ABSTRACT
Outcomes research in pediatric liver transplant (LT) has focused on mortality and morbidity but there is a need to also evaluate functional outcomes. Standardized cognitive testing was administered to a cohort of children with infantile chronic liver disease who were transplanted at the University of Alberta during their preschool years. Thirty children had comprehensive assessments with the Bayley Scales of Infant Development or Wechsler testing. Patient variables potentially associated with cognitive delay were analyzed with multiple regression analysis. The mean DQ/IQ score (developmental quotient/intelligence quotient) was 81 +/- 17. Delay (DQ/IQ score < 70), and borderline delay (DQ/IQ 70-84) were each present in 27% of the cohort, with only 46% demonstrating normal cognition. Regression analysis demonstrated that the decreased IQ was associated with pretransplant growth retardation and elevated calcineurin inhibitor levels. Performance IQ had strong correlation with pretransplant growth retardation and elevated serum ammonia, R(2)= 45%, compared to verbal IQ that was associated was elevated calcineurin inhibitor levels, R(2)= 23%. Children post-LT are at high risk for cognitive delay or borderline delay. This is the first study to demonstrate the association calcineurin inhibitors with impaired IQ and also the unique finding of different variables predictive of impaired verbal intelligence quotient (VIQ) versus performance intelligence quotient (PIQ).
Subject(s)
Cognition Disorders/etiology , Developmental Disabilities/etiology , Liver Transplantation , Adaptation, Psychological , Adaptor Proteins, Signal Transducing , Alberta , Calcineurin/blood , Child , Child, Preschool , Chronic Disease , Cognition Disorders/diagnosis , Cohort Studies , Developmental Disabilities/diagnosis , Female , Humans , Infant , Liver Diseases/complications , Liver Diseases/surgery , Male , Neuropsychological Tests , Outcome Assessment, Health CareABSTRACT
OBJECTIVES: To establish the prevalence of fetal alcohol exposure; to compare physical, behavioural and learning patterns of children with significant alcohol exposure in utero with those of a group of children exposed to minimal alcohol; to assess the usefulness of a fetal alcohol syndrome (FAS)/fetal alcohol effect (FAE) score; and to provide feedback to parents, schools and communities. DESIGN: Parent questionnaire, complete physical examinations of children, psychometric tests of the children using elements of the Pediatric Early Elementary Examination (PEEX) and the Pediatric Examination of Educational Readiness (PEER), ADD-H comprehensive teachers rating scale (ACTeRS) score, the newly developed FAS/FAE Score, and the Brigance Comprehensive Inventory of Basic Skills to assess language and mathematical achievement. Testers were blinded to the results of the assessments and questionnaires. SETTING: Grades 1 to 3 at Sir Alexander MacKenzie School in Inuvik, Northwest Territories. RESULTS: Twenty-four per cent of mothers reported frequent or binge drinking, and 76% of mothers reported abstinence or moderate alcohol intake. There were significant ethnic differences; none of the Caucasian mothers reported frequent or binge drinking during pregnancy compared with 40% of Inuvialuit and 33% of Indian mothers. Children with exposure to frequent or binge drinking in utero had smaller palpebral fissures (2.3+/-0.1 cm versus 2.5+/-0.3 cm, P<0.01), smaller palpebral fissure to intercanthal distance ratios (0.77+/-0.05 versus 0.86+/-0.10, P<0.01) and smaller head circumferences (52.1+/-1.6 cm versus 53.6+/-1.6 cm, P<0.01) than those exposed to moderate drinking or abstinence. Children exposed to frequent or binge drinking in utero also demonstrated poorer coordination (P<0.005) and cortical function (P<0.01), attention problems, hyperactivity (ACTeRS), and poorer scholastic achievement in language (P<0.001) and mathematics (P<0.01) than their minimally exposed counterparts. In children in grades 2 and 3, a significant negative correlation was found between FAS/FAE scores and language (r=-0.55, P<0.001) and mathematical achievement (r=-0.28, P=0.20). CONCLUSIONS: The prevalence of drinking during pregnancy in the northern population studied was high, and exposure in utero was associated with physical abnormalities, difficulties with coordination and cortical function, and significant delays in language and mathematical achievement. The FAS/FAE score may be useful in predicting success or failure in language development.