In a groundbreaking, large-scale prospective cohort study involving over half a million Chinese adults, researchers have illuminated the complex, sex-specific relationships between the number of biological offspring and long-term health outcomes. Drawing on data from the China Kadoorie Biobank (CKB), which comprises more than 500,000 men and women aged 30 to 79 from 10 diverse regions across China, this study employed a phenome-wide association study (PheWAS) methodology to evaluate disease risks across an extensive spectrum of health conditions in relation to parenthood.
At the core of this research lies a pioneering effort to transcend traditional reproductive health studies, which often focus narrowly on women and select health outcomes. By integrating a phenome-wide approach, the study systematically examined comprehensive medical records coded by the International Classification of Diseases, Tenth Revision (ICD-10) to identify associations between offspring numbers and morbidity and mortality across multiple organ systems. Analyses were meticulously stratified by sex, reflecting the necessity of acknowledging inherent biological and social differences in men’s and women’s health trajectories.
The PheWAS framework employed here proved pivotal in unraveling the myriad ways reproductive history imprints upon health. In essence, the approach scans the entire phenome, or full spectrum of health phenotypes, to identify statistical associations with a given exposure—in this case, parity, or number of children. By contrasting individuals without offspring to those with one child, as well as comparing those with more than one child to those with exactly one, the research team was able to isolate nuanced patterns of health risk and benefit linked to reproductive history.
Advanced statistical modeling underpinned the prospective component of the study, wherein Cox proportional-hazards models were applied to longitudinally assess incident morbidity and mortality over a robust 12-year follow-up period. This allowed calculation of hazard ratios (HRs), providing a dynamic estimate of instantaneous risk that accommodates time-to-event data and censoring – essential for accurate epidemiological inference. Crucially, all models adjusted comprehensively for potential confounders, including sociodemographic factors, lifestyle behaviors, and baseline health status, thereby enhancing the credibility of identified associations as likely reflective of parity’s independent effects.
The PheWAS screening revealed compelling signals even after stringent correction for multiple testing using the conservative Bonferroni method. Among the most notable findings was the heightened risk of schizophrenia linked to childlessness in both men and women, pointing toward a profound neuropsychiatric vulnerability associated with reproductive inactivity or failure. Furthermore, having more than one offspring—relative to a single child—was associated with varying disease risks across several bodily systems, underscoring the complex interplay of reproductive burden and health.
Prospective analyses provided granular insights into specific disease categories affected by parity status. Men lacking biological children exhibited significantly increased risks in nine disease categories, prominently including mental and behavioral disorders, cardiovascular disease, and respiratory ailments. In parallel, childless women demonstrated elevated risks in five disease categories, notably mental health disorders and cardiovascular conditions, affirming shared yet sex-differentiated health vulnerabilities linked to childlessness.
Remarkably, the study found each additional offspring correlated with a reduction in mental and behavioral disorder risk by approximately seven percent in both sexes, suggesting protective psychosocial or biological effects conferred by higher parity on mental health. For women, this trend extended to an 18 percent lowered risk of breast cancer per additional child, aligning with established literature on parity’s protective effect against hormone-sensitive malignancies. Conversely, an incremental increase in women’s risk for gallbladder diseases—cholelithiasis and cholecystitis—by four percent per child highlighted the trade-offs inherent in reproductive patterns.
Mortality analyses added a further layer of complexity and significance. Among over 280,000 participants with pre-existing self-reported diseases at baseline, nearly 45,000 deaths occurred during follow-up. Notably, childless patients exhibited dramatically increased all-cause mortality risks—37 percent higher in men and 27 percent higher in women—relative to those with offspring. Among men, each additional child conferred a modest four percent mortality risk reduction; for women, the mortality advantage peaked at three to four children, beyond which benefits plateaued or potentially diminished.
This sex-specific and nonlinear association between offspring number and survival underscores the importance of considering both biological mechanisms—such as hormonal and immunological modulation—and social factors, including caregiving networks and psychological well-being fostered by parenthood. These findings open fertile avenues for multidisciplinary inquiry into how reproductive history shapes lifelong health trajectories through intertwined behavioral, physiological, and social pathways.
Dr. Dianjianyi Sun and colleagues from the School of Public Health at Peking University Health Science Center emphasize that their work marks a major methodological and conceptual advance. By harnessing large-scale population data with rigorous analytical techniques, the study elucidates a systemic, nuanced portrait of how reproductive choices and circumstances intersect with disease susceptibility and longevity. The evidence calls for health systems and policymakers to recognize the distinct vulnerabilities of both ends of the parity spectrum—those without children and those with larger families—tailoring health monitoring and support interventions accordingly.
The implications of this research extend beyond China’s borders, offering a model for global health studies aimed at integrating reproductive history into precision medicine and public health frameworks. The detailed mapping of parity-associated morbidity and mortality risk profiles could inform targeted screening strategies, mental health services, and preventive measures tailored to reproductive backgrounds. Further research is urged to validate causal mechanisms and explore culturally and genetically diverse populations, moving towards integrative care that holistically addresses the lifelong health ramifications of parenthood.
Ultimately, this study underscores the fundamental interconnection between reproductive biology and human health, affirming that reproductive histories are not merely social or demographic statistics but critical determinants of complex health outcomes. As societies evolve and fertility patterns shift, understanding these relationships gains urgency, allowing science and medicine to better anticipate and mitigate emerging health challenges linked to reproductive behavior.
Subject of Research: People
Article Title: A phenome-wide spectrum of morbidity and mortality risks related to the number of offspring among 0.5 million Chinese men and women: A prospective cohort study
News Publication Date: 9-Oct-2025
Web References: http://dx.doi.org/10.1097/CM9.0000000000003815
Image Credits: Dianjianyi Sun from Peking University Health Science Center
Keywords: Health and medicine, Human health, Human biology, Public health, Family medicine, Health care, Population studies, Clinical medicine, Diseases and disorders
