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

Li, Chihua; Zhou, Zhenwei; Lumey, L. H.

doi:10.1073/pnas.2102809118

Cited by 4 publications

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“…We thank Li et al (1) for their interest in our paper (2) and agree that different approaches to estimating famine intensity, expressed here as the cohort size shrinkage index (CSSI), could affect estimates of its association with tuberculosis (TB) risk in the birth cohort directly impacted by famine. We acknowledge their contention that our published CSSI estimates could be biased upward due to postfamine increases in fertility that suggest delayed births.…”

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confidence: 73%

“…Positive associations at or near 95% significance are observed in all cases, including the model that directly estimates and removes delayed births from the postfamine cohort (CSSI pre post mean adjusted ). We note that our estimates are made using full 2000 census data (7), in contrast with the household sample (∼1%) used by Li et al, which explains the difference between our CSSI pre fixed metaregression parameter estimate and the estimate reported in their correspondence (1). While CSSI estimators based on interpolating between prefamine and postfamine cohort sizes may be susceptible to influence by postfamine fertility increases or other changes in population dynamics, estimators ignoring secular trends in cohort size risk underestimating famine intensity.…”

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confidence: 80%

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Reply to Li et al.: Estimate of the association between TB risk and famine intensity is robust to various famine intensity estimators

Cheng

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et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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confidence: 73%

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confidence: 80%

Reply to Li et al.: Estimate of the association between TB risk and famine intensity is robust to various famine intensity estimators

Cheng

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Head

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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“…This may not be appropriate, as grain production in China was not the major cause of the famine [ 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 ]. To better assess famine intensity at the local or regional level, relevant information from documents and studies in other disciplines including history, demography, and economics can also be examined to generate a severity grouping of three or four levels that is consistent across disciplines [ 69 , 88 , 89 ]. A robust indicator of famine intensity of this nature will facilitate the identification of potential dose–response effects and the comparison of results across studies.…”

Section: Discussionmentioning

confidence: 99%

Early-Life Exposure to the Chinese Famine of 1959–1961 and Type 2 Diabetes in Adulthood: A Systematic Review and Meta-Analysis

Lumey

2022

Nutrients

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Background: The fast-growing literature suggests that the Chinese famine of 1959–1961 drives current and future type 2 diabetes (T2D) epidemics in China. This conclusion may be premature, as many Chinese famine studies have major methodological problems. We examine these problems, demonstrate how they bias the study results, and formulate recommendations to improve the quality of future studies. Methods: We searched English and Chinese databases for studies that examined the relationship between prenatal exposure to the Chinese famine and adult T2D from inception to 8 February 2022. We extracted information on T2D cases and study populations of individuals born during the famine (famine births), before the famine (prefamine births), and after the famine (postfamine births). We used random-effects models to compare the odds of T2D in famine births to several control groups, including postfamine births, combined pre- and postfamine births, and prefamine births. We used meta-regressions to examine the impacts of age differences between comparison groups on famine effect estimates and the role of other characteristics, including participant sex, age, and T2D assessments; famine intensity; residence; and publication language. Potential sources of heterogeneity and study quality were also evaluated. Results: Twenty-three studies met our inclusion criteria. The sample sizes ranged from less than 300 to more than 360,000 participants. All studies defined the famine exposure based on the participants’ dates of birth, and 18 studies compared famine births and postfamine births to estimate famine effects on T2D. The famine and postfamine births had an age difference of three years or more in all studies. The estimates of the famine effect varied by the selection of controls. Using postfamine births as controls, the OR for T2D among famine births was 1.50 (95% CI 1.34–1.68); using combined pre- and postfamine births as controls, the OR was 1.12 (95% CI 1.02–1.24); using prefamine births as controls, the OR was 0.89 (95% CI 0.79–1.00). The meta-regressions further showed that the famine effect estimates increased by over 1.05 times with each one-year increase in ignored age differences between famine births and controls. Other newly identified methodological problems included the poorly assessed famine intensity, unsuitable study settings for famine research, and poor confounding adjustment. Interpretation: The current estimates of a positive relationship between prenatal exposure to the Chinese famine and adult T2D are mainly driven by uncontrolled age differences between famine births and postfamine births. Studies with more rigorous methods, including age-balanced controls and robust famine intensity measures, are needed to quantify to what extent the famine exposure is related to current T2D patterns in China.

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“…For example, our recent studies provided alternative methods to assess famine intensity at different regional levels. 77,100,101 There is a need therefore to develop a robust famine intensity measurement to facilitate the identification of potential dose-response effects and the comparison of results across studies.…”

Section: Discussionmentioning

confidence: 99%

“…All too often, adverse health outcomes are linked to the early-life exposure of Chinese famine without proper consideration of these methodological problems. 4,5,66,100,101,103 The universal use of post-famine births as controls in Chinese famine studies is the reason why most studies have reported negative famine effects on different health outcomes.…”

Section: Discussionmentioning

confidence: 99%

Early-life exposure to the Chinese famine of 1959-61 and type 2 diabetes in adulthood: a systematic review and meta-analysis

Lumey

2022

Preprint

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Background The Chinese famine of 1959-61 has been widely interpreted as an important driver of current and future type 2 diabetes (T2D) epidemics. We conducted a systematic review and meta-analysis of prenatal famine exposure and type 2 diabetes (T2D) in China to summarize study characteristics, examine impacts of control selections and other selected characteristics on study results, identify other characteristics influencing results, and formulate recommendations for future studies. Methods We searched English and Chinese databases for studies that examined the relationship between T2D and prenatal exposure to the Chinese famine up to February 8th, 2022. From included studies, we extracted information on the number of T2D cases and populations at risk among individuals born during the famine (famine births), before the famine (pre-famine births), and after the famine (post-famine births). We compared the risk of T2D in famine births to different controls: post-famine births, pre- and post-famine births combined, and pre-famine births. Heterogeneity across studies was assessed, and random-effects models were used to calculate summary estimates. Meta-regressions were used to examine the relationship between effect estimates and age differences. Subgroup analyses were performed based on selected characteristics, including participants' sex, age, T2D measurement, famine intensity, residence, and publication language. Findings In total, 23 studies met our inclusion criteria. Sample sizes ranged from below 300 to over 350,000. All studies defined famine exposure based on participants' date of birth, and 18 studies compared famine births to controls of post-famine births to estimate famine effects on T2D. Famine and post-famine births had an age difference of three years and over in each study. Using post-famine births as controls, a random-effects model shows an increased risk of T2D (OR 1.50, 95% CI 1.34-1.68) among famine births. In contrast, a marginally increased risk of T2D (OR 1.12, 95% CI 1.02-1.24) can be observed using pre- and post-famine births combined as controls, and a decreased risk (OR 0.89, 95% CI 0.79-1.00) using pre-famine births as controls. Studies with larger age differences between comparison groups had larger famine effects. Effect estimates comparing famine births to pre- and post-famine births combined depend on none of above selected characteristics. Studies showed a large variation in sampling sources, famine intensity assessment, and confounding adjustment. Interpretation Current estimates of a positive relation between prenatal exposure to the Chinese famine and adult T2D are mainly driven by uncontrolled age differences between famine births and post-famine controls. Marginal or no effects remain after controlling for the differences in most Chinese famine studies. It remains an open question to what extent the famine is related to current T2D patterns in China. Studies with more rigorous methods including age-balanced controls and robust famine intensity measures will be needed to quantify this relationship. Funding None.

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

Cited by 4 publications

References 4 publications

Reply to Li et al.: Estimate of the association between TB risk and famine intensity is robust to various famine intensity estimators

Reply to Li et al.: Estimate of the association between TB risk and famine intensity is robust to various famine intensity estimators

Early-Life Exposure to the Chinese Famine of 1959–1961 and Type 2 Diabetes in Adulthood: A Systematic Review and Meta-Analysis

Early-life exposure to the Chinese famine of 1959-61 and type 2 diabetes in adulthood: a systematic review and meta-analysis

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