Prenatal famine exposure and adult mortality from cancer, cardiovascular disease, and other causes through age 63 years.
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ABSTRACT:
SUBMITTER: Ekamper P
PROVIDER: S-EPMC4325678 | biostudies-literature | 2015 Feb
REPOSITORIES: biostudies-literature
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Prenatal famine exposure and adult mortality from cancer, cardiovascular disease, and other causes through age 63 years.
Ekamper Peter P van Poppel Frans F Stein Aryeh D AD Bijwaard Govert E GE Lumey L H LH
American journal of epidemiology 20150127 4
Nutritional conditions in early life may affect adult health, but prior studies of mortality have been limited to small samples. We evaluated the relationship between pre-/perinatal famine exposure during the Dutch Hunger Winter of 1944-1945 and mortality through age 63 years among 41,096 men born in 1944-1947 and examined at age 18 years for universal military service in the Netherlands. Of these men, 22,952 had been born around the time of the Dutch famine in 6 affected cities; the remainder s ...[more]
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Project description:Background Early-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. Methods This 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. Results There 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. Conclusions There 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.
| S-EPMC9280834 | biostudies-literature
Project description:BackgroundUndernutrition 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.MethodsWe 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.ResultsWomen 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]).ConclusionsThese 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.
| S-EPMC8892724 | biostudies-literature
Project description:Epidemiological studies have shown a clear association of adverse intrauterine environment and an increased risk of cardiovascular diseases and hypertension in adult life. The present study tested the hypothesis that prenatal cocaine exposure causes reprogramming of vascular reactivity, leading to an increased risk of hypertension in adult offspring. Pregnant rats received cocaine (30 mg kg(-1) day(-1)) or saline from days 15 to 21 of gestational age, and experiments were conducted in 3-month-old offspring. Cocaine had no effect on the baseline blood pressure but significantly increased norepinephrine-stimulated blood pressure and decreased the baroreflex sensitivity in male but not female offspring. The cocaine treatment significantly increased norepinephrine-induced contractions in pressurized resistance-sized mesenteric arteries but not in aortas, which was primarily because of a loss of endothelial NO synthase-mediated inhibition and an enhanced Ca(2+) sensitivity in mesenteric arteries. In addition, the cocaine treatment significantly attenuated the endothelium-dependent relaxation in mesenteric arteries in male but not female offspring. Endothelial NO synthase protein levels in aortas but not mesenteric arteries were significantly increased in the cocaine-treated animals. However, cocaine significantly decreased phosphorylation levels of endothelial NO synthase in both aortas and mesenteric arteries. The results suggest that prenatal cocaine exposure programs vascular contractility via changes in endothelial NO synthase-regulated Ca(2+) sensitivity of myofilaments in the sex- and tissue-dependent manners in resistance arteries leading to an increased risk of hypertension in male offspring.
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Project description: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.
| S-EPMC9008050 | biostudies-literature
Project description:Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life.
| S-EPMC4246417 | biostudies-literature
Project description:BackgroundPrenatal exposure to famine and adulthood obesity have been independently related to the risk of type 2 diabetes; however, little is known about the joint effects of these risk factors at different stages of life on adulthood diabetes risk.MethodsThe analysis included 88 830 participants of the China Kadoorie Biobank, who were born around the time of the Chinese Great Famine and without diabetes, cardiovascular diseases, or cancer at baseline. We defined famine exposure subgroups as nonexposed (born between 1 October 1962 and 30 September 964), fetal-exposed (born between 1 October 1959 and 30 September 1961) and early-childhood exposed (born between 1 October 1956 and 30 September 1958). General obesity was assessed by body mass index (BMI: overweight ≥ 24.0, obesity ≥ 28.0) and abdominal obesity assessed by waist-to-hip ratio (WHR, men/women: moderate ≥ 0.90/0.85, high ≥ 0.95/0.90).ResultsDuring a median 7.3 years (642 552 person-years) of follow-up, we identified 1372 incident cases of type 2 diabetes. Compared with nonexposed and early-childhood exposed participants combined as a single comparison group, fetal-exposed participants showed an increased risk of diabetes in adulthood [hazard ratio (HR) = 1.25; 95% confidence interval (CI): 1.07-1.45]. The association between general obesity and diabetes was consistent across subgroups according to famine exposure (P for interaction > 0.05). A stronger association between abdominal obesity and diabetes was observed in the fetal-exposed subgroup than in other subgroups (P for interaction = 0.025 in the whole population). This interaction was more obvious in women (P = 0.013) but not in men (P = 0.699). Compared with normal-BMI and -WHR participants, those with both general (BMI ≥ 24.0) and abdominal (WHR ≥ 0.90/0.85) obesity in adulthood had 5.32 (95% CI: 3.81-7.43)-, 3.13 (2.48-3.94)- and 4.43 (3.45-5.68)-fold higher risks if these were carried during, before and after times of famine, respectively.ConclusionsCoexistence of prenatal experience of undernutrition and abdominal obesity in adulthood was associated with a higher risk of type 2 diabetes.
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Project description:BACKGROUND:Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms. METHODS:A subsample (n = 1,311) of the Avon Longitudinal Study of Parents and Children (Bristol, UK) was selected, and mercury (Hg) concentrations were measured in freeze-dried umbilical cord tissue as a measure of MeHg exposure. A total of 1135 children had available data on 247 single-nucleotide polymorphisms (SNPs) within relevant genes, as well as the Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) scores at age 8 years. Multivariate regression models were used to assess the associations between MeHg exposure and IQ and to determine possible gene-environment interactions. RESULTS:Hg concentrations indicated low background exposures (mean = 26 ng/g, standard deviation = 13). Log10-transformed Hg was positively associated with IQ, which attenuated after adjustment for nutritional and sociodemographic cofactors. In stratified analyses, a reverse association was found in higher social class families (for performance IQ, P value for interaction = 0.0013) among whom there was a wider range of MeHg exposure. Among 40 SNPs showing nominally significant main effects, MeHg interactions were detected for rs662 (paraoxonase 1) and rs1042838 (progesterone receptor) (P < 0.05) and for rs3811647 (transferrin) and rs2049046 (brain-derived neurotrophic factor) (P < 0.10). CONCLUSIONS:In this population with a low level of MeHg exposure, there were only equivocal associations between MeHg exposure and adverse neuropsychological outcomes. Heterogeneities in several relevant genes suggest possible genetic predisposition to MeHg neurotoxicity in a substantial proportion of the population. Future studies need to address this possibility.
| S-EPMC6477679 | biostudies-literature
Project description:Importance:Although antibiotics are associated with obesity in animal models, the evidence in humans is conflicting. Objective:To assess whether antibiotic exposure during pregnancy and/or early childhood is associated with the development of childhood obesity, focusing particularly on siblings and twins. Design, Setting, and Participants:This cross-sectional national study included 284 211 participants (132 852 mothers and 151 359 children) in New Zealand. Data analyses were performed for 150 699 children for whom data were available, 30 696 siblings, and 4188 twins using covariate-adjusted analyses, and for 6249 siblings and 522 twins with discordant outcomes using fixed-effects analyses. Data analysis was performed November 2017 to March 2019. Exposure:Exposure to antibiotics during pregnancy and/or early childhood. Main Outcomes and Measures:The main outcome is odds of obesity at age 4 years. Anthropometric data from children born between July 2008 and June 2011 were obtained from the B4 School Check, a national health screening program that records the height and weight of 4-year-old children in New Zealand. These data were linked to antibiotics (pharmaceutical records) dispensed to women before conception and during all 3 trimesters of pregnancy and to their children from birth until age 2 years. Results:The overall study population consisted of 132 852 mothers and 151 359 children (77 610 [51.3%] boys) who were aged 4 to 5 years when their anthropometrical measurements were assessed. Antibiotic exposure was common, with at least 1 course dispensed to 35.7% of mothers during pregnancy and 82.3% of children during the first 2 years of life. Results from covariate-adjusted analyses showed that both prenatal and early childhood exposures to antibiotics were independently associated with obesity at age 4 years, in a dose-dependent manner. Every additional course of antibiotics dispensed to the mothers yielded an adjusted odds ratio (aOR) of obesity in their children (siblings) of 1.02 (95% CI, 0.99-1.06), which was similar to the odds across pregnancy for the whole population (aOR, 1.06; 95% CI, 1.04-1.07). For the child's exposure, the aOR for the association between antibiotic exposure and obesity was 1.04 (95% CI, 1.03-1.05) among siblings and 1.05 (95% CI, 1.02-1.09) among twins. However, fixed-effects analyses of siblings and twins showed no associations between antibiotic exposure and obesity, with aORs of 0.95 (95% CI, 0.90-1.00) for maternal exposure, 1.02 (95% CI, 0.99-1.04) for child's exposure, and 0.91 (95% CI, 0.81-1.02) for twins' exposure. Conclusions and Relevance:Although covariate-adjusted analyses demonstrated an association between antibiotic exposure and odds of obesity, further analyses of siblings and twins with discordant outcomes showed no associations. Thus, these discordant results likely reflect unmeasured confounding factors.
| S-EPMC6991276 | biostudies-literature
Project description:BackgroundPrevious reports suggest that prenatal phthalate exposure is associated with lower scores on measures of motor skills in infants and toddlers. Whether these associations persist into later childhood or preadolescence has not been studied.MethodsIn a follow up study of 209 inner-city mothers and their children the concentrations of mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monomethyl phthalate (MEP), mono-carboxy-isooctyl phthalate (MCOP), and four di-2-ethylhexyl phthalate metabolites (ΣDEHP) were measured in spot urine sample collected from the women in late pregnancy and from their children at ages 3, 5, and 7 years. The Bruininks-Oseretsky Test of Motor Proficiency short form (BOT-2) was administered at child age 11 to assess gross and fine motor skills.ResultsThe total number of children included in the study was 209. Of the 209 children, 116(55.5%) were girls and 93 were (45%) boys. Among girls, prenatal MnBP(b=-2.09; 95%CI: [-3.43, -0.75]), MBzP (b=-1.14; [95%CI: -2.13, -0.14]), and MiBP(b=-1.36; 95%CI: [-2.51, -0.21] and MEP(b=-1.23 [95%CI: -2.36, -0.11]) were associated with lower total BOT-2 composite score. MnBP (b= -1.43; 95% CI: [-2.44, -0.42]) was associated with lower fine motor scores and MiBP(b = -0.56; 95% CI: [-1.12, -0.01]) and MEP (b = -0.60; 95% CI: [-1.14, -0.06])was associated with lower gross motor scores. Among boys, prenatal MBzP (b = -0.79; 95% CI: [-1.40, -0.19]) was associated with lower fine motor composite score. The associations between MEP measured at age 3 and the BOT-2 gross motor, fine motor and total motor score differed by sex. In boys, there was an inverse association between ΣDEHP metabolites measured in childhood at ages 3 (b = -1.30; 95% CI: [-2.34, -0.26]) and 7 years (b = -0.96; 95% CI: [-1.79, -0.13]), and BOT-2 fine motor composite scores.ConclusionsHigher prenatal exposure to specific phthalates was associated with lower motor function among 11- year old girls while higher postnatal exposure to ΣDEHP metabolites was associated with lower scores among boys. As lower scores on measures of motor development have been associated with more problems in cognitive, socioemotional functioning and behavior, the findings of this study have implications related to overall child development.
| S-EPMC6814270 | biostudies-literature
Project description:ObjectiveEvidence from the 1944-1995 Dutch Hunger Winter and the 1959-1961 Chinese famines suggests that those conceived or in early gestation during famines, have a 2-fold increased risk of developing schizophrenia in adult life. We tested the hypothesis in a second Chinese population and also determined whether risk differed between urban and rural areas.MethodThe risk of schizophrenia was examined in Liuzhou prefecture of Guangxi autonomous region. Rates were compared among those conceived before, during, and after the famine years. Based on the decline in birth rates, we predicted that those born in 1960 and 1961 would have been exposed to the famine during conception or early gestation. All psychiatric case records in Liuzhou psychiatric hospital for the years 1971 through 2001 were examined and clinical/sociodemographic data extracted by psychiatrists blind to exposure status. Data on births and deaths in the famine years were also available, and cumulative mortality was estimated from later demographic surveys. Evidence of famine was verified, and results were adjusted for mortality. Relative risks (RRs) for schizophrenia were calculated for the region as a whole and for urban and rural areas separately.ResultsMortality-adjusted RR for schizophrenia was 1.5 (1960) and 2.05 (1961), respectively. However, the effect was exclusively from the rural areas RR = 1.68 (1960) and RR = 2.25 (1961).ConclusionsWe observe a 2-fold increased risk of schizophrenia among those conceived or in early gestation at the height of famine with risk related to severity of famine conditions.
| S-EPMC2669578 | biostudies-literature