Down's syndrome and paternal age in Norway

Area of Science:

• Reproductive Epidemiology
• Human Genetics
• Perinatal Health

Background:

• Maternal age is a known risk factor for Down's syndrome.
• The potential impact of paternal age on Down's syndrome risk remains uncertain and requires further investigation.
• Large-scale population data are essential for accurately assessing paternal age effects, especially with robust control for maternal age.

Purpose of the Study:

• To investigate the association between paternal age and Down's syndrome risk.
• To determine if paternal age has an independent effect on Down's syndrome risk after accounting for maternal age.
• To analyze a large dataset to provide a definitive conclusion on the paternal age effect.

Main Methods:

• Utilized data from the Medical Birth Registry of Norway (1967-1998).
• Included 1,738,852 births in the analysis, with a Down's syndrome incidence of 10.3 per 10,000 newborns.
• Employed logistic regression models, carefully adjusting for maternal age (in 5-year intervals), birth year, and place of birth.

Main Results:

• Initial analysis with categorical maternal age adjustment showed a residual confounding effect, suggesting a paternal age effect.
• When the maternal age effect was precisely modeled, the estimated paternal age effect became weak (1.11-fold increased risk per 10 years).
• The calculated paternal age effect was not statistically significant (95% CI of odds ratio 0.99, 1.22), indicating no conclusive link.

Conclusions:

• The study provides strong evidence that maternal age is the primary parental age factor influencing Down's syndrome risk.
• After rigorous adjustment for maternal age, paternal age does not demonstrate a statistically significant independent effect on the risk of Down's syndrome.
• The findings suggest that interventions or counseling regarding parental age and Down's syndrome risk should primarily focus on maternal age.