Early-life exposure to the Great Chinese Famine and gut microbiome disruption across adulthood for type 2 diabetes: three population-based cohort studies.

BACKGROUND: The early life stage is critical for the gut microbiota establishment and development. We aimed to investigate the lifelong impact of famine exposure during early life on the adult gut microbial ecosystem and examine the association of famine-induced disturbance in gut microbiota with type 2 diabetes. METHODS: We profiled the gut microbial composition among 11,513 adults (18-97 years) from three independent cohorts and examined the association of famine exposure during early life with alterations of adult gut microbial diversity and composition. We performed co-abundance network analyses to identify keystone taxa in the three cohorts and constructed an index with the shared keystone taxa across the three cohorts. Among each cohort, we used linear regression to examine the association of famine exposure during early life with the keystone taxa index and assessed the correlation between the keystone taxa index and type 2 diabetes using logistic regression adjusted for potential confounders. We combined the effect estimates from the three cohorts using random-effects meta-analysis. RESULTS: Compared with the no-exposed control group (born during 1962-1964), participants who were exposed to the famine during the first 1000 days of life (born in 1959) had consistently lower gut microbial alpha diversity and alterations in the gut microbial community during adulthood across the three cohorts. Compared with the no-exposed control group, participants who were exposed to famine during the first 1000 days of life were associated with consistently lower levels of keystone taxa index in the three cohorts (pooled beta - 0.29, 95% CI - 0.43, - 0.15). Per 1-standard deviation increment in the keystone taxa index was associated with a 13% lower risk of type 2 diabetes (pooled odds ratio 0.87, 95% CI 0.80, 0.93), with consistent results across three individual cohorts. CONCLUSIONS: These findings reveal a potential role of the gut microbiota in the developmental origins of health and disease (DOHaD) hypothesis, deepening our understanding about the etiology of type 2 diabetes.

The Mediating Role of Systemic Inflammation in the Effects of Fetal Famine Exposure on Cardiovascular Disease in Adults: A Cohort Study.

BACKGROUND: A few studies have reported the association between famine exposure during fetal development and risk of CVD, but no mechanisms have been explored. OBJECTIVES: The objective of this study was to examine risk of CVD in adulthood after exposure to famine during the fetal stage and explore the mediating role of systemic inflammation. METHODS: A total of 59,416 participants of the Kailuan Study without CVD were included. All participants were divided into 3 groups based on date of birth, including the unexposed group (1963-1974), the fetal-exposed group (1959-1962), and the childhood-exposed group (1949-1958). Systemic immune-inflammation index (SII) (neutrophils × platelets / lymphocytes) and systemic inflammatory response index (SIRI) (neutrophils × monocytes / lymphocytes) are 2 novel systemic inflammation indexes that represent the level of systemic inflammation. Time-weighted Cox regression was used to test the effect of famine exposure on risk of CVD, and a mediation model was used to calculate the role of systemic inflammation. RESULTS: During a median follow-up period of 12.36 (12.69, 13.16) y, a total of 3772 cases of CVD were documented. Compared with unexposed participants, the fetal-exposed group had an increased risk of CVD (HR: 1.19; 95% CI: 1.04, 1.38) and stroke (HR: 1.28; 95% CI: 1.09, 1.51) but not MI. No association was observed in the childhood-exposed group. In mediation analysis, SII mediated an estimated 24.43% of the association between fetal exposure and CVD (24.61% for stroke and 23.27% for MI). For SIRI, this percentage was 30.20% for CVD (29.94% for stroke and 31.25% of MI). CONCLUSIONS: Fetal exposure to famine may increase risk of CVD in adulthood. Systemic inflammation may play an intermediary role in the effect of fetal famine exposure on CVD.

Secular trend of non-communicable chronic disease prevalence throughout the life span who endured Chinese Great Famine (1959-1961).

BACKGROUND: Famine is a risk factor for non-communicable chronic diseases (NCDs), which account for over 80% of deaths in China. The effect of famine on the prevalence of NCDs in terms of various age groups, time periods and cohorts is currently poorly understood. OBJECTIVE: This study aims to explore long-term trends in the impact of China's Great Famine (1959-1961) on NCDs in China. METHODS: This study used data from the 2010-2020 China Family Panel Longitudinal Survey across 25 provinces in China. The subjects were aged 18-85 years, and the total number of subjects was 174,894. The prevalence of NCDs was derived from the China Family Panel Studies database (CFPS). An age-period-cohort (APC) model was used to estimate the age, period and cohort effects of NCDs in 2010-2020 and the effect of famine on the risk of NCDs in terms of cohort effects. RESULTS: The prevalence of NCDs increased with age. Additionally, the prevalence did not clearly decrease over the survey period. Regarding the cohort effect, people born in the years adjacent to the famine period had a higher risk of NCDs; additionally, females, those born in rural areas, and those who lived in provinces with severe famine and post-famine had a higher likelihood of NCDs. CONCLUSIONS: Experiencing famine at an early age or the experience of famine in a close relative's generation (births after the onset of famine) are associated with an increased risk of NCDs. Additionally, more severe famine is associated with a higher risk of NCDs.

Effect modification of socioeconomic status on the association of exposure to famine in early life with osteoporosis in women.

BACKGROUND: The present study aimed to explore the effect of modification of socioeconomic status (SES) on the association between famine exposure in early life and osteoporosis in adulthood via the baseline data from the Henan Rural cohort study. METHODS: A total of 2669 exposed to famine participants were selected from the Henan Rural cohort, and the questionnaires, physical examination and bone mineral density measurement were completed. Specific birth years were used to define five groups: the fetal exposed group, early-childhood exposed group, mid-childhood exposed group, late-childhood exposed group and unexposed group. And the age-matched control group was a combination of the unexposed group and late-childhood exposed group. Multivariable logistic regression models were utilised to analyse the association of famine exposure in early life with osteoporosis in adulthood. RESULTS: The prevalence rates of osteoporosis of participants exposed to famine during the fetal period, early-childhood, mid-childhood and the age-matched group were 21.67%, 25.76%, 23.90% and 18.14%, respectively. The adjusted odds ratios (95% confidence interval) of participants suffering from famine during the fetal period, early-childhood and mid-childhood versus age-matched group were 1.19 (0.82-1.73), 1.40 (1.04-1.88) and 1.57 (1.16-2.13), respectively. The female participants yielded consistent results. The risk of osteoporosis was higher in more severe famine eara. Moreover, an attenuated effect of early life famine exposure on osteoporosis was observed in female participants with high SES. CONCLUSIONS: Exposure to famine in early life showed a sex-specific association with an increased risk of osteoporosis in adulthood and the severity of famine may exacerbate this association. In addition, the risk could be modified by SES.

Prenatal and early-life exposure to the Great Chinese Famine increased the risk of tuberculosis in adulthood across two generations.

Global food security is a major driver of population health, and food system collapse may have complex and long-lasting effects on health outcomes. We examined the effect of prenatal exposure to the Great Chinese Famine (1958-1962)-the largest famine in human history-on pulmonary tuberculosis (PTB) across consecutive generations in a major center of ongoing transmission in China. We analyzed >1 million PTB cases diagnosed between 2005 and 2018 in Sichuan Province using age-period-cohort analysis and mixed-effects metaregression to estimate the effect of the famine on PTB risk in the directly affected birth cohort (F1) and their likely offspring (F2). The analysis was repeated on certain sexually transmitted and blood-borne infections (STBBI) to explore potential mechanisms of the intergenerational effects. A substantial burden of active PTB in the exposed F1 cohort and their offspring was attributable to the Great Chinese Famine, with more than 12,000 famine-attributable active PTB cases (>1.23% of all cases reported between 2005 and 2018). An interquartile range increase in famine intensity resulted in a 6.53% (95% confidence interval [CI]: 1.19-12.14%) increase in the ratio of observed to expected incidence rate (incidence rate ratio, IRR) in the absence of famine in F1, and an 8.32% (95% CI: 0.59-16.6%) increase in F2 IRR. Increased risk of STBBI was also observed in F2. Prenatal and early-life exposure to malnutrition may increase the risk of active PTB in the exposed generation and their offspring, with the intergenerational effect potentially due to both within-household transmission and increases in host susceptibility.

Early-life exposure to the Chinese famine and risk of hyperuricaemia in adult females in Qingdao.

Two population-based cross-sectional surveys involving randomly selected Chinese adults aged 35-74 years were conducted in Qingdao, China in 2006 and 2009. Nine thousand fifty-five subjects from the two surveys were grouped into four birth groups of fetal/infant exposed (born between 1 January 1959 and 31 December 1962), childhood exposed (born between 1 January 1950 and 31 December 1958), adolescence exposed (born between 1 January 1942 and 31 December 1949) and the unexposed (born before 1941 and after 1963). Multivariate logistic regression models were used to calculate the OR and 95 % CI of hyperuricaemia in different exposed groups. Overall, famine exposure in the fetal/infant period, childhood and adolescence was not associated with adulthood hyperuricaemia (all P > 0·05). In females, childhood exposed group (OR = 1·59, 95 % CI 1·25, 2·02) and adolescence exposed group (OR = 1·74, 95 % CI 1·30, 2·33) both had higher risks to have hyperuricaemia in adult. However, this difference was not found in fetal/infant exposed group. In males, no significant relation was observed in any famine exposed group (all P > 0·05). Exposure to famine in childhood and adolescence is associated with an increased risk of hyperuricaemia for adulthood of females, but not in males. Adequate nutrition during early life appears to be beneficial to prevent hyperuricaemia of adult females.

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.

Early life exposure to the Chinese Famine of 1959 - 1961 is an independent risk factor of adulthood elevated homocysteine, hyperuricemia, high LDL, and hypertension.

Famine exposure in early life was associated with cardiovascular diseases in later life. Whether biochemical surrogates of cardiovascular diseases, such as homocysteine and uric acid, are also associated with famine exposure is unknown so far. Data were derived from a population-based cross-sectional study in the Hunan Province of China, which was heavily affected by the Famine in 1959 - 1961. A total of 1,150 adults born between 1952 and 1964 were selected, and 5 cohorts were defined: no exposure, fetal, early childhood, mid-childhood, and late childhood exposure. Compared with the no-famine exposure group, participants exposed to famine in their fetal period had a higher risk of high homocysteine in adulthood with OR of 2.21 (95% CI: 1.01 - 4.83), whereas famine exposures in early, mid, or late childhood were not significantly associated with high homocysteine in adulthood. Similarly, participants in the fetal famine exposure group had a 1.59-fold higher risk of hyperuricemia (OR = 2.59, 95% CI: 1.07 - 5.30) and a 2.03-fold higher risk of high low-density lipoprotein cholesterol (LDL) (OR = 0.03, 95% CI: 1.35 - 6.78) in adulthood compared to those without famine exposure, respectively. We furthermore conducted a meta-analysis including 16 studies regarding the association between fetal famine exposure and adulthood hypertension, including our study. The meta-analysis, including 34,804, subjects showed that fetal famine exposure is associated with a higher risk of adulthood hypertension (OR = 1.22, 95% CI: 1.07 - 1.40). Taken together, fetal famine exposure is related to higher odds of cardio-metabolic risk factors, such as high homocysteine, hyperuricemia, and LDL as well as hypertension, suggesting that undernutrition during fetal life may affect metabolism of homocysteine, uric acid, and LDL in adulthood.

Differential effect of prenatal exposure to the Great Ethiopian Famine (1983-85) on the risk of adulthood hypertension based on sex: a historical cohort study.

BACKGROUND: The consequence of the Great Ethiopian Famine (1983-1985) on mortality had been well documented. However, the long term assaults of the famine on adulthood health, particularly on the risk of hypertension, has never been documented. The aim of this study was twofold: to examine the association of prenatal-exposure to the Great Ethiopian Famine and hypertension in adulthood and investigate if there existed sex difference in the risk estimate. METHODS: Participants were recruited using multistage stratified random sampling and grouped as prenatal famine exposed and non-exposed cohorts based on their reported date of birth and current age. Independent sample T test was employed to compare continuous outcomes between the groups. A multivariable logistic regression was used to examine the association between prenatal famine exposure and risk of hypertension in adults. RESULTS: Compared to the non-exposed groups, prenatal famine exposed cohorts had higher systolic blood pressure by 1.05 mmHg, (95% CI 0.29, 4.42) and diastolic by 2.47 mmHg (95% CI 1.01, 3.95). In multivariable logistic regression analysis, both unadjusted (COR = 2.50; 1.575, 3.989) and adjusted model for covariates (OR: 2.306 95% CI (1.426, 3.72) indicated a positive association between prenatal famine exposure and the risk of adult hypertension. However, in sex disaggregated analysis, the positive association was only significant in females (AOR = 3.95 95% CI 1.76, 8.85) indicating nearly four folds of odds of hypertension among females, while the corresponding figure for males was not significant (AOR = 1.201 (0.69, 2.07). CONCLUSIONS: Famine exposure during prenatal period could have differential impact on the development of hypertension based on sex, where adult exposed females had higher risk of hypertension as compared to males. Contextualized primary prevention programs with special focus on gender is critical undertaking in hunger spots and regions with historical famine.

Prenatal exposure to the Dutch famine is associated with more self-perceived cognitive problems at 72 years of age.

BACKGROUND: Undernutrition during critical periods of neurodevelopment can hinder the developing brain with lasting negative consequences for brain size, structure and function. In this study, we describe self-perceived cognitive problems of men and women who were born around the time of the Dutch famine of 1944-45. METHODS: We compared self-perceived cognitive problems between men and women who had been exposed to the 1944-45 Dutch famine in late, mid or early gestation and those who were born before or conceived after the famine (and had thus not been exposed prenatally). We included 595 participants aged 71-74 years. RESULTS: Women who had been exposed to famine in late gestation more often reported cognitive problems compared to those who had not been exposed (OR 2.2 [95% CI 1.1-4.4]), whereas for men, this was the case for those exposed in early gestation (OR 2.3 [0.9-5.5]). Furthermore, men and women exposed in early gestation more often reported consulting a healthcare practitioner for cognitive problems in the past 12 months (OR 3.2 [1.3-8.1]). Especially men exposed in early gestation reported having consulted a healthcare practitioner more often than unexposed men (OR 4.4 [1.2-16.0]). CONCLUSIONS: These findings suggest that prenatal undernutrition does not only have lasting effects on brain size, but also on its function, with more self-perceived cognitive problems at older age, which also require more medical attention. Also, the effects of undernutrition depend on sex and its timing during gestation.

Starvation Genocide: Myocardial Infarction in the Lodz Ghetto.

BACKGROUND: Medical records discovered after the liberation of ghettos in Nazi-occupied Europe are unique documents that report on the suffering of inmates, on ravaging infectious diseases, and on starvation-related organ degeneration and the resulting mortality. We offer a pathogenetic explanation for the scarcity of acute myocardial infarction in the Lodz Ghetto, Poland, 1941-1944.

Starvation Ketosis and the Kidney.

BACKGROUND: The remarkable ability of the body to adapt to long-term starvation has been critical for survival of primitive man. An appreciation of these processes can provide the clinician better insight into many clinical conditions characterized by ketoacidosis. SUMMARY: The body adapts to long-term fasting by conserving nitrogen, as the brain increasingly utilizes keto acids, sparing the need for glucose. This shift in fuel utilization decreases the need for mobilization of amino acids from the muscle for purposes of gluconeogenesis. Loss of urinary nitrogen is initially in the form of urea when hepatic gluconeogenesis is dominant and later as ammonia reflecting increased glutamine uptake by the kidney. The carbon skeleton of glutamine is utilized for glucose production and regeneration of consumed HCO3-. The replacement of urea with NH4+ provides the osmoles needed for urine flow and waste product excretion. Over time, the urinary loss of nitrogen is minimized as kidney uptake of filtered ketone bodies becomes more complete. Adjustments in urine Na+ serve to minimize kidney K+ wasting and, along with changes in urine pH, minimize the likelihood of uric acid precipitation. There is a sexual dimorphism in response to starvation. Key Message: Ketoacidosis is a major feature of common clinical conditions to include diabetic ketoacidosis, alcoholic ketoacidosis, salicylate intoxication, SGLT2 inhibitor therapy, and calorie sufficient but carbohydrate-restricted diets. Familiarity with the pathophysiology and metabolic consequences of ketogenesis is critical, given the potential for the clinician to encounter one of these conditions.

Euglycaemic ketoacidosis in pregnant women with COVID-19: two case reports.

BACKGROUND: Euglycaemic ketoacidosis (EKA) is an infrequent but serious condition which usually follows a period of starvation, severe vomiting or illness in individuals with or without diabetes. Ketoacidosis is associated with materno-fetal morbidity and mortality necessitating prompt diagnosis and management. Physiological increases in insulin resistance render pregnancy a diabetogenic state with increased susceptibility to ketosis. COVID-19 is associated with worse clinical outcomes in patients with diabetes and is an independent risk factor for ketoacidosis in normoglycaemic individuals. CASE PRESENTATIONS: We describe two cases of SARS-CoV-2 positive pregnant women presenting with normoglycaemic metabolic ketoacidosis. Both cases were associated with maternal and fetal compromise, requiring aggressive fluid and insulin resuscitation and early delivery. CONCLUSION: We discuss possible physiology and propose a management strategy for euglycaemic ketoacidosis in pregnancy.

Premature brain aging in humans exposed to maternal nutrient restriction during early gestation.

BACKGROUND: Prenatal exposure to undernutrition is widespread in both developing and industrialized countries, causing irreversible damage to the developing brain, resulting in altered brain structure and decreased cognitive function during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now enabling studies of the effects of prenatal undernutrition during gestation on brain aging in late adulthood. METHODS: We hypothesized that study participants prenatally exposed to maternal nutrient restriction (MNR) would demonstrate altered brain structure resembling premature brain aging in late adulthood, expecting the effect being stronger in men. Utilizing the Dutch famine birth cohort (n = 118; mean age: 67.5 ± 0.9 years), this study implements an innovative biomarker for individual brain aging, using structural neuroimaging. BrainAGE was calculated using state-of-the-art pattern recognition methods, trained on an independent healthy reference sample, then applied to the Dutch famine MRI sample, to evaluate the effects of prenatal undernutrition during early gestation on individual brain aging in late adulthood. RESULTS: Exposure to famine in early gestation was associated with BrainAGE scores indicative of an older-appearing brain in the male sample (mean difference to subjects born before famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in individual BrainAGE scores in the male sample, maternal age at birth, head circumference at birth, medical treatment of hypertension, history of cerebral incidences, actual heart rate, and current alcohol intake emerged to be the most influential variables (adjusted R2 = 0.63, p < 0.01). INTERPRETATION: The findings of our study on exposure to prenatal undernutrition being associated with a status of premature brain aging during late adulthood, as well as individual brain structure being shaped by birth- and late-life health characteristics, are strongly supporting the critical importance of sufficient nutrient supply during pregnancy. Interestingly, the status of premature brain aging in participants exposed to the Dutch famine during early gestation occurred in the absence of fetal growth restriction at birth as well as vascular pathology in late-life. Additionally, the neuroimaging brain aging biomarker presented in this study will further enable tracking effects of environmental influences or (preventive) treatments on individual brain maturation and aging in epidemiological and clinical studies.

Post-bariatric surgery starvation ketoacidosis and lipase elevation in the absence of DKA or pancreatitis.

We report a case of post bariatric surgery by laparoscopic sleeve gastrectomy who presented with post-surgical poor oral tolerance and high anion gap metabolic ketoacidosis, who was initially misdiagnosed with diabetic ketoacidosis and treated with volume supplementation without improvement. The metabolic derangements were found to be caused by starvation ketoacidosis, which was then treated with glucose supplementation, and the anion gap quickly closed. Moreover, this patient also presented with non-pancreatitis lipase elevation. This case highlights the recognition and management of post-bariatric surgery starvation ketoacidosis; additionally, clinicians should be vigilant about the interpretation and management of elevated lipase without clinical pancreatitis.

A possible link between famine exposure in early life and future risk of gastrointestinal cancers: Implications from age-period-cohort analysis.

The Chinese famine in 1958-1962 was one of the worst in human history, but its potential influence on cancer risks is uncertain. Using cancer incidence data in Shanghai, China, during 1983-2007, we calculated age-specific incidence rates of gastrointestinal cancers in birth cohorts exposed to the Chinese famine in different periods of life and a non-exposed reference cohort. Age-period-cohort regressions estimated the overall relative risks of gastrointestinal cancers in each birth cohort. A total of 212,098 new cases of gastrointestinal cancer were identified during the study period (129,233 males and 82,865 females), among whom 18,146 had esophageal cancer, 71,011 gastric cancer, 55,864 colorectal cancer, 42,751 liver cancer, 9,382 gallbladder cancer and 14,944 had pancreatic cancer. The risk of esophageal, gastric, colorectal and liver cancers was higher in cohorts exposed to the Chinese famine in early life than in the reference cohort, except for esophageal cancer in women. The risk of esophageal, liver and colorectal cancers was particularly high in men exposed to famine during early childhood (0-9 years). There were no clear associations between famine exposure and the risk of pancreatic or gallbladder cancer. This study suggests an increased risk of esophageal, gastric, liver and colorectal cancers associated with childhood exposure to the Chinese famine. These findings indicate a need for further investigations confirming the results and identifying the underlying mechanisms.

Prenatal famine exposure has sex-specific effects on brain size.

Early nutritional deprivation might cause irreversible damage to the brain. Prenatal exposure to undernutrition has been shown to be associated with increased central nervous system anomalies at birth and decreased cognitive function in adulthood. Little is known about the potential effect on the brain in older age. We investigated brain size and structure at age 68 years after prenatal famine exposure. T1-weighted structural magnetic resonance images of the brain were made in 118 Dutch famine birth cohort members. Of these 118 (44% male, age range 65-69 years), 41 had been exposed to famine in early gestation and 77 had been prenatally unexposed. Structural volumes were automatically assessed using FreeSurfer. Diffusion tensor imaging was performed and anisotropy and diffusivity were computed. Fluid attenuated inversion recovery was performed to assess white matter hyperintensities. Exposure to famine in early gestation was associated with smaller intracranial volume in males, but not females. Volumes of total brain, grey and white matter were also smaller in early exposed males, but these differences disappeared after adjusting for intracranial volume. Prenatally exposed males but not females, had a smaller intracranial and total brain volume compared to unexposed subjects. Our findings show that prenatal undernutrition permanently affected brain size.media-1vid110.1093/brain/aww132_video_abstractaww132_video_abstract.

Osteoporosis: A Future Public Health Problem for Israel? Medical and Legal Obligations.

BACKGROUND: Starvation in early life can lead to premature metabolic syndrome and bone demineralization. Osteoporosis in the Jewish population may not yet be a recognized syndrome, but the harsh conditions to which Holocaust survivors were exposed may have increased the incidence of the condition. Immigrants and refugees who came to Israel from East Africa and Yemen - whether decades ago or more recently - may have been at increased risk of under-nutrition during pregnancy, affecting both the mother and consequently the offspring. This malnutrition may be further exacerbated by rapid overfeeding in the adopted developed country. This problem was also recognized at the turn of the 21st century in poor and underdeveloped countries and is becoming a global public health issue. In this review, the risks for premature metabolic syndrome and bone demineralization are enumerated and preventive measures outlined.

Prenatal Undernutrition and Autonomic Function in Adulthood.

OBJECTIVES: Early-life adversity has been shown to be associated with cardiovascular disease and mortality in later life, but little is known about the mechanisms that underlie this association. Prenatal undernutrition, a severe early-life stressor, is associated with double the risk of coronary heart disease and increased blood pressure responses to psychological stress. In the present study, we tested the hypothesis that prenatal undernutrition induces alterations in the autonomic nervous system, which may increase the risk of developing heart disease. METHODS: We studied autonomic function in 740 men and women (mean [SD] age, 58 [0.9] years) who were members of the Dutch famine birth cohort. We compared those exposed to famine during early (n = 64), mid (n = 107), or late gestation (n = 127) to those unexposed to famine in utero (n = 442). Participants underwent a series of 3 psychological stressors (Stroop, mirror tracing, and speech) while their blood pressure and heart rate were recorded continuously. RESULTS: Data had sufficient quality in 602 participants for derivation of autonomic function indices by spectral analysis. The stress protocol led to significant sample-level changes in systolic blood pressure, heart rate, and all cardiovascular control measures (all p values < .001). None of the autonomic function parameters, at rest or in response to stress, differed significantly (all p values > .050) according to prenatal famine exposure. CONCLUSIONS: Prenatal undernutrition was not associated with autonomic function in late adulthood. We conclude that altered autonomic function does not seem to explain our previous findings of increased coronary heart disease risk among those exposed to famine prenatally.

Fetal and infant exposure to the Chinese famine increases the risk of fatty liver disease in Chongqing, China.

BACKGROUND AND AIM: Early life exposure to the famine may affect the susceptibility to the metabolic disorders. The objective of this study was to examine the associations of early life exposure to the Chinese Famine (1959-1961) with the risk of fatty liver disease, obesity, hypertension, and hyperglycemia in adulthood. METHODS: We used the data of 10,935 adults born between 1956 and 1965 in Chongqing from check-up center at the 1st Affiliated Hospital of Chongqing Medical University in 2011. Logistic regression models were used to explore the effects of famine on the risk of fatty liver disease, obesity, hypertension, and hyperglycemia. RESULTS: In Chongqing, prevalences of fatty liver disease among adults in non-exposed (1956-1958 plus 1963-1965) group and born in 1959, 1960, 1961, and 1962 were 34.01%, 36.42%, 34.63%, 40.27%, and 36.09%, respectively. Prevalences of fatty liver disease, obesity, hypertension, and hyperglycemia were significantly higher in males versus females. The risk of fatty liver disease was about 1.375-fold (1.303 (95% confidence interval, 1.066-1.594) for male, 1.547(95% confidence interval, 1.195-2.002) for female) higher in subjects born in 1961, and 1.142-fold (1.117 (95% confidence interval, 0.957-1.305) for male, 1.242 (95% confidence interval, 1.003-1.537) for female) higher in subjects born in 1962 after adjustment of age and sex, compared with non-exposed subjects. Early life exposure to the Chinese famine was also associated with the increased risk of obesity and hyperglycemia. CONCLUSIONS: Exposure to the Chinese famine during fetal life and infancy was associated with an increased risk of fatty liver disease in adulthood.