Researchers have uncovered an unexpected link between early-life diseases and lifetime childlessness in couples.

In a study, the research team analyzed the association between 414 early-life diseases and childlessness in over 2.5 million people born in Finland and Sweden. They found a "significant" link between 74 early-life diseases and the chance of being childless throughout life. The findings were published in Nature Human Behavior.

According to estimates, 15-20% of people around the age of 50 in Western European and East Asian countries are without children. While various social, economic and individual factors that contribute to the situation have been examined, there have been limited studies on how the occurrence of specific diseases before peak reproductive age affects lifelong childlessness.

"Various factors are driving an increase in childlessness worldwide, with postponed parenthood being a significant contributor that potentially heightens the risk of involuntary childlessness. Our study is the first to systematically explore how multiple early-life diseases relate to lifetime childlessness and low parity in both men and women," said Dr. Aoxing Liu, lead author of the study from the University of Helsinki's Institute for Molecular Medicine in Finland.

To understand the association between diseases and childlessness, the team analyzed 71,524 full-sister and 77,622 full-brother pairs who showed differences in their childlessness status.

"Interestingly, the association between disease and childlessness was more alike between childless individuals and their siblings who had only one child, in comparison to those with more children," the researchers wrote.

Of the 1.1 million men studied, 25% were childless. Among 1.4 million women, the rate of childlessness was 16.6%.

Out of 74 diseases with significant links with childlessness, 33 were prevalent both in men and women. More than half of them were mental-behavioral disorders. The study also uncovered novel associations between autoimmune and inflammatory diseases and childlessness. The complete list of diseases is available on an interactive dashboard here.

Researchers said gender differences affected the relationships between diseases and childlessness. While schizophrenia and acute alcohol intoxication showed stronger associations with childlessness in men, diabetes-related diseases and congenital anomalies had stronger associations among women.

The age of disease onset affects childlessness in men and women differently. There were stronger associations seen in women diagnosed with diseases at 21-25 years and in men diagnosed at the age of 26-30.

"This study reveals a connection between early-life diseases and childlessness, influencing both single and partnered women and men differently. By assessing the role of multiple early-life diseases on childlessness for 2.5 million people across Finland and Sweden, this study paves the way for a better understanding of how disease contributes to involuntary childlessness and the need for improved public health interventions," said Andrea Ganna, senior author from the University of Helsinki's Institute for Molecular Medicine, Finland.