Background and objectives Poor cognition can affect educational attainment, but the extent of neurocognitive impairment in children with CKD is not well understood. This systematic review assessed global and domainspecific cognition and academic skills in children with CKD and whether these outcomes varied with CKD stage.Design, setting, participants, & measurements Electronic databases were searched for observational studies of children with CKD ages 21 years old or younger that assessed neurocognitive or educational outcomes. Risk of bias was assessed using a modified Newcastle-Ottawa scale. We used random effects models and expressed the estimates as mean differences with 95% confidence intervals stratified by CKD stage.Results Thirty-four studies (25 cross-sectional, n=2095; nine cohort, n=991) were included. The overall risk of bias was high because of selection and measurement biases. The global cognition (full-scale intelligence quotient) of children with CKD was classified as low average. Compared with the general population, the mean differences (95% confidence intervals) in full-scale intelligence quotient were 210.5 (95% confidence interval, 213.2 to 27.72; all CKD stages, n=758), 29.39 (95% confidence interval, 212.6 to 26.18; mild to moderate stage CKD, n=582), 216.2 (95% confidence interval, 233.2 to 0.86; dialysis, n=23), and 211.2 (95% confidence interval, 217.8 to 24.50; transplant, n=153). Direct comparisons showed that children with mild to moderate stage CKD and kidney transplants scored 11.2 (95% confidence interval, 2.98 to 19.4) and 10.1 (95% confidence interval, 21.81 to 22.0) fullscale intelligence quotient points higher than children on dialysis. Children with CKD also had lower scores than the general population in executive function and memory (verbal and visual) domains. Compared with children without CKD, the mean differences in academic skills (n=518) ranged from 215.7 to 21.22 for mathematics, from 29.04 to 20.17 for reading, and from 214.2 to 2.53 for spelling.Conclusions Children with CKD may have low-average cognition compared with the general population, with mild deficits observed across academic skills, executive function, and visual and verbal memory. Limited evidence suggests that children on dialysis may be at greatest risk compared with children with mild to moderate stage CKD and transplant recipients.

Aim We examined key features of two outcome measures for social dysfunction and autism spectrum disorder traits, the Social Responsiveness Scale, Second Edition (SRS‐2) and the Social Skills Improvement System – Rating Scales (SSIS‐RS), in children with neurofibromatosis type 1 (NF1). The aim of the study was to provide objective evidence as to which behavioural endpoint should be used in clinical trials. Method Cross‐sectional behavioural and demographic data were pooled from four paediatric NF1 tertiary referral centres in Australia and the United States (N=122; 65 males, 57 females; mean age [SD] 9y 2mo [3y], range 3–15y). Results Distributions of SRS‐2 and SSIS‐RS scores were unimodal and both yielded deficits, with a higher proportion of severely impaired scores on the SRS‐2 (16.4%) compared to the SSIS‐RS (8.2%). Pearson’s product‐moment correlations revealed that both questionnaires were highly related to each other (r=−0.72, p<0.001) and to measures of adaptive social functioning (both p<0.001). Both questionnaires were significantly related to attention‐deficit/hyperactivity disorder symptoms, but only very weakly associated with intelligence. Interpretation The SRS‐2 and SSIS‐RS capture social dysfunction associated with NF1, suggesting both may be suitable choices for assessing social outcomes in this population in a clinical trial. However, careful thought needs to be given to the nature of the intervention when selecting either as a primary endpoint. What this paper adds The Social Responsiveness Scale, Second Edition yielded a large deficit relative to population norms. The Social Skills Improvement System – Rating Scales yielded a moderate deficit relative to population norms. Both scales were highly correlated, suggesting that they are measuring a unitary construct.

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