Prenatal Famine Exposure Research Articles

Women exposed to famine in early gestation have increased mortality up to age 76 years.

We have previously shown that exposure to famine in early gestation was associated with poorer adult health and, in women, with reduced survival up to age 64. Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately. We studied adult mortality (>18 years) in men (n = 989) and women (n = 1002) born as term singletons around the time of the 1944-1945 Dutch famine. We compared overall and cause-specific mortality among men and women exposed to famine in late, mid, or early gestation to that among unexposed persons (born before or conceived after the famine) using Cox regression. In total, 500 persons (25.1%) had died after age 18. Women exposed to famine in early gestation had higher overall (HR 1.49, 95% CI 1.00, 2.23), cancer (HR 2.17, 95% CI 1.32,3.58) and cardiovascular mortality (HR 2.33, 95% CI 0.91, 5.95) compared to unexposed women. Mortality rates among men were not different between exposure groups. This study showed that women, but not men, exposed to famine in early gestation had increased overall, cardiovascular and cancer mortality up to age 76. Although prenatal famine exposure affects adult health of both men and women, it seems to only lead to increased mortality among women.

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

BackgroundExposure 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.MethodsNMR 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.ResultsPrenatal 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.ConclusionsPrenatal 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.

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.

Brain activity during Stroop task performance at age 74 after exposure to the Dutch famine during early gestation

ObjectivePoorer performance on the Stroop task has been reported after prenatal famine exposure at age 58, potentially indicating cognitive decline. We investigated whether brain activation during Stroop task performance at age 74 differed between individuals exposed to famine prenatally, individuals born before and individuals conceived after the famine. MethodIn the Dutch famine birth cohort, we performed a Stroop task fMRI study of individuals exposed (n = 22) or unexposed (born before (n = 18) or conceived after (n = 25)) to famine in early gestation. We studied group differences in task-related mean activation of the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and posterior parietal cortex (PPC). Additionally, we explored potential disconnectivity of the DLPFC using psychophysiological interaction analysis. ResultsWe observed similar activation patterns in the DLPFC, ACC and PPC in individuals born before and individuals exposed to famine, while individuals conceived after famine had generally higher activation patterns. However, activation patterns were not significantly different between groups. Task-related decreases in connectivity were observed between left DLPFC-left PPC and right DLPFC-right PPC, but were not significantly different between groups. ConclusionsAlthough not statistically significant, the observed patterns of activation may reflect a combined effect of general brain aging and prenatal famine exposure.

Intergenerational relationship between parental famine exposure and offspring’s obesity risks

BackgroundThe intergenerational relationship between parental famine exposure and the obesity risks of offspring has not been well studied.MethodsUsing a cohort of 3654 respondents whose parents were born between 1950 and...

A Link between Prenatal Stage of Life during the Great Chinese Famine and Subsequent Depressive Symptoms among Middle-Aged and Older Adults

Prenatal malnutrition may increase the risk of depressive symptoms in adulthood. This study investigated the association between prenatal exposure to malnutrition with risk of depressive symptoms in middle-aged and older adults using the Chinese Great Famine of 1959–1961 as a natural experiment. Data were obtained from the China Health and Retirement Longitudinal Study baseline survey (2011). A total of 5391 individuals born from 1956 to 1965 were included in the study. Depressive symptoms were ascertained via the Center for Epidemiological Studies Depression Scale short form. Famine severity was measured using the cohort size shrinkage index. Difference-in-differences models were used to explore the association between prenatal famine exposure and later-life depressive symptoms. Compared with the post-famine cohort (1963–1965), famine cohorts (1959–1962) were 4.74 times (95% CI = 1.28–8.20) as likely to develop depressive symptoms. The stratified analysis found that prenatal exposure to famine was associated with depressive symptoms in rural residents but not those living in urban areas. In rural females, prenatal malnutrition was associated with a higher risk of depressive symptoms. However, there was no significant association between prenatal malnutrition and depressive symptoms in rural males. Our results indicated that prenatal malnutrition may contribute to a higher risk for depressive symptoms in later life among female rural residents.

Effects of prenatal exposure to the 1944–45 Dutch famine and glucocorticoid receptor polymorphisms on later life PTSD susceptibility

ABSTRACT Background: Exposure to adversity in utero is thought to increase susceptibility to develop posttraumatic stress disorder (PTSD) following later life trauma, due to neurobiological programming effects during critical developmental periods. It remains unknown whether effects of prenatal adversity on PTSD susceptibility are modulated by genetic variations in neurobiological pathways implicated in PTSD susceptibility. Objective: We investigated whether genetic variation in the glucocorticoid receptor (GR) modulated effects of prenatal famine exposure on late adulthood PTSD symptom severity after trauma exposure in childhood and mid-to-late adulthood. Method: We included N = 439 term-born singleton adults (mean age: 72 years, 54.2% women) from the Dutch Famine Birth Cohort, born around the time of the Dutch Famine of 1944/1945, divided into exposure and control groups based on timing of the famine during gestation. Participants filled out self-report questionnaires on childhood (Childhood Trauma Questionnaire) and mid-to-late adulthood (Life Events Checklist for DSM-5) trauma, and current PTSD symptom severity (PTSD Checklist for DSM-5). GR haplotypes were determined from four functional GR single nucleotide polymorphisms (ER22/23EK, N363S, BclI and exon 9β) in previously collected DNA. Linear regression analyses were performed to investigate associations of GR haplotype and prenatal famine exposure in conjunction with later life trauma on PTSD symptom severity. Results: We observed a significant three-way interaction between the GR Bcll haplotype, famine exposure during early gestation, and adulthood trauma exposure on PTSD symptom severity in late adulthood. Only participants exposed to famine during early gestation without the GR Bcll haplotype showed a significantly stronger positive association between adulthood trauma and PTSD symptom severity than non-exposed participants, indicating increased PTSD susceptibility. Conclusions: Our results illustrate the importance of integrated approaches considering genetics and environmental contexts throughout various life periods, including the rarely investigated prenatal environment, to elucidate how PTSD susceptibility evolves throughout life. HIGHLIGHTS Adversity during pregnancy is thought to increase offspring’s PTSD risk following later life trauma, but exact neurobiological mechanisms underlying this process remain unknown. We found that effects of prenatal famine exposure on PTSD symptom severity were influenced by genetic variation in the glucocorticoid receptor, which signals effects of the stress hormone cortisol. Integrated approaches considering genetics and environmental contexts throughout both early and later life are important to understand how PTSD risk evolves throughout life.

Do prenatal factors shape the risk for dementia?: A systematic review of the epidemiological evidence for the prenatal origins of dementia.

Prenatal factors such as maternal stress, infection and nutrition affect fetal brain development and may also influence later risk for dementia. The purpose of this systematic review was to provide an overview of all studies which investigated the association between prenatal factors and later risk for dementia. We systematically searched MEDLINE and Embase for original human studies reporting on associations between prenatal factors and dementia from inception to 23 November 2022. Prenatal factors could be any factor assessed during pregnancy, at birth or postnatally, provided they were indicative of a prenatal exposure. Risk of bias was assessed using the Newcastle Ottawa Scale. We followed PRISMA guidelines for reporting. A total of 68 studies met eligibility criteria (including millions of individuals), assessing maternal age (N = 30), paternal age (N = 22), birth order (N = 15), season of birth (N = 16), place of birth (N = 13), prenatal influenza pandemic (N = 1) or Chinese famine exposure (N = 1), birth characteristics (N = 3) and prenatal hormone exposure (N = 4). We observed consistent results for birth in a generally less optimal environment (e.g. high infant mortality area) being associated with higher dementia risk. Lower and higher birth weight and prenatal famine exposure were associated with higher dementia risk. The studies on season of birth, digit ratio, prenatal influenza pandemic exposure, parental age and birth order showed inconsistent results and were hampered by relatively high risk of bias. Our findings suggest that some prenatal factors, especially those related to a suboptimal prenatal environment, are associated with an increased dementia risk. As these associations may be confounded by factors such as parental socioeconomic status, more research is needed to examine the potential causal role of the prenatal environment in dementia.

The need for appropriate 'age-balanced' controls and transparent reporting in Chinese famine studies: a re-analysis of the China Patient-centred Evaluative Assessment of Cardiac Events million persons project.

We read with interest the study by Chen et al.1 on an increased risk of adulthood cardiovascular diseases (CVD) after prenatal Chinese famine exposure. We re-examined the data with alternative analytical strategies of using different age-balanced controls and found that overlooking the assumption of a linear relationship between age and CVD among non-famine controls can lead to biased results. We encourage more rigorous epidemiological research methods and greater transparency in disclosing data and findings in future studies. First, Chen et al.1 compared CVD among famine births of 1958–1961 to those among ‘age-balanced’ controls of pre- and post-famine births (1949–1958 and 1963–1972) and found an increased CVD risk (odds ratio, OR = 1.28, 95% CI 1.16–1.41). This estimate was made with adjustments for age, sex, BMI, and others. In contrast, we calculated the crude OR based on CVD cases and the population at risk in Figure 1, which is smaller (OR = 1.03, 95% CI 0.94–1.13). This discrepancy between crude and adjusted ORs should be disclosed and explored because it is unclear the adjustment for which covariate(s) led to a bigger effect estimate.2,3 It is also questionable to adjust for BMI when examining the famine-CVD association because BMI can be the mediator and/or effect modifier in this relationship.2

Is it just a cure? Re-evaluating the effects of prenatal exposure to the Great Chinese Famine on the risk of infectious diseases in adulthood

BackgroundVery limited studies focused on the early-life adversities on infectious diseases. Taking the Great Chinese famine as a natural experiment, this study re-evaluated the long-term effect of prenatal famine exposure on infectious diseases by using nationally representative data. MethodsUsing difference-in-difference (DID) models, we analyzed 215,216 adults who participated in the Second National Sample Survey on Disability in 2006 across 734 counties of China to detect the effects of prenatal exposure to the Great Chinese Famine on the risk of infectious diseases in adulthood. Infectious diseases were ascertained by using the combination of self-reports or family members’ reports and on-site medical diagnosis by experienced specialists, and the severity of famine was measured by the cohort size shrinkage index (CSSI) at the county level. ResultsAll DID estimates of the effects of famine on the probability of infectious diseases were insignificant, with a coefficient of 0.0007 (−0.0024, 0.0026) for all participants and coefficients of 0.0001 (−0.0041, 0.0043) and −0.0002 (−0.0036, 0.0033) for males and females, respectively. That is, the famine cohort dwelling in regions with a greater intensity of famine had similar levels of infectious disease risks than the cohorts with post-famine prenatal exposure experience in less affected famine regions. Furthermore, there were no significant famine and post-famine cohort differences in the DID estimates by examining the variations in subgroups with different types of infectious diseases (trachoma, poliomyelitis, tuberculosis, maternal infections and other infectious diseases). ConclusionNo significant impact of prenatal exposure to the Chinese famine was observed on the risk of infectious diseases in adulthood. Famine survivors may be “cured” by the famine and were resilient to adverse environments in their life course because selective mortality may weaken the association between adverse prenatal exposure and later health.

ABCB9 polymorphism rs61955196 is associated with schizophrenia in a Chinese Han population.

BACKGROUNDSchizophrenia (SCZ) is a complex disease which can be affected by both genetic and environmental factors. Prenatal famine exposure may cause changes in DNA methylation levels of genes. Meanwhile, maternal nutrition during pregnancy is a pivotal environmental factor in the development of SCZ. DNA methylation may be an intermediate factor mediating exposure to famine during pregnancy and SCZ, and DNA methylation quantitative trait loci might serve as a promising tool for linking SCZ and prenatal famine. AIMTo analyze the association between prenatal famine exposure and SCZ risk in Northeast Han Chinese through analysis of DNA methylation related loci.METHODSA total of 954 Han Chinese from Northeast China were recruited, including 443 patients with SCZ and 511 healthy controls. The participants were further divided into famine (born in 1960-1962) and non-famine (born in 1963-1965) groups to investigate the effect of prenatal famine exposure. Four single-nucleotide polymorphisms (SNPs) selected according to the relevant literature were genotyped, namely, rs11917047 in PTPRG, rs2239681 in IGF2, rs3842756 in INSIGF, and rs61955196 in ABCB9. DNA were extracted from peripheral blood samples, and the genotypes of these SNP loci were detected using the improved Multiple Ligase Detection Reaction multiple SNP typing technique. The associations of the DNA methylation related SNPs with SCZ risk and prenatal famine, and their interactions were analyzed using logistic regression analysis and generalized multifactor dimensionality reduction (GMDR) software.RESULTSBased on the sequencing data, genotype distributions and allele frequencies of the four selected SNPs were determined. All genotype frequencies of the four SNPs in the healthy control group were tested for deviation from Hardy-Weinberg equilibrium (P > 0.05). Logistic regression analysis showed that rs61955196 was significantly associated with SCZ risk in the log-additive model [odds ratio (OR): 1.22; 95% confidence interval (CI): 1.01-1.48; P = 0.040]. We also found that the rs61955196 allele was related with an enhanced risk of SCZ (G>C, OR: 1.22; 95%CI: 1.01-1.47; P = 0.042). However, no associations were observed between rs11917047, rs2239681, or rs3842756 and SCZ risk. Under the optimal genetic model, no significant association of famine with the four SNPs was seen. Though the gene–gene interactions between rs2239681 and rs61955196 were found in GMDR analysis, none of the gene-gene interactions and gene-famine interactions were associated with the risk of SCZ.CONCLUSIONOur study suggested that rs61955196 in ABCB9 is associated with SCZ susceptibility in Northeast Han Chinese, providing insight into genetic effects on SCZ.

Thyroid Function at Age Fifty After Prenatal Famine Exposure in the Dutch Famine Birth Cohort.

BackgroundEarly-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women.MethodsThis study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation.ResultsThere were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women.ConclusionsThere are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation 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

BackgroundThe 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.MethodsParticipants 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.ResultsCompared 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).ConclusionsFamine 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.

Impact of prenatal famine exposure on adulthood fasting blood glucose level

In the past decade, in low-income countries, there have been a rapid rise in prevalence of diabetes among adult population. Hence, understanding the context specific drivers of this change including the impacts of childhood nutrition adversaries on adult metabolic conditions is critical undertaking. This study investigates the potential effects of prenatal famine exposure to the Ethiopian great famine (1983–1985) on adulthood blood glucose level of survivors. A total of 441 adults (222 exposed and 219 controls) were included in the study. Self-reported place of birth and, date of birth and/or age were used to identify participants. A multivariable linear regression analysis was used to analyze the impact of prenatal famine exposure on the level of fasting blood glucose. In linear regression, unadjusted model (Model 1), fasting blood glucose level was increased by 4.13 (β = 4.13; 95% CI .41, 7.42) points in prenatal famine exposed groups, compared with non-exposed. Similarly, the positive association of prenatal famine exposure and fasting blood glucose level was maintained after adjusted for sex (Model 2) (β = . 4.08 95% CI .056, 7.50). Further adjusted for age, residence, educational status, wealth index and family size (Model 3) resulted in 4.10 (β = . 4.10 95% CI .45, 7.56) points increases in fasting blood glucose level. In model 4 adjusting for dietary pattern, physical activity level and family history of diabetes, alcohol and cigarette smoking resulted in 3.90 (β = 3.90, 95% CI 039, 7.52) points increase in fasting glucose level. In the he full adjusted model (Model 5) prenatal exposure to famine was resulted in 3.78 (β = 3.78, 95% CI .22, 7.34) increases in fasting blood glucose level after adjusted for BMI and waist to height ratio. There existed a positive association of prenatal famine exposure and adulthood blood glucose levels. In this population, establishing effective overweight/obesity prevention programs to minimize the co-impact of early famine exposure on blood glucose control are important.

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

Although there has been increasing recognition that famine exposure in the fetal stage damages liver function in adulthood, this deteriorated effect could be extended to the next generation remains vague. This study aimed to explore whether famine exposure was associated with liver function in the two consecutive generations, and its association with the mediation role of inflammatory markers. We analyzed the data of 2,681 participants from Suihua rural area, Heilongjiang Province, China. According to the date of birth, the participants were classified as fetal exposed and nonexposed. The F2 subjects were classified as having no parents exposed to famine, maternal famine exposure, paternal famine exposure, or parental famine exposure. In the mixed-effect models, prenatal exposure to famine was associated with the elevation of Δ aspartate aminotransferase (ΔAST) (β: 0.22, 95% CI: 0.01, 0.43) and Δ alanine aminotransferase (ΔALT) (β: 0.42, 95% CI: 0.19, 0.66) levels in F1 adults. The mediation analysis showed that the inflammatory markers including serum C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) might mediate the famine-liver function association. This longitudinal data were consistent with the hypothesis that the inflammatory markers explained part of the influence of prenatal famine exposure on liver function injury, and the natal mechanism was needed to be elucidated in the future study.

Prenatal famine exposure and adult health outcomes: an epigenetic link.

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

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

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

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

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

Consequences of exposure to prenatal famine on estimated glomerular filtration rate and risk of chronic kidney disease among survivors of the great Ethiopian famine (1983\u201385): a historical cohort study

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

Consequences of early life exposure to the 1983-1985 Ethiopian Great Famine on cognitive function in adults: a historical cohort study.

ObjectivesTo investigate the association between early life famine exposure and cognitive function in adults.DesignHistorical cohort studySettingNorth Wollo Zone, Northeast Ethiopia.ParticipantsWe recruited 1047 adult men and women aged 30–38 years who had history of early life exposure to Ethiopian great famine. Based on self-reported age and birth date, participants were categorised into famine exposed in early life (prenatal/postnatal) and non-exposed groups.Outcome measuresThe primary outcome measure of this study was cognitive function in adults after early life exposure to famine. Cognitive function was measured using Montreal Cognitive Assessment—basic. Associations between exposure and outcome variables were examined by linear regression analysis models.ResultsAdjusted for covariates, early life exposure to famine showed 1.29 (β=−1.29; 95% CI −2.16 to -0.52) points lower cognitive function score compared with non-exposed. Based on subanalysis for timing of famine exposure, postnatal exposure to famine resulted in 2.26 (β=−2.26; 95% CI −3.12 to -1.36) points lower cognitive function score compared with non-exposed groups. Prenatal famine exposure had 1.26 (β=−1.26; 95% CI −2.35 to 0.94) points lower cognitive function score although not statistically significant.ConclusionsFamine exposure in early life was associated with cognitive functions in adults. While the overall findings highlight the importance of optimal nutrition in early life for brain growth and development, the association observed between postnatal famine exposure and adult cognitive function may indicate the relative importance of learning and experience during early childhood for optimal brain development after birth. Further studies are needed to elucidate the potential mechanism behind this association.