TY - JOUR

T1 - Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring

AU - Urhøj, Stine Kjær

AU - Mortensen, Laust Hvas

AU - Andersen, Anne-Marie Nybo

PY - 2015/12

Y1 - 2015/12

N2 - OBJECTIVE: Previous research suggests that advanced paternal age increases the risk of musculoskeletal congenitalanomalies (CAs) in offspring, but findings are inconsistent. This study aims to investigate the risk of musculoskeletal CAsaccording 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 healthand administrative registers. The association between paternal age and overall musculoskeletal CAs, limb anomalies,craniosynostosis, skeletal dysplasias, syndromic musculoskeletal CAs, and other musculoskeletal CAs were investigatedby multiple logistic regression analysis. RESULTS: For overall musculoskeletal CAs, a slightly higher risk per 10-yearincrease 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 syndromicmusculoskeletal 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 allother subgroups of musculoskeletal CAs were increased for fathers aged 50+ years. CONCLUSIONS: A slightly higherrisk for overall musculoskeletal CAs in offspring was found with increasing paternal age, mainly due to an excess riskof syndromic musculoskeletal CAs for fathers aged 40+ years. While associations between paternal age 50+ years andincreased risk of all subtypes of musculoskeletal CAs were indicated, advanced paternal age likely plays a minor role inthe etiology of these anomalies.

AB - OBJECTIVE: Previous research suggests that advanced paternal age increases the risk of musculoskeletal congenitalanomalies (CAs) in offspring, but findings are inconsistent. This study aims to investigate the risk of musculoskeletal CAsaccording 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 healthand administrative registers. The association between paternal age and overall musculoskeletal CAs, limb anomalies,craniosynostosis, skeletal dysplasias, syndromic musculoskeletal CAs, and other musculoskeletal CAs were investigatedby multiple logistic regression analysis. RESULTS: For overall musculoskeletal CAs, a slightly higher risk per 10-yearincrease 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 syndromicmusculoskeletal 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 allother subgroups of musculoskeletal CAs were increased for fathers aged 50+ years. CONCLUSIONS: A slightly higherrisk for overall musculoskeletal CAs in offspring was found with increasing paternal age, mainly due to an excess riskof syndromic musculoskeletal CAs for fathers aged 40+ years. While associations between paternal age 50+ years andincreased risk of all subtypes of musculoskeletal CAs were indicated, advanced paternal age likely plays a minor role inthe etiology of these anomalies.

U2 - 10.1002/bdrb.21167

DO - 10.1002/bdrb.21167

M3 - Journal article

C2 - 26663788

VL - 104

SP - 273

EP - 280

JO - Birth Defects Research Part B - Developmental and Reproductive Toxicology

JF - Birth Defects Research Part B - Developmental and Reproductive Toxicology

SN - 1542-0752

IS - 6

ER -