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

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.

Early-life exposure to the Chinese famine and tuberculosis risk: Unrecognized biases from different measures of famine intensity

“…Our aim was to quantify potential biases arising from including postfamine births in calculating CSSI. Including prefamine and postfamine births as done by Cheng et al (1), our estimated CSSI distribution (median 0.488, interquartile range [IQR]: 0.450 to 0.523) is in close agreement with Cheng et al (median 0.488, IQR: 0.438 to 0.521) (1, 7). However, with birth cohorts in nonfamine years only represented by prefamine births, we see a significant decline in CSSI (median 0.418, IQR: 0.325 to 0.466) (Fig.…”

“…2, green regression line). We expect that Cheng et al (1) in their data will be able to demonstrate a similar decrease.…”

“…The metaregression results reported by Cheng et al (1) are also sensitive to including postfamine births as a counterfactual estimate of cohort size in the absence of famine. Again using the public access datafile (6), we estimate a 0.52 unit increase in log F1 famine incidence rate ratio (IRR) associated with a oneunit increase in CSSI when including prefamine and postfamine births (IRR 0.52, 95% CI: −0.23 to 1.28) (Fig.…”

“…We are concerned that Cheng et al (1) did not take all famine-related changes in cohort size into account for their estimates of tuberculosis risk in relation to intensity of early-life nutrition deprivation in the Chinese province of Sichuan.…”

“…To confirm the analysis by Cheng et al (1), we used the public access datafile for Sichuan Province from the 2000 China census (6). Our aim was to quantify potential biases arising from including postfamine births in calculating CSSI.…”