Fetal and infant exposure to severe Chinese famine increases the risk of adult dyslipidemia

Published today in BMC Public Health, a new study examines the evidence on the association between fetal and infant Chinese famine exposure and the risk of dyslipidemia in adulthood using data from the China Health and Retirement Longitudinal Study (CHARLS) 2011-2012 baseline survey. Here lead author Dr. Zhenghe Wang tells us more.

Dyslipdemia

Dyslipidemia is an important risk factor of coronary heart disease (CHD), which is one of the leading causes of death in developing and developed countries.

Based on the Chinese national data, the prevalence of dyslipidemia was 26.7% among workers aged 18-59 years in 2012, and was 33.5% among Chinese aged greater than 45-years-old. The emerging pandemic was partially caused by population growth, rapidly aging and changes of diet and lifestyle.

However, recent studies indicated that the early life famine exposure might also increase the later susceptibility to some common chronic diseases, including metabolic syndrome, diabetes, and fatty liver disease.

Famine exposure

The famine resulted in approximately 30 million premature deaths, and the excess mortality during famine periods was used to reflect the severity of famine exposure.

Due to the radical collectivization movement and inclement climate conditions, almost the entirety of Mainland China suffered from extreme food shortage during 1959-1961. The famine severity was different across provinces due to variation of climate, population density, and policies regarding shortage of foods.

The famine resulted in approximately 30 million premature deaths, and the excess mortality during famine periods was used to reflect the severity of famine exposure.

The provinces with excess mortality ≥ 50% were defined as severe famine affected areas; other provinces were defined as less severely affected areas. For example, the excess mortality of Anhui province was the highest, up to 474.9%; Tianjin province was lowest, at only 14.9%.

The study

In this study, the dyslipidemia prevalence of the non-exposed cohort, fetal stage, infant stage, and preschool stage-exposed cohorts in adulthood were 15.7%, 23.1%, 22.0%, and 18.6%, respectively. Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusting for age.

Early-life exposure to the Chinese famine significantly increased LDL cholesterol concentrations in adulthood after adjusting for age.

The risks of dyslipidemia in fetal and infant stage-exposed cohorts were significantly higher than the non-exposed cohort after adjusting for gender and current family economic status.

However, following gender stratification, we found that fetal, infant, and preschool stage exposure to severe famine aggravated the risk of dyslipidemia only in female adults; a similar association was not observed for male adults.

Gender bias?

We speculated that this gender-specific effect might be associated with the hypothesis that parents in China traditionally prefer boys to girls. In China, male children took precedence over females due to gender bias, and thus they may potentially be sufficiently nourished during the famine.

Additionally, survivor bias may be another reason to interpret the lack of “effect” on males. Prenatal Males were more vulnerable than females to both short and long term effects of famine and die at higher rates. Thus, male survivors could be healthier than female survivors.

Explaining the link

Several mechanisms might explain the link in early-life famine exposure and elevated dyslipidemia risk in later life. Firstly, severe maternal under-nutrition during pregnancy could alter the synthesis of cholesterol, increasing the plasma concentration; this has been shown in animal models.

Secondly, individuals who suffered from severe intrauterine malnutrition are more likely to consume a high-fat diet in adulthood while reducing the level of physical activity, thereby increasing atherogenic lipid profile, as observed by a Dutch famine study. In the present study, we did not explore the correlation between famine exposure and dietary and physical behavior due to lack of relevant data.

Lipid metabolic gene methylation level may play a pivotal role in malnutrition during pregnancy, which renders it sensitive to abnormal lipid metabolism.

Thirdly, lipid metabolic gene methylation level may play a pivotal role in malnutrition during pregnancy, which renders it sensitive to abnormal lipid metabolism. Elmar et al. comprehensively assessed the associations of prenatal malnutrition and differentially methylated regions (P-DMRs) in humans and found that CPTIA was involved in fatty acid oxidation and KLF13 involved in cholesterol metabolism.

The methylation level as one of the principal components of epigenetics, could effectively adjust the expression level of the gene. In addition, epigenetic plasticity may play an important role in the postnatal period and result in “metabolic imprinting” which could be another biological mechanism beneath the association of early life malnutrition with metabolic diseases in adulthood.

Despite China now being food secure, many people are still exposed to food shortages in low-income and middle-income countries. Hence many children are still at short term risk of malnutrition associated mortality and morbidity, but also at long-term risk of adult non-communicable diseases. The heavily short and long-term adverse effects from severe food shortage ask us to implement the urgent interventions to lower their occurrence or improve their consequences.

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