Examining the impact of advanced paternal age on obstetrical and fetal outcomes

Advanced paternal age (APA), defined as 40 years or older at time of conception, is associated with poor outcomes with assisted reproductive technologies. Review of literature suggests APA may be associated with infertility, miscarriage, preterm delivery, and placental abnormalities.
Proposed mechanisms of these adverse outcomes include pre-meiotic damage, poor DNA integrity, and changes in sperm morphology or motility. However, research on the relationship between APA and a variety of obstetrical outcomes remains limited, often yielding conflicting results.
We aim to investigate the relationship between APA and adverse obstetrical outcomes such as hypertensive disorders of pregnancy and gestational diabetes, in addition to adverse fetal outcomes such as large for gestational age (LGA) and small for gestational age (SGA) fetus.
To examine our question, we were granted access to the CDC Pregnancy Risk Assessment of Monitoring System data (CDC PRAMS) - a state-based surveillance system. For all variables of interest, descriptive statistics were performed. To evaluate the relationship between APA and various obstetrical outcomes, Chi-square test was used. Binary logistic regression was later performed to examine statistically significant relationships previously identified. We evaluated Standard Core and Phase 8 responses with SPSS 28 software in this prospective observational study.
Approximately 3.1 million males were surveyed with 8,614 males being 40 years and older. Paternal age cutoffs were defined as less than 17 years of age or 40 years of age and older. When the latter was used as a risk factor, there were significantly increased odds for maternal development of gestational diabetes (OR 1.052; 95% CI 1.045 to 1.058) and LGA fetus (OR 1.019; 95% CI 1.013 to 1.026). Association with hypertensive disorders during pregnancy was not significant (OR 0.999; 95% CI 0.993 to 1.004). Interestingly, APA was associated with a significantly decreased risk of SGA fetus at one and two standard deviations (OR 0.986; 95% CI 0.980 to 0.993, OR 0.983; 95% CI 0.966 to 0.999).
 APA is a strong risk factor that contributes to maternal morbidity with significantly increased risk of gestational diabetes and LGA fetus, along with a significantly reduced risk for SGA fetus. We suggest mechanisms such as epigenetic modification through histone and DNA methylation or gene expression may contribute to aberrant embryonic and placental development , however, specific underlying mechanisms have yet to be elucidated. Gestational diabetes contributes to LGA fetus as excess blood glucose causes increased body fat deposition at the fetal shoulders and trunk. There still remains much unknown about the link between APA singularly and the above obstetrical, neonatal outcomes even in combination with advanced maternal age, necessitating further investigation.