Validation of transcutaneous bilirubin nomogram for identifying neonatal hyperbilirubinemia in healthy Chinese term and late-preterm infants: a multicenter study / Validação de um nomograma de bilirrubina transcutânea para identificação de hiperbilirrubinemia neonatal em neonatos a termo e pré-termo tardios saudáveis na China: um estudo multicêntrico

OBJECTIVE: to prospectively validate a previously constructed transcutaneous bilirubin (TcB) nomogram for identifying severe hyperbilirubinemia in healthy Chinese term and late-preterm infants. METHODS: this was a multicenter study that included 9,174 healthy term and late-preterm infants in eight hospitals of China. TcB measurements were performed using a JM-103 bilirubinometer. TcB values were plotted on a previously developed TcB nomogram, to identify the predictive ability for subsequent significant hyperbilirubinemia. RESULTS: in the present study, 972 neonates (10.6%) developed significant hyperbilirubinemia. The 40th percentile of the nomogram could identify all neonates who were at risk of significant hyperbilirubinemia, but with a low positive predictive value (PPV) (18.9%). Of the 453 neonates above the 95th percentile, 275 subsequently developed significant hyperbilirubinemia, with a high PPV (60.7%), but with low sensitivity (28.3%). The 75th percentile was highly specific (81.9%) and moderately sensitive (79.8%). The area under the curve (AUC) for the TcB nomogram was 0.875. CONCLUSIONS: this study validated the previously developed TcB nomogram, which could be used to predict subsequent significant hyperbilirubinemia in healthy Chinese term and late-preterm infants. However, combining TcB nomogram and clinical risk factors could improve the predictive accuracy for severe hyperbilirubinemia, which was not assessed in the study. Further studies are necessary to confirm this combination. .

OBJETIVO: validar de forma prospectiva um nomograma de bilirrubina transcutânea (BTc) para identificar hiperbilirrubinemia grave em neonatos a termo e pré-termo tardios saudáveis na China. MÉTODOS: foi realizado um estudo multicêntrico que incluiu 9174 neonatos a termo e pré-termo tardios saudáveis em oito unidades da China. Foram realizadas dosagens de BTc utilizando um bilirrubinômetro. Os valores de BTc foram traçados em um nomograma de BTc para identificara capacidade de predição de hiperbilirrubinemia significativa. RESULTADOS: 972 recém-nascidos (10,6%) desenvolveram hiperbilirrubinemia significativa. O percentil 40 de nosso nomograma pode identificar todos os recém-nascidos com risco de hiper-bilirrubinemia significativa, porém com baixo valor preditivo positivo (VPP) (18,9%). De 453 recém-nascidos acima do percentil 95, 275 recém-nascidos desenvolveram posteriormente hiperbilirrubinemia significativa, com VPP elevado (60,7%), porém com baixa sensibilidade (28,3%). O percentil de 75 foi altamente específico (81,9%) e moderadamente sensível (79,8%). A área sob a curva (ASC) de nosso nomograma de BTc foi de 0,875. CONCLUSÕES: este estudo validou o nomograma de BTc, que pode ser utilizado para prever hiperbilirrubinemia significativa em neonatos a termo e pré-termo tardios saudáveis na China. Contudo, combinar o nomograma de BTc e fatores de risco clínicos pode melhorar a precisãode predição da hiperbilirrubinemia grave, o que não foi avaliado neste estudo. São necessários estudos adicionais para confirmar essa combinação. .

Predicting neonatal hyperbilirubinemia using first day serum bilirubin levels.

Objective. To determine the first day total serum bilirubin (TSB) value which will predict with reasonable accuracy, neonates likely to develop subsequent significant hyperbilirubinemia. Methods. Serum bilirubin was estimated for all enrolled cases within 18 to 30 hr of life by microcapillary. The babies were then followed up clinically by 2 observers for the appearance and progression of jaundice every 12 hr till discharge and then daily upto fifth day of life. TSB estimation was repeated if the clinical assessment of jaundice was more than 10 mg/dl by any observer using Kramers Rule. Hyerbilirubinemia was defined as TSB level ≥12 mg/dl between 24 to 48 hr of life ≥15 mg/dl between 48 to 72 hr of life and 17 mg/dl beyond 72 hours of life. Results. A total of 200 neonates were enrolled in the study. Of these, 24 neonates (i.e., 12%) developed hyperbilirubinemia. The mean first day TSB value in the neonates who subsequently developed hyperbilirubinemia was 7.716 mg/dl as compared to a value of 5.154 mg/dl in those who did not. The difference was significant (p=0.000). Using Receiver operating characteristic (ROC) curve analysis, a value of 6.4 mg/dl (first day TSB) was determined to have the best predictive ability for subsequent hyperbilirubinemia with a sensitivity of 87.5%, specificity of 80.11%, positive predictive value of 37.5% and a negative predictive value of 97.92%. Conclusion. First day TSB estimation can serve as a reliable screening test for neonates at risk for subsequent hyperbilirubinemia. Neonates with the first day TSB level of less than 6.4 mg/dl have minimum risk of subsequent hyperbilirubinemia.

The effect of clofibrate with phototherapy in late pre-term newborns with non-hemolytic jaundice.

Background : Despite an understanding of the enzymatic pathways leading to bilirubin production and degradation, very few pharmacologic interventions are utilized and the mainstay of treatment remains phototherapy. Aims : To evaluate the efficacy of clofibrate in reducing total serum bilirubin levels in late pre-term neonates with non-hemolytic jaundice. Design and Setting : Double-blind, placebo-controlled, randomized trial; tertiary level neonatal unit. Materials and Methods : A randomized controlled study was carried out in the neonatal ward of Children's Hospital, Tabriz, Iran, over a 1-year period. Sixty-eight healthy late pre-term infants readmitted with non-hemolytic hyperbilirubinemia were randomized to receive phototherapy and clofibrate (n= 35) or phototherapy and placebo (n= 33). Statistical Analysis Used : Chi-square test and independent sample 't' test. Results : There were no significant differences in the weight, gender, modes of delivery and age of neonates between the two groups. Similarly the mean total serum bilirubin (TSB) level at the time of admission was not significantly different between the two groups [mean± SD: 19.72 ± 1.79 (95% confidence interval: 19.12-20.54 mg/dL) vs. 20.05 ± 2.82 (95% confidence interval, 19.54-22.04 mg/dL), P= 0.57]. The mean TSB 48 hours after phototherapy [mean± SD: 8.06± 1.34 (95% confidence interval: 7.94-10.18 mg/dL) vs.10.94 ± 2.87 (95% confidence interval: 9.92-12.16 mg/dL), P= 0.02] and the mean duration of phototherapy [mean± SD: 64.32 ± 12.48 (95% confidence interval: 60-81.6 hours) vs. 87.84 ± 29.76 (95% confidence interval: 79.2-108 hours), P< 0.001] were significantly lower in the clofibrate-treated group. Conclusions : Clofibrate is an effective adjunctive drug in neonatal hyperbilirubinemia, which results in decreased TSB level and reduced duration of phototherapy in late pre-term newborns.

Transcutaneous bilirubinometry in preterm neonates.

This prospective study was conducted to evaluate the accuracy of transcutaneous bilirubinometry in preterm newborns less than 32 weeks of gestation. Serum bilirubin values measured by direct spectrophotometry were considered as standard, the range was 2.2-12.5 mg/dL. 32 jaundiced infants of less than 32 weeks of gestation without phototherapy, including 10 ELBW neonates, were enrolled. Close correlation (R=0.933) existed between total serum bilirubin and transcutaneous bilirubin values measured over sternum.

Comparação entre a dosagem transcutânea e plasmática de bilirrubina / Comparison of transcutaneous and plasma bilirubin measurement

OBJETIVOS: Comparar dosagens transcutâneas de bilirrubina pelo Bilicheck com a dosagem plasmática capilar pelo bilirrubinômetro Unistat (Leica). MÉTODOS: Foram realizadas 200 dosagens concomitantes (transcutânea e plasmática), calculadas a correlação e concordância entre elas e feita avaliação da influência do peso de nascimento, raça, idade gestacional, idade pós-natal e uso de fototerapia. RESULTADOS: A correlação linear foi de 0,92, e a média da diferença entre as dosagens foi de 0,72 (±1,57) mg/dL, com intervalo de confiança em 95 por cento de -2,42 a +3,86. A curva ROC realizada com a dosagem transcutânea em 14 mg/dL demonstrou melhor sensibilidade (88,2 por cento) e especificidade (97,8 por cento), com valor preditivo positivo de 78,9 por cento, valor preditivo negativo de 98,9 e área abaixo da curva de 0,98. CONCLUSÃO: A dosagem realizada pelo Bilicheck pode substituir a dosagem plasmática capilar até o valor de 14 mg/dL. Acima deste nível, deve ser considerada apenas como rastreador na seleção de pacientes que devem ser submetidos a dosagem sangüínea.

OBJECTIVES: To compare transcutaneous bilirubin measurements made using Bilicheck equipment with assays of capillary plasma using the Unistat bilirubinometer (Leica). METHODS: Two hundred concomitant assays were performed (transcutaneous and in plasma), and the correlation and level of agreement between them was calculated. An assessment was also made of the influence of birth weight, skin color, gestational age, postnatal age and phototherapy. RESULTS: The linear correlation coefficient was 0.92, and the mean difference between assays was 0.72 (±1.57) mg/dL, with a 95 percent confidence interval from -2.42 to +3.86. The best of a series of ROC curves demonstrated that transcutaneous assays at 14 mg/dL offer the best sensitivity (88.2 percent) and specificity (97.8 percent), with a positive predictive value of 78.9 percent, negative predictive value of 98.9 and are below the curve of 0.98. CONCLUSIONS: Assays performed using Bilicheck can be substituted for capillary plasma assays up to 14 mg/dL. Above this level the device should only be used for screening for patients whose bilirubin should be assayed in blood.

The value of routine bilirubin screening to detect significant hyperbilirubinemia in Thai healthy term newborns.

OBJECTIVE: To evaluate the clinical value and the predictive usefulness of the routine pre-discharge bilirubin screening in term newborn at 48-72 hours after birth. MATERIAL AND METHOD: Blood samples of 1983 healthy term newborns for measuring total serum bilirubin level were drawn at the same time as the routine metabolic screening at Prapokklao Hospital. Newborns with total serum bilirubin levels > or = 5 mg/dL in the first 24 hours, > or = 10 mg/dL at 25 to 48 hours, > or = 13 mg/dL at 49-72 hours, and > or = 15 mg/dL at > 72 were defined to have hyperbilirubinemia and were started on phototherapy. RESULTS: Two hundred and seventy-nine newborns (14.07%) with hyperbilirubinemia, including seven (0.35%) with severe hyperbilirubinemia were detected by the bilirubin screening program. Newborns without hyperbilirubinemia at the time of screening test were unlikely to develop subsequent significant hyperbilirubinemia. The costs for detecting hyperbilirubinemia and severe hyperbilirubinemia were 6.22 US$ and 247.87 US$ per case, respectively. CONCLUSION: The bilirubin screening program was cost-effective and could detect a number of unexpected severe hyperbilirubinemia. Newborns without hyperbilirubinemia were unlikely to develop subsequent significant hyperbilirubinemia.

Brainstem evoked response audiometry (BAER) in neonates with hyperbilirubinemia.

OBJECTIVES: To evaluate Brainstem Evoked Response Audiometry (BAER) as an objective testing of hearing assessment in icteric babies and correlate the abnormalities with serum bilirubin levels. METHODS: BAER recordings were taken in 30 icteric ferm neonates at birth, at peak of serum bilirubin levels and on a follow-up visit at 2-4 months of age. RESULTS: Mean latency of waves and interwave intervals on the BAER records were prolonged in icteric babies compared to the control group suggesting early bilirubin encephalopathy. Abnormal records were obtained in 73.3% cases and the abnormality persisted in the follow-up tracings of 23.3% of the study group. CONCLUSION: BAER is a sample, reliable and effective technique for determining auditory functions in the neonates especially changes of early bilirubin toxicity.

Hiperbilirrubinemia neonatal prolongada devido à associação entre síndrome de Gilbert e doença hemolítica por incompatibilidade RhD / Persistent neonatal hyperbilirubinemia resulting from Gilbert's syndrome in association with RhD hemolytic disease

OBJETIVO: Relatar associação infreqüente de patologia que cause aumento considerável de produção de bilirrubina e outra diminuição importante na sua excreção. DESCRIÇÃO: Mãe tercigesta, Rh negativo. Na primeira gestação, gerou recém-nascido normal, de termo, não tendo recebido imunoglobulina humana anti-RhD. A segunda gestação complicou-se por isoimunização Rh, dando à luz neonato de termo, o qual necessitou três exsanguinotransfusões e faleceu com 8 dias de vida. Na gestação atual, conseguiu dar à luz a termo recém-nascido tipo ORh positivo, Coombs direto positivo, bilirrubina de cordão 6,5 mg/dl e hematócrito 44 por cento. Com 5 horas de vida, estava ictérico, tendo sido iniciados fenobarbital (por 3 dias) e fototerapia intensiva. A hiperbilirrubinemia foi logo controlada, porém ascendia rapidamente sempre que a fototerapia era suspensa. No 10° dia de vida, a criança foi transfundida por anemia importante. Em vista da persistência da icterícia, no 13° dia de vida pensou-se em associação com síndrome de Gilbert, e o seqüenciamento de DNA foi solicitado. O resultado mostrou genótipo mutante homozigoto UDPT1A1[TA]7TAA. Permaneceu em fototerapia até o 17° dia de vida. Recebeu alta no dia seguinte, após controle de bilirrubinemia. Voltou para acompanhamento ambulatorial e apresentou desenvolvimentos pondo-estatural e neurológico normais. COMENTARIOS: O caso ressalta a importância da associação do aumento de produção/diminuição de excreção de bilirrubina na gênese de hiperbilirrubinemias prolongadas, intensas e passíveis de causar kernicterus, se não tratadas vigorosamente. Demonstra, ainda, a eficácia da fototerapia intensiva, reduzindo os riscos de tratamentos mais agressivos. Ressalta, também, a importância do acompanhamento das icterícias neonatais até a completa remissão dos sintomas.

Relationship between serum bilirubin and coagulation test results in 1-month-old infants.

OBJECTIVE: Although the connection between cholestasis and conjugated hyperbilirubinemia is well known, mild hepatic dysfunction or cholestasis may also be associated with unconjugated hyperbilirubinemia in some infants with prolonged jaundice. The aim of this study was to investigate the relationship between serum bilirubin levels and alanine aminotransferase levels, aspartate aminotransferase levels, prothrombin time, activated partial thromboplastin time, and international normalization ratio findings in a group of infants. METHODS: The study included 77 healthy, term, breast-fed infants with jaundice and 56 age-matched, healthy, term, non-jaundiced controls. The 133 babies were divided into three subgroups according to their total bilirubin levels [group I (controls) < 50 micromol/L, group II = 50-100 micromol/L, and group III > 100 micromol/L, and the findings for the noted parameters were compared]. RESULTS: The mean conjugated bilirubin level was significantly higher, and the mean activated partial thromboplastin time significantly longer in group III than in group I. A significant positive correlation was found between bilirubin levels and PT and APTT results. CONCLUSION: Clinical vitamin K deficiency appeared unlikely to develop in this group of infants with prolonged unconjugated hyperbilirubinemia. However, a significant positive correlation between bilirubin levels and PT and APTT suggest that a higher bilirubin load to the liver may cause some degree of vitamin K deficiency due to mild cholestasis. The importance of this finding, and the possible benefits of vitamin K supplementation in 1-month-old breast-fed infants with bilirubin levels higher than 100 micromol/L require further investigation.

relationship between glucose 6-phosphate dehydrogenase deficiency and neonatal hyperblirubinemia

Studies have shown that G6PD deficiency results in indirect hyperbilirubinemia in newborns. Determining the relationship between G6PD deficiency and neonatal hyperbilirubinemia. Through a case-control study, 200 neonates with indirect hyperbilirubinemia were equally divided into two case and control groups and examined for G6PD deficiency using a commercial G6PD kit and a fluorometric analysis. The data were further analyzed statistically. Results showed that out of 200 neonates, 24 had G6PD deficiency [10 in case group and 14 in control group]. There was no statistically significant difference between two groups. Since the prevalence of G6PD deficiency among nonicteric group [control group] was higher than the icteric group [case group], it seems that the performance of a screening test to measure the G6PD activity in all neonates to be useful