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Advanced Paternal Age and Risk of Musculoskeletal Congenital Anomalies in Offspring
Stine Kjaer Urhoj1, Laust Hvas Mortensen1, Anne-Marie Nybo Andersen1
1Section of Social Medicine, Department of Public Health, University of Copenhagen, Denmark.
Insights
Advanced paternal age is linked to a slightly increased risk of musculoskeletal congenital anomalies in children. This risk is primarily associated with syndromic musculoskeletal conditions, particularly when fathers are 40 years or older.
Area of Science:
- Reproductive medicine
- Pediatric health
- Genetics and public health
Background:
- Paternal age is a potential factor influencing offspring congenital anomalies.
- Previous studies on paternal age and musculoskeletal congenital anomalies (CAs) have yielded inconsistent results.
- Understanding the specific risks associated with paternal age is crucial for public health initiatives.
Purpose of the Study:
- To investigate the association between paternal age at birth and the risk of musculoskeletal congenital anomalies in a large, unselected population.
- To analyze the risk of various subtypes of musculoskeletal CAs, including limb anomalies, craniosynostosis, and syndromic CAs, in relation to paternal age.
Main Methods:
- A prospective, register-based cohort study involving 1,605,885 children born in Denmark between 1978 and 2004.
- Utilized linked health and administrative registers for comprehensive data.
- Employed multiple logistic regression analysis to assess the association between paternal age and different categories of musculoskeletal CAs.
Main Results:
- A slight increase in the risk of overall musculoskeletal CAs was observed with each 10-year increase in paternal age (OR = 1.06).
- Fathers aged 50 and older had a 26% higher risk of offspring having musculoskeletal CAs compared to fathers aged 30-34.
- Increased risks for syndromic musculoskeletal CAs were noted for fathers aged 40 and older, with notable associations for paternal age 50+ across all musculoskeletal CA subtypes.
Conclusions:
- Increasing paternal age is associated with a slightly elevated risk of musculoskeletal congenital anomalies in offspring.
- The primary driver for this increased risk appears to be syndromic musculoskeletal congenital anomalies, particularly in offspring of fathers aged 40 and above.
- While advanced paternal age (50+) suggests an increased risk across all musculoskeletal CA subtypes, its overall role in the etiology of these anomalies is considered minor.
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.
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