Association of Prenatal Famine Exposure With Inflammatory Markers and Its Impact on Adulthood Liver Function Across Consecutive Generations

Abstract

Although there has been increasing recognition that famine exposure in the fetal stage damages liver function in adulthood, this deteriorated effect could be extended to the next generation remains vague. This study aimed to explore whether famine exposure was associated with liver function in the two consecutive generations, and its association with the mediation role of inflammatory markers. We analyzed the data of 2,681 participants from Suihua rural area, Heilongjiang Province, China. According to the date of birth, the participants were classified as fetal exposed and nonexposed. The F2 subjects were classified as having no parents exposed to famine, maternal famine exposure, paternal famine exposure, or parental famine exposure. In the mixed-effect models, prenatal exposure to famine was associated with the elevation of Δ aspartate aminotransferase (ΔAST) (β: 0.22, 95% CI: 0.01, 0.43) and Δ alanine aminotransferase (ΔALT) (β: 0.42, 95% CI: 0.19, 0.66) levels in F1 adults. The mediation analysis showed that the inflammatory markers including serum C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) might mediate the famine-liver function association. This longitudinal data were consistent with the hypothesis that the inflammatory markers explained part of the influence of prenatal famine exposure on liver function injury, and the natal mechanism was needed to be elucidated in the future study.

Association of Dietary Inflammatory Index and Dietary Oxidative Balance Score with All-Cause and Disease-Specific Mortality: Findings of 2003–2014 National Health and Nutrition Examination Survey

“…To investigate whether inflammatory markers could act as mediators in the relationship between DII/DOBS and mortality, mediation statistical models were constructed with adjustment for the above covariables. The process of designing and developing mediation statistical models has been described elsewhere [ 56 ].…”

The hunger strikes back: an epigenetic memory for autophagy

“…Population-based cohort studies based on participants recruited from the Suihua rural area that was affected by the great Chinese famine that occurred between the spring of 1959 and the end of 1961, may offer better understanding of the effect of maternal under-nutrition during gestation. Indeed, these demographical data revealed that prenatal exposure to starvation was associated with elevated risks of developing hyperglycemia, type 2 diabetes, renal dysfunction, and chronic kidney disease in adulthood across two consecutive generations [ 14 – 17 ]. According to the date of birth, F1 subjects were classified as fetal exposed and nonexposed (where the F0 mothers experience famine during their pregnancies).…”

“…In the F1 parental generation, prenatal exposure to malnutrition was significantly associated with greater risks of having hyperglycemia and type 2 diabetes [ 14 ], as well as of renal dysfunction (as measured by estimated glomerular filtration rate) and chronic kidney disease [ 15 ]. One generation down, in the F2 offspring generation, participants from exposed parents, especially those from both exposed parents, still exhibited an increased risk for hyperglycemia and renal dysfunction during adulthood [ 14 – 17 ]. Additional human cohort also based on the great Chinese famine further revealed that parents experience famine in utero or early in life was associated with decreased of their cognitive function.…”