Neurodevelopmental Outcome of Young Children with Biliary Atresia and Native Liver: Results from the ChiLDReN Study.

OBJECTIVES: To assess neurodevelopmental outcomes among participants with biliary atresia with their native liver at ages 12 months (group 1) and 24 months (group 2), and to evaluate variables predictive of neurodevelopmental impairment. STUDY DESIGN: Participants enrolled in a prospective, longitudinal, multicenter study underwent neurodevelopmental testing with either the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition. Scores (normative mean = 100 ± 15) were categorized as ≥100, 85-99, and <85 for χ2 analysis. Risk for neurodevelopmental impairment (defined as ≥1 score of <85 on the Bayley Scales of Infant Development, 2nd edition, or Bayley Scales of Infant and Toddler Development, 3rd edition, scales) was analyzed using logistic regression. RESULTS: There were 148 children who completed 217 Bayley Scales of Infant and Toddler Development, 3rd edition, examinations (group 1, n = 132; group 2, n = 85). Neurodevelopmental score distributions significantly shifted downward compared with test norms at 1 and 2 years of age. Multivariate analysis identified ascites (OR, 3.17; P = .01) and low length z-scores at time of testing (OR, 0.70; P < .04) as risk factors for physical/motor impairment; low weight z-score (OR, 0.57; P = .001) and ascites (OR, 2.89; P = .01) for mental/cognitive/language impairment at 1 year of age. An unsuccessful hepatoportoenterostomy was predictive of both physical/motor (OR, 4.88; P < .02) and mental/cognitive/language impairment (OR, 4.76; P = .02) at 2 years of age. CONCLUSION: Participants with biliary atresia surviving with native livers after hepatoportoenterostomy are at increased risk for neurodevelopmental delays at 12 and 24 months of age. Those with unsuccessful hepatoportoenterostomy are >4 times more likely to have neurodevelopmental impairment compared with those with successful hepatoportoenterostomy. Growth delays and/or complications indicating advanced liver disease should alert clinicians to the risk for neurodevelopmental delays, and expedite appropriate interventions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00061828 and NCT00294684.

Medical status of 219 children with biliary atresia surviving long-term with their native livers: results from a North American multicenter consortium.

OBJECTIVES: To examine the medical status of children with biliary atresia (BA) with their native livers after hepato- portoenterostomy (HPE) surgery. STUDY DESIGN: The Childhood Liver Disease Research and Education Network database was utilized to examine subjects with BA living with their native livers 5 or more years after HPE and to describe the prevalence of subjects with BA with an "ideal" outcome, defined as no clinical evidence of chronic liver disease, normal liver biochemical indices (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, platelet count, total bilirubin, international normalized ratio, and albumin), and normal health-related quality of life 5 or more years after HPE. RESULTS: Children with BA (n = 219; 43% male) with median age 9.7 years were studied. Median age at HPE was 56 (range 7-125) days. Median age- and sex-adjusted height and weight z-scores at 5-year follow-up were 0.487 (IQR -0.27 to 1.02) and 0.00 (IQR -0.74 to 0.70), respectively. During the 12 preceding months, cholangitis and bone fractures occurred in 17% and 5.5%, respectively. Health-related quality of life was reported normal by 53% of patients. However, only 1.8% met the study definition of "ideal" outcome. Individual tests of liver synthetic function (total bilirubin, albumin, and international normalized ratio) were normal in 75%, 85%, and 73% of the study cohort. CONCLUSION: Cholangitis and fractures in long-term survivors underscore the importance of ongoing medical surveillance. Over 98% of this North American cohort of subjects with BA living with native livers 5 or more years after HPE have clinical or biochemical evidence of chronic liver disease.

Extrahepatic anomalies in infants with biliary atresia: results of a large prospective North American multicenter study.

UNLABELLED: The etiology of biliary atresia (BA) is unknown. Given that patterns of anomalies might provide etiopathogenetic clues, we used data from the North American Childhood Liver Disease Research and Education Network to analyze patterns of anomalies in infants with BA. In all, 289 infants who were enrolled in the prospective database prior to surgery at any of 15 participating centers were evaluated. Group 1 was nonsyndromic, isolated BA (without major malformations) (n = 242, 84%), Group 2 was BA and at least one malformation considered major as defined by the National Birth Defects Prevention Study but without laterality defects (n = 17, 6%). Group 3 was syndromic, with laterality defects (n = 30, 10%). In the population as a whole, anomalies (either major or minor) were most prevalent in the cardiovascular (16%) and gastrointestinal (14%) systems. Group 3 patients accounted for the majority of subjects with cardiac, gastrointestinal, and splenic anomalies. Group 2 subjects also frequently displayed cardiovascular (71%) and gastrointestinal (24%) anomalies; interestingly, this group had genitourinary anomalies more frequently (47%) compared to Group 3 subjects (10%). CONCLUSION: This study identified a group of BA (Group 2) that differed from the classical syndromic and nonsyndromic groups and that was defined by multiple malformations without laterality defects. Careful phenotyping of the patterns of anomalies may be critical to the interpretation of both genetic and environmental risk factors associated with BA, allowing new insight into pathogenesis and/or outcome.