RESUMO
OBJECTIVES: The aim of the study was to assess neurodevelopmental outcomes among children with biliary atresia (BA) surviving with their native liver at ages 3 to 12 years and evaluate variables that associate with neurodevelopment. METHODS: Participants (ages 3-12 years) in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with Weschler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III, ages 3-5 years) and Weschler Intelligence Scale for Children, 4th edition (WISC-IV, ages 6-12 years). Continuous scores were analyzed using Kolmogorov-Smironov tests compared with a normal distribution (meanâ=â100â±â15). Effect of covariates on Full-Scale Intelligence Quotient (FSIQ) was analyzed using linear regression. RESULTS: Ninety-three participants completed 164 WPPSI-III (mean age 3.9) and 51 WISC-IV (mean age 6.9) tests. WPPSI-III FSIQ (104â±â14, Pâ<â0.02), Verbal IQ (106â±â14, Pâ<â0.001), and General Language Composite (107â±â16, Pâ<â0.001) distributions were shifted higher compared with test norms. WISC-IV FSIQ (105â±â12, Pâ<â0.01), Perceptual Reasoning Index (107â±â12, Pâ<â0.01), and Processing Speed Index (105â±â10, Pâ<â0.02) also shifted upwards. In univariate and multivariable analysis, parent education (Pâ<â0.01) was a significant predictor of FSIQ on WPPSI-III and positively associated with WISC-IV FSIQ. Male sex and higher total bilirubin and gamma glutamyl transferase (GGT) predicted lower WPPSI-III FSIQ. Portal hypertension was predictive of lower WISC-IV FSIQ. CONCLUSIONS: This cohort of children with BA and native liver did not demonstrate higher prevalence of neurodevelopmental delays. Markers of advanced liver disease (higher total bilirubin and GGT for age ≤5 years; portal hypertension for age ≥6) correlate with lower FSIQ and may identify a vulnerable subset of patients who would benefit from intervention.
Assuntos
Atresia Biliar/psicologia , Transtornos do Neurodesenvolvimento/epidemiologia , Atresia Biliar/sangue , Atresia Biliar/patologia , Bilirrubina/sangue , Criança , Desenvolvimento Infantil , Pré-Escolar , Escolaridade , Feminino , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/psicologia , Fígado/patologia , Estudos Longitudinais , Masculino , Transtornos do Neurodesenvolvimento/etiologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Escalas de Wechsler , gama-Glutamiltransferase/sangueRESUMO
OBJECTIVE: To investigate the impact of corticosteroid therapy on the growth of participants in the Steroids in Biliary Atresia Randomized Trial (START) conducted through the Childhood Liver Disease Research Network. The primary analysis in START indicated that steroids did not have a beneficial effect on drainage in a cohort of infants with biliary atresia. We hypothesized that steroids would have a detrimental effect on growth in these infants. STUDY DESIGN: A total of 140 infants were enrolled in START, with 70 randomized to each treatment arm: steroid and placebo. Length, weight, and head circumference were obtained at baseline and follow-up visits to 24 months of age. RESULTS: Patients treated with steroids had significantly lower length and head circumference z scores during the first 3 months post-hepatoportoenterostomy (HPE), and significantly lower weight until 12 months. Growth trajectories in the steroid and placebo arms differed significantly for length (P < .0001), weight (P = .009), and head circumference (P < .0001) with the largest impact noted for those with successful HPE. Growth trajectory for head circumference was significantly lower in patients treated with steroids irrespective of HPE status, but recovered during the second 6 months of life. CONCLUSIONS: Steroid therapy following HPE in patients with biliary atresia is associated with impaired length, weight, and head circumference growth trajectories for at least 6 months post-HPE, especially impacting infants with successful bile drainage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00294684.
Assuntos
Corticosteroides/efeitos adversos , Atresia Biliar/tratamento farmacológico , Atresia Biliar/cirurgia , Insuficiência de Crescimento/induzido quimicamente , Sarcopenia/induzido quimicamente , Corticosteroides/uso terapêutico , Atresia Biliar/mortalidade , Peso Corporal/efeitos dos fármacos , Cefalometria/métodos , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Método Duplo-Cego , Insuficiência de Crescimento/epidemiologia , Insuficiência de Crescimento/fisiopatologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Monitorização Fisiológica/métodos , Portoenterostomia Hepática/métodos , Portoenterostomia Hepática/mortalidade , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Valores de Referência , Medição de Risco , Sarcopenia/epidemiologia , Sarcopenia/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To prospectively assess the value of serum total bilirubin (TB) within 3 months of hepatoportoenterostomy (HPE) in infants with biliary atresia as a biomarker predictive of clinical sequelae of liver disease in the first 2 years of life. STUDY DESIGN: Infants with biliary atresia undergoing HPE between June 2004 and January 2011 were enrolled in a prospective, multicenter study. Complications were monitored until 2 years of age or the earliest of liver transplantation (LT), death, or study withdrawal. TB below 2 mg/dL (34.2 µM) at any time in the first 3 months (TB <2.0, all others TB ≥ 2) after HPE was examined as a biomarker, using Kaplan-Meier survival and logistic regression. RESULTS: Fifty percent (68/137) of infants had TB < 2.0 in the first 3 months after HPE. Transplant-free survival at 2 years was significantly higher in the TB < 2.0 group vs TB ≥ 2 (86% vs 20%, P < .0001). Infants with TB ≥ 2 had diminished weight gain (P < .0001), greater probability of developing ascites (OR 6.4, 95% CI 2.9-14.1, P < .0001), hypoalbuminemia (OR 7.6, 95% CI 3.2-17.7, P < .0001), coagulopathy (OR 10.8, 95% CI 3.1-38.2, P = .0002), LT (OR 12.4, 95% CI 5.3-28.7, P < .0001), or LT or death (OR 16.8, 95% CI 7.2-39.2, P < .0001). CONCLUSIONS: Infants whose TB does not fall below 2.0 mg/dL within 3 months of HPE were at high risk for early disease progression, suggesting they should be considered for LT in a timely fashion. Interventions increasing the likelihood of achieving TB <2.0 mg/dL within 3 months of HPE may enhance early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00061828 and NCT00294684.
Assuntos
Atresia Biliar/cirurgia , Bilirrubina/sangue , Progressão da Doença , Portoenterostomia Hepática , Ascite/epidemiologia , Atresia Biliar/epidemiologia , Biomarcadores/sangue , Canadá/epidemiologia , Pré-Escolar , Bases de Dados Factuais , Coagulação Intravascular Disseminada/epidemiologia , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Hipoalbuminemia/epidemiologia , Lactente , Recém-Nascido , Transplante de Fígado/estatística & dados numéricos , Modelos Logísticos , Prognóstico , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: To assess health-related quality of life (HRQOL) in children with Alagille syndrome (ALGS) in comparison with healthy and other liver disease cohorts, and to identify determinants of HRQOL in patients with ALGS. STUDY DESIGN: Within the Childhood Liver Disease Research Network prospective study of cholestasis, Pediatric Quality of Life Inventory (PedsQL) questionnaires were administered to 70 children with ALGS, 95 children with alpha-1-antitrypsin deficiency (A1ATD), and 49 children with other causes of chronic intrahepatic cholestasis (IHC) aged 5-18 years. Parent proxy PedsQL scores were recorded for children aged 2-18 years (98 ALGS, 123 A1ATD, and 68 IHC). RESULTS: Mean ages and total bilirubin (mg/dL) were ALGS 9.4 years; 4.4, A1ATD 9.5 years; 0.7, and IHC 10.3 years; 2.9. ALGS child PedsQL scores were lower than in healthy children and children with A1ATD (mean 73 vs 83; P = .001). Children with ALGS and IHC were similar, except in physical scores (73 vs 79; P = .05). Parents of children with ALGS perceived their children to have worse HRQOL than A1ATD (P ≤ .001) and marginally lower compared with IHC. Univariate analysis revealed ALGS child-reported scores were positively associated with better growth and inversely with total bilirubin. Growth failure, elevated international normalized ratio, and an intracardiac defect were predictive of poor parental scores (P ≤ .05). In multivariate analysis, only weight z-score remained significant for child- and parent-reported scores. CONCLUSIONS: HRQOL is impaired in children with ALGS compared with healthy and children with A1ATD, similar to children with IHC and is associated with growth failure, which is a potentially treatable cause of impaired HRQOL.