Is natural experiment a cure? Re-examining the long-term health effects of China’s 1959-1961 famine

The fetal origins hypothesis posits that adverse prenatal exposures, particularly malnutrition, increase the risk of poor adult health. Studies using famine as a natural experiment to test the fetal origins hypothesis present conflicting findings, partly because of data limitations and modeling flaws. Capitalizing on the biomarker data and prefecture-level geographic information from the 2011 China Health and Retirement Longitudinal Study, this study estimates the effects of prenatal exposure to China's 1959-61 famine on later-life risks of cardiovascular and metabolic diseases. Our analysis addresses the problems of measurement error and intrinsic cohort differences that challenge prior studies. We use provincial and prefecture-level geographic variations in famine severity, a proxy for prenatal malnutrition, for model identification. We construct instrumental variables from geocoded newspaper archive data to adjust for measurement error in famine exposure. We find that estimates of the famine effects are highly sensitive to the choices of health indicators, measures of famine severity, and regression model specifications. Overall, we find little evidence supporting the fetal origins hypothesis. In fact, it appears that prenatal exposure to famine reduces later-life disease risks in certain cases. We interpret this finding as evidence of mortality selection among the famine survivors at work. We conclude that using famine as a natural experiment in itself does not guarantee correct statistical inference about the long-term health impacts of prenatal malnutrition when other analytical challenges remain unresolved. (C) 2015 Elsevier Ltd. All rights reserved.