Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720.
Department of Statistics, University of Michigan, Ann Arbor, MI 48109.
Proc Natl Acad Sci U S A. 2020 Nov 3;117(44):27549-27555. doi: 10.1073/pnas.2008336117. Epub 2020 Oct 19.
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.
全球食品安全是人口健康的主要驱动因素，而粮食系统崩溃可能对健康结果产生复杂且持久的影响。我们研究了产前暴露于中国历史上最大的饥荒（1958-1962 年）对中国一个主要持续传播中心连续几代人肺结核（PTB）的影响。我们使用年龄-时期-队列分析和混合效应荟萃回归分析了四川省 2005 年至 2018 年期间诊断的超过 100 万例肺结核病例，以估计饥荒对直接受影响的出生队列（F1）及其可能后代（F2）的肺结核风险的影响。我们还对某些性传播和血液传播感染（STBBI）进行了重复分析，以探索代际效应的潜在机制。暴露于饥荒的 F1 队列及其后代中大量活动性肺结核的负担归因于中国大饥荒，其中超过 12000 例与饥荒有关的活动性肺结核病例（占 2005 年至 2018 年报告的所有病例的 1.23%以上）。饥荒强度每增加一个四分位间距，F1 中观察到的与预期发病率的比值（发病率比，IRR）就会增加 6.53%（95%置信区间[CI]：1.19-12.14%），而 F2 的 IRR 则会增加 8.32%（95% CI：0.59-16.6%）。F2 中也观察到性传播和血液传播感染风险增加。产前和生命早期暴露于营养不良可能会增加暴露代和其后代中活动性肺结核的风险，代际效应可能既与家庭内传播有关，也与宿主易感性增加有关。
