABE by evaluating signs of mental sensorium, muscle tone, and cry patterns over 1 year. RESULTS: 12% (81 out of 674) of the newborns admitted for neonatal hyperbilirubinemia had a BIND score > 1. Their admission age was 6 ± 4.1 days; total serum bilirubin (TSB) was 31.2 ± 10 mg/dL (range 17.5-75.2). Of these newborns, 40.7% and 21% had evidence of haemolysis and sepsis, respectively. Overall mortality was 9.9%; 58% of the newborns showed signs of mild-to-moderate BIND at discharge, while 32.1% survived with an apparently normal outcome. Admission BIND score was significantly correlated with admission TSB (r = 0.476, P < 0.001). Similarly, BIND score at discharge was correlated with admission TSB (r = 0.442, P < 0.001) and admission BIND score (r = 0.888, P < 0.001). The regression model showed that admission TSB (P < 0.001) and maternal illiteracy (P = 0.034) were predictors of the BIND score at admission, while admission BIND score was the best indicator of the discharge score (P < 0.001). CONCLUSIONS: ABE is still a major problem in our community. Admission TSB and maternal illiteracy are good predictors of bilirubin encephalopathy at admission and discharge.


Assuntos
Hiperbilirrubinemia Neonatal/epidemiologia , Unidades de Terapia Intensiva Neonatal , Kernicterus/epidemiologia , Bilirrubina/sangue , Egito/epidemiologia , Feminino , Hemólise , Mortalidade Hospitalar , Humanos , Recém-Nascido , Alfabetização , Masculino , Mães , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Neurodesenvolvimento/etiologia , Estudos Prospectivos , Sepse/epidemiologia , Índice de Gravidade de Doença , Centros de Atenção Terciária
8.
Ir Med J ; 111(4): 739, 2018 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30488686

RESUMO

Kernicterus is a relatively rare consequence of hyperbilirubinemia. There is an important role for MRI imaging for this entity in the appropriate clinical context as there are distinct signal changes in the globus pallidus. A case report and image findings are presented


Assuntos
Imagem de Difusão por Ressonância Magnética , Globo Pálido/diagnóstico por imagem , Globo Pálido/patologia , Kernicterus/diagnóstico por imagem , Kernicterus/patologia , Neuroimagem , Feminino , Humanos , Hiperbilirrubinemia/complicações , Lactente , Kernicterus/etiologia
9.
Sci Rep ; 8(1): 13690, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30209300

RESUMO

Bilirubin neurotoxicity has been studied for decades and has been shown to affect various mechanisms via significant modulation of gene expression. This suggests that vital regulatory mechanisms of gene expression, such as epigenetic mechanisms, could play a role in bilirubin neurotoxicity. Histone acetylation has recently received attention in the CNS due to its role in gene modulation for numerous biological processes, such as synaptic plasticity, learning, memory, development and differentiation. Aberrant epigenetic regulation of gene expression in psychiatric and neurodegenerative disorders has also been described. In this work, we followed the levels of histone 3 lysine 14 acetylation (H3K14Ac) in the cerebellum (Cll) of the developing (2, 9, 17 days after the birth) and adult Gunn rat, the natural model for neonatal hyperbilirubinemia and kernicterus. We observed an age-specific alteration of the H3K14Ac in the hyperbilirubinemic animals. The GeneOntology analysis of the H3K14Ac linked chromatin revealed that almost 45% of H3K14Ac ChiP-Seq TSS-promoter genes were involved in CNS development including maturation and differentiation, morphogenesis, dendritogenesis, and migration. These data suggest that the hallmark Cll hypoplasia in the Gunn rat occurs also via epigenetically controlled mechanisms during the maturation of this brain structure, unraveling a novel aspect of the bilirubin-induced neurotoxicity.


Assuntos
Bilirrubina/metabolismo , Cerebelo/metabolismo , Histonas/metabolismo , Kernicterus/metabolismo , Acetilação , Animais , Animais Recém-Nascidos/metabolismo , Cerebelo/anormalidades , Deficiências do Desenvolvimento/metabolismo , Modelos Animais de Doenças , Malformações do Sistema Nervoso/metabolismo , Plasticidade Neuronal/fisiologia , Ratos , Ratos Gunn
10.
PLoS One ; 13(8): e0201022, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30106954

RESUMO

Hyperbilirubinemia (jaundice) is caused by raised levels of unconjugated bilirubin in the blood. When severe, susceptible brain regions including the cerebellum and auditory brainstem are damaged causing neurological sequelae such as ataxia, hearing loss and kernicterus. The mechanism(s) by which bilirubin exerts its toxic effect have not been completely understood to date. In this study we investigated the acute mechanisms by which bilirubin causes the neurotoxicity that contributes to hearing loss. We developed a novel mouse model that exhibits the neurological features seen in human Bilirubin-Induced Neurological Dysfunction (BIND) syndrome that we assessed with a behavioural score and auditory brainstem responses (ABR). Guided by initial experiments applying bilirubin to cultured cells in vitro, we performed whole genome gene expression measurements on mouse brain tissue (cerebellum and auditory brainstem) following bilirubin exposure to gain mechanistic insights into biochemical processes affected, and investigated further using immunoblotting. We then compared the gene changes induced by bilirubin to bacterial lipopolysaccharide (LPS), a well characterized inducer of neuroinflammation, to assess the degree of similarity between them. Finally, we examined the extent to which genetic perturbation of inflammation and both known and novel anti-inflammatory drugs could protect hearing from bilirubin-induced toxicity. The in vitro results indicated that bilirubin induces changes in gene expression consistent with endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). These gene changes were similar to the gene expression signature of thapsigargin-a known ER stress inducer. It also induced gene expression changes associated with inflammation and NF-κB activation. The in vivo model showed behavioural impairment and a raised auditory threshold. Whole genome gene expression analysis confirmed inflammation as a key mechanism of bilirubin neurotoxicity in the auditory pathway and shared gene expression hallmarks induced by exposure to bacterial lipopolysaccharide (LPS) a well-characterized inducer of neuroinflammation. Interestingly, bilirubin caused more severe damage to the auditory system than LPS in this model, but consistent with our hypothesis of neuroinflammation being a primary part of bilirubin toxicity, the hearing loss was protected by perturbing the inflammatory response. This was carried out genetically using lipocalin-2 (LCN2)-null mice, which is an inflammatory cytokine highly upregulated in response to bilirubin. Finally, we tested known and novel anti-inflammatory compounds (interfering with NF-κB and TNFα signalling), and also demonstrated protection of the auditory system from bilirubin toxicity. We have developed a novel, reversible, model for jaundice that shows movement impairment and auditory loss consistent with human symptoms. We used this model to establish ER-stress and inflammation as major contributors to bilirubin toxicity. Because of the rapid and reversible onset of toxicity in this novel model it represents a system to screen therapeutic compounds. We have demonstrated this by targeting inflammation genetically and with anti-inflammatory small molecules that offered protection against bilirubin toxicity. This also suggests that anti-inflammatory drugs could be of therapeutic use in hyperbilirubinemia.


Assuntos
Bilirrubina/toxicidade , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Perda Auditiva/etiologia , Kernicterus/etiologia , Síndromes Neurotóxicas/etiologia , Doença Aguda , Animais , Anti-Inflamatórios/farmacologia , Ataxia/etiologia , Ataxia/metabolismo , Bilirrubina/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Feminino , Perda Auditiva/metabolismo , Perda Auditiva/prevenção & controle , Humanos , Hiperbilirrubinemia/complicações , Hiperbilirrubinemia/metabolismo , Inflamação/etiologia , Inflamação/metabolismo , Kernicterus/metabolismo , Lipocalina-2/deficiência , Lipocalina-2/genética , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos CBA , Camundongos Knockout , NF-kappa B/metabolismo , Síndromes Neurotóxicas/metabolismo
11.
J Perinatol ; 38(8): 947-953, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29997396

RESUMO

Given the urgency of double volume exchange transfusion (ExT) in an infant with intermediate to advanced stages of acute bilirubin encephalopathy (ABE), it has been suggested that emergency release uncross-matched packed red blood cells (ER-PRBC) be used. The efficacy of an ExT in removing bilirubin from the brain, however, is a direct function of the mass of albumin exchanged. The very low albumin content of ER-PRBC may fail to be neuroprotective. Predicted changes in total serum bilirubin (TSB), serum albumin, the bilirubin/albumin (B/A) ratio, plasma volume (PV), and bilirubin equilibration from the extravascular space during ER-PRBC ExT are described. ExT using ER-PRBC is efficacious in lowering the TSB. However, this result is falsely reassuring as significant concurrent serum albumin loss, resultant hypoalbuminemia, contraction of PV, limited bilirubin clearance from the extravascular space, and sustained B/A ratio elevations above recommended ExT treatment thresholds suggest that bilirubin neurotoxicity will continue.


Assuntos
Bilirrubina/sangue , Transfusão de Eritrócitos , Transfusão Total , Kernicterus/terapia , Humanos , Recém-Nascido , Kernicterus/sangue , Albumina Sérica Humana/análise
12.
Pediatr Res ; 84(2): 228-232, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29892033

RESUMO

BACKGROUND: Galactosemia has not been recognized as a cause of extreme neonatal hyperbilirubinemia, although growing evidence supports this association. METHODS: In a retrospective cohort study, we identified children with galactosemia due to GALT deficiency using the Danish Metabolic Laboratory Database. Among these, we identified children with extreme neonatal hyperbilirubinemia or symptoms of ABE. Extreme neonatal hyperbilirubinemia was defined as maximum total serum bilirubin (TSBmax)) level ≥450 µmol/L and a ratio of conjugated serum bilirubin/TSB <0.30. RESULTS: We identified 21 children with galactosemia (incidence:1:48,000). Seven children developed extreme neonatal hyperbilirubinemia (median [range] TSBmax level: 491 [456-756] µmol/L), accounting for 1.7% of all extreme neonatal hyperbilirubinemia cases. During the first 10 days of life, hyperbilirubinemia was predominantly of unconjugated type. Four children developed symptoms of intermediate/advanced ABE. One additional child had symptoms of intermediate/advanced ABE without having extreme neonatal hyperbilirubinemia. On follow-up, one child had KSD. CONCLUSIONS: Galactosemia is a potential cause of extreme neonatal hyperbilirubinemia, ABE, and KSD. It is crucial that putative galactosemic children are treated aggressively with phototherapy to prevent ABE and KSD. Thus it is important that galactosemia is part of the work up for unconjugated hyperbilirubinemia.


Assuntos
Bilirrubina/sangue , Galactosemias/complicações , Hiperbilirrubinemia Neonatal/sangue , Kernicterus/sangue , Adolescente , Encefalopatias/sangue , Encefalopatias/complicações , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Hiperbilirrubinemia Neonatal/complicações , Lactente , Recém-Nascido , Kernicterus/complicações , Masculino , Mutação , Fototerapia , Estudos Retrospectivos
13.
Blood Cells Mol Dis ; 72: 10-13, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29880417

RESUMO

Herein we report a case series of seven newborn infants, all apparently well at birth, who in the period since 2009 were cared for in the State of Utah with acute bilirubin encephalopathy (ABE). This report summarizes our attempts to define common features of these seven through a state-wide voluntary registry, as a step toward devising new means of preventing such cases in the future. In previous reports of ABE, many of the affected neonates had no clearly defined explanation for their progressive hyperbilirubinemia. Our efforts to identify clear explanations in all seven cases included next generation DNA sequencing, testing a panel of 28 genes involved in bilirubin production and metabolism. We found that hemolytic disease was a unifying feature of these seven; two had DAT (+) Anti-D or anti-c hemolysis, while five had confirmed mutations in genes involved in bilirubin production and or metabolism that were previously unrecognized in these families.


Assuntos
Bilirrubina/genética , Kernicterus/genética , Bilirrubina/análise , Hemólise , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Recém-Nascido , Kernicterus/etiologia , Mutação , Sistema de Registros , Utah
14.
Pediatr Int ; 60(8): 684-690, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29906300

RESUMO

In 1992, Kobe University proposed treatment criteria for hyperbilirubinemia in newborns using total serum bilirubin and serum unbound bilirubin reference values. In the last decade, chronic bilirubin encephalopathy has been found to develop in preterm infants in Japan because it can now be clinically diagnosed based on an abnormal signal of the globus pallidus on T2-weighted magnetic resonance imaging and abnormal auditory brainstem response with or without apparent hearing loss, along with physical findings of kinetic disorders with athetosis. We therefore revised the Kobe University treatment criteria for preterm hyperbilirubinemic infants in 2017. The three revised points are as follows: (i) newborns are classified under gestational age at birth or corrected gestational age, not birthweight; (ii) three treatment options were created: standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion; and (iii) initiation of standard phototherapy, intensive phototherapy, and albumin therapy and/or exchange blood transfusion is decided based on the total serum bilirubin and serum unbound bilirubin reference values for gestational weeks at birth at <7 days of age, and on the reference values for corrected gestational age at ≥7 days of age. Studies are needed to establish whether chronic bilirubin encephalopathy can be prevented using the 2017 revised Kobe University treatment criteria for preterm infants in Japan.


Assuntos
Hiperbilirrubinemia Neonatal/terapia , Doenças do Recém-Nascido/terapia , Albuminas/uso terapêutico , Terapia Combinada , Transfusão Total , Humanos , Hiperbilirrubinemia Neonatal/diagnóstico , Recém-Nascido , Doenças do Recém-Nascido/diagnóstico , Recém-Nascido Prematuro , Japão , Kernicterus/etiologia , Kernicterus/prevenção & controle , Fototerapia/métodos , Guias de Prática Clínica como Assunto
17.
J Perinatol ; 38(7): 873-880, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29593357

RESUMO

BACKGROUND: Acute bilirubin encephalopathy (ABE) is an important cause of neonatal morbidity in Nigeria, accounting for 5-14% of neonatal deaths. Most newborns with severe ABE have irreversible damage before receiving treatment emphasizing the need for timely pre-admission monitoring and referral. There is limited evidence that educational interventions targeting mothers and health care providers will reduce delayed care. OBJECTIVE: To provide baseline data on the incidence of ABE and associated pre-admission risk factors in five centers of Nigeria in order to evaluate the effect of subsequent educational interventions on outcome. STUDY DESIGN: The incidence of ABE among newborns treated for hyperbilirubinemia was documented prospectively. Bivariate analysis and multivariate logistic regression were used to evaluate risk factors for acute bilirubin encephalopathy and reasons for regional differences in its occurrence. RESULTS: Of 1040 infants, 159 treated for hyperbilirubinemia (15.3%) had mild to severe bilirubin encephalopathy (including 35 deaths), but the incidence ranged from 7 to 22% between centers. Logistic regression identified four common predictors: total serum bilirubin (odds ratio 1.007 per mg/dl rise), out-of-hospital births (OR 2.6), non-alloimmune hemolytic anemia (OR 2.8), and delayed care seeking (OR 4.3). CONCLUSION: The high occurrence of bilirubin encephalopathy in Nigeria is due in large part to a delay in seeking care. A planned intervention strategy will target conditions leading to severe hyperbilirubinemia and delay.


Assuntos
Hiperbilirrubinemia Neonatal/complicações , Mortalidade Infantil/tendências , Kernicterus/epidemiologia , Kernicterus/terapia , Doença Aguda , Estudos de Coortes , Diagnóstico Tardio/efeitos adversos , Países em Desenvolvimento , Feminino , Mortalidade Hospitalar/tendências , Humanos , Hiperbilirrubinemia Neonatal/diagnóstico , Incidência , Lactente , Recém-Nascido , Kernicterus/etiologia , Kernicterus/fisiopatologia , Modelos Logísticos , Masculino , Nigéria/epidemiologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença
18.
Arch Dis Child ; 103(10): 927-929, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29472193

RESUMO

OBJECTIVE: To investigate the burden of clinically significant neonatal jaundice (SNJ) in Taiwan, 2000-2010. STUDY DESIGN: The nationwide, population-based health insurance database in Taiwan was used to investigate the incidence, kernicterus rate and mortality rates of SNJ cohort born between 2000 and 2010. RESULTS: From 2000 to 2010, up to 242 546 patients admitted with neonatal jaundice (NJ) were identified. The incidence of SNJ was 5.9% in 2000 and increased to 13.7% in 2010 (P<0.001). The mortality rate significantly decreased from 0.51% in 2000 to 0.26% in 2010 (P<0.001) and the average incidence of kernicterus was 0.86 per 100 000 live births, indicating dramatically decreased rates compared with earlier rates in Taiwan. CONCLUSIONS: In spite of the increased incidence rates, the rates of mortality and kernicterus in patients with NJ significantly declined in Taiwan. The public health prevention programme, clinicians' awareness and effective management might contribute to the reduction of these acute severe sequelae.


Assuntos
Icterícia Neonatal , Kernicterus , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Recém-Nascido , Icterícia Neonatal/mortalidade , Icterícia Neonatal/terapia , Kernicterus/epidemiologia , Kernicterus/prevenção & controle , Masculino , Mortalidade , Determinação de Necessidades de Cuidados de Saúde , Taiwan/epidemiologia
19.
PLoS One ; 13(2): e0193108, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29474382

RESUMO

BACKGROUND: Neonatal jaundice (NNJ) is common, but few root cause analyses based on national quality registries have been performed. An online registry was established to estimate the incidence of NNJ in Turkey and to facilitate a root cause analysis of NNJ and its complications. METHODS: A multicenter prospective study was conducted on otherwise healthy newborns born at ≥35 weeks of gestation and hospitalized for only NNJ in 50 collaborator neonatal intensive care units across Turkey over a 1-year period. Patients were analyzed for their demographic and clinical characteristics, treatment options, and complications. RESULTS: Of the 5,620 patients enrolled, 361 (6.4%) had a bilirubin level ≥25 mg/dL on admission and 13 (0.23%) developed acute bilirubin encephalopathy. The leading cause of hospital admission was hemolytic jaundice, followed by dehydration related to a lack of proper feeding. Although all infants received phototherapy, 302 infants (5.4%) received intravenous immunoglobulin in addition to phototherapy and 132 (2.3%) required exchange transfusion. The infants who received exchange transfusion were more likely to experience hemolytic causes (60.6% vs. 28.1%) and a longer duration of phototherapy (58.5 ± 31.7 vs. 29.4 ± 18.8 h) compared to infants who were not transfused (p < 0.001). The incidence of short-term complications among discharged patients during follow-up was 8.5%; rehospitalization was the most frequent (58%), followed by jaundice for more than 2 weeks (39%), neurological abnormality (0.35%), and hearing loss (0.2%). CONCLUSIONS: Severe NNJ and bilirubin encephalopathy are still problems in Turkey. Means of identifying at-risk newborns before discharge during routine postnatal care, such as bilirubin monitoring, blood group analysis, and lactation consultations, would reduce the frequency of short- and long-term complications of severe NNJ.


Assuntos
Registros Eletrônicos de Saúde , Hospitalização , Internet , Icterícia Neonatal , Fototerapia , Sistema de Registros , Feminino , Seguimentos , Humanos , Recém-Nascido , Icterícia Neonatal/epidemiologia , Icterícia Neonatal/terapia , Kernicterus/epidemiologia , Kernicterus/terapia , Masculino , Estudos Prospectivos , Turquia/epidemiologia
20.
Brain Behav Immun ; 70: 166-178, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29458193

RESUMO

All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities. Current therapies rely on the use of phototherapy and, in unresponsive cases, exchange transfusion, which is performed only in specialized centers. During bilirubin-induced neurotoxicity different molecular pathways are activated, ranging from oxidative stress to endoplasmic reticulum (ER) stress response and inflammation, but the contribution of each pathway in the development of the disease still requires further investigation. Thus, to increase our understanding of the pathophysiology of bilirubin neurotoxicity, encephalopathy and kernicterus, we pharmacologically modulated neurodegeneration and neuroinflammation in a lethal mouse model of neonatal hyperbilirubinemia. Treatment of mutant mice with minocycline, a second-generation tetracycline with anti-inflammatory and neuroprotective properties, resulted in a dose-dependent rescue of lethality, due to reduction of neurodegeneration and neuroinflammation, without affecting plasma bilirubin levels. In particular, rescued mice showed normal motor-coordination capabilities and behavior, as determined by the accelerating rotarod and open field tests, respectively. From the molecular point of view, rescued mice showed a dose-dependent reduction in apoptosis of cerebellar neurons and improvement of dendritic arborization of Purkinje cells. Moreover, we observed a decrease of bilirubin-induced M1 microglia activation at the sites of damage with a reduction in oxidative and ER stress markers in these cells. Collectively, these data indicate that neurodegeneration and neuro-inflammation are key factors of bilirubin-induced neonatal lethality and neuro-behavioral abnormalities. We propose that the application of pharmacological treatments having anti-inflammatory and neuroprotective effects, to be used in combination with the current treatments, may significantly improve the management of acute neonatal hyperbilirubinemia, protecting from bilirubin-induced neurological damage and death.


Assuntos
Hiperbilirrubinemia Neonatal/fisiopatologia , Hiperbilirrubinemia Neonatal/terapia , Animais , Animais Recém-Nascidos , Bilirrubina , Encefalopatias/fisiopatologia , Modelos Animais de Doenças , Inflamação , Kernicterus/fisiopatologia , Camundongos , Minociclina/farmacologia , Neuroimunomodulação/fisiologia , Fármacos Neuroprotetores , Síndromes Neurotóxicas , Fototerapia/métodos
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