Gestational exposure to the great Chinese famine: early life undernutrition impact on prostatic hyperplasia in adulthood.

Introduction: Benign prostatic hyperplasia (BPH) is a frequent illness in aged men that impacts their quality of life; early childhood exposure to famines may have long-term effects on the chance of developing BPH. The aim of this study is to investigate the relationship between early-life famine exposure and benign prostatic hyperplasia (BPH) risk in Chinese men born during 1959-1961. Methods: We used medical records from a large, comprehensive hospital to screen people born in China during the years of famine (1959-1961). Birthplaces were identified as indicators of famine exposure status. In the time window between 2017 and 2022, people born during the famine years who had prostatic ultrasonic examinations were selected, and their medical records were retrieved from the database. Univariate and multivariate logistic regression analyses investigated the relationship between famine exposure and BPH risk. Results: A total of 3,009 subjects were included in this study. Patients with heavy famine exposure had older age, shorter height, lighter weight, lower cholesterol, lower uric acid (UA), lower aspartate aminotransferase (ALT), and a higher incidence of BPH than those with light famine exposure (all p < 0.05). Univariate logistic regression showed that BPH was positively related to famine exposure, age, height, weight, and body mass index (BMI) but negatively related to UA (all p < 0.05). Multivariate logistic regression showed that age and famine exposure were still independent risk factors (p < 0.05), while UA was an independent protective factor for BPH (p < 0.05). Heavy famine exposure increased the risk of BPH (adjusted OR = 1.214, 95% CI = 1.05-1.467, p = 0.045). Conclusions and recommendation: Famine and malnutrition exposure during early life may be independent risk factors for BPH in Chinese adults. This relationship provides additional evidence to support the fetal origins of adult diseases and offers clues for the pathological mechanisms of BPH.

Association between famine exposure during infancy and childhood and the risk of chronic kidney disease in adulthood.

BACKGROUND: Famine exposure in childhood is proven to be associated with multiple chornic disease in adult but has not been studied with chronic kidney disease (CKD). AIMS: This study was conducted to identify the relationship between famine exposure during infancy and childhood - specifically, the Chinese famine of 1959-1961 - and the risk of adult-onset chronic kidney disease (CKD) among Chinese individuals. METHODS: This study included 2937 individuals from the Qingdao Diabetes Prevention Program. They were stratified by birth year into infancy-exposed (1956-1958), childhood-exposed (1950-1955) and unexposed (1963-1971) groups. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. CKD was defined as an eGFR of <90 mL/min/1.73 m2 . RESULTS: The mean eGFR values for the infancy-exposed and childhood-exposed groups were 107.23 ± 12.53 and 103.23 ± 12.44 mL/min/1.73 m2 , respectively, both of which were lower than that of the unexposed group (114.82 ± 13.39 mL/min/1.73 m2 ; P < 0.05). In the crude model, the odds ratio (OR) for CKD was 2.00 (95% confidence interval (CI): 1.39-2.88) in the infancy-exposed group and 2.92 (95% CI: 2.17-3.93) in the childhood-exposed group. Further adjustments for urban/rural residence, body mass index, age, current smoking, type 2 diabetes, systolic blood pressure, diastolic blood pressure and total cholesterol did not significantly alter the association between famine exposure and CKD. The corresponding ORs were 1.71 (95% CI: 1.17-2.50) and 2.48 (95% CI: 1.81-3.40) for the infancy-exposed and childhood-exposed groups respectively. CONCLUSIONS: Famine exposure during infancy and childhood is associated with a long-term decline in eGFR and an increased adult-onset CKD risk. Early intervention for high-risk individuals may mitigate the risk of adult-onset CKD.

Exposure to Chinese famine in early life and height across 2 generations: a longitudinal study based on the China Health and Nutrition Survey.

BACKGROUND: Poor nutrition early in life is associated with short stature, which is associated with increased risk of cardiovascular disease and mortality in later life. Less evidence is available about the impact of early-life nutrition on height growth in the subsequent generation. OBJECTIVES: This study investigated the associations of famine exposure in utero and early childhood with height across 2 generations. METHODS: We used longitudinal data from the China Health and Nutrition Survey. We included 5401 participants (F1) born in 1955-1966 (calendar year around the Chinese famine in 1959-1961) and their 3930 biological offspring (F2). We classified F1 participants into subgroups by famine exposure status (unexposed/exposed) and timing (fetal-/childhood-exposed) according to their birth year and grouped F2 by their parents' exposure. Linear regression models were applied to examine the associations of famine exposure with adult height of F1 and F2. Linear mixed effect models with fractional polynomial functions were performed to estimate the difference in height between exposure groups of F2 during childhood. RESULTS: Participants (F1) exposed to famine in utero or in childhood were shorter than those unexposed by 0.41 cm (95% CI: 0.03, 0.80) and 1.12 cm (95% CI: 0.75, 1.48), respectively. Offspring (F2) of exposed fathers were also shorter than those of unexposed parents by 1.07 cm (95% CI: 0.28, 1.86) during childhood (<18 y) and by 1.25 cm (95% CI: 0.07, 2.43) in adulthood (≥18 y), and those with exposed parents had a reduced height during childhood by 1.29 cm (95% CI: 0.68, 1.89) (all P values < 0.05). The associations were more pronounced among child offspring of highly-educated F1, particularly for paternal exposure and among female offspring (all P for interaction < 0.05). CONCLUSIONS: The findings support the intergenerational associations of famine exposure in early life with height in Chinese populations, indicating the public health significance of improving the nutritional status of mothers and children in the long run.

Early Famine Exposure Results in Left Ventricular Remodeled, Diastolic Dysfunction and Systolic Function Preserved in Adults.

INTRODUCTION: Malnutrition during a critical window of development in a fetus or infant can result in abnormal cardiac remodeling and function. It is uncertain whether the contribution of these effects continues to impact the cardiac remodeling and function of adults over the course of several decades of growth. Our study examined the impact of early Chinese famine exposure on cardiac remodeling, left ventricular (LV) diastolic function, and LV systolic function in adults. METHODS: Participants at high risk of cardiovascular disease from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project (PEACE MPP) were enrolled. The famine in China lasted from 1959 to 1962. A total of three groups were formed based on the participants' birth dates: pre-famine group, famine exposure group, and post-famine group. Logistic regression and linear mixed models were used to explore the association between famine exposure and cardiac remodeling, LV diastolic function and LV systolic function in adults. RESULTS: The study included 2,758 participants, the mean age was 57.05 years, 62.8% were female, 26.4% had LV hypertrophy (LVH), 59.6% had LV diastolic dysfunction (LVDD), and 10.5% had reduced global longitudinal strain (GLS). Compared to post-famine exposure, participants had independently increased risk of LVH in the famine exposure group (OR: 2.02, 95% CI: 1.60-2.56) and pre-famine exposure (OR: 1.36, 95% CI: 1.06-1.76). Compared to post-famine exposure, the risk of LVDD remarkably increased in the famine exposure group (OR: 3.04, 95% CI: 2.49-3.71) and pre-famine exposure group (OR: 1.87, 95% CI: 1.52-2.31). Famine exposure had no significant impact on GLS but was associated with a significant increase in LV ejection fraction (LVEF) and LV end-diastolic diameter (LVEDD). Significant interactions were observed between the effects of famine exposure and other clinical/sociodemographic variables (gender, systolic blood pressure [SBP] ≥140 mm Hg or not, high school or above or not, and annual income <50,000 RMB or not) on these outcomes. CONCLUSION: Exposure to famine, particularly during fetal and infant stages, increases the risk of LVH and LVDD in adults. However, the LV systolic function remains preserved. These impacts are more pronounced in females, individuals with SBP ≥140 mm Hg, those with low income, or those with high educational status.

Separate and combined effects of famine exposure and menarche age on metabolic syndrome among the elderly: a cross-sectional study in China.

BACKGROUND: Epidemiological studies have revealed multiple risk factors for metabolic syndrome. However, there are no consistent findings on the association between famine exposure, age at menarche, and the prevalence of metabolic syndrome. This cross-sectional study aimed to reveal the individual and combined effects of famine exposure and age at menarche on the prevalence of metabolic syndrome among elderly women. METHODS: Four thousand seven hundred seventy participants between 60 and 93 years of age were selected from the China Health and Retirement Longitudinal Study. Statistical differences between the baseline characteristics of famine exposure, age at menarche, and metabolic syndrome were evaluated using the t-test, F-test, and Chi-square test. Three multivariable-adjusted logistic regression models were used to test the association between famine exposure, age of menarche, and the odds ratio of metabolic syndrome. RESULTS: Two thousand one hundred ninety-eight (46.08%) participants had metabolic syndrome, while 2572 (53.92%) participants did not. Furthermore, 3068 (64.32%) women reported onset of menarche under 15 years of age, while 1702 (35.68%) women reported onset of menarche above 16 years of age. Regarding the separate association of famine exposure and age of menarche with metabolic syndrome, in model three, the adolescence/adulthood famine exposure group vs. no famine exposure group odds ratio was 2.45 (95% CI 2.02, 2.97), and the older than 16 years vs. younger than 15 years group odds ratio was 1.23 (95% CI 1.09, 1.39), which was the highest odds ratio among the three models. Regarding the combined association of famine exposure and age of menarche with metabolic syndrome, in model three, among the age of menarche ≤ 15 years group, the adolescence/adulthood famine exposure vs. no famine exposure group odds ratio was 2.45 (95% CI: 1.91, 3.14); among the menarche age ≥ 16 years group, the adolescence/adulthood famine exposure stages vs. exposed group odds ratio was 3.27 (95% CI: 2.44, 4.38), which was the highest odds ratio among the three models. CONCLUSION: These findings suggested that famine exposure and age at menarche, either separately or in combination, were positively associated with the prevalence of metabolic syndrome among older women.

Intergenerational relationship between parental famine exposure and offspring's obesity risks.

BACKGROUND: The intergenerational relationship between parental famine exposure and the obesity risks of offspring has not been well studied. METHODS: Using a cohort of 3654 respondents whose parents were born between 1950 and 1964 from the national data of the China Family Panel Studies, this study examines the associations between parental exposure to the 1959-1961 Chinese famine and offspring's body mass index (BMI). A cross-sectional difference-in-difference design was used to estimate the effects of parental famine exposures on offspring's BMI by exploiting temporal variations in the duration and period of famine across the parental birth cohorts between 1950 and 1964, and geographical variations in the famine severity at the province level. RESULTS: After adjusting individual characteristics and province-level fixed effects, we found that parental famine exposures in the preschool and school-age stages were associated with an increased BMI of offspring while there was not a significant association between prenatal famine exposure and offspring's BMI. The stratified analyses further show that the effects of parental famine exposure did not follow the same trajectory in subgroups. CONCLUSIONS: Famine experiences of parents were associated with increased BMI of offspring, suggesting an intergenerational impact of severe malnutrition on obesity risks.

The association between prenatal famine, DNA methylation and mental disorders: a systematic review and meta-analysis.

BACKGROUND: Undernutrition in pregnant women is an unfavorable environmental condition that can affect the intrauterine development via epigenetic mechanisms and thus have long-lasting detrimental consequences for the mental health of the offspring later in life. One epigenetic mechanism that has been associated with mental disorders and undernutrition is alterations in DNA methylation. The effect of prenatal undernutrition on the mental health of adult offspring can be analyzed through quasi-experimental studies such as famine studies. The present systematic review and meta-analysis aims to analyze the association between prenatal famine exposure, DNA methylation, and mental disorders in adult offspring. We further investigate whether altered DNA methylation as a result of prenatal famine exposure is prospectively linked to mental disorders. METHODS: We conducted a systematic search of the databases PubMed and PsycINFO to identify relevant records up to September 2022 on offspring whose mothers experienced famine directly before and/or during pregnancy, examining the impact of prenatal famine exposure on the offspring's DNA methylation and/or mental disorders or symptoms. RESULTS: The systematic review showed that adults who were prenatally exposed to famine had an increased risk of schizophrenia and depression. Several studies reported an association between prenatal famine exposure and hyper- or hypomethylation of specific genes. The largest number of studies reported differences in DNA methylation of the IGF2 gene. Altered DNA methylation of the DUSP22 gene mediated the association between prenatal famine exposure and schizophrenia in adult offspring. Meta-analysis confirmed the increased risk of schizophrenia following prenatal famine exposure. For DNA methylation, meta-analysis was not suitable due to different microarrays/data processing approaches and/or unavailable data. CONCLUSION: Prenatal famine exposure is associated with an increased risk of mental disorders and DNA methylation changes. The findings suggest that changes in DNA methylation of genes involved in neuronal, neuroendocrine, and immune processes may be a mechanism that promotes the development of mental disorders such as schizophrenia and depression in adult offspring. Such findings are crucial given that undernutrition has risen worldwide, increasing the risk of famine and thus also of negative effects on mental health.

Famine Exposure during Early Life and Risk of Cancer in Adulthood: A Systematic Review and Meta-Analysis.

OBJECTIVES: Emerging evidences have explored the association between famine exposure during early life and cancer risk in adulthood, but the results remain controversial and inconsistent. This study aimed to provide a comprehensive evidence on the relation of famine exposure to later cancer risk. DESIGN: Systematic review and meta-analysis. METHODS: Relevant reports published up to March, 2022 were identified by searching PubMed, Embase, Web of sciences and Medline databases. Pooled relative ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the effect famine exposure on cancer risk. RESULTS: Totally, 18 published articles with 6,061,147 subjects were included in this study. Compared with unexposed group, early life famine exposure dramatically increased the risk of cancer in adulthood (RR=1.13, 95% CI: 1.04-1.22). The pooled RRs were different in terms of sex, exposure severity, exposure period, famine type, study design type and cancer location. A remarkably elevated risk for cancer was discerned in women exposed to famine (RR=1.09, 95% CI: 1.00-1.18), severe exposure (RR=1.12, 95% CI: 1.02-1.22) and adolescence exposure (RR=1.76, 95% CI: 1.02-2.50), Chinese famine exposure (RR=1.55, 95% CI: 1.29-1.82) and cohort studies (RR=1.28, 95% CI: 1.13-1.42). Moreover, a significant association of early-life famine exposure with increased risk of breast (RR=1.16, 95% CI: 1.05-1.27) and stomach cancers (RR=1.89, 95% CI: 1.24-2.54) was observed. CONCLUSION: This meta-analysis suggests that exposure to famine during early life may increase the risk of cancer in adulthood. The above-mentioned association is pronounced in women exposed to famine, severe exposure, adolescence exposure, Chinese famine, cohort studies, breast and stomach cancers. It is essential for decision-makers to take targeted measures for improving population awareness regarding the long-term effect of early life nutritional status.

Correlation of Great Chinese Famine Exposure During Early Life to Prevalence of Kidney Stone in Adulthood.

Background: The Great Chinese Famine, as the famine of 1959-1961 was often known. Famine exposure during early life was proven to be associated with some kidney diseases but has not been studied with kidney stone. We aimed to investigate the relationship between exposure to the Great Chinese Famine in early life and the incidence of kidney stone in adulthood. Methods: From 1 January 2017 to 31 December 2018, a total of 19,658 eligible adults were recruited in a cross-sectional survey who were born between 1 October 1952 and 30 September 1964 in Guangdong, China. Participants were separated into kidney stone and none-kidney stone groups based on kidney stone status. According to birth data, participants were divided into non-exposed, fetal-exposed, early-, mid-, and late-childhood-exposed groups. Multivariate logistic regression, subgroup analysis and interaction test were used to estimate the odds ratios (ORs) and confidence intervals (CIs) between famine exposure and kidney stone. Results: In total, 19,658 (12,246 female, mean age 59.31 ± 3.68 years) subjects were enrolled, and 3219 (16.38%) participants with kidney stone. The prevalence of kidney in none-, fetal-, early-, mid-, and late-childhood-exposed groups were 645 (14.9%), 437 (15.9%), 676 (16.3%), 743 (17.0%), and 718 (17.6%), respectively (P<0.001). When compared with the unexposed group, the fully adjusted ORs for kidney stone from fetal-exposed, early-, mid- to late-childhood-exposed groups were 1.37 (95% CI: 1.13, 1.68, P=0.002), 1.98 (95% CI: 1.45, 2.72, P<0.001), 2.94 (95% CI: 1.96, 4.42, P<0.001), and 3.48 (95% CI: 2.11, 5.72, P<0.001), respectively (P for trend<0.001). Subgroup analyses revealed no interactions between the famine effect on kidney stones and body mass index, gender, smoking status, history of diabetes or hypertension (all P for interaction >0.05). Conclusion: This study found that exposure to the Great Chinese Famine during early life was independently associated with the increased incidence of kidney stone in adulthood.

Parental exposure to famine in early life and child overweight in offspring in Chinese populations.

BACKGROUND: Little is known about the transgenerational effect of nutrition deficiency in early life. This study aimed to evaluate the associations of fetal and childhood exposure to famine of parents with their offspring's risk of overweight during childhood. METHODS: This analysis included a total of 3734 participants of the China Health and Nutrition Survey aged 1-17 years whose fathers and/or mothers were born in 1955-1966. These children were classified into subgroups according to parental famine exposure status (unexposed and exposed) and timing (fetal-exposed and childhood-exposed). Random effects models were applied to evaluate the associations of parental famine exposure with body mass index (BMI) and overweight of offspring. Fractional polynomial functions were adopted to describe trajectories of BMI against age. RESULTS: Compared with children of unexposed parents, there was a lower risk of overweight among offspring of childhood-exposed fathers [OR (95%CI): 0.80 (0.61, 1.04)] or exposed parents [0.84 (0.68, 1.04)], particularly among male offspring, but not among those with exposed mothers only [0.98 (0.65, 1.47)]. For BMI, children with exposed mothers only had a slightly higher BMI [ß(95%CI): 0.17 (-0.15, 0.49)], while those with exposed fathers only had no difference [-0.02 (-0.23, 0.19)] or exposed parents had a slightly lower BMI [-0.17 (-0.33, 0.00)] (p < 0.05 for interaction between maternal and paternal exposures). Stratified analysis showed little heterogeneity between male and female offspring, but the association between paternal childhood exposure to famine and lower overweight risk in offspring was more evident in high (vs low) paternal education group (p for interaction< 0.05). CONCLUSIONS: The transgenerational associations of early-life exposure to famine with lower risks of child overweight may be via the paternal line and differ by the educational levels of parents. Further studies are warranted to confirm the results and reveal the biological mechanisms underlying.

Association of early-life famine exposure with low bone mass in adulthood.

Famine exposure in early life has been found to have a long-term effect on metabolic diseases, but its effect on bone health was not clear. In this study, we found women, who suffered from famine exposure during their childhood or adolescence period, had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. The risk of clinical fracture was also elevated in adolescence-exposed women. PURPOSE: To investigate the correlation between famine exposure at certain stages and bone mass in adulthood. METHODS: We enrolled participants born in 1943-1962 from the China Osteoporosis Prevalence Study (COPS), which were classified into three famine exposure groups according to their birth year: fetal-famine exposure (1959-1962, n = 1693), childhood-famine exposure (1949-1958, n = 5557), and adolescence-famine exposure (1943-1948, n = 1530). We also selected age-balanced non-exposed participants as the control groups for men and women separately. Bone mineral density (BMD) and vertebral fractures (VFs) were measured by dual X-ray absorptiometry (DXA) and X-ray, respectively. The associations of famine exposure in early life with BMD were assessed via multiple linear regression. Logistic regression was performed to examine the association of famine exposure in early life with fracture risk with adjustments for covariates. RESULTS: In women, the childhood-exposed and adolescence-exposed groups had significantly decreased BMD at several skeletal sites compared to the age-matched non-exposed groups. No significant decreased BMD was found in the fetal-exposed groups compared to the non-exposed groups in both sexes. Multiple linear regression analysis showed that famine exposure during childhood and adolescence was negatively associated with BMD at the femoral neck after adjusting for covariates in women. The risk of clinical fracture was also elevated in adolescence-exposed women. CONCLUSION: Famine exposure during early life especially childhood and adolescence is associated with decreased bone mass in adulthood in women but did not affect bone mass in men.

Famine exposure during early life and risk of metabolic syndrome in adulthood in China: a meta-analysis / 中华内分泌代谢杂志

Objective:To analyze the relationship between early-life famine exposure and the risk of metabolic syndrome in Chinese population.Methods:Relevant literature on the relationship between early-life famine exposure and the risk of metabolic syndrome in the Chinese population was retrieved from databases such as CNKI, Wanfang, VIP, CBM, Web of Science, and PubMed. The search was conducted from the inception of the databases up to October 2022. Two researchers independently extracted and systematically evaluated the data from the literature, and meta-analysis was performed using Stata 16.0 software. Results:A total of 12 publications met the inclusion criteria, including 71 470 study subjects. Meta-analysis results showed that early-life famine exposure increased the risk of metabolic syndrome in the Chinese population( OR=1.28, 95% CI 1.16-1.40). Subgroup analysis showed that both fetal famine exposure( OR=1.25, 95% CI 1.03-1.52) and childhood famine exposure( OR=1.29, 95% CI 1.15-1.45) increased the risk of developing metabolic syndrome compared to the non-exposed group, and this significant association was only found in the female population. Conclusion:Early-life exposure to famine may increase the risk of developing metabolic syndrome in adulthood in the Chinese population, particularly among females.

Association between severe famine exposure in different life cycles and central obesity in adulthood / 公共卫生与预防医学

Objective To investigate the association between famine exposure in different life cycles and the risk of central obesity. Methods A total of 2234 spermanent residents were recruited to participate in the China Multi-Ethnic Cohort (CMEC) Study ,they were grouped into four birth cohorts of fetal-exposed (born between January 1,1959, and December 31,1961,95 cases), childhood-exposed (born between January 11,949, and December 31,1958,533 cases), adolescence/adult-exposed (born between January 1,1931, and December 31,1948,256 cases),unexposed cohorts（born after January 1, 1975，871 cases).we used logistic regression model to assess the effect of famine exposure on central obesity in adulthood. Results After adjusting for confounding factors, females in the fetal/infant exposure group（OR=3.283,95%CI：1.472～7.321,P＜0.001）、childhood- exposed group (OR=3.557,95%CI：2.374～5.313,P＜0.001) and adolescence/adult-exposed group (OR=5.785，95%CI：3.536～9.492，P＜0.001) had a higher risk of adult central obesity than the control group.After excluding the subjects with coronary heart disease、cancer、diabetes、stroke or obesity, sensitivity analysis was carried out. The risk of central obesity increased in the female / fetal、childhood、adolescent / adult exposure group,which was unfound in males. Conclusion Severe famine exposure in fetal/infant、childhood and adolescence/adulthood can increase the risk of central obesity in adulthood in females. Therefore, the prevention and control of central obesity in female should start from the early life.

Early life exposure to famine and risk of dyslipidemia in adults: a systematic review and Meta-analysis.

Background: Dyslipidemia is the major contributor to the global disease burden. Earlier epidemiologic research has linked early-life famine exposure to dyslipidemia and altered lipid profiles in adulthood, but a uniform perspective has yet to be established. In response, this systematic review and meta-analysis is aimed to investigate the association of early life famine exposure and dyslipidemia in adults. Methods: Scopus, Medline and Google scholar databases were searched for articles published until October 2020. Studies of famine exposure during prenatal and early postnatal life and their association with dyslipidemia and lipid profiles in adults were included. Random effect model in the Meta-analysis and Mantel- Haenszel model was used to calculate odds ratios and their 95% confidence intervals to evaluate the strength of association between famine exposure and dyslipidemia. The lipid profiles of the exposed and non-exposed groups were compared using the standardized mean difference (SMD). Heterogeneity between studies were assessed using I2 values. Results: We identified 17 studies for assessing the association between early life famine exposure and risk of dyslipidemia in adults. About 11 studies were included for meta-analysis. Prenatal exposure to famine was associated with increased risk of dyslipidemia [OR = 1.74 (95% CI: 1.31, 2.31)], total cholesterol [SMD = 2.07 (95% CI: 1.40, 2.74)], LDL-cholesterol [SMD = 1.16 (95% CI: 0.25, 0.26)] and decreased HDL-cholesterol [SMD = -0.05 (95% CI: -0.10, -0.01)]. Likewise, famine exposure during early postnatal period was associated with increased risk of total cholesterol [SMD = 0.18 (95% CI: 0.11, 0.25), I 2 = 29%] and LDL-cholesterol [SMD = 0.15 (95% CI: 0.07, 0.23), I 2 = 61%]. Conclusions: Famine exposure in early life was found to have an association with increased risk of dyslipidemia and altered lipide profile during adulthood. Our findings highlight the need for promoting better nutrition during pregnancy and infancy to prevent dyslipidemia during adulthood. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01062-8.

The association between early-life famine exposure and adulthood obesity on the risk of dyslipidemia.

BACKGROUND AND AIMS: The joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia. METHODS AND RESULTS: We conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/m2, obesity≥28.0 kg/m2) and waist-to-hip ratio (WHR, men/women: moderate≥0.90/0.85, high≥0.95/0.90). Dyslipidemia was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Compared with nonexposed participants, fetal-exposed individuals had significantly increased risk of dyslipidemia (OR:1.24, 95%CI: 1.03-1.50) in the whole study. Significant increased risk of dyslipidemia related to famine exposure was observed in women [ORs (95%CIs) were 1.36 (1.05-1.76) and 1.70 (1.22-2.37) for the fetal and childhood-exposed group, respectively] but not in men. Moreover, both general and central obesity had significant multiplicative interactions with famine exposure for the risk of dyslipidemia (P for interaction = 0.0001 and < 0.0001, respectively). Significant additive interaction was found between famine exposure and WHR on risk of dyslipidemia in women, with the relative excess risk due to interaction (RERI) and 95% CI of 0.43 (0.10-0.76). CONCLUSION: Coexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.

Association between Early Life Famine Exposure and Metabolic Syndrome in Adulthood.

To analyze the relationship between famine exposure at different stages of early life and the risk of developing metabolic syndrome (MetS) in adulthood, 11,865 study participants from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance Program were enrolled and then divided into a non-exposed group, fetal exposure group, early childhood exposure group, middle childhood exposure group and late childhood exposure group according to their birth time and famine exposure. MetS was defined by the NCEP ATP III criteria. Using logistic regression to explore the association between famine exposure at different stages of early life and the increased risk of developing MetS in adulthood. After adjusting other factors, compared with the non-exposure group, famine exposure during the fetal period (OR = 1.23, 95% CI = 1.00-1.51), early childhood (OR = 1.44, 95% CI = 1.11-1.87), middle childhood (OR = 1.50, 95% CI = 1.13-1.99) and late childhood (OR = 1.67, 95% CI = 1.21-2.30) had a higher risk of developing MetS in adulthood. Stratified analysis found an association between early life famine exposure and the increased risk of MetS in adulthood in females, overweight or obese participants and those who lived in areas of severe famine, in city areas and in southern China. Compared with the non-exposed group, the fetal, early childhood, middle childhood and late childhood famine-exposed groups are more likely to suffer from MetS in adulthood, especially the subjects who are females, overweight or obese and had lived in severe famine areas, city areas and southern China.

The Relationship Between Famine Exposure During Early Life and Left Ventricular Hypertrophy in Adulthood.

Background: Although the evidence was still limited, some studies suggested that childhood malnutrition might affect cardiac function and structure in adulthood. To address the knowledge gap, this study investigated if the Great Chinese Famine exposure during early life had affected left ventricular hypertrophy (LVH). Methods: This research was a cross-sectional study. It included participants who had cardiac ultrasound assessments and were born in Guangdong, China, from 1 October 1952 to 30 September 1964. They were classified according to their exposure period to famine, namely, no exposure, fetal-, early-, mid-, and late childhood. Multivariate logistic regression and subgroup analysis have been conducted to determine the odds ratio (OR) and confidence intervals (CIs) between famine exposure and LVH. Results: This research included 2,543 participants, 1,612 women, their mean age was 59.07 ± 3.65 years, and 704 participants had LVH. LVH prevalence was 122 (23.6%), 87 (25.1%), 133 (27.3%), 184 (29.2%), and 178 (31.7%), in non-, fetal-, early-, mid-, and late-childhood exposed groups, respectively (p = 0.031), while in the non-exposed group, the ORs for developing carotid plaque as a result of fetal, early-, mid- to late-childhood exposure were 1.08 (95% CI: 0.76, 1.59, p = 0.619), 1.24 (95% CI: 1.03, 1.79, p = 0.031), 1.49 (95% CI: 1.10, 2.01, p = 0.009), and 1.64 (95% CI: 1.25, 2.18, p = 0.001), respectively (p for trend = 0.003). There was no interactive effect between gender, obesity, or hypertension history with how the famine influenced LVH, as the subgroups analyses demonstrated (all p for interaction > 0.05). Conclusion: This research has demonstrated the potential relationship between Great Chinese Famine exposure during childhood and LVH in adults.

Early life famine exposure and anthropometric profile in adulthood: a systematic review and Meta-analysis.

BACKGROUND: Previous famine studies reported the association between early life famine exposure and adulthood anthropometric profile. However, the findings were variable. Thus, a systematic review and meta-analysis was conducted to clarify the association of famine exposure in early life with the anthropometric profiles in adults. METHODS: Potentially relevant studies were searched through Scopus, Medline, Google Scholar and Google for gray literature and reference lists of previous studies. The random effects model (REM) and I2 test was used to adapt the pooling method and assess heterogeneity, respectively. RESULTS: Prenatal famine exposure was associated with increased risk of body mass index [SMD = 0.10 (95% CI: 0.02, 0.18)], waist circumference [SMD = 0.21 (95% CI: 0.11, 0.31)] in adults. Likewise, famine exposure during prenatal life was associated with decreased adult height [SMD) = - 0.26 (95% CI: - 0.44, - 0.09)]. Moreover, famine exposure during early childhood was associated with increased risk of waist circumference [SMD = 0.09 (95% CI: 0.01, 0.16)] and decreased adult height [SMD = - 0.16 (95% CI: - 0.27, - 0.04)]. CONCLUSION: Our finding indicates that exposure to famine during early life was associated with the anthropometric profile of adults. In terms of public health significance, the results of the study further underscore the importance of improving the nutritional status of mothers and children to prevent adulthood diseases in the long run. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020168424.

Early-life exposure to Chinese famine and stroke risk in mid- to late life: the mediating roles of cognitive function and depression.

BACKGROUND: Limited research has examined the role that famine exposure plays in adulthood stroke risk. We aim to explore the causal implications of early exposure to the Great Chinese Famine on stroke risk and determine whether these associations were mediated by cognitive function, and depression. METHODS: We sampled 12,681 individuals aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) and divided them into fetally exposed, childhood-exposed, adolescence/adulthood-exposed and unexposed groups. Stroke was defined by self- or proxy-reported physician diagnosis. Based on a counterfactual framework, marginal structural models were used to estimate the natural direct effect and the natural indirect effects through cognitive function and depression for causal inference. RESULTS: We found that early-life exposure to Chinese famine was directly related to increased stroke risk in mid- to late life. Cognitive function and depression accounted for a greater part of the effect for childhood famine exposure, mediating 36.35% (95%CI: 14.19, 96.19%) of the overall association between famine exposure and incident stroke, than for the fetal, adolescence/adulthood famine exposure groups. However, the natural indirect effect through depression was not significant in the fetally exposed group. The results were robust in the sensitivity analysis of model specification and unobserved confounding. CONCLUSIONS: Our findings are consistent with the latency, pathway, and accumulation models, supporting the life-course theory. Early stages of life exposed to the Chinese Famine were associated with higher risk of stroke in mid- to late life. Enhanced cognitive and depression interventions may reduce stroke risk in middle-aged and older Chinese adults who exposure to famine in early life.

The relationship between famine exposure during early life and ascending aorta dilatation in adults.

The relationship between exposure to famine in early life and the risk of ascending aorta dilatation (AAD) in adulthood is still unclear; therefore, we aimed to examine the association in the Chinese population. We investigated the data of 2598 adults who were born between 1952 and 1964 in Guangdong, China. All enrolled subjects were categorised into five groups: not exposed to famine, exposed during fetal period, and exposed during early, mid or late childhood. AAD was assessed by cardiac ultrasound. Multivariate logistic regression and interaction tests were performed to estimate the OR and CI on the association between famine exposure and AAD. There were 2598 (943 male, mean age 58·3 ± 3·68 years) participants were enrolled, and 270 (10·4 %) subjects with AAD. We found that famine exposure (OR = 2·266, 95 % CI 1·477, 3·477, P = 0·013) was associated with elevated AAD after adjusting for multiple confounders. In addition, compared with the non-exposed group, the adjusted OR for famine exposure during fetal period, early, mid or late childhood were 1·374 (95 % CI 0·794, 2·364, P = 0·251), 1·976 (95 % CI 1·243, 3·181, P = 0·004), 1·929 (95 % CI 1·237, 3·058, P = 0·004) and 2·227 (95 % CI 1·433, 3·524, P < 0·001), respectively. Subgroup analysis showed that the effect of famine exposure on the association with AAD was more pronounced in female, current smokers, people with BMI ≥ 24 kg/m2 and hypertensive patients. We observed that exposure to famine during early life was linked to AAD in adulthood.