Early-life undernutrition increases the risk of death from chronic diseases in adulthood: a population-based cohort study

Abstract

Background: Early-life undernutrition, particularly during critical developmental periods, may have lasting impacts on non-communicable diseases (NCDs) in adulthood. The Chinese Great Famine (1959-1961) provides a unique opportunity to evaluate these effects in a large-scale population study. To investigate the impact of early-life undernutrition on adult mortality due to NCDs in individuals exposed to the Chinese Great Famine.

Methods: We analyzed data from a medical insurance database in Hua County, China, including 15,088 individuals born during the famine (1959-1961) and 49,924 individuals deemed unexposed because they were born after the famine (1962-1964), with follow-up from 2012 to 2023. Multivariable Cox regression and competing risks regression were used to assess the association between early-life undernutrition and mortality.

Results: Early-life undernutrition was associated with increased risks of all-cause mortality (HR_adjusted = 1.49, 95% CI 1.37-1.62), cancer mortality (HR_adjusted = 1.41, 95% CI 1.22-1.64), cardiovascular and cerebrovascular diseases mortality (HR_adjusted = 1.51, 95% CI 1.34-1.71), and chronic obstructive pulmonary disease mortality (HR_adjusted = 4.37, 95% CI 2.51-7.61). Subgroup analysis revealed that the exposed group had a higher risk of death from lung, esophageal, gastric, hepato-biliary, and pancreatic cancers, cerebrovascular disease and cardiovascular disease.

Conclusions: This study demonstrates the long-term adverse effects of early-life undernutrition on NCD mortality in adulthood, underscoring the importance of nutritional interventions during critical developmental periods to reduce the burden of NCDs.

Clinical trial registration: Endoscopic Screening for Esophageal Cancer in China (ESECC) randomized controlled trial (Clinical trial: NCT01688908).

Keywords: Chinese great famine; Chronic non-communicable diseases; Early-life undernutrition; Mortality.

Fig. 1

Cumulative incidence curves of all-cause death (A), cancer death (B), cardiovascular and cerebrovascular diseases death (C), and chronic obstructive pulmonary disease death (D) in early-life undernutrition exposed and unexposed cohorts in Hua County, China, 2012–2023. HR hazard ratio, CI confidence interval

Fig. 2

The effect of early-life undernutrition exposure on death from NCDs in late adulthood, among 65,012 residents in Hua County, 2012–2023. ^* The HRs were adjusted for sex. ^*All-cause mortality was analyzed using Cox proportional hazards models, while cancer, cardiovascular and cerebrovascular diseases, and chronic obstructive pulmonary disease mortality were assessed using competing risks regression models

Fig. 3

The effect of early-life undernutrition exposure on mortality estimated using multivariable models, among 8137 subjects with individual-level covariate information from the ESECC trial and AECCS in Hua County, 2012–2023. ^a The HRs from Model 0 were adjusted for sex. ^b The HRs from Model 1 were adjusted for age at enrollment, sex, education, occupation, and marital status. ^c The HRs from Model 2 were adjusted for age at enrollment, sex, education, occupation, marital status, cigarette smoking and alcohol drinking. ^d The HRs from Model 3 were adjusted for age at enrollment, sex, education, occupation, marital status, cigarette smoking, alcohol drinking and body mass index (BMI). ^e Cancer family history was added to all the models for cancer mortality. ^*All-cause mortality was analyzed using Cox proportional hazards models, while cancer, cardiovascular and cerebrovascular diseases, and chronic obstructive pulmonary disease mortality were assessed using competing risks regression models