Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations

• Authors: Qu Cheng, University of California Berkeley; Robert Trangucci, University of Michigan; Kristin Nelson, Emory University; Wenjiang Fu, University of Houston; Philip A. Collender, University of California Berkeley; Jennifer R. Head, University of California Berkeley; Christopher M. Hoover, University of California Berkeley; Nicholas K. Skaff, University of California Berkeley; Ting Li, Emory University; Yue You, University of California Berkeley; Liqun Fang, Institute of Microbiology and Epidemiology; Song Liang, University of Florida; Changhong Yang, Sichuan Center for Disease Control and Prevention; Jin'ge He, Sichuan Center for Disease Control and Prevention; Justin V. Zelner, University of Michigan; Justin Remais, Emory University
• Journal Title: Proceedings of the National Academy of Sciences
• Volume: Volume 117, Number 44
• Publisher: National Academy of Sciences | 2020-11-03, Pages 27549-27555
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1073/pnas.2008336117
• Subjects: Health Sciences, Nutrition; Health Sciences, Public Health; Health Sciences, Human Development; Health Sciences, Epidemiology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; food systems; tuberculosis; Great Chinese Famine; infectious disease; nutrition; Birth weights; Dutch famine; Cohort Studies; Age; Period; Undernutrition; Disease

Abstract

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958–1962)—the largest famine in human history—on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age–period–cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19–12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59–16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.