Abstract
Paternal age has been associated with offspring congenital heart defects (CHDs), which might be caused by increased mutations in the germ cell line because of cumulated cell replications. Empirical evidences, however, remain inconclusive. Furthermore, it is unknown whether all subtypes of CHDs are affected by paternal age. We aimed to explore the relationship between paternal age and the risk of offspring CHDs and its five common subtypes using national register data in Denmark. A total of 1 893 899 singletons born in Denmark from 1977 to 2008 were included in this national-based cohort study. Cox’s proportion hazards model with robust sandwich estimate option was used to estimate the hazards ratio (95% confidence interval) for the associations between paternal age and all CHDs, as well as subtypes of CHDs (patent ductus arteriosus (PDA), ventricular septal defect (VSD), atrial septal defect (ASD), tetralogy of fallot (TOF) and coarctation of the aorta (CoA)). We did not observe an overall association between paternal age and offspring CHDs. However, compared to the paternal age of 25–29 years, paternal age of older than 45 years was associated with a 69% increased risk of PDA (HR45+ = 1.69, 95%CI:1.17–2.43). We observed similar results when subanalyses were restricted to children born to mothers of 27–30 years old. After taking into consideration of maternal age, our data suggested that advanced paternal age was associated with an increased prevalence of one subtype of offspring congenital heart defects (CHDs), namely patent ductus arteriosus (PDA).
Highlights
Congenital heart defects (CHDs) are the most common congenital malformations, affecting 5–10 per 1000 live births [1,2,3] but the etiology of congenital heart defects (CHDs) remains to be identified
Compared to the reference group, there was no difference in the prevalence of overall CHDs in different paternal age groups by model 1 and model 2 (Table 2)
No statistically significant associations were observed between paternal age and prevalence of atrial septal defect (ASD), ventricular septal defect (VSD), TOF, and CoA
Summary
Congenital heart defects (CHDs) are the most common congenital malformations, affecting 5–10 per 1000 live births [1,2,3] but the etiology of CHDs remains to be identified. Race, ethnicity, and chemical agents have been proposed as potential risk factors [4,5,6]. It was reported that there is gender difference in the prevalence of CHDs [7]. Postponement of maternal age for first child birth could be observed in many countries since 1970s. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
