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

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.

Prenatal famine exposure and adult health outcomes: an epigenetic link

Numerous human chronic pathological conditions depend on epigenetic modifications induced by environmental triggers throughout sensitive stages early in development. Developmental malnutrition is regarded as one of the most important risk factors in these processes. We present an overview of studies that the initiation and progression of many diseases are largely dependent on persisting epigenetic dysregulation caused by environmental insults early in life. For particular disorders, candidate genes were identified that underlie these associations. The current study assessed the most convincing evidence for the epigenetic link between developmental malnutrition and adult-life disease in the human population. These findings were obtained from quasi-experimental studies (so-called ‘natural experiments’), i.e. naturally occurring environmental conditions in which certain subsets of the population have differing levels of exposure to a supposed causal factor. Most of this evidence was derived on the DNA methylation level. We discussed DNA methylation as a key player in epigenetic modifications that can be inherited through multiple cell divisions. In this Perspective article, an overview of the quasi-experimental epidemiological evidence for the role of epigenetic mechanisms in the developmental programming by early-life undernutrition is provided.

222Long-term mortality after early famine exposure: findings from the China Kadoorie Biobank

Background Previous studies suggested that increased risks of chronic diseases in China might be attributable to early experience of the Chinese Great Famine during last century, but the reliable evidence for adult mortality was rare. This study is to investigate the association of early famine exposure with death risks in the middle age. Methods A number of 94 051 participants from China Kadoorie Biobank were categorized as non-famine births (born between 10/1/1956 and 9/30/1958, and 10/1/1962 and 9/30/1964) and famine births (born between 10/1/1959 and 9/30/1961). The outcomes were total and cause specific mortality. Cox regression was used to estimate hazard ratio (HR) for famine exposure. Results During a median 10.2 years of follow-up, we documented 2802 total deaths in all participants. Prenatal famine exposure was only associated with the risks of ischemic heart disease (IHD) mortality in adulthood (310 deaths, HR [95% CI]: 1.34 [1.02, 1.75]), compared with non-famine births. We also observed the association of famine with total mortality (HR [95% CI]: 1.42 [1.12, 1.78]) in daily alcohol drinkers, but not in non-daily drinkers (P for interaction: 0.025). Conclusions This study indicated that early famine exposure was associated with an increased death risk of heart disease and such risk may be modified by adult alcohol consumption. Key messages Early Chinese famine experience might impact adult IHD deaths. Coexistence of early famine experience and adult alcohol consumption was associated with higher risks of total mortality.

Overweight and obesity at age 19 after pre-natal famine exposure

Background Weight for height has been used in the past as an indicator of obesity to report that prenatal exposure to the Dutch famine of 1944–1945 determined subsequent obesity. Further evaluation is needed as unresolved questions remain about the possible impact of social class differences in fertility decline during the famine and because being overweight is now defined by a Body Mass Index (BMI: kg/m2) from 25 to <30 and obesity by a BMI of 30 or more. Methods We studied heights and weights of 371,100 men in the Netherlands born between 1943 and 1947 and examined for military service at age 19. This group includes men with and without prenatal exposure to the Dutch famine. Results There was a 1.3-fold increase in the risk of being overweight or obese in young adults at age 19 after prenatal famine exposure in early gestation. The increase was only seen in sons of manual workers born in the large cities of Western Netherlands and not among those born in smaller cities or rural areas in the West. Social class differentials in fertility decline during the famine did not bias study results. Conclusions The long-term adverse impact of prenatal famine on later life type 2 diabetes and mortality through age 63 is already showing at age 19 in this population as a significant increase in overweight risk.

Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983–85): a historical cohort study

Background The impact of an adverse prenatal environment such as famine exposure on the development of adulthood non-communicable chronic illnesses, including diabetes and hypertension has been well articulated in the recent past and supported by evidence. However, there exist few longitudinal studies conducted on the long term consequences of prenatal famine exposure on adulthood kidney function. Hence, we set out to examine whether prenatal exposure to the Ethiopian Great Famine (1983–1985) was associated with changes in estimated glomerular filtration rate (eGFR) and the risk of developing chronic kidney disease (CKD) later in adult life. Methods The study was conducted in 219 famine exposed and 222 non exposed cohorts in Raya Kobo district, North Wollo Zone, Northern Ethiopia. Estimated GFR was computed from standardized serum creatinine using the CKD Epidemiology Collaboration (CKD-EPI) equation. The definition of CKD includes those with an eGFR of less than 60 ml/min/1.73 m2 on at least in two occasions of 90 days apart (with or without markers of kidney damage). Linear and logistic regression analyses were employed to examine the independent effect of prenatal famine exposure on eGFR and CKD respectively. Results The mean (SD) serum creatinine of exposed and non-exposed groups were 0.78 (0.2) and 0.75 (0.2) respectively. The mean (SD) eGFR of exposed groups was 107.95 (27.49) while the non-exposed 114.48 (24.81) ml/min. In linear regression, the unadjusted model to examine the association between famine exposure and eGFR resulted in a significant negative beta coefficient (β = − 0.124: 95% CI: − 11.43, − 1.64). Adjusting the exposure for outstanding covariates of kidney health, including systolic blood pressure, fasting blood sugar and blood glucose did not alter the inverse relationship (β = −.114 95% CI: − 10.84, − 1.17). In the unadjusted bivariate logistic regression model, famine exposure resulted in nearly 2.7 times higher odds of developing CKD (OR: 2.68, 95% CI: 1.16, 6.2). The odds remained equivalent after adjusting for systolic blood pressure, fasting blood glucose and body mass index (OR = 2.61: 95% CI: 1.120, 6.09). Conclusion In the study setting, prenatal exposure to the Great Ethiopian Famine was associated with decreased eGFR and higher risk of developing CKD among survivors. These findings may imply that famine in early life may play a significant role in the development of kidney dysfunction in adulthood.

Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983-85): a historical cohort study

Background: The impact of an adverse prenatal environment such as famine exposure on the development of adulthood non-communicable chronic illnesses, including diabetes and hypertension has been well articulated in the recent past and supported by evidence. However, there exist few longitudinal studies conducted on the long term consequences of prenatal famine exposure on adulthood kidney function. Hence, we set out to examine whether prenatal exposure to the Ethiopian Great Famine (1983–1985) was associated with changes in estimated glomerular filtration rate (eGFR) and the risk of developing chronic kidney disease (CKD) later in adult life.Methods: The study was conducted in 219 famine exposed and 222 non exposed cohorts in Raya Kobo district, North Wollo Zone, Northern Ethiopia. Estimated GFR was computed from standardized serum creatinine using the CKD Epidemiology Collaboration (CKD-EPI) equation. The definition of CKD includes those with an eGFR of less than 60 ml/min/1.73m2 on at least in two occasions of ninety days apart (with or without markers of kidney damage). Linear and logistic regression analyses were employed to examine the independent effect of prenatal famine exposure on eGFR and CKD respectively.Results: The mean (SD) serum creatinine of exposed and non-exposed groups were 0.78 (0.2) and 0.75 (0.2) respectively. The mean (SD) eGFR of exposed groups was 107.95 (27.49) while the non-exposed 114.48 (24.81) ml/min. In linear regression, the unadjusted model to examine the association between famine exposure and eGFR resulted in a significant negative beta coefficient (β = -0.124: 95% CI: -11.43, -1.64). Adjusting the exposure for outstanding covariates of kidney health, including systolic blood pressure, fasting blood sugar and blood glucose did not alter the inverse relationship (β = -.114 95% CI: -10.84, -1.17). In the unadjusted bivariate logistic regression model, famine exposure resulted in nearly 2.7 times higher odds of developing CKD (OR: 2.68, 95% CI: 1.16, 6.2). The odds remained equivalent after adjusting for systolic blood pressure, fasting blood glucose and body mass index (OR= 2.61: 95% CI: 1.120, 6.09).Conclusion: In the study setting, prenatal exposure to the Great Ethiopian Famine was associated with decreased eGFR and higher risk of developing CKD among survivors. These findings may imply that famine in early life may play a significant role in the development of kidney dysfunction in adulthood.

Consequences of Exposure to Prenatal Famine on Estimated Glomerular Filtration Rate and Risk of Chronic Kidney Disease Among Survivors of the Great Ethiopian Famine (1983-85): A Historical Cohort Study

Background: The impact of an adverse prenatal environment such as famine exposure on development of adulthood non communicable chronic illnesses, including diabetes and hypertension has been well articulated in the recent past and supported by evidence. However, there exist a limited number of longitudinal studies on long term consequences of prenatal famine on adulthood kidney function. Hence, we set out to examine whether prenatal exposure to the Ethiopian Great Famine (1983–1985) was associated with changes in estimated glomerular filtration rate (GFR) and risk of developing chronic kidney disease (CKD) during adulthood.Methods: The study was conducted in 219 famine exposed and 222 non exposed cohorts in Raya Kobo district, North Wollo Zone, Northern Ethiopia. Estimated GFR was computed using the CKD Epidemiology Collaboration (The CKD-EPI) equation. CKD was defined as eGFR= <60 mL/min per 1.73 m2. Linear and logistic regression analyses were employed to examine the independent effect of prenatal famine exposure on eGFR and CKD respectively.Results: The mean (SD) serum creatinine of exposed and non-exposed groups were 0.78 (0.2) and 0.75 (0.2) respectively. The mean (SD) eGFR of exposed groups was 107.95 (27.49) while the non-exposed 114.48 (24.81) ml/min. In linear regression, unadjusted model to examine the association between famine exposure and eGFR resulted in a significant negative beta coefficient (β = -0.124: 95% CI: -11.43, -1.64). Adjusting the exposure for outstanding covariates of kidney health, including systolic blood pressure, fasting blood sugar and blood glucose did not alter the inverse relationship (β = -.114 95% CI:-10.84, -1.17). In binary unadjusted logit model, famine exposure resulted in nearly 2.7 times increased odds of developing CKD (OR: 2.68, 95% CI: 1.16, 6.2). The odds remained equivalent after adjusting for systolic blood pressure, fasting blood glucose and BMI (OR= 2.61: 95% CI: 1.120, 6.09).Conclusion: prenatal exposure to the Great Ethiopian Famine was associated with decreased eGFR and greater risk of CKD among survivors. These findings may imply that famine in early life may play significant role in the development of kidney dysfunction in adulthood.

Effects of prenatal exposure to the 1983–1985 Ethiopian great famine on the metabolic syndrome in adults: a historical cohort study

The Ethiopian great famine was one of the severe forms of global famines ever documented in Africa as well as in the recent history of the world. Earlier famine studies, as natural experiments, had tested the association between prenatal famine exposure and the metabolic syndrome and reported heterogeneous findings. Hence, this study aimed at evaluating the effects of prenatal exposure to the 1983–1985 Ethiopian great famine on the metabolic syndrome in adults. Self-reported birth date and age of the study subjects were used to classify the status of famine exposure. The International Diabetes Federation criterion was used to assess the metabolic syndrome. Multivariable logistic regression models were fitted to examine relationship between prenatal famine exposure and the metabolic syndrome. The findings showed that, adjusted for covariates, adults who had prenatal exposure to famine were 2·94 times more likely to develop the metabolic syndrome compared with non-exposed groups (adjusted OR (AOR) 2·94, 95 % CI 1·66, 5·27). More specifically, famine exposure during prenatal life was associated with increased waist circumference (AOR 2·27 cm, 95 % CI 0·28, 4·26), diastolic blood pressure (AOR 2·47 mmHg, 95 % CI 0·84, 4·11), TAG (AOR 0·20 mmol/l, 95 % CI 0·10, 0·28) and fasting blood glucose (AOR 0·24 mmol/l, 95 % CI 0·04, 0·43) compared with the control groups. Higher proportion of the metabolic syndrome, risky anthropometric and dyslipidaemic parameters were observed among exposed groups. This finding adds further evidence on fetal origin of adult diseases hypothesis. The finding may imply that one potential means of preventing adulthood metabolic syndrome is to optimise maternal nutrition during pregnancy.

Early famine exposure and adult disease risk based on a 10-year prospective study of Chinese adults

ObjectiveTo comprehensively examine the potential impacts of prenatal experience of the Chinese Great Famine on chronic disease risks in the middle age.MethodsThis study included 92 284 participants aged 39–51 years from China Kadoorie Biobank born around the famine period and without major chronic diseases at baseline. We categorised participants into non-famine births (born between 1 October 1956 and 30 September 1958, and 1 October 1962 and 30 September 1964) and famine births (born between 1 October 1959 and 30 September 1961). The outcomes were incident cardiovascular disease, cancer and respiratory system disease. Cox regression was used to estimate adjusted HR and 95% CI for famine exposure. Subgroup analyses were performed according to baseline characteristics.ResultsDuring a median 10.1 years of follow-up, we identified 4626 incident ischaemic heart disease (IHD) cases, 7332 cerebrovascular disease cases, 3111 cancer cases and 16 081 respiratory system disease cases. In the whole population, prenatal famine exposure was not statistically associated with the risks of developing any chronic diseases in adulthood. However, for urban participants, compared with non-famine births, famine births had a higher risk of cerebrovascular disease (HR 1.18; 95% CI 1.09 to 1.28); such association was not shown for rural participants (p for interaction <0.001). Also, we observed the associations of prenatal famine exposure with IHD (HR 1.15; 95% CI 1.05 to 1.26) and cerebrovascular disease (HR 1.13; 95% CI 1.05 to 1.21) in participants with lower physical activity level, but not in those with higher ones (all p for interaction=0.003).ConclusionOur findings indicate that prenatal exposure to the Chinese famine might be associated with an increased cardiovascular risk and such risk may be modified by adult lifestyle.