Early-life famine exposure and risk of osteoporosis and low bone mineral density: a systematic review and meta-analysis.

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 I2 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], I2 = 88%) and fractures (OR = 1.58, 95%CI [1.07, 2.33], I2 = 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.

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.

Famine exposure in early life increases risk of cataracts in elderly stage.

Background: Epidemiological studies have shown that early-life nutritional deficiencies are associated with an increased risk of diseases later in life. This study aimed to explore the correlation between famine exposure during the early stages of life and cataracts. Methods: We included 5,931 participants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2018 cross-sectional data in our study. Subjects were categorized into three groups by their age during the famine: adulthood group, school age famine exposure group, and teenage famine exposure group. Utilizing binary logistic regression models, we investigated the relationship between early-life famine exposure and cataracts. Results: Compared to the adulthood group, both the school age exposure group (OR = 2.49, 95%CI = 1.89-3.27) and teenage exposure group (OR = 1.45, 95%CI = 1.20-1.76) had a heightened risk of developing cataracts in elderly stage. And the sex differences in the impact of famine during early years on elderly cataract risk were observed, particularly indicating a higher risk among women who experienced childhood famine compared to men with similar exposure. Conclusion: Famine exposure during the early stages of life is associated with a heightened risk of developing cataracts in old age. To prevent cataracts in elderly individuals, particularly in females, measures should be taken to address nutritional deficiencies in these specific periods.

Early life malnutrition and risk of T2DM adulthood: evidence from the lower socioeconomic status of northwest Chinese population.

Objective: This study aimed to explore whether famine exposure during early life are associated with a high risk of Type 2 Diabetes Mellitus (T2DM) in adulthood and the role of socioeconomic status (SES) on this effect. Materials and methods: We conducted a secondary data analysis based on data from a cross-sectional survey, collected 3,355 participants born between January 1, 1941 and December 31, 1966. Participants were categorized into four groups based on their date of birth, unexposed (individuals born in 1963-1966), infant exposed (individuals born in 1959-1962), childhood exposed (individuals born in 1949-1958), and adolescent exposed (born in 1941-1948). The association of famine exposure with T2DM risk in adults and conducted separately in plain area and mountain area was assessed using logistics regression model. Result: 22.35% of participants were diagnosed with T2DM, of which 43.47% were from the childhood famine-exposed group, representing the highest proportion among all subgroups (p < 0.001). Participants exposed to famine during childhood and adolescence from the lower SES mountain areas showed a significantly higher prevalence of T2DM in adulthood than those from the plain areas (p < 0.001). The adolescence stage exposed famine will increase the risk of T2DM in the mountain area (OR 2.46, 95% CI 1.61, 3.77). Conclusion: No strong evidence demonstrates that exposure to famine during the early life stage increases the risk of developing T2DM in adulthood. However, populations with lower SES are likely to be exposed to more risk factors for T2DM.

Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases.

BACKGROUND: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease. METHODS: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. RESULTS: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3 × 10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index. CONCLUSIONS: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.

Perinatal Famine Exposure and Young-Onset Cancer-Lessons from China Health and Nutrition Survey.

Background/Objectives: Perinatal exposure to malnutrition has been hypothesised to influence the development of young-onset cancer (≤50 years of age). This study aimed to determine if perinatal malnutrition in individuals exposed to the Great Famine of China increased their risk of developing young-onset cancer compared to other individuals born prior to the famine. Subjects/Methods: This cross-sectional study involved 7272 participants from the China Health and Nutrition Survey who were classified into four groups based on birth year: participants born between 1953 and 1955 (before the famine) were designated as the pre-famine group (unexposed); the remainder formed perinatal exposure groups comprised of those exposed during the famine (1959-1961), those exposed in the early post-famine period (1962-1964), and those exposed in the late post-famine period (1965-1967). Multivariable adjusted log-binomial regression models were used to calculate the RR and 95% CI of young-onset cancer (including genitourinary cancer) across four groups. Results: Perinatal exposure to early post-famine (RR 2.08; 95%CI 1.04, 4.34; p = 0.043) and the female sex (RR 15.6, 95%CI 4.54, 60.3; p < 0.001) were noted to have a significantly increased risk of young-onset cancer. In addition, the early (RR 13.8; 95%CI 2.68, 253; p = 0.012) and late post-famine (RR 12.3; 95%CI 2.16, 231; p = 0.020) cohorts demonstrated a significantly increased risk of young-onset genitourinary cancer. The latter was accompanied by an increased risk of hypertension (RR 3.30; 95%CI 1.28, 7.87; p = 0.009). Conclusions: Perinatal exposure to famine, especially in females, was associated with a higher risk of young-onset cancer. This was particularly evident for young-onset genitourinary cancers. These findings highlight the potential long-term impact of perinatal malnutrition on young-onset carcinogenesis.

Accelerated biological aging six decades after prenatal famine exposure.

To test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural-experiment birth-cohort study of survivors of in-utero exposure to famine conditions caused by the German occupation of the Western Netherlands in Winter 1944 to 1945, matched controls, and their siblings. We conducted DNA methylation analysis of blood samples collected when the survivors were aged 58 to quantify biological aging using the DunedinPACE, GrimAge, and PhenoAge epigenetic clocks. Famine survivors had faster DunedinPACE, as compared with controls. This effect was strongest among women. Results were similar for GrimAge, although effect-sizes were smaller. We observed no differences in PhenoAge between survivors and controls. Famine effects were not accounted for by blood-cell composition and were similar for individuals exposed early and later in gestation. Findings suggest in-utero undernutrition may accelerate biological aging in later life.

OFAC, Famine, and the Sanctioning of Afghanistan: A Catastrophic Policy Success.

On August 15, 2021, American military forces withdrew from Kabul, and the sanctioning of Afghanistan began. Marred by the usual problems-ineffective, counterproductive, unwieldy-these sanctions revealed three additional puzzles. First, although grounded in targeted sanctions, they transformed into de facto comprehensive sanctions. Secondly, that transformation was instantaneous and unprompted. Thirdly, a near-famine followed within weeks. I make nested analytical, functional, and explanatory arguments. The analytical argument is that targeted sanctions are best understood not as tools of international coercion but primarily as domestic regulations. The functional argument is that the Office of Foreign Asset Control (OFAC) uses tactical and strategic ambiguity to maximize its regulatory reach over financial intuitions, humanitarian aid organizations, and money transfer organizations. The explanatory argument returns to the puzzles. I argue that, without any signal from OFAC, which was the signal, and reflecting OFAC's regulatory domination, when the Taliban took Kabul, the international financial community, humanitarian aid organizations, and remittance providers all dissociated from Afghanistan with immediate effect and particularly acute consequences on food entitlements.

Prenatal Exposure to the 1944-45 Dutch Famine and Risk for Dementia up to Age 75: An Analysis of Primary Care Data.

BACKGROUND: A poor prenatal environment adversely affects brain development. Studies investigating long-term consequences of prenatal exposure to the 1944-45 Dutch famine have shown that those exposed to famine in early gestation had poorer selective attention, smaller brain volumes, poorer brain perfusion, older appearing brains, and increased reporting of cognitive problems, all indicative of increased dementia risk. OBJECTIVE: In the current population-based study, we investigated whether dementia incidence up to age 75 was higher among individuals who had been prenatally exposed to famine. METHODS: We included men (n=6,714) and women (n=7,051) from the Nivel Primary Care Database who had been born in seven cities affected by the Dutch famine. We used Cox regression to compare dementia incidence among individuals exposed to famine during late (1,231), mid (1,083), or early gestation (601) with those unexposed (born before or conceived after the famine). RESULTS: We did not observe differences in dementia incidence for those exposed to famine in mid or early gestation compared to those unexposed. Men and women exposed to famine in late gestation had significantly lower dementia rates compared to unexposed individuals (HR 0.52 (95%CI 0.30-0.89)). Sex-specific analyses showed a lower dementia rate in women exposed to famine in late gestation (HR 0.39 (95%CI 0.17-0.86)) but not in men (HR 0.68 (95%CI 0.33-1.41)). CONCLUSION: Although prenatal exposure to the Dutch famine has previously been associated with measures of accelerated brain aging, the present population-based study did not show increased dementia incidence up to age 75 in those exposed to famine during gestation.

Vestiges of famine: Long-term mortality impacts of early-life exposure to the 1840s famine in Estonia.

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.

Consequences of Exposure to Famine Exposure on the Later Life eGFR Decline Among Survivors of the Great Chinese Famine: A Retrospective Study.

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 m2. RESULTS: Average eGFR values were 103.0, 96.8, 91.2, and 76.3 mL/min/1.73 m2 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.

Optimisation of the biological production of levulinic acid in a mixed microbial culture fed with synthetic grape pomace.

Levulinic acid (LA) is a polymer with a vast industrial application range and can be co-produced as a minor by-product during the biological production of polyhydroxyalkanoates (PHA). However, the influence of key parameters as tools for favouring the production of LA over PHA is still unclear. In this study, we investigated how several critical operational conditions, i.e., carbon-nitrogen ratio (C/N), organic loading rate (OLR) and airflow, can be optimised to favour LA accumulation over PHA production by a mixed microbial culture (MMC), using synthetic grape pomace (GP) hydrolysate as the substrate. The results showed that it was possible to direct the MMC towards LA accumulation instead of PHA. The maximum LA yield was 2.7 ± 0.2 g LA/(L·d) using a C/N of 35, an airflow of 5 L/min and an OLR of 4 g sCOD/(L·d). The OLR and, to a lesser extent, the C/N ratio were the main factors significantly and positively correlated with the biological synthesis of LA.

Phosphorus removal from fermented dairy manure concurrent with polyhydroxybutyrate-co-valerate synthesis under aerobic conditions.

Wastewater phosphorus removal achieved biologically is associated with the process known as enhanced biological phosphorus removal (EBPR). In contrast with canonical EBPR operations that employ alternating anaerobic-aerobic conditions and achieve asynchronous carbon and phosphorus storage, research herein focused on phosphorus removal achieved under aerobic conditions synchronously with volatile fatty acid (VFA) storage as polyhydroxybutyrate-co-valerate (PHBV). 90.3 ± 3.4 % soluble phosphorus removal was achieved from dairy manure fermenter liquor; influent and effluent concentrations were 38.6 ± 9.5 and 3.7 ± 0.8 mgP/L, respectively. Concurrently, PHBV yield ranged from 0.17 to 0.64 mgCOD/mgCOD, yielding 147-535 mgCODPHBV/L. No evidence of EBPR mechanisms was observed, nor were canonical phosphorus accumulating organisms present; additionally, the polyphosphate kinase gene was not present in the microbial biomass. Phosphorus removal was primarily associated with biomass growth and secondarily with biomass complexation. Results demonstrate that concurrent PHBV synthesis and phosphorus recovery can be achieved microbially under aerobic dynamic feeding conditions when fed nutrient rich wastewater.

Severe prenatal shocks and adolescent health: Evidence from the Dutch Hunger Winter.

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.

Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases.

Background: Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type-2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to provide a deeper insight into the metabolic changes associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and explore their link to disease. Methods: NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. Results: Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3x10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type-2 diabetes (r = 0.77, p = 3x10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1x10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2x10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index. Conclusions: Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.

Beyond feast and famine: Cultivating hydrodynamic oxygenic photogranules with better performances under permanent feast regime.

Oxygenic photogranules (OPGs) are currently obtained in permanent famine or cyclic feast-famine regimes. Whether photogranulation occurs under a permanent feast regime and how these regimes impact OPGs are unknown. Herein, the three regimes, each applied in two replicate hydrodynamic reactors, were established by different feeding frequencies. Results showed that OPGs were successfully cultivated in all regimes after 24-36 days of photogranulation phases with similar microbial community functions, including filamentous gliding, extracellular polymeric substances production, and carbon/nitrogen metabolism. The OPGs were then operated under the same sequencing batch mode and all achieved efficient removal of chemical oxygen demand (>91 %), ammonium (>96 %), and total nitrogen (>76 %) after different adaptation periods (19-41 days). Notably, the permanent feast regime obtained OPGs with the best physicochemical properties, the shortest adaptation period, and the lowest effluent turbidity, thus representing a novel means of hydrodynamic cultivating OPGs with better performances for sustainable wastewater treatment.

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.