Discussion
This nationwide birth cohort study of more than 2.45 million Taiwanese children assessed the impact of paternal age on offspring mortality and perinatal outcomes. Population analyses suggested that paternal age was not associated with offspring under-five and under-one mortality; however, the sibling analyses suggest that younger siblings have a lower mortality risk within the same family. For perinatal outcomes, among sib pairs with the same familial predisposition, younger siblings had higher risks of premature birth and LGA and lower risks of low birth weight, SGA, congenital defects and low 5 min Apgar Score.
Children born to older fathers have been shown to be at a higher risk of under-five mortality in a Danish population-based study and in a pooled analysis in low-income and middle-income countries;8 9 however, these findings may be confounded by shared familial factors or secular trends. Two Swedish studies with 1.9 million and 5.2 million births between 1938 and 1960,31 and 1932 and 1987,32 respectively, suggested that the association between advanced paternal age and offspring adult mortality may be explained by secular increases in longevity during the extended study period. This study explored the independent role of advanced paternal age in offspring under-five mortality among 2.45 million Taiwanese births from 2001 to 2015, which is a relatively short period in modern society. In the main cohort, we observed that both paternal and maternal age categories had a U-shaped relationship with the offspring’s under-five and under-one mortality and that both paternal age >35 years and maternal age >35 years were associated with a higher risk of offspring under-five and under-one mortality in the univariate analysis. However, these associations were attenuated towards the null hypothesis after adjusting for potential confounding factors. Notably, adjusting for categorical and continuous maternal age produced slightly different estimates of paternal age associations. Furthermore, with our sibling comparison analyses that removed invariant family characteristics, younger siblings with older parental age had a lower risk of under-five and under-one mortality. Similar trends were also found in the maternal age-stratified analyses. Taken together, the observed negative consequences of reproductive ageing for under-five mortality may be counterbalanced by a more supportive and well-resourced familial environment provided by older parents as well as by a secular trend of improving society.
Previous evidence of the association between advanced paternal age and adverse perinatal outcomes has been inconsistent. A study with 1.5 million births in Italy observed that advanced paternal age was associated with offspring preterm birth;14 however, this association was not observed in another study with 1 million births in Ohio.40 A study with 2.6 million births in the USA found higher risks for preterm birth, low birth weight, SGA and low Apgar Score among children born to fathers <20 years of age, but not fathers >30 years.41 A large-scale study with over 40 million individuals born between 2007 and 2016 in the USA showed that children born to fathers of advanced paternal age have an increased risk of premature birth, low birth weight and low Apgar Score,11 and these findings were replicated in a study with 17 million individuals born between 2016 and 2021 in the USA.15 Simultaneously, our population-based analyses in Taiwan of East Asian populations observed that paternal age >35 years was associated with higher risks of premature birth, low birth weight, LGA and low 5 min Apgar Score. The associations for premature birth and LGA were replicated in our sibling-comparison analyses. However, younger siblings with advanced parental age had lower risks of low birth weight, SGA, congenital defects and low 5 min Apgar Score among sib pairs with the same familial predisposition, suggesting the confounding roles of familial factors and secular improvements in medical technology, such as prenatal examination.
The population-based analyses demonstrated an increased risk of mortality and several perinatal outcomes in children born to very young fathers, which is consistent with the results of previous studies.8 11 15 30 32 41 Early parenthood interferes with education and employment,42–44 which leads to adverse familial economics, unsupportive home environments, adverse parenting behaviours, and subsequent adverse perinatal outcomes and offspring mortality.
This study has several limitations that should be noted when interpreting our findings. First, information on parental education was not available, and we adjusted for the family insurance amount as a proxy for the family’s socioeconomic status in the population-based analyses. Our sibling comparison analyses eliminated unmeasured familial time-invariant confounders. Second, within-family sibling comparisons cannot explicitly differentiate the paternal age effect from the maternal age effect, because paternal age and maternal age have the same change from one sibling to the next within a family. Third, compared with the total cohort, the sample size is much reduced in the sibling-comparison cohort (table 1); thus, selection bias is possible. The post-traumatic experience from the previous child might influence the willingness for bearing subsequent children; therefore, our sibling-comparison analyses may have recruited a healthier proportion of the total study population. Finally, our sibling-comparison analyses may be biased due to carryover effects.45 The family already having an older child with adverse perinatal outcomes may lead to paying more attention in preparing for and during subsequent pregnancies. Time-varying and non-shared family confounding factors were not considered in sibling comparison analyses. Family socioeconomic status and parenting behaviours may improve over time between older and younger children, and the association of paternal age with offspring’s risk of mortality and perinatal outcomes may be biased towards the null hypothesis.