title: Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring.
abstract: OBJECTIVE
  Previous research suggests that advanced paternal age increases the risk of musculoskeletal congenital anomalies (CAs) in offspring, but findings are inconsistent. This study aims to investigate the risk of musculoskeletal CAs according to paternal age at birth in an unselected population covering cohort of children.
  
  
  METHODS
  A register-based prospective study of 1,605,885 children born in Denmark, 1978-2004, using information from record-linked health and administrative registers. The association between paternal age and overall musculoskeletal CAs, limb anomalies, craniosynostosis, skeletal dysplasias, syndromic musculoskeletal CAs, and other musculoskeletal CAs were investigated by multiple logistic regression analysis.
  
  
  RESULTS
  For overall musculoskeletal CAs, a slightly higher risk per 10-year increase in paternal age was found (odds ratio [OR] = 1.06 [95% CI: 1.01-1.11; where CI is confidence interval]). A 26% (95% CI: 2-56%) excess risk was found for fathers aged 50+ years compared to fathers aged 30-34 years. For syndromic musculoskeletal CAs, excess risks were found for fathers aged 40+ years, compared to fathers aged 30-34 years (40-44: OR = 1.38 [95% CI: 1.01-1.88], 45-49: OR = 1.45 [95% CI: 0.89-2.34], 50+: OR = 1.42 [95% CI: 0.73-2.79]). The risks in all other subgroups of musculoskeletal CAs were increased for fathers aged 50+ years.
  
  
  CONCLUSIONS
  A slightly higher risk for overall musculoskeletal CAs in offspring was found with increasing paternal age, mainly due to an excess risk of syndromic musculoskeletal CAs for fathers aged 40+ years. While associations between paternal age 50+ years and increased risk of all subtypes of musculoskeletal CAs were indicated, advanced paternal age likely plays a minor role in the etiology of these anomalies.
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Stine Kjaer
authors.initials: SK
authors.lastname: Urhoj
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Laust Hvas
authors.initials: LH
authors.lastname: Mortensen
authors.affiliation: Section of Social Medicine, Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Nybo Andersen
mesh_terms: D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D000013:Congenital Abnormalities / Q000453:epidemiology*; D003718:Denmark / Q000453:epidemiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D009139:Musculoskeletal Abnormalities / Q000453:epidemiology*; D016017:Odds Ratio; D010331:Paternal Age; D012307:Risk Factors
keywords: birth defects; morbidity; musculoskeletal system; paternal age; perinatal epidemiology