The Diagnostic Yield of Investigating Developmental Regression in Children: A Systematic Review and Meta-Analysis

This systematic review evaluates the diagnostic yield of investigations requested for children with developmental regression. Online databases MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane were searched to identify published records that reported a diagnostic yield for children with developmental regression. Random effects meta-analyses were performed using R software with meta package. Our search identified 11,283 published records, of which 347 were assessed for eligibility, and 15 (596 children) were included in the final systematic review and meta-analysis. Subgroup analysis assessed the diagnostic yield for investigating children with different presentations and developmental regression. Diagnostic yield results were 68% for children with neurological symptoms (two records, six children, 95%CI 32-100) and children with epileptic symptoms (two records, 56 children, 95%CI 15-100); 40% for children with neurodevelopmental delay (six records, 294 children, 95%CI 3-78); 9% for autistic children (three records, 138 children, 95%CI 0-26). Pooled analysis could not be completed for metabolic (one record, 29 children) or genetic presentations (one record, 73 children). The diagnostic yield for genetic/genomic investigations (six records, 142 children, 95%CI, 47-92) was 70%, compared with 28% for metabolic (five records, 286 children, 95%CI 0-64), 13% for neurophysiological (two records, 127 children, 95%CI 0-39) and 6% for neuroimaging (two records, 41 children, 95%CI 0-20). Investigations for children with developmental regression and neurological or epileptic symptoms resulted in the highest diagnostic yield. These results are clinically meaningful and will inform future research to advance towards an agreed investigative approach yet lack statistical significance due to small samples.