Lisa G. Sorensen

Cognitive and Academic Outcomes after Pediatric Liver Transplantation: Functional Outcomes Group (FOG) Results

This multicenter study examined prevalence of cognitive and academic delays in children following liver transplant (LT). One hundred and forty‐four patients ages 5–7 and 2 years post‐LT were recruited through the SPLIT consortium and administered the Wechsler Preschool and Primary Scale of Intelligence, 3rd Edition (WPPSI‐III), the Bracken Basic Concept Scale, Revised (BBCS‐R), and the Wide Range Achievement Test, 4th edition (WRAT‐4). Parents and teachers completed the Behavior Rating Inventory of Executive Function (BRIEF). Participants performed significantly below test norms on intelligence quotient (IQ) and achievement measures (Mean WPPSI‐III Full Scale IQ = 94.7 ± 13.5; WRAT‐4 Reading = 92.7 ± 17.2; WRAT‐4 Math = 93.1 ± 15.4; p < 0001). Twenty‐six percent of patients (14% expected) had ‘mild to moderate’ IQ delays (Full Scale IQ = 71–85) and 4% (2% expected) had ‘serious’ delays (Full Scale IQ ≤ 70; p < 0.0001). Reading and/or math scores were weaker than IQ in 25%, suggesting learning disability, compared to 7% expected by CDC statistics (p < 0.0001). Executive deficits were noted on the BRIEF, especially by teacher report (Global Executive Composite = 58; p < 0.001). Results suggest a higher prevalence of cognitive and academic delays and learning problems in pediatric LT recipients compared to the normal population.

School outcomes in children registered in the studies for pediatric liver transplant (SPLIT) consortium

School performance is an important aspect of functional outcomes for pediatric liver transplant (LT) recipients. This longitudinal analysis conducted through the Studies of Pediatric Liver Transplantation (SPLIT) research consortium examines several indicators of school function in these patients. A total of 39 centers participated in data collection using a semistructured questionnaire designed specifically for this study. The survey queried school attendance, performance and educational outcomes including the need for special educational services. Participants included 823 of 1133 (73%) eligible patients, mean age 11.34 ± 3.84 years, 53% female, median age at LT 4.6 (range 0.05‐17.8) years, and mean interval from transplant was 5.42 ± 2.79. Overall, 34% of patients were receiving special educational services and 20% had repeated a grade, with older participants more likely to have been held back (P = 0.0007). Missing more than 10 days of school per year was reported by one‐third of the group, with this level of absence being more common in older participants (P = 0.0024) and children with shorter intervals from LT (P < 0.0001). Multivariate analysis revealed the following factors were associated with the need for special educational services; type of immunosuppression at 6 months post‐LT, cyclosporine A (odds ratio [OR] = 1.8, confidence interval [CI] = 1.1‐3.1), or other (OR = 4.9, 95% CI = 1.4‐17.6) versus tacrolimus, symptomatic cytomegalovirus infection within 6 months of liver transplantation (OR = 3.1, CI = 1.6‐6.1), and pretransplant special educational services (OR = 22.5, CI = 8.6‐58.4). Liver Transpl 16:1041–1048, 2010.

Callosal efficiency is related to sustained attention.

The purpose of this study was to determine whether there is a relationship between the efficiency of interhemispheric communication (IHC) and the ability to sustain attention. Children were tested on a vigilance task in which the amount of time between target presentations (interstimulus intervals; ISI) was varied. IHC was assessed by comparing within-field and between-field matches on a tachistoscopic task. Subjects who showed better IHC had faster RTs on the long ISI trials of the vigilance task, suggesting callosal involvement in the ability to sustain attention over a long period of time in the absence of sensory input.

Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation.

OBJECTIVE To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. STUDY DESIGN Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). RESULTS Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ. CONCLUSIONS More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome.

Cognitive development following pediatric solid organ transplantation.

Purpose of reviewCognitive development and school function are important psychosocial outcomes that should be monitored closely in children following transplantation. This review includes discussion of a small number of studies published within the past year and details future directions in this area of research. Recent findingsAn analysis of school-aged kidney transplant recipients revealed normal intelligence, but suggested significant impairment in gross motor and fine motor skills. Another study of adults who received kidney transplantation as children revealed that these patients rated their quality of life relatively high despite ongoing medical problems, delayed educational goals and a higher rate of unemployment than the general population. Psychoeducational outcomes of 30 pediatric liver transplant recipients who had onset of chronic liver disease in early infancy revealed that 27% of the group had intelligence scores that were more than 2 standard deviations below test norms. Progress in studying these outcomes in heart and intestinal transplant recipients has been slow and there was no new report published in this time frame. SummaryThere are considerable gaps in our knowledge of these types of outcomes, but current studies support neurocognitive delay as an important problem for children receiving organ transplantation.

Psychosocial Adjustment Over a Two–Year Period in Children Referred for Learning Problems: Risk, Resilience, and Adaptation

Children with learning difficulties have an increased prevalence of psychosocial adjustment problems. We hypothesized that within the context of a risk and resilience model contextual variables influence adjustment, over and above any effects of academic performance. The Behavior Assessment System for Children (BASC) was used to evaluate the relationship between psychosocial adjustment, changes in academic skills, and contextual factors longitudinally over a two–year period in 100 children (ages 7 to 11) referred for learning problems. Although there was little improvement in academic skills, contextual factors contributed to observed psychosocial outcome. Different factors were salient for parents, teachers, and children. Context–derived vulnerability and protective factors can be important determinants of adjustment in children with learning problems, even though the academic difficulties can remain chronic.

Improved neurocognitive function after radiologic closure of congenital portosystemic shunts.

Congenital portosystemic shunts are rare vascular anomalies causing direct shunting of blood from the portal circulation into the central venous circulation (1,2). They are often a consequence of persistence of elements from the fetal circulation, in particular the ductus venosus. Patients with congenital portosystemic shunts often have no signs or symptoms of disease until adulthood, at which time encephalopathy is the leading presenting symptom (3–6). Shunts may be discovered during surgery for other reasons and as incidental findings during sonography or computed tomography. Recent advances in interventional radiology have provided an opportunity to change management strategies from surgical to less invasive interventions (7–9). We report two children with symptomatic portosystemic shunts in whom interventional radiology was used to obliterate the shunts. Clinical symptoms and neurocognitive function improved in both children after the shunts were obliterated and hepatic portal venous perfusion restored.

Neuropsychological functioning and health-related quality of life: Pediatric acute liver failure study group results

Objectives: Pediatric acute liver failure (PALF) is a rare but serious event, with poorly understood functional outcomes. The goal was to determine the prevalence of reduced neuropsychological functioning and health-related quality of life (HRQOL) following PALF. Methods: This multicenter study examined neuropsychological functioning and HRQOL 1 to 6 (median 3.8) years after PALF. Participants ages 6 to 16 (median 9.9) years were recruited from the PALF registry and administered measures of intelligence, visual spatial/visual motor coordination, attention, executive function, depression, and adaptive skills. HRQOL and fatigue were assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL 4.0) and PedsQL Multidimensional Fatigue Scale. Results: A total of 36 patients participated; 50% were boys and 67% were white. Median age at PALF was 5.6 years. A history of grade 3 or 4 hepatic encephalopathy was reported in 5/36 (14%) participants and 23/36 (64%) received a liver transplant. Visual spatial ability was significantly better than norms (P = 0.009), but motor coordination was worse (P = 0.04). Teachers (P = 0.04 to P < 0.0001) and parents (P = 0.005) reported more executive deficits versus norms, and participants had worse attention (P = 0.02). Participants did not differ significantly from norms on IQ, depression, or adaptive functioning. All of the child self-report PedsQL Generic Core and fatigue scales were significantly lower than a matched healthy sample (P = 0.001 to P < 0.0001) and parent proxy report was lower on the fatigue scales (P = 0.001 to P < 0.0001). Conclusions: Long-term PALF survivors demonstrate average IQ and visual spatial ability, but greater than expected impairments in motor skills, attention, executive function, HRQOL, and fatigue.

Initial assessment of the infant with neonatal cholestasis-Is this biliary atresia?

Introduction Optimizing outcome in biliary atresia (BA) requires timely diagnosis. Cholestasis is a presenting feature of BA, as well as other diagnoses (Non-BA). Identification of clinical features of neonatal cholestasis that would expedite decisions to pursue subsequent invasive testing to correctly diagnose or exclude BA would enhance outcomes. The analytical goal was to develop a predictive model for BA using data available at initial presentation. Methods Infants at presentation with neonatal cholestasis (direct/conjugated bilirubin >2 mg/dl [34.2 μM]) were enrolled prior to surgical exploration in a prospective observational multi-centered study (PROBE–NCT00061828). Clinical features (physical findings, laboratory results, gallbladder sonography) at enrollment were analyzed. Initially, 19 features were selected as candidate predictors. Two approaches were used to build models for diagnosis prediction: a hierarchical classification and regression decision tree (CART) and a logistic regression model using a stepwise selection strategy. Results In PROBE April 2004-February 2014, 401 infants met criteria for BA and 259 for Non-BA. Univariate analysis identified 13 features that were significantly different between BA and Non-BA. Using a CART predictive model of BA versus Non-BA (significant factors: gamma-glutamyl transpeptidase, acholic stools, weight), the receiver operating characteristic area under the curve (ROC AUC) was 0.83. Twelve percent of BA infants were misclassified as Non-BA; 17% of Non-BA infants were misclassified as BA. Stepwise logistic regression identified seven factors in a predictive model (ROC AUC 0.89). Using this model, a predicted probability of >0.8 (n = 357) yielded an 81% true positive rate for BA; <0.2 (n = 120) yielded an 11% false negative rate. Conclusion Despite the relatively good accuracy of our optimized prediction models, the high precision required for differentiating BA from Non-BA was not achieved. Accurate identification of BA in infants with neonatal cholestasis requires further evaluation, and BA should not be excluded based only on presenting clinical features.

Pediatric solid organ transplantation and end stage disease: A slow journey towards understanding neurocognitive outcomes and their ramifications for clinical care

The attempt to characterize neurocognitive outcomes of solid organ disease and transplantation in children has slowly been gathering momentum over the past three decades. With improvements in care over time (e.g., living donor transplantation, use of immunosuppressants, non-transplant interventions), mortality, and morbidity have improved, and many more patients are surviving longer. Yet, this population remains relatively rare, resulting in mostly small, single center samples providing limited insights into neurocognitive outcomes. More recently, larger, multicenter studies have capitalized upon the infrastructure of various working groups and data registries such as Studies of Pediatric Liver Transplantation (SPLIT) and Chronic Kidney Disease in Children Prospective Cohort Study (CKiDS). At this juncture, we need to take stock of what we know, and what the implications are for clinical care of the child with solid organ disease. We also need to acknowledge the gaps in our understanding, and consider how best as a field to fill these gaps with both careful methodology and expediency, to optimize functional outcomes for these patients.