Shi-Heng WangJIAN-TE LEEMei-Chen LinChi-Shin WuWesley K ThompsonChun-Chieh Fan2025-02-062025-02-062024-11https://scholars.lib.ntu.edu.tw/handle/123456789/725163Background The causal relationship between advanced paternal age and offspring health is unclear, owing to familial confounders. This study examined the association of paternal age with offspring’s under-five mortality and perinatal outcomes, using sibling comparison analyses to account for familial confounding factors. Methods A nationwide birth cohort study was designed based on Taiwan’s single-payer compulsory National Health Insurance programme. Individuals born between 2001 and 2015 were included, resulting in 2454 104 live-born singletons. Among them, 1513 222 individuals had full sibling(s) who were included in the sibling-comparison analyses. Logistic regression analyses were used to evaluate the main study cohort whereas conditional logistic regressions were used in the sibling-comparison analyses. Results In the main cohort, paternal age categories showed a U-shaped relationship with offspring’s under-five mortality in the crude analysis, which attenuated towards the null hypothesis after accounting for the measured potential confounders. There was an increased risk of premature birth (gestational age <37 weeks), low birth weight (<2500 g), large for gestational age (90th percentile) and low 5 min Apgar Score (<7) in individuals with a paternal age of >35 years. Sibling-comparison analyses that accounted for unmeasured familial time-invariant confounders showed that younger siblings with older paternal age had a lower risk of under-five mortality, low birth weight, small for gestational age (10th percentile), congenital defects and low 5 min Apgar Score, and a higher risk of premature birth and large for gestational age. Conclusions Children with older fathers had lower risks of under-five mortality, low birth weight, small for gestational age, congenital defects and low 5 min Apgar Score.[SDGs]SDG3journal article10.1136/bmjph-2024-001113