The relationship of major diseases with childlessness: a sibling matched case-control and population register study in Finland and Sweden

The percentage of women born 1965-1975 remaining childless is [~]20% in many Western European and [~]30% in some East Asian countries. Around a quarter of childless women do that voluntary, suggesting a remaining role for disease. Single diseases have been linked to childlessness, mostly in women, yet we lack a comprehensive picture of the effect of early-life diseases on lifetime childlessness. We examined all individuals born 1956-1968 (men) and 1956-1973 (women) in Finland (n=1,035,928) and Sweden (n=1,509,092) to completion of reproduction in 2018 (age 45 women; 50 men). Leveraging nationwide registers, we associated sociodemographic and reproductive information with 414 diseases across 16 categories, using a population and matched pair case-control design of siblings discordant for childlessness (71,524 full-sisters, 77,622 full-brothers). The strongest associations were mental-behavioural, particularly amongst men (schizophrenia, acute alcohol intoxication), congenital anomalies and endocrine-nutritional-metabolic disorders (diabetes), strongest amongst women. We identified novel associations for inflammatory (e.g., myocarditis) and autoimmune diseases (e.g., juvenile idiopathic arthritis). Associations were dependent on age at onset, earlier in women (21-25 years) than men (26-30 years). Disease association was mediated by singlehood, especially in men and by educational level. Evidence can be used to understand how disease contributes to involuntary childlessness. O_TEXTBOXText box:Defining Childlessness We use the term childlessness to describe individuals that have had no live-born children by the end of their reproductive lifespan (age 45 for women; 50 for men). Childlessness is defined in the literature as being both involuntary, related to biology and fecundity (e.g., infertility, inability to find a partner) and voluntary or childfree1 (e.g., active choice, preference2). It has been estimated that 4-5% of the current 15-20% women who are childless in Europe are voluntary childless3. Childless individuals are subjected to discrimination and marginalization in many societies4, with infertile women globally experiencing multiple types of violence and coercion5. A parallel line of work, which is not the position of this paper or authors, is to problematize and stigmatize childless individuals as egoistic and place blame on this group for producing a so-called demographic disaster of shrinking and ageing populations and collapse of social security systems6. The approach of this paper is to provide a neutral, data-driven, and factual examination of early-life diseases related to childlessness, with the aim to design a better understanding of health to prevent childlessness among those who want to have children. C_TEXTBOX