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The influence of paternal preconception health on birth defects and head circumference: A scoping review
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DOI：10.1371/journal.pgph.0005953.png)
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Abstract
En 中文
While paternal environmental exposures and lifestyle factors can influence sperm epigenetic states and affect fetal development, this area of research remains relatively underexplored. This comprehensive scoping review aimed to identify, compile, and analyze the literature on paternal preconception health and its impact on fetal development, specifically related to congenital birth defects (CBDs) and head circumference. We conducted a scoping review following the Joanna Briggs Institute methodology and a published protocol. Five databases were searched for articles that included men in the preconception period and outcomes for CBDs and head circumference. Studies were published in English up to July 16, 2025. Two independent reviewers screened titles and abstracts and extracted data from eligible studies using Covidence. Forty-eight studies were included in the review. We identified several paternal factors associated with CBDs, including paternal physical health (metabolic syndrome, viral infections, cancer), smoking and alcohol use, and environmental exposures (solvents, metals, pesticides). Most medications were not associated with increased risks; however, metformin and diazepam were identified as potential risk factors for increased CBD risk. The limited studies on head circumference also suggest a potential relationship; however, the findings are not widely applicable due to the small number of included studies. We also identified important knowledge gaps and methodological limitations that require further research to advance this field. Our findings indicate that paternal preconception health and exposures-particularly paternal health, substance use, environmental factors, and certain medications-significantly influence offspring health outcomes, including congenital defects and infant head circumference. These findings highlight the need to expand preconception counselling and preventive strategies to explicitly include fathers, with targeted efforts to improve paternal health, eliminate tobacco and alcohol use, and reduce occupational and environmental exposures. Incorporating paternal health into preconception frameworks is essential to understanding mechanistic pathways, decreasing congenital risks, and developing precision strategies for improving reproductive and neonatal outcomes.
Keywords:
ADVERSE PREGNANCY
DRUG EXPOSURE
OUTCOMES
RISK
METHOTREXATE
MEN
CHILDREN
COHORT
ASSOCIATION
ENVIRONMENT
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