Paternal Age and risk of Congenital Anomalies and birth outcomes: A Population-based Cohort Study

Objective: To explore the impact of paternal age on the risk of congenital anomalies and birth outcomes in U.S. infants born between 2016 and 2021. Methods: : This retrospective cohort study was based on live births in the National Vital Statistics System database between 2016 and 2021. All newborns were divided into 4 groups based on paternal age (44 years old groups) and using 25-34 years groups as reference . The primary outcomes were congenital anomalies including structural anomalies, and chromosome anomalies, while the secondary outcomes included preterm birth, low birth weight, severe neonatal perinatal asphyxia, admission to neonatal intensive care units, etc. The association between paternal age and outcomes was detected by multivariable logistic analysis. Results: : After the exclusion process, a total of 17,764,695 live births were included in the final analyses. After adjustment for confounding factors, compared with the paternal age of 25-34 years group, advanced paternal age of more than 44 years was associated with increased odds of congenital anomalies (aOR=1.17, 95%CI 1.12-1.21), mainly for the chromosomal anomalies (aOR=1.59, 95%CI 1.40-1.78) but not the structure anomalies (aOR=1.03, 95%CI 0.97-1.09). Advanced paternal age also increased the risk of preterm delivery, low birth weight, and admission to NICU in their infants. Conclusion: Advanced paternal age increases the risk of congenital anomalies in their offspring, especially chromosomal anomalies, which implies more intensive prenatal or pre-conceptional investigation, including genetic tests, should be taken in the high-risk paternal populations.