More than two-third of included studies showed neurodevelopmental deficits in children with liver diseases, affecting all neurodevelopmental areas. Knowledge on risk factors for impaired neurodevelopment is limited and lack of long-term follow-up is worrying, especially considering the increasing survival rates, resulting in more at-risk patients. Studying early predictors and risk factors of abnormal developmental trajectories of children with liver diseases is indicated to assess strategies to improve their long-term neurodevelopmental outcomes.

To tackle the phenotypic heterogeneity of schizophrenia, data-driven methods are often applied to identify subtypes of its symptoms and cognitive deficits. However, a systematic review on this topic is lacking. The objective of this review was to summarize the evidence obtained from longitudinal and cross-sectional data-driven studies in positive and negative symptoms and cognitive deficits in patients with schizophrenia spectrum disorders, their unaffected siblings and healthy controls or individuals from general population. Additionally, we aimed to highlight methodological gaps across studies and point out future directions to optimize the translatability of evidence from data-driven studies. A systematic review was performed through searching PsycINFO, PubMed, PsycTESTS, PsycARTICLES, SCOPUS, EMBASE and Web of Science electronic databases. Both longitudinal and cross-sectional studies published from 2008 to 2019, which reported at least two statistically derived clusters or trajectories were included. Two reviewers independently screened and extracted the data. In this review, 53 studies (19 longitudinal and 34 cross-sectional) that conducted among 17,822 patients, 8729 unaffected siblings and 5520 controls or general population were included. Most longitudinal studies found four trajectories that characterized by stability, progressive deterioration, relapsing and progressive amelioration of symptoms and cognitive function. Cross-sectional studies commonly identified three clusters with low, intermediate (mixed) and high psychotic symptoms and cognitive profiles. Moreover, identified subgroups were predicted by numerous genetic, sociodemographic and clinical factors. Our findings indicate that schizophrenia symptoms and cognitive deficits are heterogeneous, although methodological limitations across studies are observed. Identified clusters and trajectories along with their predictors may be used to base the implementation of personalized treatment and develop a risk prediction model for high-risk individuals with prodromal symptoms.

To assess long-term neurodevelopmental outcomes in school-aged children with biliary atresia (BA). Study designAll Dutch children (6-12y), diagnosed with BA, were invited to participate in this study. We used validated neurodevelopmental tests to assess motor skills and cognition, and questionnaires to assess behavior. Scores were compared to age-and gender-matched Dutch norms, by means of one-sample tests. Results are given as number and percentages, or mean ± standard deviation. ResultsWe included 46 children, with a median age of 11 years (6-13y). Thirty-six children had undergone a liver transplantation (LTx; 78%). Twelve children (26%) received special education (vs 2.4% in the norm population; p<0.01). Motor outcomes were significantly affected compared to the norm population (p<0.01), with 25% normal (vs 85%), 25% borderline (vs 10%) and 50% low scores (vs 5%). Total IQ was lower in BA patients, compared to the norm population (91±18 vs 100±15; p<0.01). There were no significant differences in test scores between children with native liver and post-LTx. ConclusionsSchool-aged children with BA show neurodevelopmental impairments compared to the norm population, especially in motor skills. Our data strongly warrant evaluation of neurodevelopmental intervention programs to assess whether long-term outcomes could be improved.