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OBJECTIVE: To compare the association of unbound bilirubin (UB), total serum bilirubin (TSB), and bilirubin:albumin molar ratio (BAMR) with acute bilirubin encephalopathy (ABE), as assessed by bilirubin-induced neurologic dysfunction (BIND) score, in infants with significant hyperbilirubinemia (TSB ≥20 mg/dL or underwent exchange transfusion). STUDY DESIGN: In this prospective cohort study, infants ≥34 weeks of gestational age with significant hyperbilirubinemia during the first 2 postnatal weeks were eligible, unless they had craniofacial malformations, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus and herpes simplex) infections, surgery, or a family history of congenital deafness. TSB, serum albumin, and UB were measured at hospital admission using the colorimetric, bromocresol green, and modified peroxidase method, respectively. Infants were evaluated on admission for ABE using a standardized neurologic examination and assigned a BIND score by trained physicians. Infants with a total BIND score of 0 were deemed to not have ABE, whereas those with a score ≥1 were deemed to have ABE. RESULTS: A total of 151 infants were studied, among whom 37 (24.5%) had ABE. Of these, 19 had mild ABE (BIND score 1-3) and 18 had moderate-to-severe ABE (BIND score 4-9). On logistic regression, UB, but not TSB or BAMR, was associated with ABE (aOR 1.64; 95% CI 1.17-2.3). On ordered logistic regression, UB, but not TSB or BAMR, was associated with severity of ABE (aOR 1.76; 95% CI 1.28-2.4). CONCLUSIONS: Our findings of the association between UB and ABE indicate that BIND scoring may be useful for evaluation of ABE in infants ≥34 weeks of gestational age.

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OBJECTIVE: To evaluate the effect of intravenous (IV) ceftriaxone on free bilirubin concentrations in infants with unconjugated hyperbilirubinemia born at term. STUDY DESIGN: A prospective study was performed with subjects serving as their own controls. Our inclusion criteria were infants born at term <7 days old with sepsis and receiving IV antibiotics for >3 days and resolving hyperbilirubinemia with total serum bilirubin levels between 6 and12 mg/dL by day 4 of life. Free bilirubin concentrations were measured by the peroxidase method using a UB analyzer and a Zone Fluidics device before (baseline) and 15 minutes after (follow-up) IV ceftriaxone administration on postnatal days 4 to 6. Paired measurements of free bilirubin were analyzed using a Student paired t-test or Wilcoxon signed-rank test. RESULTS: In total, 27 infants were studied. The mean free bilirubin (µg/dL) at follow-up was not different from that at baseline when measured by the UB analyzer (P = .78). The mean free bilirubin was significantly lower at follow-up compared with baseline when measured by the Zone Fluidics device (P = .02). The ratio of a free bilirubin with and without ceftriaxone, an index of displacing effect, was 1.02 (95% CI 0.89-1.14) using the UB analyzer and 0.58 (95% CI 0.30-0.86) using the Zone Fluidics device. CONCLUSIONS: Ceftriaxone is not associated with a bilirubin-displacing effect in infants with a mild unconjugated hyperbilirubinemia. Home therapy with once-daily intramuscular ceftriaxone may be an alternative option for management of sepsis in asymptomatic infants with a mild unconjugated hyperbilirubinemia born at term.

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Introducción: Las pautas para prevención y tratamiento de hiperbilirrubinemia neonatal recomiendan medición de bilirrubina sérica total (BST) o bilirrubina transcutánea (BTc) para determinar el grado de ictericia antes del alta del recién nacido (RN); ésta última no invasiva, proporciona información instantánea y de calidad superior a la evaluación clínica. A pesar de ello aún no ha sido aplicada en forma sistemática en los hospitales de Paraguay. Objetivo: evaluar la aplicación en nuestro medio de la medición de bilirrubinemia transcutánea antes del alta correlancionando con la bilirrubina sérica. Materiales y Métodos: Estudio observacional, descriptivo con componente analítico, de corte transversal. Fueron incluidos RN con edad gestacional ≥ a 35 semanas, con peso ≥ a 2000 gramos, luego de las 24 hs de vida hasta los 8 días; bajo consentimiento informado de los padres, durante un año. Los datos fueron consignados en una planilla de Microsoft Excel y procesado por el software IBM SPSS Statistics ®. Resultados: De 271 RN que ingresaron al estudio, en la primera medición con el Bilirrubinómetro transcutáneo, cumplían con criterios para toma de bilirrubina sérica 90 (33,2%) de ellos. En los restantes 181 RN (66,8%), los datos emparejados no estaban disponibles debido a que siguiendo las recomendaciones de las guías actuales no fue necesario medir la bilirrubina sérica. El valor del coeficiente de correlación para la primera medición fue r = 0.574. Para la segunda medición las medidas emparejadas estaban disponibles para 131 RN. En este caso se encontró correlación positiva entre ambos métodos de 0,590. Conclusión: La bilirrubina transcutánea puede utilizarse en forma rápida, segura y válida, como un test de screening para la detección de hiperbilirrubinemia y podría evitar una proporción importante de toma de muestras sanguíneas, mejorando la seguridad del paciente.

Introduction: The guidelines for prevention and treatment of neonatal hyperbilirubinemia recommend measurement of total serum bilirubin (BST) or transcutaneous bilirubin (BTc) to determine the degree of jaundice before discharge of the newborn (NB); the latter non-invasive method provides instant information which is superior to the clinical evaluation. Despite this, it has not yet been systematically applied in hospitals in Paraguay. Objective: to evaluate transcutaneous measurement of bilirubin concentration as compared to serum bilirubin levels prior to discharge in our setting. Materials and Methods: This was an observational, cross-sectional, descriptive study with an analytical component. For a period of one year, we tracked NBs with a gestational age ≥ 35 weeks, weighing ≥ 2000 grams, from 24 hours of life until 8 days of life, obtaining the informed consent of the parents. The data was entered in a Microsoft Excel spreadsheet and processed by the IBM SPSS Statistics ® software. Results: Of 271 NBs who entered the study, 90 (33.2%) met criteria for measurement of serum bilirubin at their first measurement with the transcutaneous bilirubinometer. In the remaining 181 RN (66.8%), the paired data were not available as measurement of serum bilirubin was not required per the recommendations of current guidelines. The correlation coefficient value for the first measurement was r = 0.574. For the second measurement, paired measurements were available for 131 NBs. In this case, a positive correlation was found between both methods of 0.590. Conclusion: Transcutaneous bilirubin can be used quickly, safely and accurately as a screening test for the detection of hyperbilirubinemia and could avoid a significant proportion of blood sampling, improving patient safety.

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OBJECTIVE: To evaluate the associations between unbound bilirubin (UB) and total serum bilirubin (TSB), bilirubin:albumin molar ratio (BAMR), and bilirubin albumin binding affinity (Ka) as a function of gestational age (GA) in infants born at 24-33 weeks GA. STUDY DESIGN: In a prospective observational study, TSB and UB were measured twice daily at least 8 hours apart during the first postnatal week. Serum albumin was measured to calculate BAMR on each day. The highest UB on each day, corresponding TSB, and serum albumin were used to calculate the Ka on each day. RESULTS: For the 166 infants studied, peak UB significantly correlated with concomitant Ka (r = -0.44, P = .001) but not with concomitant TSB or BAMR after adjusting for GA. On multiple regression analyses, there was a significant association of concomitant Ka (-0.06, 95% CI -0.08 to -0.04, P = .0001), but not concomitant TSB or BAMR with peak UB after controlling for GA, birth weight, race, and sex. GA group was a significant effect modifier for the association between Ka and peak UB (0.03, 95% CI 0.02-0.04, P < .001). Interaction analyses showed the association between concomitant Ka and peak UB was significant for the 24-30 weeks GA group infants, but not for the 301/7-33 weeks GA group infants. CONCLUSIONS: Peak UB was primarily associated with a decrease in binding affinity in infants ≤30 weeks GA. Interventions aimed at improving binding affinity may be important in decreasing the risk of bilirubin-induced neurotoxicity.

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OBJECTIVE: This study evaluates whether unbound bilirubin is a better predictor of auditory neuropathy spectrum disorder (ANSD) than total serum bilirubin (TSB) or the bilirubin:albumin molar ratio (BAMR) in late preterm and term neonates with severe jaundice (TSB ≥20 mg/dL or TSB that met exchange transfusion criteria). STUDY DESIGN: Infants ≥34 weeks' gestation with severe jaundice during the first 2 weeks of life were eligible for the prospective observational study. A comprehensive auditory evaluation was performed within 72 hours of peak TSB. ANSD was defined as absent or abnormal auditory brainstem evoked response waveform morphology at 80-decibel click intensity in the presence of normal outer hair cell function. TSB, serum albumin, and unbound bilirubin were measured using the colorimetric, bromocresol green, and modified peroxidase method, respectively. RESULTS: Five of 44 infants developed ANSD. By logistic regression, peak unbound bilirubin but not peak TSB or peak BAMR was associated with ANSD (OR, 4.6; 95% CI, 1.6-13.5; P = .002). On comparing receiver operating characteristic curves, the area under the curve for unbound bilirubin (0.92) was significantly greater (P = .04) compared with the area under the curve for TSB (0.50) or BAMR (0.62). CONCLUSIONS: Unbound bilirubin is a more sensitive and specific predictor of ANSD than TSB or BAMR in late preterm and term infants with severe jaundice.

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