Evidence from Finland and Sweden on the relationship between early-life diseases and lifetime childlessness in men and women

Abstract

The percentage of people without children over their lifetime is approximately 25% in men and 20% in women. Individual 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 in 1956-1968 (men) and 1956-1973 (women) in Finland (n = 1,035,928) and Sweden (n = 1,509,092) to the completion of their reproductive lifespan in 2018. 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 and 77,622 full brothers). The strongest associations were mental-behavioural disorders (particularly among men), congenital anomalies and endocrine-nutritional-metabolic disorders (strongest among women). We identified new associations for inflammatory and autoimmune diseases. Associations were dependent on age at onset and mediated by singlehood and education. This evidence can be used to understand how disease contributes to involuntary childlessness.

Fig. 1. Schematic overview of the study.

a, The birth cohorts, the follow-up period and the number of Finns and Swedes included in the analyses. A total of three generations of familial relationships were considered: for the index persons, the parental information used to match sibling pairs, the children’s information to define the main outcome of childlessness and the registered spouse’s information to determine the secondary outcome of singlehood. Map adapted with permission from MapChart. b, The statistical approach used in the main analyses, where only families with same-sex siblings discordant for childlessness were included. Within each family, we randomly selected one childless sibling as a case, and, as the control, the sibling with children that was the closest in birth order to the case. Within a sibling pair, disease diagnoses were considered only if they occurred at least one year before the birth of the first child or within the corresponding age at which the sibling was childless, since sibling ages differ.

Fig. 2. Relationship of 403 disease diagnoses with childlessness by age 45 in women and age 50 in men in 71,524 full-sister and 77,622 full-brother pairs who were discordant on childlessness, using a matched case–control design.

a,b, Odds ratios (ORs) are computed for each disease diagnosis (left) and averaged over disease categories (right). The error bars indicate 95% CIs. Only disease diagnoses that are significantly associated with childlessness after multiple-testing correction (P < 1.5 × 10⁻⁴) are coloured. Labels are assigned only for certain disease diagnoses that are described in the text.

Fig. 3. Sex-specific and age-of-onset-dependent effects for the association between disease diagnoses and childlessness in 71,524 full-sister and 77,622 full-brother pairs who were discordant on childlessness.

a, Odds ratios for 60 disease diagnoses that significantly increased the odds of childlessness in either men or women. The error bars indicate 95% CIs. Only disease diagnoses that are significantly different between sexes at a nominal P value are coloured. b, The average effect associated with childlessness across 30 disease diagnoses in women and 31 in men, for each age category, as obtained from an age-of-onset-stratified analysis. c, Age-of-onset-stratified odds ratios associated with childlessness for three major diseases/disorders for which we observe a significant trend. The estimate for each age category is computed only if the number of individuals with this disease within the age group is more than five.