Introduction: The effects of advanced maternal age on perinatal outcomes have been well-documented, with several studies demonstrating a significant risk for women over 35 years. Other studies have identified potential associations between advanced paternal age and adverse perinatal outcomes. This study aimed to expand upon such findings by assessing the risks associated with the tertiary variable of parental-age differences. Methods: A retrospective cohort analysis was performed using data compiled from the National Vital Statistics System for 21,021,091 US births between 2012-2018. Logistic regression controlling for demographic and health-related covariates was used to assess odds of low birthweight, very low birthweight, preterm birth, very preterm birth, small size for gestational age, low 5-minute APGAR score, congenital defects, and chromosomal anomalies. Results: Increased parental-age differences were associated with significant risks for all adverse outcomes, aside from congenital defects, even when controlling for maternal age. Restricting maternal age to the reference range of 25-29 years, infants born to fathers aged 5-8 years younger (n = 87,032) had 19% (OR 1.19, 95% CI 1.17 – 1.21) higher odds of having any adverse perinatal outcome. Conversely, infants born to fathers aged > 16 years older (n = 100,971) had 11% (OR 1.11, 95% CI 1.09 – 1.13) higher odds of having any adverse perinatal outcome. Conclusions: Large differences in parental age are associated with adverse birth outcomes and exhibit a bimodal distribution. Older mothers paired with younger fathers had the highest risks, even when maternal age was below 35 years. Potential mechanisms as to why younger fathers may elevate outcome risks include sperm genetic or epigenetic instability, lower socioeconomic status, unstable social and familial environments, or precarious lifestyle factors associated with this age group. Clinically, parental-age differences should be considered alongside maternal and paternal age when assessing risks of adverse perinatal outcomes for potential parents. SOURCE OF Funding: NIH Ruth L. Kirschstein National Research Service Award (NRS) institutional training grant (T35DK103596)
