Overweight and obesity at age 19 after pre-natal famine exposure.
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ABSTRACT: Background
Weight 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.Methods
We 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.Results
There 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.Conclusions
The 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.
SUBMITTER: Lumey LH
PROVIDER: S-EPMC8310790 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceThe long-term impacts of early-life famine exposure on Type 2 Diabetes Mellitus (T2DM) have been widely documented across countries, but it remains less clear what is the critical time window and if there is a dose-response between famine intensity and risk of T2DM.ObjectiveTo establish the relation between prenatal famine exposure and adult Type 2 diabetes mellitus (T2DM).DesignA national cross-sectional study.SettingThe man-made Ukrainian Holodomor famine of 1932-1933.ParticipantsA total number of 128,225 T2DM cases diagnosed at age 40 or over from the national diabetes register 2000-2008 in Ukraine. The population at risk includes 10,186,016 Soviet Ukraine births (excepting one oblast/province) between 1930-1938 classified by month and year and oblast of birth.ExposureBirths born in January-June 1934 from oblasts that experienced extreme, severe, or significant famine in 1932-1933. Famine intensity was measured based on the excess mortality during the famine.Main outcomes and measuresT2DM diagnosis was based on WHO (1999) criteria.ResultsWe observed in univariate analysis a 1.8-fold increase in T2DM (OR 1.80; 95% CI 1.74-1.85) among individuals born in the first half-year of 1934 in regions with extreme, severe, or significant famine. We observed no increase among individuals born in regions with no famine. In multivariate analysis across regions and adjusting for season of birth we observed a larger than 2-fold increase (OR 2.21; 95% CI 2.00-2.45). There was a dose-response by famine intensity, with ORs increasing from 1.94 to 2.39 across regions. The pattern was similar in men and women.Conclusions and relevanceBirths in the first half-year of 1934 were conceived at the height of the Ukraine famine in 1933. This relation for T2DM outcomes points to early gestation as a critical time window relating maternal nutrition in pregnancy to offspring health in later life. Further studies of biological mechanisms should focus on this time window for which changes in DNA methylation and later body size have also been observed.
| S-EPMC10723511 | biostudies-literature
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.
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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:The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother-child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
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Project description:Hurricane Maria was the worst recorded natural disaster to affect Puerto Rico. Increased stress in pregnant women during and in the aftermath of the hurricane may have induced epigenetic changes in their infants, which could affect gene expression. Stage of gestation at the time of the event was associated with significant differences in DNA methylation in the infants, especially those who were at around 20-25 weeks of gestation when the hurricane struck. Significant differences in DNA methylation were also associated with maternal mental status assessed after the hurricane, and with property damage. Hurricane Maria could have long lasting consequences to children who were exposed to this disaster during pregnancy.
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Project description:ObjectivesTo examine the association of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with anthropometry in the offspring of mothers with gestational diabetes mellitus (GDM).MethodsWe performed a retrospective cohort study in 1263 GDM mother-child pairs. General linear models and Logistic regression models were used to assess the single and joint associations of maternal pre-pregnancy BMI (normal weight, overweight, and obesity) and GWG (inadequate, adequate and excessive GWG) with anthropometry and overweight status in the offspring from birth to 1-5 years old.ResultsMaternal pre-pregnancy BMI and GWG were positively associated with birth weight for gestational age Z score and birth weight for length for gestational age Z score at birth, and weight for age Z score, length/height for age Z score, and weight for length/height Z score at of 1-5 years old offspring. Maternal pre-pregnancy overweight, obesity, and excessive GWG were associated with increased risks of large for gestational age [ORs 95% CIs = 1.87 (1.37-2.55), 2.98 (1.89-4.69), and 2.93 (2.07-4.13), respectively] and macrosomia [ORs 95% CIs = 2.06 (1.50-2.84), 2.89 (1.78-4.70), and 2.84 (1.98-4.06), respectively] at birth and childhood overweight at 1-5 years old [ORs 95% CIs = 1.26 (0.92-1.73), 1.96 (1.24-3.09), and 1.59 (1.15-2.21), respectively].ConclusionsOffspring born to GDM mothers with pre-pregnancy overweight/obesity or excessive GWG were associated with increased risks of large for gestational age and macrosomia at birth, and childhood overweight at 1-5 years old, compared with those born to GDM mothers with pre-pregnancy normal weight and adequate GWG.
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Project description:BACKGROUND:A healthy diet is important for normal growth and development. Exposure to undernutrition during important developmental periods such as childhood and adolescence can have effects later in life. Inhabitants of the west of the Netherlands were exposed to severe undernutrition during the famine in the last winter of the second World War (1944-1945). OBJECTIVE:We investigated if exposure of women to the Dutch famine during childhood and adolescence was associated with an unhealthy lifestyle later in life. DESIGN:We studied 7,525 women from the Prospect-EPIC cohort, recruited in 1993-97 and aged 0-18 years during the Dutch famine. An individual famine score was calculated based on self-reported information about experience of hunger and weight loss. We investigated the association between famine exposure in early life and four lifestyle factors in adulthood: smoking, alcohol consumption, physical activity level and a Mediterranean-style diet. RESULTS:Of the 7,525 included women, 46% were unexposed, 38% moderately exposed and 16% severely exposed to the Dutch famine. Moderately and severely exposed women were more often former or current smokers compared to women that did not suffer from the famine: adjusted prevalence ratio 1.10 (95% CI: 1.05; 1.14) and 1.18 (1.12; 1.25), respectively. They also smoked more pack years than unexposed women. Severely exposed women were more often physically inactive than unexposed women, adjusted prevalence ratio 1.32 (1.06; 1.64). Results did not differ between exposure age categories (0-9 and 10-17 years). We found no associations of famine exposure with alcohol consumption and no dose-dependent relations with diet. CONCLUSIONS:Exposure to famine early in female life may be associated with higher prevalence of smoking and physical inactivity later in life, but not with unhealthy diet and alcohol consumption.
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Project description:The current opioid crisis, which has ravaged all segments of society, continues to pose a rising public health concern. Importantly, dependency on prescription opioids such as oxycodone (oxy) during and after pregnancy can significantly impact the overall brain development of the exposed offspring, especially at the synapse. A significant knowledge gap that remains is identifying distinct synaptic signatures associated with these exposed offspring. Accordingly, the overall goal of this current study was to identify distinct synaptic vesicle (SV) proteins as signatures for offspring exposed to oxy in utero (IUO) and postnatally (PNO). Using a preclinical animal model that imitates oxycodone exposure in utero (IUO) and postnatally (PNO), we used a quantitative mass spectrometry-based proteomics platform to examine changes in the synaptic vesicle proteome on post-natal day 14 (P14) IUO and PNO offspring. We identified MEGF8, associated with carpenter syndrome, to be downregulated in the IUO offspring while LAMTOR4, associated with the regulator complex involved in lysosomal signaling and trafficking, was found to be upregulated in the PNO groups, respectively. Their respective differential expression was further validated by Western blot. In summary, our current study shows exposure to oxy in utero and postnatally can impact the SV proteome in the exposed offspring and the identification of these distinct SV signatures could further pave the way to further elucidate their downstream mechanisms including developing them as potential therapeutic targets.
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Project description:Background and Purpose: Early age exposure to the Chinese Great Leap Forward famine (1959-1961) is associated with the incidence of risk factors for ischemic stroke. This study aims to examine the relationship between early age famine exposure and 12-month stroke recurrence. We sought to explore the interaction between famine exposure status and metabolic phenotypes on stroke recurrence and how the adherence of crucial evidence-based key performance indicators (KPI) would modify this interaction. Methods: We analyzed data of patients who were born between 1953 and 1964 in the China National Stroke Registry II (CNSR-II). The study population was further divided into five subgroups for comparing 12-month stroke recurrence. A multivariate Cox proportional hazard regression model was used in analyzing the impact of the concurrence of metabolic phenotypes-type 2 diabetes (T2D) or metabolic syndrome (MetS)-and early-age famine exposure on recurrent risk. The influence of the adherence to predefined KPI and concurrency of metabolic phenotype was also evaluated. Results: Concurrent T2D and early age famine exposure was associated with an increased recurrence risk of ischemic stroke with 12 months [adjusted hazard ratio (HR): 1.63, 95% confidence interval (CI) 1.28-2.07]. Optimal adherence to KPI was not associated with significantly reduced risk of 12-month stroke recurrence (adjusted HR: 0.80, 95% CI: 0.51-1.26). Conclusions: Concurrency of early-age famine exposure and diabetes mellitus was associated with a higher risk of stroke recurrence within 12 months, and adherence to evidence-based KPI did not reduce the risk significantly.
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