A Review and Meta-Analysis on Altered Brain Structure in Patients Born with Non-Syndromic Cleft Lip and/or Palate

ObjectiveTo determine if there is evidence for a relationship between the presence of a non-syndromic cleft lip and/or palate (NSCL/P) and altered brain structure in cleft affected individuals.DesignElectronic database (MEDLINE; EMBASE; Cochrane library) and manual searches were performed and were limited to English language texts published between 1st of January 1969 until 1st of June 2024. Data extraction and risk of bias assessment were carried out independently by two reviewers. A meta-analysis on 9 publications was performed using a random effects model.Main outcome measureComparison of brain structure between patients born with cleft lip and/or palate and unaffected healthy individuals.ResultsThe review identified 11 studies, of which 9 were included in the meta-analysis. The latter comprised 398 individuals with NSCL/P compared to 458 unaffected controls. There was statistical evidence to suggest a reduction in the overall intracranial volume and the total cerebellar volume in the NSCL/P cases compared to the controls (Hedges' g and 95% confidence intervals: -0.36 [95% CI: -0.65, -0.08] and -0.69 [95% CI: -0.84, -0.53], respectively). For the cortical gray matter, straight gyrus, and total cerebral volume, there was no statistical evidence to suggest a difference between the NSCL/P cases and the controls.ConclusionIn individuals with NSCL/P, the overall intracranial volume and the total cerebellar volume were both smaller than in unaffected controls.