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Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver

Daniel H Leung1, Lisa G Sorensen2, Wen Ye3

  • 1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Texas Children's Hospital, Baylor College of Medicine, Houston, TX.

Journal of Pediatric Gastroenterology and Nutrition
|October 25, 2021
PubMed

Insights

Children with Alagille syndrome (ALGS) face higher risks of lower intelligence, while progressive familial intrahepatic cholestasis (PFIC) and alpha-1 antitrypsin deficiency (A1AT) do not show this trend. Liver disease severity and malnutrition impact cognitive outcomes.

Area of Science:

  • Pediatric Hepatology
  • Neurodevelopmental Pediatrics
  • Genetics

Background:

  • Inherited cholestatic liver diseases, including Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha-1 antitrypsin deficiency (A1AT), can impact overall child development.
  • Evaluating neurodevelopmental status is crucial for understanding the long-term health implications of these conditions.

Purpose of the Study:

  • To assess the neurodevelopmental status of children with ALGS, PFIC, and A1AT, focusing on Full Scale Intelligence Quotient (FSIQ).
  • To identify variables that predict cognitive impairment in these pediatric liver disease populations.

Main Methods:

  • A longitudinal, multicenter study involving 215 children diagnosed with ALGS, PFIC, or A1AT.
  • Neurodevelopmental status was evaluated using the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV.
  • Statistical analyses included univariate linear regression to identify risk factors associated with FSIQ, stratified by disease.

Main Results:

  • Children with ALGS had a significantly lower mean FSIQ (94) compared to those with A1AT (101).
  • The frequency of FSIQ below 85 was highest in ALGS (29%), exceeding expected rates.
  • ALGS patients showed deficits across most cognitive domains, while A1AT patients exhibited impairments in working memory and processing speed. PFIC patients did not differ from norms.
  • Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ.

Conclusions:

  • ALGS is associated with an increased risk of lower FSIQ, unlike A1AT and PFIC.
  • Working memory and processing speed deficits in ALGS and A1AT suggest potential attention/executive function impairments.
  • Malnutrition, liver disease severity, and sociodemographic factors are linked to FSIQ deficits, highlighting potential targets for early intervention.
Abstract

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