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. STUDY DESIGN: 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.