Pediatric Biliary Atresia Linked to Neurodevelopmental Delays and Autism

A significant proportion of young children with biliary atresia (BA) display general neurodevelopmental delays and autism-related traits, according to findings published in The Journal of Pediatrics.

Biliary atresia is a rare, progressive pediatric liver disease typically requiring early surgical intervention. While prior studies have documented cognitive and behavioral issues in older children with BA, this study is among the first to investigate these concerns in children younger than 5 years of age and examine associations with disease-specific variables.

Researchers conducted a 3-part investigation at King’s College Hospital and affiliated research centers in London.

1. Survey of Children With BA:
   A neurodevelopmental survey was completed by 107 children (mean age, 7.8 years; range 7 months to 12 years) receiving care for biliary atresia (BA) at King’s College Hospital.
2. Developmental and Autism Assessments:
   A subgroup of 50 children with BA younger than 5 years of age (mean age, 2.3 years) underwent standardized assessments of general development using the Vineland Adaptive Behavior Scales (VABS) and the Mullen Scales of Early Learning (MSEL). Autism-related traits were assessed using the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).
3. Reference Cohort Comparison:
   An age- and sex-matched reference group was randomly selected from the Brain Imaging in Babies Study (ClinicalTrials.gov Identifier: NCT04443179). The cohort included children with both a high (n=43) and low (n=50) likelihood of neurodevelopmental conditions.

Concerns regarding their child’s development was common among parents (37%) and other childcare professionals (eg, teachers, nursery assistants; 28%). Overall, 47% of children in the cohort received support services such as speech and language therapy or psychological care with speech and language therapy being the most accessed (20%).

Compared with both the low- and high-likelihood reference cohorts, children younger than 5 years old with BA had significantly lower VABS adaptive behavioral composite scores (F=18.26; η2=0·215; P <.001). In the sub-analysis, children with BA had significantly lower scores in 3 sub-domains: communication, social, and motor skills (η2=0.096, η2=0.224, and η2=0.149, respectively).

Additionally, children younger than 5 years old with BA had lower MSEL early learning composite scores (F=9.981; η2 = 0·131; P <.001), significantly in the expressive language, visual reception, and receptive language sub-domains (η2=0.095, η2=0.189), and η2=0.094, respectively).

Among the 35 children with BA eligible for ADOS-2 evaluation, 20 were assessed and 45% (n=9) scored above the diagnostic threshold for autism. A clinical autism diagnosis or research diagnosis of autism occurred in approximately 30% of the cohort. In the BA group, boys were significantly more likely to score above the autism threshold (69%; t[18]=3.44; P <.001; d=1.615).

Regression analyses revealed that younger age at Kasai portoenterostomy and faster jaundice resolution at 1-month post-surgery were linked to better general developmental outcomes (P =.047 and P =.012, respectively). However, these disease-related factors were not associated with autism traits.

Study limitations include a modest sample size, cross-sectional design, missing ADOS-2 data in some children, lack of full autism diagnostic tools, and potential confounding effects from the COVID-19 pandemic.

“Even before 2 years, infants with BA show global neurodevelopmental deficits suggesting that the developing brain in these babies is adversely affected,” the researchers concluded.

This research was supported by MowatLabs, Kings College Hospital, NIHR Maudsley Biomedical Research Centre at South London, Maudsley NHS Foundation Trust, King’s College London.