The non-genetic paternal factors for congenital heart defects: A systematic review and meta-analysis

Background Advances have been made in identifying genetic etiologies and maternal risk factors of congenital heart defects (CHDs), while few literatures are available regarding paternal risk factors for CHDs. Thus, we aim to conduct a meta-analysis and systematic review about the non-genetic paternal risk factors for CHDs. Methods We searched the PubMed, MEDLINE, and Cochrane Library online databases and identified 31 studies published between 1990 and 2018 according to the inclusion criteria. Paternal risk factors were divided into subgroups, and summarized odd ratios (OR) were calculated. Results Paternal age between 24 and 29 years decreased the risk of CHDs in the offspring (OR = 0.90 [0.82, 0.98]), while paternal age >= 35 years old increased the risk of CHDs (35-39 years old: OR = 1.14 [1.09, 1.19], and >= 40 years: OR = 1.27 [1.14, 1.42]). Paternal cigarette smoking increased the risk of CHDs in a dose-dependent way. Paternal wine drinking (OR = 1.47 [1.05, 2.07]) and exposure to chemical agents or drugs (OR = 2.15 [1.53, 3.02]) also increased the risk of CHDs. Some specific paternal occupations were also associated with increased risk for CHDs or CHD subtypes including factory workers, janitors, painters, and plywood mill workers. Conclusions This meta-analysis and systematic review suggested that advanced paternal age, cigarette smoking, wine drinking, exposure to chemical agents or drugs and some specific occupations were associated with an increased risk of CHDs. More measures should be taken to reduce occupational and environment exposures. At the same time, fertility at certain age and establishment of healthy life habits are strongly recommended.