Background. Approximately 20% of men and 15% of women remain childless at the end of their reproductive lifespan, with childlessness increasing over time, yet we lack a comprehensive understanding of the role and relative importance of diseases associated with childlessness, particularly among men.
Methods. We examined all individuals born in Finland (n=1,035,928) and Sweden (n=1,509,092) between 1956 and 1968 (men) or 1956 and 1973 (women) and followed them up until the end of 2018. Socio-demographic, health, and reproductive information was obtained from nationwide registers. We assessed the association of 414 diseases across 16 categories with having no children by age 45 (women) and 50 (men) using a matched pair case-control design based on 71,524 pairs of full-sisters and 77,622 full-brothers who were discordant for childlessness as well as a population-based approach.
Findings. Mental-behavioral, congenital anomalies, and endocrine-nutritional-metabolic disorders had the strongest associations with childlessness. Novel associations were discovered with inflammatory (eg. myocarditis) and autoimmune diseases (eg. juvenile idiopathic arthritis). Mental-behavioral disorders had stronger associations amongst men, particularly for schizophrenia and acute alcohol intoxication, while congenital anomalies, obesity-related diseases such as diabetes, and inflammatory diseases had stronger associations amongst women. Associations were dependent on the age at onset of the disease, with the strongest association observed earlier in women (21-25 years old) than men (26-30 years old). For most diseases, the association with childlessness was mediated by singlehood, especially in men. Some diseases, however, remained associated with childlessness among partnered individuals, including some mood- and endocrine-nutritional-metabolic disorders. All results can be explored in an interactive online dashboard.
Interpretation. We provide evidence that disease burden across multiple domains is associated with childlessness, identifying modifiable mental-behavioral disorders and novel autoimmune and inflammatory diseases. Evidence can be used for targeted health interventions to counter decreasing fertility, reproductive health, involuntary childlessness, and shrinking populations.