The association between the presence of genetic disease in the offspring and the paternal age: A systematic review

Abstract

Objective: To determine the association between the presence of genetic disease in the offspring and the paternal age. Methods: We carried out a systematic review in: Medline (Ovid), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), from inception to October 2022. We included RCTs, Cohort, case-control and cross-sectional studies. Every study was evaluated according to eligibility criteria. Meta-analysis was not possible given the clinical and methodological heterogeneity. Results: We identified 502 studies through the database search. Forty-five studies were selected for data collection and were included in the qualitative analysis. In this systematic review we did not find associations with anomalies such as Trisomy 18, Obsessive Compulsive Disorder, Tourette syndrome, schizoaffective disorder, adverse perinatal outcomes, hematologic disturbances, microcephaly, hydrocephalus, gastrointestinal disturbances, cleft lip with or without cleft palate, cleft palate, and genitourinary disturbances. In contrast, we found a tendency of association between older fathers and psychiatric disorders (schizophrenia, autism, bipolar disorder syndrome, intellectual disability), nervous system cancer and overall musculoskeletal congenital anomalies. Conclusion: There is a tendency of association among the advanced paternal age and an increased number of birth defects regarding some specific conditions.