Elevated risk of infectious diseases in adulthood after prenatal or early postnatal exposure to the Great Chinese Famine

Q Qi Li P Philip A. Collender (Science Branch, Santa Clara County Public Health Department) H Hailan Yu (Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) K Kristin N. Nelson (Department of Biostatistics, Rollins School of Public Health, Emory University) J Jon Zelner (Department of Epidemiology, School of Public Health, University of Michigan) X Xinqiang Wang (Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) X Xiaolu Wang (Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) J Jiayi Tang (College of Pharmaceutical Sciences) L Leonardo Martinez (Department of Epidemiology, School of Public Health, Boston University) J Justin V. Remais (Division of Environmental Health Sciences, University of California) C Changhong Yang (Institute of Health Informatics, Sichuan Center for Disease Control and Prevention) Q Qu Cheng (Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology)

Abstract

Although prenatal exposure to famine is known to increase the risk of various noncommunicable conditions, its effects on infectious diseases remain poorly understood. We examined the effect of prenatal exposure to the Great Chinese Famine on risks for 11 notifiable infectious diseases in two consecutive generations through the analysis of >4.4 million surveillance records in Sichuan Province, China. Using an approach combining cohort models with counterfactual effect imputation, we estimated the ratio of observed to expected incidence rates (incidence rate ratio, IRR) in the absence of famine among both the directly affected birth cohort (F1) and their possible offspring (F2). We further examined whether there was a dose–response relationship between famine severity and infectious disease outcomes using meta-regression at the prefecture level. We found that the risk of acquiring any of the 11 infectious diseases studied increased significantly among both the F1 (IRR: 1.13, 95% CI: 1.04 to 1.21) and the F2 cohort (IRR: 1.08, 95% CI: 1.00 to 1.15). IRRs for the F1 generation were higher in prefectures that experienced more severe famine, with one interquartile range increase in famine severity associated with a 3.95% (95% CI: 1.87 to 6.05%) increase in F1 IRR. Positive associations of varying magnitudes were estimated between increased risks in the F1 cohort and famine intensity for most individual diseases. Prenatal exposure to famine may have long-term and potential intergenerational impacts on the risk of a broad range of infectious diseases. Ensuring adequate prenatal nutrition may be crucial in reducing the burden of infectious diseases across generations.

Article Details

Volume / Issue Vol. 122, Issue 48
Published December 02, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (12)

Q

Qi Li

P

Philip A. Collender

Science Branch, Santa Clara County Public Health Department

H

Hailan Yu

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology

K

Kristin N. Nelson

Department of Biostatistics, Rollins School of Public Health, Emory University

J

Jon Zelner

Department of Epidemiology, School of Public Health, University of Michigan

X

Xinqiang Wang

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology

X

Xiaolu Wang

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology

J

Jiayi Tang

College of Pharmaceutical Sciences

L

Leonardo Martinez

Department of Epidemiology, School of Public Health, Boston University

J

Justin V. Remais

Division of Environmental Health Sciences, University of California

C

Changhong Yang

Institute of Health Informatics, Sichuan Center for Disease Control and Prevention

Q

Qu Cheng

Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology