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1.
Eur J Pediatr ; 183(7): 2819-2830, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38581462

RESUMO

Measurement of transcutaneous bilirubin (TcB) is a non-invasive, widely used technique to estimate serum bilirubin (SB). However, its reliability in multiethnic populations during and after phototherapy is still controversial even in covered skin. The aim of this study was to determine the reliability of TcB in covered (cTcB) and exposed (eTcB) skin during and after phototherapy in a multiethnic population of term and preterm neonates according to Neomar's neonatal skin color scale. Prospective, observational study comparing SB and TcB. We determined SB when clinically indicated and, at the same time, measured cTcB under a photo-opaque patch and eTcB next to it with a jaundice meter (Dräger JM-105TM). All dyads TcB-SB were compared, both globally and according to skin color. We obtained data from 200 newborns (color1: 44, color2: 111, color3: 41, color4: 4) and compared 296 dyads TcB/SB. Correlation between cTcB and SB is strong during (0.74-0.83) and after (0.79-0.88) phototherapy, both globally and by color group. The SB-cTcB bias depends on gestational age during phototherapy and on skin color following phototherapy. The correlation between eTcB and SB during phototherapy is not strong (0.54), but becomes so 12 h after discontinuing phototherapy (0.78).  Conclusions: Our study supports the reliability of cTcB to assess SB during and after phototherapy, with differences among skin tones after the treatment. The use of cTcB and Neomar's scale during and mainly after phototherapy may help reduce the number of blood samples required. What is Known: • Controversies exist on the reliability of jaundice meters during and after phototherapy in covered skin. Only a few studies have analyzed their accuracy in multiethnic populations, but none has used a validated neonatal skin color scale. What is New: • We verified correlation between serum and transcutaneous bilirubin in covered skin in a multiethnic population depending on skin color based on our own validated neonatal skin color scale during and after phototherapy.


Assuntos
Bilirrubina , Icterícia Neonatal , Fototerapia , Pigmentação da Pele , Humanos , Bilirrubina/sangue , Bilirrubina/análise , Recém-Nascido , Estudos Prospectivos , Reprodutibilidade dos Testes , Feminino , Fototerapia/métodos , Icterícia Neonatal/terapia , Icterícia Neonatal/sangue , Icterícia Neonatal/diagnóstico , Masculino , Triagem Neonatal/métodos , Recém-Nascido Prematuro , Idade Gestacional
2.
Cureus ; 16(3): e55608, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586621

RESUMO

This comprehensive review thoroughly examines the historical evolution, physiological foundations, and contemporary advancements in the application of phototherapy for neonatal hyperbilirubinemia. Neonatal hyperbilirubinemia, a common condition resulting from the immature hepatic processes in newborns, poses potential risks, including neurotoxicity, if left untreated. The review traces the historical progression from early recognition of neonatal jaundice to the development of various phototherapy modalities, showcasing the dynamic landscape of neonatal care. Emphasizing the physiological intricacies of bilirubin metabolism in neonates, the study underscores the vulnerability of newborns to hyperbilirubinemia due to delayed hepatic maturation. Phototherapy is a cornerstone in managing hyperbilirubinemia, demonstrating consistent efficacy in reducing unconjugated bilirubin levels. The implications for clinical practice are significant, offering healthcare professionals insights into tailoring treatment strategies based on individual neonatal characteristics and the severity of jaundice. Integrating advanced monitoring and control systems enhances the precision and safety of phototherapy. Recommendations for future research emphasize the need to investigate long-term outcomes, explore adjunctive therapies, and address resource limitations to ensure global access to effective neonatal care. Overall, this review contributes to the ongoing refinement of neonatal care practices, offering a comprehensive understanding of neonatal hyperbilirubinemia and its evolving treatment landscape.

3.
S Afr Fam Pract (2004) ; 66(1): e1-e5, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38572885

RESUMO

Persistent challenges in addressing severe neonatal hyperbilirubinaemia in resource-constrained settings have led to ongoing and often unacceptable rates of morbidity, disability and mortality. These challenges stem from limitations such as inadequate, inefficient or financially inaccessible diagnostic and therapeutic options. However, over the past decade, noteworthy innovations have emerged to address some of these hurdles, and these innovations are increasingly poised for broader implementation. This review provides a concise summary of these novel, economically viable diagnostic solutions, encompassing point-of-care assays and smartphone applications, as well as treatment modalities, notably more effective phototherapy and filtered sunlight. These advancements hold promise and have the potential to meaningfully reduce the burden of neonatal hyperbilirubinaemia, signifying a promising shift in the landscape of neonatal healthcare.


Assuntos
Hiperbilirrubinemia Neonatal , Icterícia Neonatal , Recém-Nascido , Humanos , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/terapia , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Fototerapia , Luz Solar , Estudos Longitudinais
5.
Clin Exp Pediatr ; 67(5): 249-256, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38549357

RESUMO

BACKGROUND: The effect of vitamin E supplementation on bilirubin levels in infants was previously explored, but the results were inconclusive. PURPOSE: To examine the effect of vitamin E supplementation on bilirubin levels in term infants in the neonatal intensive care unit (NICU). METHODS: This interventional double-blind randomized clinical trial was conducted in the Sanandaj Besat Hospital NICU. Enrolled newborns were between 37 and 42 weeks and 6 days of gestation and required phototherapy according to American Academy of Pediatrics clinical guidelines. A total of 138 infants were randomly assigned to vitamin E (n=68) or placebo (n=70) groups. In addition to phototherapy, the vitamin E group received 0.5 mL (5 IU) of supplemental vitamin E daily, whereas the placebo group received 0.5 mL of oral dextrose daily. STATA 17 was used for the data analysis. RESULTS: Changes in bilirubin levels at 24 hours postintervention did not differ significantly from baseline in either group. Vitamin E supplementation did not significantly reduce total bilirubin levels at 24 hours postintervention (mean difference [MD], -0.18; P=0.204; 95% confidence interval [CI], -1.39 to 1.02). However, the vitamin E group exhibited lower total bilirubin levels than the placebo group at 48 hours postintervention (MD, 0.18; P=0.365; 95% CI, -0.89 to 1.27) and 72 hours (MD, 0.36; P=0.356; 95% CI, -2.34 to 1.61), although the differences were not statistically significant. A subgroup analysis revealed that female infants experienced a greater reduction in total bilirubin levels than male infants. CONCLUSION: Infants administered vitamin E versus placebo demonstrated similar reductions in bilirubin levels and hospital stays. Although the average bilirubin changes did not differ significantly between groups, the vitamin E group showed a more noticeable reduction over time, indicating a positive effect of vitamin E supplementation on serum bilirubin reduction. Trial registration: IRCT20220806055625N2 (registered December 26, 2022; http://irct.ir/trial/67135).

6.
BMC Pediatr ; 24(1): 114, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350890

RESUMO

BACKGROUND: Neonatal jaundice is a condition caused by elevated levels of bilirubin in the bloodstream. Laboratory determination of serum bilirubin concentration by total serum bilirubin (TSB) test is still considered as gold standard for clinical guidance and practice. In developed countries, diagnosis of neonatal jaundice is shifting towards point-of-care medical devices. BiliDx is a device developed to allow a fast, blood-based determination of bilirubin levels at the point of care. This study aimed to determine the accuracy of the BiliDx device relative to a standard laboratory total serum bilirubin to diagnose and monitor jaundice among neonates admitted at Muhimbili National Hospital (MNH). MATERIAL AND METHODOLOGY: This was a prospective hospital-based observational study conducted at the Neonatal Ward - MNH, Dar-es-Salaam, Tanzania from November 2022 to January 2023. A total of 180 neonates admitted at the neonatal ward with jaundice and whose parents consented were enrolled in the study. Blood samples were collected; 2 ml of venous blood into the vacutainer bottle for standard laboratory measurement of total serum bilirubin (TSB) and 25µL blood collected into a transfer pipette tube and applied to BiliDx. STATA version 15.1 was used for data analysis. RESULTS: Out of 180 neonates, 39.4% (71/180) had birth weight between 1500 - 2499.9 g, approximately 2/3rd (120/180) were preterm, 92/180 (51.1%) were males and 100/180 (55.6%) were undergoing phototherapy treatment the moment sample taken. The mean bilirubin concentration was 92 mmol/l for BiliDx and 118 mmol/l for standard laboratory TSB. The minimum and maximum values obtained with BiliDx were, 3.4 and 427.5 mmol/l respectively, compared with 10.7 and 382.1 mmol/l using standard laboratory TSB. A linear relationship and correlation coefficient of 0.8408 (p = 0.000) between BiliDx and standard laboratory TSB was found. The regression analysis showed the presence of constant error [coefficient of BiliDx/slope = 0.91, 95% CI (0.82-0.99), p = 0.000] and random error exclusively [coefficient of constant/y-intercept = 48.52, 95%CI (37.70-59.34), p = 0.000]. The Bland-Altman plot showed an acceptable mean difference of 39.1mmol/l, limits of agreement of -48.3mmol/l to 126.4mmol/l, and 179 points (179/180 = 99.4%) lying inside the limits of agreement. CONCLUSION: The results support the use of BiliDx for rapid and accurate testing of elevated levels of bilirubin in the bloodstream among neonates since 99.4% of the differences between BiliDx and standard laboratory TSB lie between the lines of agreement.


Assuntos
Icterícia Neonatal , Icterícia , Recém-Nascido , Masculino , Humanos , Feminino , Icterícia Neonatal/terapia , Bilirrubina , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Icterícia/diagnóstico , Fototerapia , Hospitais , Triagem Neonatal/métodos
7.
J Pak Med Assoc ; 74(1 (Supple-2)): S63-S67, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38385474

RESUMO

OBJECTIVE: To examine the therapeutic effects of Olea europaea L. leaves extract on carbon tetrachloride-induced liver injury in rats. Methods: The experimental study was conducted at the Department of Physiology, University of Karachi, Karachi, in July 2021, and comprised Albino Wistar male rats weighing 180-220gm. The animals were divided into control group I, carbon tetrachloride group II, Olea europaea L. + carbon tetrachloride group III and Olea europaea L. group IV. In Vitro model of hepatic toxicity was developed by carbon tetrachloride. A daily dose of 50mg/kg of aqueous extract of olive leaves was administered orally and 0.8ml/kg of carbon tetrachloride was administered twice a week subcutaneously for 28 days. On the 29th day, the animals were sacrificed, and tested for hepatic enzymes, lipid peroxidation markers and histopathology. Data was analysed using SPSS 20. RESULTS: Of the 24 rats, 6(25%) were in each of the 4 groups. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels were significantly reduced (p<0.05) in group II whereas, 4- hydroxynonenal, isoprostane and malondialdehyde levels were significantly increased (p<0.05). However, total antioxidant level increased significantly (p<0.05) in group III compared to group II. Histopathology showed severe liver damage in group II and mild damage in group III. Conclusion: Olea europaea L. leaves extract was found to have profound hepatoprotective effects.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Olea , Ratos , Masculino , Animais , Tetracloreto de Carbono/toxicidade , Tetracloreto de Carbono/metabolismo , Olea/metabolismo , Fitoterapia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fígado/patologia , Ratos Wistar , Aspartato Aminotransferases , Alanina Transaminase/metabolismo , Peroxidação de Lipídeos
8.
Biomolecules ; 14(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38254662

RESUMO

The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the "yellow players-YP") are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life.


Assuntos
Encefalopatias , Promoção da Saúde , Adulto , Idoso , Humanos , Fígado , Bilirrubina , Biliverdina , Heme , Heme Oxigenase (Desciclizante)
9.
Eur J Pediatr ; 183(2): 727-738, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37979048

RESUMO

The purpose of this research was to define the functions of MRS and ABR as predictors of bilirubin-induced neurologic dysfunction (BIND) in full-term neonates who required intervention (phototherapy and/or exchange transfusion). This prospective cohort study was done at the NICU of Tanta University Hospitals over a 2-year duration. Fifty-six full-term neonates with pathological unconjugated hyperbilirubinemia were divided according to MRS and ABR findings into 2 groups: group (1) included 26 cases with mild acute bilirubin encephalopathy (BIND-M score 1-4). Group (2) included 30 cases with neonatal hyperbilirubinemia only. In addition, 20 healthy neonates with similar ages were employed as the controls. When compared to group 2 and the control group, group 1's peak-area ratios of NAA/Cr and NAA/Cho were found to be significantly reduced (P < 0.05). As compared to group 2 and the control group, group 1's Lac/Cr ratio was significantly greater (P < 0.05), but the differences were not significant for group 2 when compared to the control group. Waves III and V peak latencies, I-III, and I-V interpeak intervals were significantly prolonged in group 1 in comparison to group 2 and controls (P < 0.05) with no significant difference between group 2 and control group.   Conclusion: When the symptoms of ABE are mild and MRI does not show any evident abnormalities, MRS and ABR are helpful in differentiating individuals with ABE from patients with neonatal hyperbilirubinemia.    Trial registration:  ClinicalTrials.gov , Identifier: NCT06018012. What is Known: • MRS can be used as a diagnostic and prognostic tool for the differential diagnosis of patients with acute bilirubin encephalopathy, from patients with neonatal hyperbilirubinemia What is New: • ABR is a useful diagnostic and prognostic tool in the care and management of neonates with significantly raised bilirubin. It can be used as early predictor of acute bilirubin encephalopathy in the earliest stage of auditory damage caused by bilirubin.


Assuntos
Hiperbilirrubinemia Neonatal , Icterícia , Kernicterus , Recém-Nascido , Humanos , Kernicterus/diagnóstico , Kernicterus/etiologia , Estudos Prospectivos , Hiperbilirrubinemia Neonatal/complicações , Hiperbilirrubinemia Neonatal/diagnóstico , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Espectroscopia de Ressonância Magnética , Bilirrubina , Encéfalo , Audiometria
10.
CoDAS ; 36(2): e20220273, 2024. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1550215

RESUMO

RESUMO Objetivo Analisar a hiperbilirrubinemia como indicador para a realização do protocolo de risco na triagem auditiva neonatal (TAN) e no monitoramento auditivo em neonatos a termo e prematuros. Método Trata-se de um estudo observacional, transversal e retrospectivo. Foram incluídas 554 crianças nascidas em uma maternidade pública, subdivididas em dois grupos: (G1) com 373 recém-nascidos a termo; (G2) com 181 neonatos prematuros. Os dados foram coletados nos prontuários dos participantes, a fim de se obter informações referentes ao resultado da TAN realizada por meio do registro do Potencial Evocado Auditivo de Tronco Encefálico, às condições de nascimento, características clínicas, intervenções realizadas, resultados do primeiro exame de bilirrubina total (BT) e bilirrubina indireta (BI) e do pico de BT e BI. Realizou-se análise estatística descritiva e inferencial dos dados, com adoção do nível de significância de 5%. Resultados No teste da TAN, foram observadas taxas de encaminhamento para reteste inferiores no G1 em relação ao G2. Não houve diferença entre os grupos quanto à ocorrência do tipo de parto, sexo, presença de incompatibilidade sanguínea Rh e ABO, deficiência de enzima G6PD e realização de fototerapia. Em relação aos níveis de BT e BI no primeiro exame e no momento do pico, não houve diferenças entre os neonatos com resultado "passa" e "falha" na TAN-teste nos dois grupos. Conclusão Os níveis de bilirrubina no período neonatal abaixo dos valores recomendados para indicação de exsanguineotransfusão não estão diretamente relacionados ao resultado "falha" na TAN em neonatos a termo e prematuros.


ABSTRACT Purpose To analyze hyperbilirubinemia as an indicator for the definition of risk protocol in newborn hearing screening (NHS) and in auditory monitoring in full-term and preterm neonates. Methods This is an observational, cross-sectional and retrospective study. A total of 554 children born in a public maternity hospital were included and divided into two groups: (G1) with 373 full-terms neonates; (G2) with 181 preterm neonates. Data were collected from the participant's medical records to obtain information regarding the result of the NHS, performed by recording the automated auditory brainstem response (AABR), birth conditions, clinical characteristics, interventions performed, and results of the first test of total bilirubin (TB) and indirect bilirubin (IB) as well as the peak of TB and IB. A descriptive statistical analysis of the results was performed, and the level of significance adopted was 5%. Results On the NHS test, quotes of retest referral rates were smaller in G1 when compared to G2. There was no significant difference between the groups regarding type of delivery, gender, presence of Rh and ABO incompatibility, G6PD enzyme deficiency, and performance of phototherapy. TB and IB levels at the first exam and at peak time did not differ between neonates with "pass" and "fail" results on the NHS test in both groups. Conclusion Bilirubin levels in the neonatal period below the recommended values for indication of exchange transfusion are not directly related to the "fail" result on the NHS tests in term and preterm neonates.

11.
Ann. afr. méd. (En ligne) ; 17(2): e5492-e5499, 2024. figures, tables
Artigo em Francês | AIM | ID: biblio-1552193

RESUMO

Contexte et objectifs. L'ictère néonatal est un symptôme fréquent. L'objectif de la présente étude était d'actualiser le profil épidémiologique et d'identifier les facteurs associés à l'ictère néonatal chez les nouveau-nés malades. Méthodes. Une étude transversale descriptive a été menée de juin 2022 à avril 2023 aux Cliniques Universitaires de Kinshasa. L'étude a concerné les nouveau-nés malades ayant présenté un ictère cutanéomuqueux. Les variables sociodémographiques, périnatales, cliniques et paracliniques ont été recherchées. Résultats. Sur 152 nouveau-nés malades, 102 (67,1%) cas d'ictère ont été identifiés. Les nouveau-nés à terme (72,5%), nés par voie basse (67,6%) et dont les mères avaient présenté des infections uro-génitales (98%) et de groupe sanguin O (53%) rhésus positif (97,1%) étaient les plus représentés. L'ictère s'est manifesté dans la première semaine de vie (85,3 %). La bilirubine sérique totale initiale se situait entre 10 et 15 mmol/L (57,8 %). L'origine infectieuse était notée dans 85 % des cas (Klebsiella pneumoniae dans 50 % des cas). La photothérapie conventionnelle a été utilisée chez 74,5 %. L'accouchement par voie basse était le seul facteur associé (p=0,001). Conclusion : L'ictère néonatal est fréquent chez les nouveau-nés malades. L'étiologie infectieuse doit être recherchée systématiquement. Une prise en charge appropriée permet de réduire la survenue de séquelles neurosensorielles.


Context and objective. Neonatal jaundice is a common symptom. The objective of the present study was to update the epidemiological profile and identify the factors associated with neonatal jaundice in sick newborns. Methods. A descriptive cross-sectional study was conducted from June 2022 to April 2023 at the Kinshasa University Hospital. The study included sick newborns who presented with mucocutaneous jaundice. Sociodemographic, perinatal, clinical and paraclinical variables were sought. Results. Out of 152 sick newborns, 102 (67.1 %) cases of jaundice were identified. Fullterm newborns (72.5 %), born vaginally (67.6 %) and whose mothers had presented with urogenital infections (98 %) and blood group O (53 %) rhesus positive (97.1 %) were the most represented. Jaundice appeared in the first week of life (85.3 %). Baseline total serum bilirubin was between 10 and 15 mmol/L (57.8 %). The infectious origin was noted in 85 % of cases (Klebsiella pneumoniae in 50 % of cases). Conventional phototherapy was used in 74.5 %. Vaginal delivery was the only associated factor (p=0.001). Conclusion. Neonatal jaundice is common in sick newborns. The infectious etiology must be systematically sought. Appropriate management helps reduce the occurrence of neurosensory aftereffects.


Assuntos
Humanos , Masculino , Feminino , Icterícia Neonatal
12.
Photobiomodul Photomed Laser Surg ; 42(1): 49-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38150176

RESUMO

Background: The current research extends previous laboratory investigations by investigating the effects of low-level laser irradiation (LLLI) on human blood plasma. Total bilirubin is of special importance because of its potential biostimulatory and modulatory actions. Objective: This study aims to analyze changes in total bilirubin content as a consequence of LLLI on human blood plasma. This study aims to determine how changes in exposure duration and laser wavelength affect these adjustments. Methodology: Plasma was isolated from a healthy adult donor's whole blood using the anticoagulant ethylenediaminetetraacetic acid (EDTA). Plasma samples were exposed to LLLI at 375 and 650 nm for 5, 10, 15, 20, and 25 min. Total bilirubin concentrations were measured both before and after irradiation using spectrophotometric analysis. The difference between 375 and 630 nm lasers was also investigated. Results: Five, 10, 15, 20, and 25 min of exposure to LLLI at 375 and 650 nm wavelengths resulted in statistically significant differences in total bilirubin content (p ˂ 0.05, p ˂ 0.001, p ˂ 0.0001). There was no statistically significant difference in total bilirubin concentration between the 375 and 630 nm lasers. Conclusions: Human blood plasma total bilirubin levels were considerably lower following LLLI at 375 and 630 nm than controls. Multiple exposures provide the same results. These findings demonstrate the role of biostimulation by laser irradiation in blood plasma applications and suggest that low-level laser treatment may control total bilirubin levels, particularly at 375 and 630 nm.


Assuntos
Lasers , Terapia com Luz de Baixa Intensidade , Adulto , Humanos , Plasma
13.
J Matern Fetal Neonatal Med ; 37(1): 2295808, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38146169

RESUMO

OBJECTIVE: To test the accuracy of transcutaneous bilirubinometry (TcB) in neonates 12 h after discontinuing phototherapy. STUDY DESIGN: In a prospective study of 91 neonates at ≥35 weeks of gestation, paired measurements of total serum bilirubin (TSB) and TcB were obtained 12 h after discontinuation of phototherapy. TcB measurements were obtained on the uncovered skin of the sternum and the covered skin of the lower abdomen. Bland-Altman plots were used to evaluate agreement between TSB and TcB. RESULTS: TcB was found to systematically underestimate TSB on both covered and uncovered skin. The smallest but statistically significant difference between TSB and TcB was found on the covered lower abdomen (-1.03, p < .0001) compared with the uncovered skin of the sternum (-1.44, p < .0001). The correlation between TSB and TcB was excellent on both covered (r = 0.86, p < .001) and uncovered skin (r = 0.90, p < .001). Bland and Altman plots showed poor agreement between TcB and TSB. CONCLUSIONS: This study demonstrated excellent correlation between TcB and TSB 12 h after phototherapy but poor TcB-TSB agreement. TcB cannot be reliably used in neonates exposed to phototherapy.


Assuntos
Icterícia Neonatal , Humanos , Recém-Nascido , Bilirrubina , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/terapia , Triagem Neonatal , Fototerapia , Estudos Prospectivos , Pele
14.
Mol Ther Methods Clin Dev ; 31: 101161, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38094199

RESUMO

(AAV)-mediated episomal gene replacement therapy for monogenic liver disorders is currently limited in pediatric settings due to the loss of vector DNA, associated with hepatocyte duplication during liver growth. Genome editing is a promising strategy leading to a permanent and specific genome modification that is transmitted to daughter cells upon proliferation. Using genome targeting, we previously rescued neonatal lethality in mice with Crigler-Najjar syndrome. This rare monogenic disease is characterized by severe neonatal unconjugated hyperbilirubinemia, neurological damage, and death. Here, using the CRISPR-Staphylococcus aureus Cas9 (SaCas9) platform, we edited the disease-causing mutation present in the Ugt1a locus of these mice. Newborn mice were treated with two AAV8 vectors: one expressing the SaCas9 and single guide RNA, and the other carrying the Ugt1a homology regions with the corrected sequence, while maintained in a temporary phototherapy setting rescuing mortality. We observed a 50% plasma bilirubin reduction that remained stable for up to 6 months. We then tested different Cas9:donor vector ratios, with a 1:5 ratio showing the greatest efficacy in lowering plasma bilirubin, with partial lethality rescue when more severe, lethal conditions were applied. In conclusion, we reduced plasma bilirubin to safe levels and partially rescued neonatal lethality by correcting the mutant Ugt1a1 gene of a Crigler-Najjar mouse model.

15.
Front Pediatr ; 11: 1276349, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928349

RESUMO

Crigler-Najjar syndrome (CNS) is an exceedingly rare autosomal recessive disease with an estimated incidence of 1 in a million live births. CNS type 1 (CNS1) is the most severe form, characterized by severe unconjugated hyperbilirubinemia since birth due to the absence of hepatic uridine 5'-diphosphate glucuronyltransferase (UGT1A1) activity. Daily phototherapy (PT) and liver transplant (LT) are the mainstays of therapy. Here, we present a higher-than-expected incidence of CNS1 in Croatia (6,1 in a million). In the last 31 years, we treated eight CNS1 patients from five families with no reported consanguinity. Four patients are descendants of an isolated enclave in Kosovo with a small gene pool and a high potential for inbreeding. Severe unconjugated hyperbilirubinemia was verified in a neonatal period and PT was initiated. Four patients underwent LT from living-related donors. One of them had unsuccessful hepatocyte transplantation earlier. LT was successful in three patients, and one patient died due to primary graft dysfunction. Four patients are currently treated with 9-12 h daily PT with inconsistent disease control, and gradually increasing bilirubin. One patient developed kernicterus before LT, while others have normal psychomotor development and no neurologic impairment. Genetic testing of the UGT1A1 gene in six patients from three families revealed three different homozygous mutations (c.722_723 delAG, c.717_718 delAG, and c.1021 C >T), all previously described in other populations. There is a possibility of the founder effect as an explanation for the higher incidence of CNS1 in at least a subgroup of Croatians.

16.
Children (Basel) ; 10(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-38002910

RESUMO

Early-term neonates (with a gestational age (GA) of 37 and 0/7 weeks to 38 and 6/7 weeks) face higher morbidities, including respiratory and neurodevelopmental issues, than full-term (39 and 0/7 weeks to 40 and 6/7 weeks) infants. This study explores whether hyperbilirubinemia necessitating phototherapy also differs between these groups. A retrospective study was conducted on neonates born from January 2021-June 2022, excluding those with specific conditions. Evaluated factors included GA, birth weight, bilirubin levels, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and feeding type, with phototherapy given as per AAP guidelines. Of 1085 neonates, 356 met the criteria. When stratifying the neonates based on the need for phototherapy, a higher proportion of early-term neonates required phototherapy compared to full-term (p < 0.05). After factoring in various risks (GA; birth weight; gender; feeding type; G6PD deficiency; transcutaneous bilirubin levels at 24 h and 24-48 h postpartum; maternal diabetes; and the presence of caput succedaneum or cephalohematoma), early-term neonates were more likely to need phototherapy than full-term babies (OR: 2.15, 95% CI: 1.21 to 3.80). The optimal cut-off for transcutaneous bilirubin levels 24-48 h postpartum that were used to predict phototherapy need was 9.85 mg/dl. In conclusion, early-term neonates are at a greater risk for developing jaundice and requiring phototherapy than full-term neonates. Monitoring bilirubin 24-48 h postpartum enhances early prediction and intervention.

17.
Children (Basel) ; 10(10)2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37892362

RESUMO

Neonatal hyperbilirubinemia is an extremely common metabolic complication of the neonatal period which may be associated with bilirubin encephalopathy and even death. Adverse neurological consequences are preventable if a timely diagnosis and treatment are provided. Phototherapy is usually the preferred option to decrease hyperbilirubinemia. Although considered to be safe, evidence in recent years has shown that this treatment may not be free of side effects and short- and long-term unfavorable outcomes. These are usually mild or rare, but should be decreased or avoided if possible. Many useful complementary measures and treatments have been described that could shorten the duration of exposure to phototherapy. However, there is no current unequivocal recommendation to use any of the methods presented in this review. Our review aims to depict the wide range of possible complementary treatments to phototherapy, and to provide the scientific and clinical evidence available regarding their usefulness. It is essential that, while utilizing the full potential of phototherapy to treat hyperbilirubinemia, caregivers are aware of its side effects and possible inherent dangers, and seek ways to minimize the exposure to phototherapy to what is really needed for the newborn. Further studies are needed to clarify the preferred complementary treatments that could reduce the duration of exposure to phototherapy without impairing its effectiveness.

18.
Pediatr Int ; 65(1): e15617, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37658617

RESUMO

BACKGROUND: This nationwide survey aimed to determine the status of jaundice management in Japan. METHODS: A questionnaire about bilirubin level measurements and neonatal jaundice treatment was sent to 330 institutions providing neonatal care. The responses were analyzed according to institution level. RESULTS: Of 330 institutions, 172 responded (52.1% response rate). Total bilirubin levels were measured in the central laboratory using spectrophotometry at 134 institutions and a blood gas analyzer at 81 institutions. Unbound bilirubin (UB) levels were measured by 79 institutions, while transcutaneous bilirubin measurements were taken at 63 institutions. There was no association between institution level and UB or transcutaneous bilirubin measurement. For phototherapy criteria, the Murata-Imura criteria were adopted by 67 institutions, Nakamura criteria by 36, and Morioka criteria by 39. Light-emitting diodes (LED) were used by 160 institutions versus fluorescent lights by 31. When a blue LED was used, 119 institutions used the high mode. There is no standard for increasing light intensity. No association was found between institution level and phototherapy criteria. UB was measured in 14 of 63 institutions using the Murata-Imura criteria. CONCLUSIONS: There is a large variation in the management and treatment of neonatal jaundice among institutes in Japan.


Assuntos
Icterícia Neonatal , Recém-Nascido , Humanos , Icterícia Neonatal/diagnóstico , Icterícia Neonatal/terapia , Japão , Transfusão Total , Fototerapia , Bilirrubina
19.
J Mol Model ; 29(10): 318, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37718354

RESUMO

CONTEXT: Bilirubin is an important molecule, used as a marker of some liver diseases, and it can also be toxic and cause jaundice, especially in newborns. The main treatment for neonatal jaundice is phototherapy with blue light, which is still widely studied because the photophysical processes involved are not fully understood. METHODS: Calculations based on the density functional theory (DFT) at M062X/6-31G(d,p) level were performed in order to evaluate the structural, electronic, and topological properties of bilirubin isomers. It was found that the ZZ conformation can form a greater number of hydrogen bonds, which gives the isomer greater energy stabilization compared to the other ZE, EZ, and EE isomers, and that the EE isomer is the conformer with the lowest energy of stabilization. The hydrogen bonds were characterized by the quantum theory of atoms in molecules (QTAIM) and for the ZZ isomer four hydrogen bonds (HBs) were found classified as intermediate, ∇2ρ(r) > 0, H(r) > 0. The ZE, EZ, and EE isomers show weak HBs, ∇2ρ(r) > 0, H(r) > 0.


Assuntos
Bilirrubina , Eletrônica , Recém-Nascido , Humanos , Ligação de Hidrogênio , Isomerismo , Teoria Quântica
20.
Early Hum Dev ; 185: 105858, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37722208

RESUMO

BACKGROUND: Transcutaneous bilirubin (TCB) measurement is a simple, painless, and time-saving alternative for the assessment of TSB (total serum bilirubin) levels. However, TCB measurements obtained during phototherapy can yield inaccurate results. We evaluated the effectiveness of TCB measurements obtained from protected skin areas in patients who underwent phototherapy. METHODS: This prospective study included neonates delivered at a gestational age of ≥340/7 weeks. TCB measurements were performed at the forehead and the lower end of the sternum using a JM-105 device. Simultaneously, blood samples were collected to determine TSB levels. During phototherapy, the forehead was covered with a photo-opaque patch. TSB and TCB were measured before, during, at the end of, and after phototherapy. RESULTS: In total, 200 neonates, including 110 (55 %) term and 90 (45 %) late preterm infants, were enrolled. Of these neonates, 162 (81 %) were Turkish while 38 (19 %) were refugees from Syria and Iraq. Notably, no statistically significant differences were observed in the TSB and TCB values between the Turkish and refugee groups (p > 0.05). Bland-Altman analysis was conducted between the TCB values obtained from the covered forehead area and TSB values; the analysis revealed moderate, high, and excellent agreements for the first bilirubin measurement and at the end of phototherapy, before phototherapy, and for the second and rebound bilirubin measurements, respectively. Regarding intraclass correlation coefficients, values >0.95, 0.94-0.85, 0.84-0.70, and < 0.7 indicated perfect, high, moderate, and unacceptable compatibilities, respectively. Although a significant association was observed between pre-phototherapy TCB obtained from the sternum and TSB levels, no significant associations were observed during phototherapy. CONCLUSIONS: Our findings indicate that the consistency observed between TCB measurements obtained from the protected skin areas and TSB values can be used to monitor phototherapy effectiveness, particularly in late preterm/term infants and those with darker skin tones. Furthermore, this approach can aid in guiding decisions related to treatment termination, evaluating rebound bilirubin levels, minimizing costs, and providing a less invasive testing option.


Assuntos
Bilirrubina , Recém-Nascido Prematuro , Recém-Nascido , Lactente , Humanos , Estudos Prospectivos , Fototerapia , Idade Gestacional
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