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

Abstract Background: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. Methods: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. Results: Among 210,129 men and 302,284 women aged 30–79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87–0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89–0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78–0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02–1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28–1.47]) and women (aHR [95% CI] = 1.27 [1.15–1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95–0.98]), while for women, the lowest risk was observed among those with three to four offspring ( P nonlinear <0.0001). Conclusions: Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.