Abstract
Abstract
Background
The independent effects of advanced maternal age on small-for-gestational-age (SGA) are well studied, but the joint effect of maternal and paternal age remains unclear. Most prior research has evaluated parental ages separately rather than as interacting exposures. Our aim was to evaluate the joint effects of advanced maternal (≥ 35 years) and paternal (≥ 40 years) age on SGA using an additive interaction framework in a contemporary U.S. nationwide cohort.
Methods
This population-based cross-sectional study included 39,016,070 singleton live births from the U.S. National Vital Statistics System (2014–2024). Multivariable Poisson regression with robust standard errors estimated adjusted risk ratios (RR) for SGA by parental age categories and a four-category joint exposure. Additive interaction was quantified using the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S). Sensitivity analyses included restriction to term deliveries, exclusion of ART conceptions, multiple imputation, and adjustment for metabolic covariates. E-values assessed unmeasured confounding.
Results
SGA prevalence was 9.9%. Maternal age showed a J-shaped association (highest RR at ≥ 45 years: 1.22, 95% CI 1.20, 1.23); paternal age also showed a J-shaped association (highest RR at ≥ 45 years: 1.36, 95% CI 1.36, 1.37). In joint analysis, "advanced paternal age only" carried the highest risk (RR 1.29, 95% CI 1.29, 1.30), while "dual-advanced age" risk was moderately elevated (RR 1.16, 95% CI 1.15, 1.16). A significant negative additive interaction was identified (RERI = − 0.151, 95% CI − 0.157, − 0.145; AP = − 0.131; S = 0.512 ; all P < 0.001). Results were robust across all sensitivity analyses.
Conclusions
Advanced parental ages exhibit a negative additive interaction on SGA, with the highest risk among younger mothers with older fathers. These findings support integrating paternal age into couple-based prenatal risk assessment.