title: Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark.
abstract: OBJECTIVE
  Based on converging observations in animal, clinical and ecological studies, we hypothesised a possible impact of ritual circumcision on the subsequent risk of autism spectrum disorder (ASD) in young boys.
  
  
  METHODS
  National, register-based cohort study.
  
  
  METHODS
  Denmark.
  
  
  METHODS
  A total of 342,877 boys born between 1994 and 2003 and followed in the age span 0-9 years between 1994 and 2013.
  
  
  METHODS
  Information about cohort members' ritual circumcisions, confounders and ASD outcomes, as well as two supplementary outcomes, hyperkinetic disorder and asthma, was obtained from national registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with foreskin status were obtained using Cox proportional hazards regression analyses.
  
  
  RESULTS
  With a total of 4986 ASD cases, our study showed that regardless of cultural background circumcised boys were more likely than intact boys to develop ASD before age 10 years (HR = 1.46; 95% CI: 1.11-1.93). Risk was particularly high for infantile autism before age five years (HR = 2.06; 95% CI: 1.36-3.13). Circumcised boys in non-Muslim families were also more likely to develop hyperkinetic disorder (HR = 1.81; 95% CI: 1.11-2.96). Associations with asthma were consistently inconspicuous (HR = 0.96; 95% CI: 0.84-1.10).
  
  
  CONCLUSIONS
  We confirmed our hypothesis that boys who undergo ritual circumcision may run a greater risk of developing ASD. This finding, and the unexpected observation of an increased risk of hyperactivity disorder among circumcised boys in non-Muslim families, need attention, particularly because data limitations most likely rendered our HR estimates conservative. Considering the widespread practice of non-therapeutic circumcision in infancy and childhood around the world, confirmatory studies should be given priority.
authors.affiliation: Department of Epidemiology Research, Division of National Health Surveillance and Research, Statens Serum Institut, DK-2300 Copenhagen S, Denmark Department of Clinical Medicine, Center for Sexology Research, Aalborg University, DK-9000 Aalborg, Denmark mfr@ssi.dk.
authors.forename: Morten
authors.initials: M
authors.lastname: Frisch
authors.affiliation: Department of Epidemiology Research, Division of National Health Surveillance and Research, Statens Serum Institut, DK-2300 Copenhagen S, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Simonsen
mesh_terms: D002562:Ceremonial Behavior; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology* / Q000209:etiology / Q000523:psychology; D002675:Child, Preschool; D002944:Circumcision, Male / Q000009:adverse effects* / Q000523:psychology; D003718:Denmark / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012067:Religion; D012189:Retrospective Studies; D012307:Risk Factors
keywords: Denmark; asthma; autism spectrum disorder; circumcision; cohort study; hyperkinetic disorder