Associations of paternal age with offspring under-five mortality and perinatal outcomes: a cohort study using claims data in Taiwan

Abstract

Background 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.