Increased Risk for Neurodevelopmental Disorders in Children With Orofacial Clefts

J Am Acad Child Adolesc Psychiatry. 2018 Nov;57(11):876-883. doi: 10.1016/j.jaac.2018.06.024. Epub 2018 Sep 18.


Objective: Children with orofacial clefts (OFC) may have an increased risk of poor mental health. This study aimed to investigate the risk of psychiatric diagnoses in individuals with OFC, stratified by cleft type.

Method: A nationwide register-based cohort of all individuals born with nonsyndromic OFC in Sweden between 1973 and 2012 (n = 7,842) was compared to a matched cohort (n = 78,409) as well as to their unaffected siblings (n = 9,637). The risk of psychiatric diagnoses, suicide attempts, and suicides was examined by crude and adjusted Cox regression models. Effect modification by sex was investigated with interaction terms in the models.

Results: Children with cleft lip (CL) had a significantly higher risk of any psychiatric disorder, intellectual disability, and language disorders; children with cleft lip and palate (CLP) had, in addition, an increased risk of autism spectrum disorder (ASD). Children with cleft palate only (CPO) had risk increases for the same diagnoses as children with CL and CLP, but with higher hazard ratios, and also for psychotic disorders, attention-deficit/hyperactivity disorder (ADHD), and other behavioral or emotional disorders in childhood. Sex stratification indicated higher risk increases among females in CL and CLP but not in CPO. Siblings without OFC were less likely to be diagnosed with any psychiatric disorder, intellectual disability, language disorder, ASD, or ADHD compared to their siblings with OFC.

Conclusion: Children with nonsyndromic clefts had a significantly higher risk of neurodevelopmental disorders. This risk is unlikely to be explained by familial influences such as inherited genetic or shared environmental factors.

Keywords: epidemiology; neurodevelopmental disorders; nonsyndromic clefts; psychiatric comorbidity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain / abnormalities*
  • Child
  • Cleft Lip / classification
  • Cleft Lip / epidemiology*
  • Cleft Lip / genetics
  • Cleft Palate / classification
  • Cleft Palate / epidemiology*
  • Cleft Palate / genetics
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Neurodevelopmental Disorders / epidemiology*
  • Registries
  • Risk Factors
  • Sex Factors
  • Sweden / epidemiology

Supplementary concepts

  • Orofacial Cleft 1