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Objectives: Early-famine exposure was reported to be associated with metabolic associated fatty liver disease (MAFLD); however, it has not been fully elucidated whether the gene-famine interaction exist in this association. We aimed to investigate the association between early-life famine exposure in different genetic risk stratifications and the risk of MAFLD in adulthood., Design, Setting, Participants, and Measurements: The study included 8213 participants from the SPECT-China study. Famine exposure subgroups was defined according to the birth year. A genetic risk score (GRS) was constructed with single nucleotide polymorphisms associated with MAFLD in East Asians. Logistic models were used to examine the association of famine exposure and GRS with MAFLD., Results: Early-life famine exposure was positively associated with MAFLD after adjusting for multiple confounders (OR (95% CI): fetal-exposure 1.3(1.11-1.53), childhood exposure 1.12(1-1.25)). Meanwhile, with per SD increment of GRS (2.49 points), the OR(95%CI) of MAFLD was 1.1(1.04-1.16). In high GRS group, fetal-exposure was positively associated with 45% higher risk of MAFLD (1.45(1.15-1.83)). In men, neither in low or high GRS subgroups observed an association between early-life famine exposure and MAFLD. But in women with high GRS of MAFLD, fetal-exposure was positively associated with even higher risk of MAFLD (1.64(1.22-2.22))., Conclusion: The positive association between early-life famine exposure and MAFLD is intensified by high genetic susceptibility of MAFLD in women and in general population in China; while this association does not exist in men or in those with low genetic risk scores., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Previous studies had reported the association between famine exposure in early life and subsequent non-communicable diseases risk. In current study, we aimed to evaluate the associations between famine exposure on multimorbidity prevalence and incidence in middle-aged and older Chinese population., Methods: A total of 13,254 participants from the China Health and Retirement Longitudinal Study 2011 were included in cross-sectional analyses. 5,780 participants were including in longitudinal analyses and were followed up in 2020. Based on the questionnaire, participants were divided into non-exposed, mild famine, moderate famine and severe famine subgroups., Results: In cross-sectional analyses, both mild, moderate and severe famine groups were significantly associated with higher multimorbidity prevalence. During the 9 years of follow-up, a total of 2,643(45.73%) participants with multimorbidity incident were identified. After adjusting for all covariates, individuals who experienced mild famine, moderate famine and severe famine were significantly associated with increased risk of multimorbidity incident, with the corresponding ORs (95%CI) being 1.32(1.14-1.52), 1.54(1.21-1.96) and 1.62(1.32-1.99), respectively., Discussion: Our findings indicate that famine exposure in mild, moderate and severe famine groups might be associated with an increased multimorbidity risk., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: All authors declare no conflict of interest. Ethical approval: The ethics application for collecting data on human subjects in CHARLS was approved by the Biomedical Ethics Review Committee of Peking University (IRB00001052-11015), and all CHARLS participants provided written informed consent. Clinical trial number: Not applicable., (© 2025. The Author(s).)

Background: People who have experienced the Chinese Great Famine (1959-1961) in their fetal period are getting old. It is particularly important for China's response to the ageing of this cohort to study the impact of the Holodomor on disability., Method: This paper presents an empirical analysis that utilizes the survey data from the 2018 China Health and Retirement Longitudinal Study (CHARLS), employing a cohort Difference-in-Differences (DID) modeling approach. It integrates the excess mortality rate (EDR) from China's Great Famine with the 2018 CHARLS survey data, selecting suitable control and experimental groups for a comprehensive study. The empirical analysis is conducted using the cohort DID model, comprising a total of 11,567 samples., Results: This study found that the experience of famine would increase the level of disability in the population, with each 0.1% increase in excess mortality increasing the level of IADL by approximately 0.019. This experience during the fetal period will increase the incidence of handicaps, mainly in the brain and hearing. This thesis finds strong heterogeneity across gender and between urban and rural areas., Conclusions: China's long-term care capacity should be improved, with attention paid to the rural disabled population and to the health of pregnant women and fetuses., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. This study used publicly available data and did not require ethical approval and consent to participate. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Over the past few decades, China has experienced significant demographic and epidemiological changes. The sharp decline in fertility and mortality rates has accelerated population aging, contributing to an increase in the prevalence of chronic diseases. The nutritional condition during early life is associated with the onset of chronic illnesses later in adulthood. However, it remains unclear whether this association also increases the risk of multimorbidity in later adulthood., Objectives: This study aimed to systematically evaluate the association between early-life famine exposure and the subsequent development of 14 chronic diseases, as well as multimorbidity, and whether there exists a discrepancy in gender, residence, and famine severity., Methods: Data are from the 2018 Wave 4 CHARLS database, a national survey covering 19,816 participants aged 45 years or older. Drawing from our past research on famine in China, we incorporated 3,867 participants, categorizing them into three groups based on their birth years. Considering that climate conditions and population density can influence the intensity of famine, we characterize its severity by establishing a threshold of 50% excess death rate. The 14 chronic diseases assessed by CHARLS were used as the main outcome indicator, with multimorbidity as a secondary outcome indicator. We conducted a stepwise logistic regression analysis to investigate the impact of exposure to famine in early life affects the development of chronic diseases in adulthood, presenting the findings as ORs and 95% CIs. Additionally, we assess multiple moderating factors such as gender, residence, and famine severity to evaluate the outcomes., Results: Of the 3,867 participants included, the prevalence of each chronic disease ranged from 1.1% (Psychiatric disease) to 10.7% (Hypertension). Overall, 27.0% of participants reported being affected by at least one chronic disease, while 9.6% indicated they had suffered from two or more chronic conditions. Early-life exposure to famine makes it more likely to develop diabetes in later adulthood OR (95% CI) of 1.85 (1.26 to2.72), stroke OR (95% CI) of 1.96 (1.17 to 3.29), kidney disease OR (95% CI) of 1.91 (1.07 to 3.40), and multimorbidity OR (95% CI) of 1.39 (1.08 to 1.80), compared to those who did not face such conditions. The moderating effects analysis revealed that less severe famine exposure during toddlerhood was associated with an increased risk of multimorbidity in adulthood OR (95% CI) of 1.43 (1.01 to 2.03). Males exposed to famine during toddlerhood had a higher risk of multimorbidity in adulthood OR (95% CI) of 2.26 (1.29 to 3.98). Compared to the unexposed group, rural residents who experienced famine exposure in their early life are at a higher risk of developing multimorbidity by about 1.5 times in adulthood., Conclusion: Experiencing famine in early childhood increases susceptibility to developing chronic diseases in later adulthood, with the risk of diabetes, stroke, and kidney disease nearly doubling. The association of multimorbidity in later adulthood varies according to the severity of the famine, gender, and residential area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhao, Zheng and Chen.)

Objectives: Chronic kidney disease (CKD) significantly contributes to the socio-economic burden both in China and worldwide. Previous research has shown that experiencing childhood famine is linked to various chronic conditions like diabetes, hypertension, and proteinuria. However, the long-term effects of early-life famine exposure on adult kidney function remain unclear. This study investigates whether exposure to the Chinese Great Famine (1959-1962) is associated with a decline in glomerular filtration rate (GFR) later in life., Design and Methods: China Health and Retirement Longitudinal Study is a population-based observational study. We analyzed data from 8,828 participants in the 2011-2012 baseline survey, updated in 2014. Participants were categorized based on their birth year into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/adult-exposed (1912-1948), and nonexposed (1963-1989) groups. The estimated GFR (eGFR) was calculated using the CKD-EPI-Cr-Cys equation (2021), with CKD defined as an eGFR below 60 mL/min/1.73 m 2 ., Results: Average eGFR values were 103.0, 96.8, 91.2, and 76.3 mL/min/1.73 m 2 for the fetal-exposed, childhood-exposed, adolescence/adult-exposed, and nonexposed groups, respectively. The eGFR in the exposed groups was significantly lower compared to the nonexposed group. Specifically, famine exposure correlated with a lower eGFR (coefficient estimates [CE] -9.14, 95% confidence interval [CI] -9.46, -8.82), with the strongest association observed in the adolescence/adult-exposed group (CE -26.74, 95% CI -27.75, -25.74). Adjusting for variables such as demographics, physical and laboratory tests, complications, and personal habits like smoking and drinking did not qualitatively alter this association (CE -1.38, 95% CI -1.72, -1.04). Further stratification by sex, body mass index, alcohol consumption history, hypertension, diabetes, Center for Epidemiologic Studies Depression score, and education level showed that the association remained consistent., Conclusions: Exposure to famine during different life stages can have enduring effects on GFR decline in humans., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Early-life exposure to famine has been hypothesized to influence long-term bone health, potentially increasing the risk of osteoporosis and fractures in later life. This systematic review and meta-analysis aimed to investigate the association between early-life famine exposure and the risk of osteoporosis, bone mineral density (BMD) loss, and fractures., Methods: A comprehensive literature search was conducted across MEDLINE/PubMed, Scopus, Web of Science, and Embase, supplemented by manual searches on Google Scholar. Observational studies examining the impact of early-life famine exposure on osteoporosis, BMD, and fracture risk were included. Data were extracted and quality assessed independently by two reviewers, and meta-analyses were performed using the Mantel-Haenszel method for odds ratios (OR) and Hedges' g for standardized mean differences (SMD). Heterogeneity was assessed using the I 2 statistic, and meta-regression analyses were conducted to explore potential sources of heterogeneity., Results: From 6147 initial studies, 10 met the inclusion criteria, with 8 included in the meta-analysis. The early-life famine-exposed group showed a significantly higher incidence of osteoporosis (OR = 2.12, 95%CI [1.35, 3.34], I 2  = 88%) and fractures (OR = 1.58, 95%CI [1.07, 2.33], I 2  = 92%) compared to non-exposed individuals. Meta-regression indicated that higher female prevalence in studies made the association with osteoporosis stronger, while higher ages strengthened the association with fractures. Exposure during fetal and childhood stages was particularly associated with increased risks of osteoporosis and fractures. Additionally, famine exposure correlated with lower BMD, particularly in the heels, femoral neck, and total hip regions., Conclusion: Early-life famine exposure is significantly associated with an increased risk of osteoporosis, fractures, and lower BMD in later life. These results emphasize the lasting effects on bones from early lack of nutrition and stress the importance of specific interventions for bone health in groups with past famine experiences. Future studies should investigate the reasons behind these connections and assess preventative approaches to reduce the negative effects on bone health in those impacted., Competing Interests: Declarations. Ethical statement: Not applicable. Consent for publication: Not applicable. Conflicts of interest: None. PROSPERO: CRD42024532153., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: Age-related cataract (ARC) is among the most common blinding eye disorders among the elderly. Prenatal nutrition may cause irreversible damage to the development of the ocular crystalline lens. Nevertheless, the potential association between prenatal malnutrition and age-related cataract has not been thoroughly examined. We investigated the prevalence of cataract at the age of 60 after prenatal exposure to Chinese famine (1959-1961) and particularly evaluated whether there was a disparity in this effect between men and women., Methods: We utilized the health examination medical record system of a large-scale comprehensive hospital to screen individuals born in Chongqing, China and undergoing eye health examinations. Participants were categorized based on their year of birth into the famine-exposed group (1960) and the non-exposed group (1963), with their medical records at age 60 extracted from the database. Univariate and multivariate logistic regression analyses were conducted to investigate the association between famine exposure and the risk of developing ARC by age 60., Results: The prevalence of ARC was significantly higher in the famine-exposed group (60.26%) compared to the non-exposed group (47.90%) (P < 0.001). After adjusting for diabetes history, body mass index (BMI), fasting blood glucose (FBG) level, and high-density lipoprotein (HDL) level using multivariate logistic regression analysis, the risk of ARC remained significantly higher in the famine-exposed group (OR:1.63; 95%CI:1.31-2.03). Subgroup analysis by sex indicated that women exposed to famine (OR: 1.77; 95% CI: 1.25-2.52) exhibited a higher risk of ARC compared to men (OR: 1.53; 95% CI: 1.16-2.03)., Conclusions: Prenatal exposure to famine might increase the risk of ARC among Chinese adults at age 60, and women exhibit a higher susceptibility than men., Competing Interests: Declarations. Ethics approval and consent to participate: The Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University has granted approval for this study, and the study protocol and accompanying materials adhere to both medical ethics principles and the requirements outlined in the Declaration of Helsinki. Prior to commencement, participants were provided with a detailed explanation of the study’s purpose and gave their informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This paper investigates the long-run effect of early-life exposure to famine on survivors' dietary behavior. By exploiting exogenous variations in local severity of the Great Chinese Famine and variations of different cohorts, we conduct a difference-in-differences analysis. Based on detailed three-day food intake records from the China Health and Nutrition Survey, we find that famine exposure led the famine cohort who was conceived or born during the famine to adopt healthier dietary behaviors, as evidenced by a higher healthy eating score and a healthier dietary composition. Additionally, the pre-famine cohort exposed to the famine at ages 9-12 in late childhood exhibited a healthier food composition, characterized by a higher share of aquatic products. However, no statistically significant effects were observed for the pre-famine cohorts that experienced the famine in early and middle childhood. The results remain robust across various sensitivity checks. We propose that early-life famine exposure influences dietary behavior through mechanisms such as awareness of healthy eating, diet knowledge and risk aversion., Competing Interests: Conflict of Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The Great Famine in China from 1959 to 1961 is recognized as one of the most severe social and public health disasters of the 20th century, with profound long-term impacts on the health of survivors, particularly on their mental health. Early-life malnutrition and psychological trauma are considered to contribute to a range of health issues in adulthood, including depression., Objective: This study aims to explore how the experience of the Chinese Great Famine from 1959 to 1961 affects the risk of depressive symptoms among the elderly. Using a mechanism analysis, the study investigates the roles of social support, socioeconomic status, and intergenerational support in this process., Methods: Using micro-level individual data from the China Health and Retirement Longitudinal Survey (CHARLS), combined with province-level excess mortality data, this study employs a cohort-based difference-in-differences model to identify the causal effects of the famine experience on depression levels among the elderly., Results: The study reveals that experiencing the Great Famine significantly increases the risk of depression among the elderly. This effect is more pronounced among rural residents, those who experienced the famine during adolescence, and in regions less influenced by Confucian culture. The mechanism analysis indicates that diminished social support, lower socioeconomic status, and insufficient intergenerational support are the primary pathways through which the famine experience influences depression levels in the elderly., Conclusions: The experience of the Great Famine has exerted a long-term and profound impact on the mental health of the elderly in China, particularly in terms of depression. The findings provide new perspectives on understanding the long-term effects of major historical events on health and offer important empirical evidence for the development of mental health intervention policies for the elderly., (© 2024. The Author(s).)

Precise estimates of the impact of famine on infant and child mortality are rare due to lack of representative data. Using vital statistics reports on the Netherlands for 1935-47, we examine the impact of the Dutch famine (November 1944 to May 1945) on age-specific mortality risk and cause of death in four age groups (stillbirths, <1 year, 1-4, 5-14) in the three largest famine-affected cities and the remainder of the country. Mortality during the famine is compared with the pre-war period January 1935 to April 1940, the war period May 1940 to October 1944, and the post-war period June 1945 to December 1947. The famine's impact was most visible in infants because of the combined effects of a high absolute death rate and a threefold increase in proportional mortality, mostly from gastrointestinal conditions. These factors make infant mortality the most sensitive indicator of famine severity in this setting and a candidate marker for comparative use in future studies.

Background: In this study, we aimed to assess the associations between early exposure to famine and the risks of diabetic complications in adult patients with type two diabetes., Methods: The participants in this study were selected from China National HbA1c Surveillance System (2009-13) and further stratified according to the birth year. The participants born between 1956-59, 1959-61, and 1962-64 were classified as foetal exposed group with 70 852, infant/toddler exposed group with 93 616, and unexposed group with 72 723 participants. The association between exposure to famine in early life and risks of diabetic complications were analysed by logistic regression. We assessed the attributing effects of the interaction between exposure to famine in early life and modifiable risk factors by the multiplicative and additive interactive models., Results: After adjustments for sex, famine severity, economic status in adulthood, body mass index, blood pressure, low-density lipoprotein cholesterol, glycated haemoglobin, diabetes duration, and the use of antidiabetic agents, the increased risks of coronary heart disease (odds ratio (OR) = 1.31; 95% CI (confidence interval) = 1.26, 1.36), cerebrovascular disease (OR = 1.32; 95% CI = 1.24, 1.41), and diabetic retinopathy (OR = 1.06; 95% CI = 1.02, 1.10) were observed in patients with early-life exposure to famine. The reduced risk of diabetic kidney disease (OR = 0.94; 95% CI = 0.90, 0.99) was observed in patients with early-life exposure to famine compared with those without famine exposure. The interaction analyses indicated that obesity might exacerbate the increased risk of coronary heart disease (OR = 1.26; 95% CI = 1.22, 1.30), cerebrovascular disease (OR = 1.26; 95% CI = 1.21, 1.32), and diabetic retinopathy associated with early-life exposure to famine (OR = 1.09; 95% CI = 1.06, 1.12) in patients with type two diabetes. Moreover, high economic status in adulthood might also exacerbate the increased risk of coronary heart disease (OR = 1.35; 95% CI = 1.30, 1.40) and cerebrovascular disease (OR = 1.33; 95% CI = 1.23, 1.43) associated with early-life exposure to famine in patients with type two diabetes., Conclusions: Early-life exposure to famine in patients with type two diabetes might be associated with increased risks of coronary heart disease, cerebrovascular disease, and diabetic retinopathy but a reduced risk of diabetic kidney disease in adulthood. Obesity and high economic status might further exacerbate the risk of diabetic complications associated with early-life exposure to famine. Improving early-life nutritional status may promote better risk prevention and management of diabetic complications in patients with type two diabetes., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and declare the following activities and relationships: Linong Ji has received fees for lecture presentations and for consulting from AstraZeneca, Merck, Metabasis, MSD, Novartis, Eli Lilly, Roche, Sanofi-Aventis and Takeda. No other support from any organisation for the submitted work other than that described above., (Copyright © 2024 by the Journal of Global Health. All rights reserved.)

The short-term impact of famines on death and disease is well documented, but estimating their potential long-term impact is difficult. We used the setting of the man-made Ukrainian Holodomor famine of 1932-1933 to examine the relation between prenatal famine and adult type 2 diabetes mellitus (T2DM). This ecological study included 128,225 T2DM cases diagnosed from 2000 to 2008 among 10,186,016 male and female Ukrainians born from 1930 to 1938. Individuals who were born in the first half-year of 1934, and hence exposed in early gestation to the mid-1933 peak famine period, had a greater than twofold likelihood of T2DM compared with that of unexposed controls. There was a dose-response relationship between severity of famine exposure and increase in adult T2DM risk.

Malnutrition early in life may have adverse effects on health later in life. The relationship between malnutrition and obesity parameters (body mass index [BMI] and waist circumference [WC]) and type 2 diabetes is inconsistent. This study aimed to identify the effects of famine exposure and obesity parameters on type 2 diabetes individually or in combination among middle-aged and older adults in China. Data were extracted from the China Health and Retirement Longitudinal Study Wave1 in 2011. The sample involved 13,065 adults aged 45 to 90. The t- or F test was employed to compare age among groups. The chi-square test was utilized to compare baseline characteristics according to the categorical WC levels/BMI levels/famine exposure and examine between-group differences in type 2 diabetes (diabetes and non-diabetes). Odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression models to estimate the individual and combined associations of BMI/WC levels and famine exposure with the prevalence of type 2 diabetes. In this study, 1559 (11.93%) individuals were exposed to Chinese famine during their fetal stage, 5132 (39.28%) and 4428 (33.89%) in childhood and adolescence/adulthood, respectively. Among BMI measurements, 3780 (28.93%) were overweight, and 1487 (11.38%) were obese, whereas WC measurements showed that 5408 (41.39%) were obesity. In addition, 831 (45.48%) males and 996 (54.52%) females reported type 2 diabetes. In multivariable-adjusted regression models, obesity parameters and famine exposure were independently associated with type 2 diabetes prevalence among all participants (P < .001). In the interaction analysis, there existed a trend of higher odds for prevalence of type 2 diabetes across all groups compared to the combination of no-exposed and normal BMI/WC level group (the most increase in odds, adolescence/adulthood-exposed group with central obesity in WC levels: OR 4.51 (95% CI = 3.42-5.95); adolescence/adulthood-exposed group with obesity in BMI levels: OR 5.84 (95% CI = 4.11-8.30; P for interaction <.001). The findings for females exhibited similar to the overall participants, when by gender stratification. Our results suggest famine exposure and obesity parameters have positive combined effects on type 2 diabetes in middle-aged and older adults in China., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The paper investigates whether exposure to a famine in the Russian Tsarist Province of Livland in 1844-1846 in early life negatively affected survival at later ages, using individual data from two rural parishes. We follow 18 birth cohorts born between 1834-1852 until age 75 and differentiate between timing and length of exposures. We find that relative to individuals born in pre- or post- crisis years, there were no significant differences in survival from age 21-75. Cohorts with longer exposure to famine conditions had increased mortality only in short term, up to age 20. Males were more vulnerable in younger ages than females. The negative effect of adverse early life exposure on survival in later life was constrained to lower social group - the landless, but for the better-off groups the effect was constrained to younger ages. The paper highlights the importance of accounting for sex and socio-economic differences in studies exploring the effects of early life conditions on later-life survival., Competing Interests: Conflict of Interest The authors report there are no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Although evidence from birth cohort analysis has indicated the metabolic risk of early-life exposure to the Great Leap Forward Famine (GLFF) in China, three confounding effects, including the exposure windows, aging, and geographical variations in famine severity, have been brought to debates for a decade. This study aimed to address these confounding effects and extensively examine how GLFF exposure is associated with diabetes risk in mid-to-late life and its interaction with urban-rural migration., Methods: Data from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed with age-stratification and stepped wedge approaches. Weighted prevalence and multivariable logistic regression were used to investigate the effects of GLFF exposure and urban-rural migration on mid-to-late life diabetes risk and the interaction between GLFF exposure and urban-rural migration. Birth provinces were controlled as a fixed effect to account for variations in famine severity across provinces., Results: Compared to those who were never exposed to GLFF, fetal GLFF exposure was associated with a higher risk of adult-onset diabetes after controlling for provinces, demographics, and health statuses. Yet, after adding the proxy of childhood growth environments into the model, fetal exposure to GLFF was not significantly associated with adult-onset diabetes risk (OR = 1.22, p = 0.10), compared to those who were never exposed to GLFF. Across the three age-stratification groups, static urban residents, in general, had a higher risk of diabetes compared to static rural residents. Interaction effects between GLFF exposure and urban-rural migration were insignificant across all three age-stratification groups., Conclusion: Fetal exposure to GLFF might have a traceable effect on adult-onset diabetes risk. Yet, the growth environment and urban lifestyle outweigh and further confound the impact of GLFF exposure on adult-onset diabetes risk., (© 2024. The Author(s).)

This paper investigates health impacts at the end of adolescence of prenatal exposure to multiple shocks, by exploiting the unique natural experiment of the Dutch Hunger Winter. At the end of World War II, a famine occurred abruptly in the Western Netherlands (November 1944-May 1945), pushing the previously and subsequently well-nourished Dutch population to the brink of starvation. We link high-quality military recruits data with objective health measurements for the cohorts born in the years surrounding WWII with newly digitised historical records on calories and nutrient composition of the war rations, daily temperature, and warfare deaths. Using difference-in-differences and triple differences research designs, we first show that the cohorts exposed to the Dutch Hunger Winter since early gestation have a higher Body Mass Index and an increased probability of being obese at age 18. We then find that this effect is partly moderated by warfare exposure and a reduction in energy-adjusted protein intake. Lastly, we account for selective mortality using a copula-based approach and newly-digitised data on survival rates, and find evidence of both selection and scarring effects. These results emphasise the complexity of the mechanisms at play in studying the consequences of early conditions., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In European and many African, Middle Eastern and southern Asian populations, lactase persistence (LP) is the most strongly selected monogenic trait to have evolved over the past 10,000 years 1 . Although the selection of LP and the consumption of prehistoric milk must be linked, considerable uncertainty remains concerning their spatiotemporal configuration and specific interactions 2,3 . Here we provide detailed distributions of milk exploitation across Europe over the past 9,000 years using around 7,000 pottery fat residues from more than 550 archaeological sites. European milk use was widespread from the Neolithic period onwards but varied spatially and temporally in intensity. Notably, LP selection varying with levels of prehistoric milk exploitation is no better at explaining LP allele frequency trajectories than uniform selection since the Neolithic period. In the UK Biobank 4,5 cohort of 500,000 contemporary Europeans, LP genotype was only weakly associated with milk consumption and did not show consistent associations with improved fitness or health indicators. This suggests that other reasons for the beneficial effects of LP should be considered for its rapid frequency increase. We propose that lactase non-persistent individuals consumed milk when it became available but, under conditions of famine and/or increased pathogen exposure, this was disadvantageous, driving LP selection in prehistoric Europe. Comparison of model likelihoods indicates that population fluctuations, settlement density and wild animal exploitation-proxies for these drivers-provide better explanations of LP selection than the extent of milk exploitation. These findings offer new perspectives on prehistoric milk exploitation and LP evolution., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long-term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR)., Methods: We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932-1933) and the WWII (1941-1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942-1945., Results: During the Holodomor and WWII, perinatal famine was associated with a 1.76-fold (p = 0.019) and 3.02-fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66-fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (p additive interaction  < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05)., Conclusion: In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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/m 2 ) 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., (© 2021. The Author(s).)

Intrauterine malnutrition has a long-term effect on human health. This study aimed to evaluate the associations between exposure to famine in early life and obesity in adulthood in Chinese adults. A total of 5033 participants (22,132 observations) of the China Health and Nutrition Survey (CHNS) in 1991-2015 were classified into three famine exposure groups according to their birth year: unexposed (1963-1966), fetal-exposed (1959-1962) and childhood-exposed (1955-1958). Compared with the unexposed group, the fetal-exposed group had higher levels of body-mass-index (BMI) and waist-circumference (WC), and higher prevalence of overweight and central obesity, whereas the childhood-exposed group had lower levels of the measurements. However, the positive associations of fetal exposure with BMI, WC and prevalence of overweight and central obesity were attenuated by additionally adjusting for age at survey. Stratified analysis showed that the adverse effect of fetal exposure to famine was only observed in subjects at several specific age-groups, and in men living in rural areas and in women living in more severe famine exposed areas ( p for interaction < 0.05). Our results provide evidence for the weak effect of fetal exposure to famine on body measurements in adulthood, and suggest the importance of severity of famine exposure and timing of exposure.

The relationship between famine and migration has not been studied adequately to date. A systematic review of scholarship centred on famine and its demographic, political, and socioeconomic effects demonstrates the paucity of academic attention to the issue. This paper surveys the dominant hypotheses and findings regarding the connection between famine and migration. It delineates key questions that an interdisciplinary and case-based exploration of the subject should address, highlighting gaps in the literature with respect to population-level analyses. Primary observations about the literature reviewed include tenuous generalisations about the linkage between famine and migration and partial examination of the role of politics in enabling or prohibiting mobility during hunger-related crises. In addition, disciplinary silos influence which particular aspects of a famine are scrutinised and which are not appraised. In view of these concerns, international legal and humanitarian norms governing migration also need to pay closer attention to its association with famine., (© 2019 The Author Disasters © 2019 Overseas Development Institute.)

Objectives: This study aimed to examine the association between early life famine exposure and adulthood cardiovascular diseases (CVDs) risk. Methods: A total of 5,504 subjects were selected using their birthdate from national baseline data of the China Health and Retirement Longitudinal Survey to analyze the association between famine exposure in early life and CVDs risk in adulthood. CVDs was defined based on the self-reported doctor's diagnosis. Results: The prevalence of CVDs in the unexposed group, fetal-exposed, infant-exposed, and preschool-exposed groups was 15.0%, 18.0%, 21.0%, and 18.3%, respectively. Compared with the unexposed group, fetal-exposed, infant-exposed and preschool-exposed groups had higher CVDs risk in adulthood ( p < 0.05). Compared with the age-matched control group, infancy exposed to famine had a significantly higher adulthood CVDs risk (OR = 1.52, 95% CI: 1.15, 2.01; p = 0.006). The association seems to be stronger among population with higher education level ( P interaction = 0.043). Sensitivity analysis revealed consistent association between early-life famine exposure and adult CVDs risk. Conclusion: Early life exposed to the China great famine may elevate the risk of CVDs in adulthood., Competing Interests: The authors declared that they had no competing interests., (Copyright © 2021 Wang, Dong, Xu, Wang, Li and Zou.)

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.

Objective: We aim to investigate the impact of ideal cardiovascular health metrics (ICVHMs) on the association between famine exposure and adulthood diabetes risk., Research Design and Methods: This study included 77,925 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study who were born around the time of the Chinese Great Famine and free of diabetes at baseline. They were divided into three famine exposure groups according to the birth year, including nonexposed (1963-1974), fetal exposed (1959-1962), and childhood exposed (1949-1958). Relative risk regression was used to examine the associations between famine exposure and ICVHMs on diabetes., Results: During a mean follow-up of 3.6 years, the cumulative incidence of diabetes was 4.2%, 6.0%, and 7.5% in nonexposed, fetal-exposed, and childhood-exposed participants, respectively. Compared with nonexposed participants, fetal-exposed but not childhood-exposed participants had increased risks of diabetes, with multivariable-adjusted risk ratios (RRs) (95% CIs) of 1.17 (1.05-1.31) and 1.12 (0.96-1.30), respectively. Increased diabetes risks were observed in fetal-exposed individuals with nonideal dietary habits, nonideal physical activity, BMI ≥24.0 kg/m 2 , or blood pressure ≥120/80 mmHg, whereas significant interaction was detected only in BMI strata ( P for interaction = 0.0018). Significant interactions have been detected between number of ICVHMs and famine exposure on the risk of diabetes ( P for interaction = 0.0005). The increased risk was observed in fetal-exposed participants with one or fewer ICVHMs (RR 1.59 [95% CI 1.24-2.04]), but not in those with two or more ICVHMs., Conclusions: The increased risk of diabetes associated with famine exposure appears to be modified by the presence of ICVHMs., (© 2020 by the American Diabetes Association.)

Objectives: Famine exposure in early life was associated with type 2 diabetes, non-alcoholic fatty liver disease and metabolic syndrome, etc. But evidence in early famine exposure and insulin resistance and beta cell dysfunction were limited. We aimed to investigate whether the association existed between famine exposure in early life and beta cell dysfunction and insulin resistance in adulthood., Methods: In all, 7912 non-diabetic participants were included in this study, based on SPECT-China study. Participants with fetal or childhood famine exposure (birth year 1949-1962) were exposure group. Insulin resistance was estimated by the homeostasis model assessment index of insulin resistance (HOMA-IR). Beta cell function, represented by insulin secretion, was estimated by the disposition index. The associations of famine exposure with HOMA-IR and disposition index were assessed via linear regression., Results: In men, we did not observe a significant association between early life famine exposure and ln(HOMA-IR) in all three models (P > 0.05 for all). However, in women, early life famine exposure were found to have significant association with ln(HOMA-IR) after adjustments for urbanization, severity of famine exposure, current smoker, waist circumference, hypertension, and dyslipidemia (unstandardized coefficients 0.055, 95% confidence interval 0.021, 0.088, P = 0.001). Early life famine exposure was observed to be negatively associated with ln(disposition index) after adjustments for the above potential confounders, both in men (model 3: unstandardized coefficients -0.042, 95% confidence interval -0.072,-0.012, P = 0.006) and women (model 3: unstandardized coefficients -0.033, 95% confidence interval -0.058,-0.009, P = 0.008)., Conclusions: In conclusion, exposure to famine in fetal- and childhood- life period is associated with beta cell dysfunction in males and females without diabetes, but early life famine exposure was only associated with insulin resistance in non-diabetic females. These results indicate that malnutrition in early life period may offer a modifiable factor for type 2 diabetes development.

Objective: To investigate whether in utero exposure to the Great Chinese Famine in 1959 to 1961 was associated with risk of intracerebral hemorrhage (ICH) in adulthood., Methods: In this cohort analysis, we included 97,399 participants of the Kailuan Study who were free of cardiovascular disease and cancer at baseline (2006). Cases of incident ICH were confirmed by medical record review. We used the Cox proportional hazards model to calculate the hazard ratio (HR) and 95% confidence interval (CI) for ICH according to in utero famine exposure status., Results: Among 97,399 participants in the current analyses, 6.3% (n = 6,160) had been prenatally exposed to the Great Chinese Famine. During a median 9.0 years of follow-up (2006-2015), we identified 724 cases of incident ICH. After adjustment for potential confounders, the HR of ICH was 1.99 (95% CI 1.39-2.85) for in utero famine-exposed individuals vs individuals who were not exposed to the famine. When exposure to famine and severity of famine were examined jointly, the adjusted HR was 2.99 (95% CI 1.21-7.39) for in utero exposure to severe famine and 1.94 (95% CI 1.32-2.84) for in utero exposure to less severe famine relative to those without exposure to famine., Conclusions: Individuals with in utero exposure to famine, especially those exposed to severe famine, were more likely to have ICH in midlife, highlighting the role of nutritional factors in susceptibility to this severe cerebral condition., (© 2020 American Academy of Neurology.)

Objective: The aim of this study was to investigate the differences in six anthropometric measurements of people born during and immediately after the 1959 to 1961 Great Chinese Famine using a regression discontinuity approach., Methods: Data were drawn from the baseline of the China Kadoorie Biobank study, and a subset of data from 76,912 participants was analyzed. We performed regression discontinuity among participants who were born during the famine (October 1959 to October 1962) and immediately after the famine period (November 1962 to October 1964) by using local linear and parametric regressions. All analyses were conducted by sex and study area., Results: Significantly, there were increases of 0.30 kg/m 2 (P = 0.007) in BMI, 0.81 kg (P = 0.028) in weight, 8.57 mm (P = 0.004) in waist circumference, and 5.07 mm (P = 0.004) in hip circumference for rural women who were exposed to famine during their fetal period compared with those who were not exposed to famine in utero. However, such statistically significant increases in anthropometric values were not observed in local linear regression and most parametric models among rural men or in the urban population., Conclusions: Rural Chinese women who were exposed to famine during the fetal period were observed to have higher levels of BMI, weight, waist circumference, and hip circumference in adulthood., (© 2020 The Obesity Society.)

A systematic review and meta-analysis of observational studies was performed to provide a deeper understanding of the associations between foetal and childhood exposure to famine and the risks of type 2 diabetes mellitus (T2DM), metabolic syndrome, hypertension, hyperglycaemia, dyslipidaemia, obesity, overweight, coronary heart disease, stroke, and nonalcoholic fatty liver disease (NAFLD) in adulthood. Both foetal and childhood exposure to famine were positively associated with the risks of T2DM (foetal exposure: RR 1.37, 95% CI, 1.23-1.52; childhood exposure: RR 1.33, 95% CI, 1.08-1.64), metabolic syndrome (RR 1.26, 95% CI, 1.07-1.50; RR 1.24, 95% CI, 1.13-1.35), hypertension (RR 1.30, 95% CI, 1.07-1.57; RR 1.33, 95% CI, 1.02-1.74), hyperglycaemia (RR 1.27, 95% CI, 1.11-1.45; RR 1.25, 95% CI, 1.10-1.42), dyslipidaemia (RR 1.48, 95% CI, 1.33-1.66; RR 1.27, 95% CI, 1.12-1.45), obesity (RR 1.19, 95% CI, 1.02-1.39; RR 1.13, 95% CI, 1.00-1.28), overweight (RR 1.17, 95% CI, 1.07-1.29; RR 1.07, 95% CI, 1.00-1.14), coronary heart disease (RR 1.22, 95% CI, 1.00-1.51; RR 1.21, 95% CI, 1.09-1.35), and moderate-to-severe NAFLD (RR 1.66, 95% CI, 1.07-2.57; RR 1.68, 95% CI, 1.41-1.99) in adulthood. No association was observed for the risks of stroke or mild NAFLD. Adjustments for age, alcohol, smoking, body mass index, and physical activity nullified some associations. The associations were generally stronger in women than in men. In summary, foetal and childhood exposure to famine may confer greater risks of developing certain cardiometabolic conditions in adulthood, particularly in women. The extent to which risks for cardiometabolic conditions are associated with early-life famine appears to be determined by certain factors in adulthood., (© 2020 World Obesity Federation.)

Schizophrenia (SCZ) is a complex, frequently disabling psychiatric disorder. Prenatal exposure to famine, an environmental factor, plays a significant role in the cause of SCZ. We used DNA methylation related sites to analyze their association with prenatal famine exposure and SCZ risk in a Northeast Han Chinese population. A total of 967 subjects (446 patients with SCZ/521 health controls) were recruited. Five single-nucleotide polymorphisms (rs2300149 in ITIH1, rs2675956 in NGEF, rs3758543 in NT5C2, rs7003288 in NA, and rs871925 in MAD1L1) were selected and genotyped. Genotype distribution and allele frequency analysis indicated that rs871925 was significantly associated with SCZ. We also found a significant association between prenatal exposure to famine and rs871925 in the recessive model in the health control group. The generalized multifactor dimensionality reduction analysis suggested a five-locus interaction model association with the risk of developing SCZ. Our data suggested that MAD1L1 rs871925 was associated with prenatal famine exposure and SCZ susceptibility in a Northeast Han Chinese population., (© 2019 International Union of Biochemistry and Molecular Biology.)

Background: Short-term starvation has been related to hyperuricemia. However, little is known about the long-term effect of early-life exposure to famine on hyperuricemia risk in adulthood., Methods: The analysis included 2383 participants from the China Health and Retirement Longitudinal Study in 2015. Hyperuricemia was diagnosed as serum uric acid ≥7 mg/dL in men and serum uric acid ≥6 mg/dL in women. Famine exposure subgroups were defined as unexposed (born between October 1, 1962, and September 30, 1964), fetal-exposed (born between October 1, 1959, and September 30, 1961), and early-childhood exposed (born between October 1, 1956, and September 1, 1958). The association between early-life famine exposure and hyperuricemia risk was assessed using multivariate logistic regression., Results: The prevalence of hyperuricemia in the unexposed, fetal-exposed, and early-childhood exposed participants was 10.7, 14.1, 11.1%, respectively. Compared with unexposed and early-childhood exposed participants combined as an age-balanced control, fetal-exposed participants showed an increased risk of hyperuricemia in adulthood (OR = 1.41; 95% CI: 1.06-1.88), after adjusting for gender, marital status, famine severity, residence, smoking, drinking, BMI, hypertension, and diabetes. The famine effect on hyperuricemia was accentuated by overweight or obesity (P for interaction = 0.042). Compared with unexposed and BMI < 24 kg/m 2 participants, the OR (95%CI) of hyperuricemia was 3.66 (2.13-6.30) for fetal-exposed and overweight/obesity participants. However, combined unexposed and early-childhood exposed participants as an age-balanced control, the interaction of famine exposure and BMI was not statistically significant (P for interaction = 0.054)., Conclusion: Famine exposure in the fetal stage was associated with an increased risk of hyperuricemia in adulthood.

Objective: To explore the association of famine exposure in early life with the risk of metabolic syndrome (MS) in the -Chinese adults., Methods: Data were obtained from the wave 2009 of the China Health and Nutrition Survey. MS was identified when 3 or more of the following components happened: (1) waist circumference >90 cm in males or >85 cm in females; (2) fasting glucose ≥6.1 mmol/L; (3) systolic blood pressure ≥130 mm Hg/diabolic blood pressure ≥85 mm Hg; (4) fasting triglyceride ≥1.70 mmol/L; and (5) high-density lipids cholesterol <1.04 mmol/L. All participants were divided into 5 groups: no exposure, born after 1961; fetal life exposure, between 1959 and 1961; early childhood exposure, between 1956 and 1958; mid-childhood exposure, between 1953 and 1955; and late childhood exposure, between 1949 and 1952. A total of 2,080 subjects were included in this study., Results: In rural, famine exposure in fetal life and early childhood was associated with the lower risk of MS (p = 0.0491 and 0.0245; OR 0.583 and 0.703; and OR, 95% CI 0.341-0.998 and 0.517-0.956, respectively). But famine exposure in late childhood was associated with the higher risk of MS (p = 0.0140; OR 3.096; and OR, 95% CI 1.257-7.625). Famine exposure in early childhood was associated with the lower risk of MS (p = 0.0120; OR 0.633; and OR, 95% CI 0.443-0.904) in males., Conclusions: Famine exposure in mid- and late-childhood was associated with the higher risk of MS, especially in rural, males, and severe famine areas., (© 2020 S. Karger AG, Basel.)

Objective: To explore the relation between famine exposure in early life and subsequent pregnancy loss, including stillbirth, and spontaneous abortion in adulthood., Design: A population-based, partly ecological study., Setting and Population: Individual data of 58 601 females born around the time of the Great Chinese Famine in 1959-1961., Methods: Associations between the famine exposure in early life and pregnancy loss (stillbirth and spontaneous abortion) in adulthood were analysed using negative binomial regression, with the non-exposure group as reference, adjusting for region, highest education, monthly income, alcohol consumption, tobacco use, body mass index in 25-year-olds and metabolic equivalent. Further analyses were stratified by rural versus urban region., Main Outcome Measures: Continuous variables of times of stillbirths and spontaneous abortions were used according to the individual self-reported reproductive history., Results: No association was found between famine exposure and spontaneous abortion. In contrast, females experiencing the famine during their prenatal period (incidence rate ratio = 1.15, 95% CI 1.00-1.33) or infant period (incidence rate ratio = 1.27, 95% CI 1.12-1.44) were more likely to report stillbirth in later adult life. Such an association appeared stronger in women living in rural regions., Conclusions: Early life exposure of famine was associated with an increased risk of stillbirth but not spontaneous abortion in adulthood. The strength of such an association appeared stronger in rural areas. Given the high potential for unmeasured confounding, these associations must be interpreted with caution. Regarding the potential implication that undernutrition in the fetal period is related to reproductive outcome in adulthood, fetal nutritional supply may play an important role in human reproduction., Tweetable Abstract: Exposure to famine in early life was associated with increased pregnancy loss in adulthood., (© 2019 Royal College of Obstetricians and Gynaecologists.)

Objectives: Recurrent famine events during the medieval period might have contributed to excess mortality during the Black Death in London, England (c. 1349-1350). Previous research using conventional methods of age estimation revealed that adult males experienced lower risks of mortality under "normal" (attritional) but not famine mortality conditions following the Black Death. However, given the biases inherent in conventional age estimation methods, this study reassesses sex differences in risks of medieval adult famine mortality using ages estimated via transition analysis, which avoids some of the limitations of conventional age estimation methods., Materials and Methods: We apply hazards analysis (the Gompertz model of adult mortality) to ages estimated for human skeletal remains (n = 1245) from London cemeteries dated to the pre-Black Death (c. 1000-1250 CE) and post-Black Death (c. 1350-1540 CE) periods., Results: The results reveal no sex differences in risks of mortality before the Black Death but indicate that adult males faced lower risks of mortality after the Black Death during conditions of normal and famine mortality., Conclusions: These findings largely support those of our previous research, which suggested that selective mortality during the Black Death or sex-biased improvements in standard of living following the epidemic reduced risk of mortality for adult males in the post-Black Death period under normal mortality conditions. However, the use of transition analysis age estimates also revealed a reduced risk of mortality for post-Black Death adult males under famine conditions., (© 2019 Wiley Periodicals, Inc.)

Adult body height appears to be a relatively accurate summary variable of early-life exposures' influence on health, and may be a useful indicator of health in populations where more traditional health-related indicators are lacking. In particular, previous studies have shown a strong, positive relationship between environmental conditions in early life (particularly nutritional availability and the disease environment) and adult height. Research has also demonstrated positive associations between height and socioeconomic status. We therefore hypothesize that height mediates the relationship between early-life conditions and later-life socio-economic outcomes. We also hypothesize that the period of exposure in early life matters, and that conditions during pregnancy or the first years of life and/or the years during puberty have the largest effects on height and socio-economic status. To test these relationships, we use a sample of 1817 Dutch military conscripts who were exposed during early life to the Dutch Potato Famine (1846-1847). We conduct mediation analyses using structural equation modelling, and test seven different time periods in early-life. We use potato prices and real wages to proxy early-life environmental conditions, and occupational status (using the HISCAM scale) to proxy socioeconomic status. We find no evidence of mediation, partial or full, in any models. However, there are significant relationships between potato prices in adolescence, height and socio-economic status. To determine causality in these relationships, further research is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: Epidemiologic studies have revealed that early life malnutrition increases later risk of metabolic diseases. The visceral adiposity index (VAI) is a novel sex-specific index that shows promise as a marker of visceral adipose dysfunction. We aimed to explore whether exposure to the Chinese famine between 1959 and 1962 during fetal and childhood periods was related to VAI in adulthood., Methods: Our data source was SPECT-China, a population-based cross-sectional study in East China. Overall, 5295 subjects from 16 sites were divided into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and non-exposed (1963-1974) groups. The associations of life periods when exposed to famine with VAI were assessed via linear regression., Results: Compared with the non-exposed women (1963-1974), the fetal- and the childhood-exposed women had significantly greater VAI values (P < 0.05), but this difference was not observed in men. In the fetal- and childhood-exposed women, there was a significant positive association of famine exposure with VAI after adjusting for age, current smoking, rural/urban residence, and economic status (both P < 0.05). Further adjustments for diabetes and hypertension did not attenuate this association (both P < 0.05). However, such association was not observed in men., Conclusions: Exposure to famine in early life may have a significant association with visceral adipose dysfunction in adult females. The fetal age and childhood may be important time windows for nutrition relief to prevent visceral adipose dysfunction.

The 'DOHaD' literature argues that stressors encountered at age t 'program' individual health at age t+n, and that this programming appears strongest when t defines critical developmental periods including gestation. Accordingly, children of ill-nourished pregnant women suffer greater later life morbidity than do offspring of well-nourished mothers. The possibility that circumstances other than access to nutritious food drive both a mother's diet and fetal development remains, however, a threat to the inference of programming in utero. Attempts to rule out this threat include tests of the hypothesis that birth cohorts in gestation during famines exhibit shorter life spans than other cohorts. The tests produce conflicting results attributed to confounding by autocorrelation, selective migration and introduction of modern medicine. We offer a test in which neither medicine nor migration nor autocorrelation could obscure the presumed effect. We apply time-series regression methods to the life span of Swedes born between 1751 and 1800 to test the hypothesis that cohorts exposed in utero to the Swedish Famine of 1773 lived shorter lives than expected from trends and other forms of autocorrelation. We use these 50 birth cohorts not only because they included those exposed to severe famine but also because they may well be the only human birth cohorts that completed life unaffected by selective migration and unaided by modern medicine and for which we know life span. We find that the cohort born in 1773 live 4.2 years longer than expected from trends over the last half of the 18th century.

Chronic diseases are gradually becoming public health challenges around the world. This study was designed to explore the relationship between early life exposure to famine in China and the risk of dyslipidemia during adulthood. A total of 604 subjects born from 1955 to 1965 received a health checkup and completed a questionnaire survey at the health management center of the tertiary hospital in Hefei, China, in 2013. A logistic regression model was used to assess dyslipidemia in famine-exposed and nonexposed individuals. Overall, exposure to famine during the fetal (OR 1.37; 95% CI: 0.90-2.10; and p = 0.14) and childhood (OR 0.97; 95% CI: 0.67-1.41; and p = 0.89) periods did not significantly increase the risk of dyslipidemia in adulthood compared with no exposure group. For females, exposure to famine during the fetal period (OR 2.00; 95% CI: 1.03-3.86; and p = 0.04) significantly increased the risk of dyslipidemia in adulthood compared to no exposure; however, this difference was not found in males. Exposure to famine in early life leads to altered lipid distribution in adulthood, and the risk of dyslipidemia significantly increased in adult women who were exposed to famine during the fetal period. Our study further validated the relationship between famine exposure during pregnancy and increased risk of dyslipidemia in female adult offspring. This study provides a scientific basis for the prevention and control of abnormal blood lipid levels in adults., (© 2019 AOCS.)

Background: Exposure to energy restriction during childhood is associated with a lower risk of developing colorectal cancer (CRC). To date, the association between this critical period of growth and prognosis of CRC has rarely been investigated. Changes in microbiota and epigenetic dysregulation may be key underlying mechanisms., Methodology: Tissues collected from patients born between 1956 and 1964 were grouped based on time-period. The differences in overall survival among patients from the three time-periods were examined via univariate analysis. The 16S rRNA gene sequencing approach was to determine differences in microbiota among the groups. Samples were randomly selected to detect BRAF mutations, microsatellite instability (MSI) and promoter CpG island methylator phenotype (CIMP) status. The chi-square test was to assess the relationship between alterations in these molecules and microbiota differences., Results: Patients from the three groups differed in terms of location of CRC (P = 0.034) and carcinoembryonic antigen (CEA) level (P = 0.036). A survival advantage was observed in the famine group compared with the other two groups. Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli were more abundant in the two comparing groups. Abundance of B. fragilis was associated with BRAF mutations, microsatellite instability (MSI) and abundance of E. coli. Moreover, the incidence of CIMP and MSI was higher in patients with greater abundance of F. nucleatum., Conclusions: Limitation of energy intake during childhood may affect the composition of gut microbiota, resulting in persistent epigenetic changes that subsequently influence the prognosis of patients with CRC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Maternal malnutrition during pregnancy may have long-lasting effects on offspring's mental health. We investigate the effect of prenatal exposure to the Dutch famine (mid November 1944 to late April 1945) on mental health in later mid-life., Methods: Data are from the Netherlands Kinship Panel Study (n = 642). We use difference-in-difference analyses to compare mental health in later midlife (measured with the MHI-5 index) across three cohorts ('pre-famine cohort', 'famine cohort', 'post-famine cohort') and across two regions (famine affected cities vs. rest of the country)., Results: In the affected cities, we find poorer mental health for the famine cohort than for the pre-famine and post-famine cohorts. In the non-affected rest of the country, no significant mental health differences between birth cohorts were found. The mental health differences between birth cohorts differ significantly between the affected cities and the rest of the Netherlands., Conclusion: Our analyses link prenatal famine exposure to poorer mental health in later midlife. This suggests that in utero malnutrition has a long-lasting detrimental effect on mental health.