Abstract
Objective: To evaluate neurodevelopmental status among children with inherited cholestatic liver diseases with native liver and variables predictive of impairment. Methods: Participants with Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha 1 antitrypsin deficiency (A1AT) enrolled in a longitudinal, multicenter study and completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV. Full Scale Intelligence Quotient (FSIQ) was analyzed continuously and categorically (>100, 85–99, 70–84, <70). Univariate linear regression was performed to study association between FSIQ and risk factors, stratified by disease. Results: Two hundred and fifteen completed testing (ALGS n = 70, PFIC n = 43, A1AT n = 102); median age was 7.6 years (3.0–16.9). Mean FSIQ in ALGS was lower than A1AT (94 vs 101, P = 0.01). Frequency of FSIQ < 85 (>1 standard deviation [SD] below average) was highest in ALGS (29%) versus 18.6% in PFIC and 12.8% in A1AT, and was greater than expected in ALGS based on normal distribution (29% vs 15.9%, P = 0.003). ALGS scored significantly lower than test norms in almost all Wechsler composites; A1AT scored lower on Working Memory and Processing Speed; PFIC was not different from test norms. Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ. Conclusions: Patients with ALGS are at increased risk of lower FSIQ, whereas our data suggest A1AT and PFIC are not. A1AT and ALGS appear vulnerable to working memory and processing speed deficits suggestive of attention/executive function impairment. Malnutrition, liver disease severity, and sociodemographic factors appear related to FSIQ deficits, potentially identifying targets for early interventions.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 96-103 |
| Number of pages | 8 |
| Journal | Journal of pediatric gastroenterology and nutrition |
| Volume | 74 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2022 |
Funding
Sources of Funding: This work was supported by funding from the Alpha-1 Foundation (University of Colorado Denver and Saint Louis University School of Medicine) and by U01 grants from the National Institute of Diabetes, Digestive and Kidney Diseases and UL1 grants from the National Center for Advancing Translational Sciences (NCATS): DK062445 [Mt. Sinai School of Medicine], DK062497 and UL1 TR000077 [Cincinnati Children's Hospital Medical Center, University of Cincinnati], DK103149 [Texas Children's Hospital], DK062470 [Children's Healthcare of Atlanta, Emory University], DK062481 and UL1 TR000003 [The Children's Hospital of Philadelphia, University of Pennsylvania], DK062456 [University of Michigan], DK084536 and UL1 TR000006 [Riley Hospital for Children, Indiana University], DK084575 and UL1 TR000423 [Seattle Children's Hospital, University of Washington], DK062500 and UL1 TR000004 [UCSF Children's Hospital, University of California San Francisco], DK062503 and UL1 TR000424 [Johns Hopkins School of Medicine], DK062466 and UL1 TR000005 [Children's Hospital of Pittsburgh, University of Pittsburgh], DK062453 and UL1 TR002535 [University of Colorado Denver, Children's Hospital Colorado], DK062452 and UL1 TR000448 [Washington University School of Medicine, St. Louis, St. Louis Children's Hospital], DK084538 and UL1 TR000130 [Children's Hospital Los Angeles, University of Southern California], DK062436 and UL1 TR000150 [Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University], DK103140 [University of Utah], DK103135 [Hospital for Sick Children (Toronto)].
Keywords
- Alagille syndrome
- Alpha-1 antitrypsin deficiency
- Intelligence quotient
- Neurocognitive
- Progressive familial intrahepatic cholestasis
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health
- Gastroenterology
