The potential impact of paternal age on risk of asthma in childhood: a study within the Danish National Birth Cohort

Background: Advanced paternal age has been associated with offspring morbidity and mortality, possibly due to de novo mutations and epigenetic changes in male germ cells. Epigenetic changes in the cord blood cells have been linked to asthma symptoms in offspring, but the role of paternal age has been less studied. Methods: From the Danish National Birth Cohort, 48,785 children who completed the 7-year follow-up were included. Parental reports of physician-diagnosed asthma had been obtained by a posted or web-based questionnaire. Paternal age at delivery was obtained through linkage with maternal civil registration number in the Danish Civil Registration System and classified into four groups: <= 24, 25-34 (reference), 35-39, and > 40 years. We calculated the prevalence proportion of asthma and prevalence ratios (PRs) with 95% confidence intervals (CIs) using log-binomial regression, adjusting for paternal smoking, paternal asthma, and paternal socioeconomic status. Results: At the 7-year follow-up, 5875 children (12%) had physician-diagnosed asthma. The prevalence of asthma in 7-year old children was higher with paternal age of <= 24 (adjusted PR 1.40; 95% CI: 1.26; 1.55) and lower with the paternal age of >= 35 years (adjusted PR 0.84; 95% CI: 0.78; 0.89) compared to the reference group. Conclusions: Paternal age of >= 35 years was associated with a lower prevalence of asthma in childhood, and paternal age of <= 24 years with higher prevalence compared with paternal age of 25-34 years. The potential causes of higher asthma prevalence among offspring of young fathers warrant further investigation.