Late-life Risk Research Articles

The LifeCycle Project-EU Child Cohort Network: a federated analysis infrastructure and harmonized data of more than 250,000 children and parents

Early life is an important window of opportunity to improve health across the full lifecycle. An accumulating body of evidence suggests that exposure to adverse stressors during early life leads to developmental adaptations, which subsequently affect disease risk in later life. Also, geographical, socio-economic, and ethnic differences are related to health inequalities from early life onwards. To address these important public health challenges, many European pregnancy and childhood cohorts have been established over the last 30 years. The enormous wealth of data of these cohorts has led to important new biological insights and important impact for health from early life onwards. The impact of these cohorts and their data could be further increased by combining data from different cohorts. Combining data will lead to the possibility of identifying smaller effect estimates, and the opportunity to better identify risk groups and risk factors leading to disease across the lifecycle across countries. Also, it enables research on better causal understanding and modelling of life course health trajectories. The EU Child Cohort Network, established by the Horizon2020-funded LifeCycle Project, brings together nineteen pregnancy and childhood cohorts, together including more than 250,000 children and their parents. A large set of variables has been harmonised and standardized across these cohorts. The harmonized data are kept within each institution and can be accessed by external researchers through a shared federated data analysis platform using the R-based platform DataSHIELD, which takes relevant national and international data regulations into account. The EU Child Cohort Network has an open character. All protocols for data harmonization and setting up the data analysis platform are available online. The EU Child Cohort Network creates great opportunities for researchers to use data from different cohorts, during and beyond the LifeCycle Project duration. It also provides a novel model for collaborative research in large research infrastructures with individual-level data. The LifeCycle Project will translate results from research using the EU Child Cohort Network into recommendations for targeted prevention strategies to improve health trajectories for current and future generations by optimizing their earliest phases of life.

Life-course social class is associated with later-life diabetes prevalence in women: evidence from the Irish Longitudinal Study on Ageing

This study aimed to investigate the independent and synergistic effects of childhood and adult social class, as well as the effect of social mobility, on type 2 diabetes (T2D) risk in later life. Cross-sectional data from The Irish Longitudinal Study of Ageing (TILDA) (n = 4,998), a nationally representative probability sample of adults aged 50 and older, were analysed. Prevalent diabetes was defined using subjective (self-reported doctor’s diagnosis) and objective data (medications usage and glycated haemoglobin testing). Social class was classified as a three-level variable based on fathers’ occupation in childhood and respondents’ primary occupation in adulthood. A five-level social mobility variable was created from cross-classification of childhood and adulthood social class. Logistic regression was employed to assess the relationship between social class variables and T2D. Mean (SD) age of the sample was 63.8y (9.9) and 46.4% were male. Incidence of T2D was 11.6% of men and 7.7% of women. Some 57.4% of the sample were classified as Manual social class in childhood. Compared to those in Professional/Managerial occupations, belonging to the Manual social class in childhood was associated with an increased risk of T2D in men (Odds Ratio (OR): 1.36, 95% CI: 0.88, 2.10) and women (OR: 2.16, 95% CI: 1.21, 3.85). This association was attenuated in women when controlled for adulthood social class (OR: 1.84, 95% CI: 1.00–3.37), suggesting that the effect of childhood social class may be modified by improving social circumstance over the life course.

Abstract A51: Mechanistic pathways for breast carcinogens can highlight early effects as predictive endpoints for chemical safety testing: Case studies for ionizing radiation and for in utero exposure to estrogens such as DES

Abstract Knowledge about established breast carcinogens can support improved 21st-century toxicologic testing by identifying key mechanistic events. To clarify mechanisms, we developed adverse outcome pathways (AOPs) for two well-established breast carcinogens: ionizing radiation (IR) and the pharmaceutical hormone diethylstilbestrol (DES). The AOP for ionizing radiation includes these elements: IR increases production of reactive oxygen and nitrogen species (RONS), and directly and indirectly causes DNA damage. DNA damage leads to mutations and proliferation, leading to increased breast cancer. RONS also increases inflammation, contributing to direct and indirect effects (effects in cells not directly reached by IR) via positive feedback to RONS, and separately increases breast cancer risk through increased proliferation of cells and increased tumor growth and invasion. Estrogen and progesterone also influence the risk of breast cancer from ionizing radiation, as does developmental stage. For in utero estrogens like DES, the AOP links gestational estrogen exposure to transcriptional activity that promotes altered signaling between the epithelial and stromal tissue compartments, leading to disrupted development, including altered tensional homeostasis and tissue architecture, inflammation, and altered cellular differentiation. These key events lead to several adverse outcomes at the tissue and organ level that increase susceptibility to breast cancer, including altered density, structure, and hormone sensitivity along with hyperplasia. Epigenetic alterations are a cellular-level outcome that propagates gestational estrogen exposure to later-life risk through cellular memory that directs ER-mediated gene expression and altered mammary development. Increased susceptibility to breast cancer follows from these adverse outcomes. Dose-response and developmental timing of exposure are discussed in both AOPs. These AOPs provide a framework for evaluating the potential for mechanistically similar stressors—e.g., genotoxicants/RONS-inducers may act like IR, or estrogenic chemicals in utero may act like DES—to affect breast cancer risk. Citation Format: Jessica Helm, Andrea Hindman, Ruthann A. Rudel. Mechanistic pathways for breast carcinogens can highlight early effects as predictive endpoints for chemical safety testing: Case studies for ionizing radiation and for in utero exposure to estrogens such as DES [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A51.

1．肥満・糖尿病の病態と腸内細菌叢 1）新生児・乳幼児期の腸内細菌叢の構築―出生早期の腸内細菌叢構築とその後の非感染性疾患リスクとの関連―

1．肥満・糖尿病の病態と腸内細菌叢 1）新生児・乳幼児期の腸内細菌叢の構築―出生早期の腸内細菌叢構築とその後の非感染性疾患リスクとの関連―

Maternal prenatal urinary bisphenol A level and child cardio-metabolic risk factors: A prospective cohort study

Exposure to endocrine disrupting chemicals during the first 1000 days of life may have long-lasting adverse effects on cardio-metabolic risk in later life. This study aimed to examine the associations between maternal prenatal Bisphenol A (BPA) exposure and child cardio-metabolic risk factors at age 2 years in a prospective cohort. During 2012–2013, 218 pregnant women were enrolled at late pregnancy from Shanghai, China. Urinary BPA concentration was measured in prenatal and child 2-year spot urine samples, and classified into high, medium and low tertiles. Child adiposity anthropometric measurements, random morning plasma glucose, serum insulin, and lipids (high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride), systolic (SBP) and diastolic blood pressure (DBP) were measured. Linear regression was used to evaluate the associations between prenatal BPA and each of the cardio-metabolic risk factors in boys and girls, respectively, adjusting for pertinent prenatal, perinatal and postnatal factors. BPA was detectable (>0.1 μg/L) in 98.2% of mothers prenatally and 99.4% of children at age 2 years. Compared to those with low prenatal BPA, mean SBP was 7.0 (95%CI: 2.9–11.2) mmHg higher, and DBP was 4.4 (95%CI: 1.2–7.5) mmHg higher in girls with high prenatal BPA levels, but these associations were not found in boys. In boys, medium maternal prenatal BPA level was associated with 0.36 (95% CI: 0.04–0.68) mmol/L higher plasma glucose. No associations were found between prenatal BPA and child BMI, skinfold thicknesses, serum lipids, or insulin in either girls or boys. There were no associations between concurrent child urinary BPA and cardio-metabolic risk factors. These results support that BPA exposure during prenatal period, susceptible time for fetal development, may be associated with increase in child BP and plasma glucose in a sex-specific manner. Further independent cohort studies are needed to confirm the findings.

Factors influencing peak bone mass gain.

Bone mass is a key determinant of osteoporosis and fragility fractures. Epidemiologic studies have shown that a 10% increase in peak bone mass (PBM) at the population level reduces the risk of fracture later in life by 50%. Low PBM is possibly due to the bone loss caused by various conditions or processes that occur during adolescence and young adulthood. Race, gender, and family history (genetics) are responsible for the majority of PBM, but other factors, such as physical activity, calcium and vitamin D intake, weight, smoking and alcohol consumption, socioeconomic status, age at menarche, and other secondary causes (diseases and medications), play important roles in PBM gain during childhood and adolescence. Hence, the optimization of lifestyle factors that affect PBM and bone strength is an important strategy to maximize PBM among adolescents and young people, and thus to reduce the low bone mass or osteoporosis risk in later life. This review aims to summarize the available evidence for the common but important factors that influence bone mass gain during growth and development and discuss the advances of developing high PBM.

DNA methylation loci in placenta associated with birthweight and expression of genes relevant for early development and adult diseases

BackgroundBirthweight marks an important milestone of health across the lifespan, including cardiometabolic disease risk in later life. The placenta, a transient organ at the maternal-fetal interface, regulates fetal growth. Identifying genetic loci where DNA methylation in placenta is associated with birthweight can unravel genomic pathways that are dysregulated in aberrant fetal growth and cardiometabolic diseases in later life.ResultsWe performed placental epigenome-wide association study (EWAS) of birthweight in an ethnic diverse cohort of pregnant women (n = 301). Methylation at 15 cytosine-(phosphate)-guanine sites (CpGs) was associated with birthweight (false discovery rate (FDR) < 0.05). Methylation at four (26.7%) CpG sites was associated with placental transcript levels of 15 genes (FDR < 0.05), including genes known to be associated with adult lipid traits, inflammation and oxidative stress. Increased methylation at cg06155341 was associated with higher birthweight and lower FOSL1 expression, and lower FOSL1 expression was correlated with higher birthweight. Given the role of the FOSL1 transcription factor in regulating developmental processes at the maternal-fetal interface, epigenetic mechanisms at this locus may regulate fetal development. We demonstrated trans-tissue portability of methylation at four genes (MLLT1, PDE9A, ASAP2, and SLC20A2) implicated in birthweight by a previous study in cord blood. We also found that methylation changes known to be related to maternal underweight, preeclampsia and adult type 2 diabetes were associated with lower birthweight in placenta.ConclusionWe identified novel placental DNA methylation changes associated with birthweight. Placental epigenetic mechanisms may underlie dysregulated fetal development and early origins of adult cardiometabolic diseases.Clinical trial registrationClinicalTrials.gov, NCT00912132

SAT-616 Associations Of Body Mass Index And Waist Circumference In Young Adulthood With Later Life Incident Diabetes

Background: Overweight and obesity are known risk factors for incident diabetes, but it remains unclear if exposures during young adulthood (age 18 to 39 years) contribute to mid and late-life (age ≥40 years, collectively labeled here as “later-life”) risk of incident diabetes independent of later-life risk factor exposures. Objective: We sought to assess the independent associations between young adult exposures to overweight and obesity, as assessed by body mass index (BMI) and waist circumference (WC), with later-life incident diabetes, accounting for later-life exposures. Methods: We pooled data from six US cohorts (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, and MESA), and imputed life-course risk factor trajectories for BMI and WC, as well as for multiple cardiometabolic risk factors, annually from age 18 years to end of follow-up for each participant. Incident diabetes was defined by observed fasting blood glucose ≥126 mg/dL, non-fasting glucose ≥200, or use of diabetes medications. We used Cox proportional hazards models to examine the independent associations between time-weighted average exposures to BMI and WC during young adulthood and incident diabetes. We also performed mediation analyses to assess whether these associations were mediated by young adult exposures to other cardiometabolic risk factors (blood pressure, lipids, insulin resistance). Results: 30,780 participants were included (mean age at first in-person visit 53.1±16.2 years; 56.1% female). Over a 9-year median follow-up, 4,323 participants had incident diabetes. Both young adult BMI and WC were associated with diabetes risk in a dose-dependent manner, independent of later-life BMI and WC. Compared to BMI 18.5–24.9 kg/m2, hazard ratios (HR) for incident diabetes were 1.27 (95%CI: 1.14–1.41) and 1.99 (95%CI: 1.67–2.37) for BMI 25–29 kg/m2 and ≥30 kg/m2, respectively. Similarly, compared to normal WC (≤80 cm women; ≤94 cm men), the HRs were 1.42 (95%CI: 1.26–1.59) for WC 81-88cm (women)/95-102cm (men) and 2.13 (95%CI: 1.87–2.43) for WC >88cm (women)/>102cm (men). Young adult homeostatic model of insulin resistance (HOMA-IR) mediated 49% (95%CI: 23–76) and 44% (95%CI: 26–62) of the association between young adult BMI and WC with later-life incident diabetes, respectively. Conclusions: Elevated BMI or WC during young adulthood were independently associated with later-life incident diabetes, after accounting for later-life BMI and WC, with insulin resistance suggested as a key mediator.

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m2; P=0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; P=0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; P=0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m2; P=0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; P=0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; P=0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm2; P=0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (P<0.01, P=0.01, and P=0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.

Phthalate Exposure During the Prenatal and Lactational Period Increases the Susceptibility to Rheumatoid Arthritis in Mice.

The prenatal and early postnatal period is highly sensitive to environmental exposures that may interfere with the developmental programming of the immune system leading to an altered disease risk in later life. To clarify the role of early influences in activation or exacerbation of autoimmune diseases like rheumatoid arthritis (RA) we investigated the effect of maternal exposure during the prenatal and lactational period of DBA/1 mice to the plasticizer benzyl butyl phthalate (BBP) on the development of RA in the offspring. Using a mild collagen-induced arthritis (CIA) model, maternal BBP-exposure increased both the prevalence and the severity of RA in the progeny compared to un-exposed dams. Additionally, maternal BBP exposure led to elevated serum IgG1 and IgG2a level in the offspring and increased the IFN-γ and IL-17 release from collagen-re-stimulated spleen cells. Transcriptome analysis of splenocytes isolated from 3-week-old pups before RA-induction revealed considerable changes in gene expression in the offspring from BBP-exposed dams. Among them were regulator of G-protein signaling 1 (rgs1), interleukin-7 receptor (il-7r) and CXC chemokine 4 (cxcr4), all genes that have previously been described as associated with RA pathology. In summary, our results demonstrate that perinatal exposure to BBP increases the susceptibility of the offspring to RA, probably via a phthalate-induced disturbed regulation of RA-relevant genes or signaling pathways.

Biochemical predictors for metabolic syndrome in preterm infants according to weight ratio.

Prematurity and low birth weight predispose preterm infants to cardiovascular disease in later life. Is the metabolic profile of these children impacted by the relation between birth weight and gestational age (GA)? This study aimed to evaluate whether the relationship between birth weight and GA of preterm infants has a positive correlation with the metabolic profile from birth to the sixth month of corrected age. This is a longitudinal, prospective study with a cohort of 70 preterm and 54 term infants, who were enrolled in the study and shared into two groups: Appropriate for GA (AGA) and Small for GA (SGA), both classified at birth by Fenton and Kim curves. Longitudinal evaluation of anthropometry measures and blood samples of total cholesterol, glucose, triglycerides, and insulin were collected at birth, NICU discharge, and the sixth month of corrected age. Data were analyzed using descriptive and inferential statistical analysis (ANOVA, Fisher test, Shapiro-Wilk, and Cochran test). The effect size was 0.15, power was 0.92, and confidence interval 95%. No significant statistical differences were observed in relation to biochemical tests between AGA and SGA groups. However, a significant increase in triglyceride results above the reference values for age in the SGA group was observed throughout the follow-up. Changes observed in the preterm infant metabolic profile show no correlation with adequacy of birth weight. Preterm lipid profile requires continuous evaluation at follow-up, due to the increased cardiovascular risk in later life.

Abstract P377: Changes in Leisure-time Physical Activity and Risk of Ischemic and Hemorrhagic Stroke: The Atherosclerosis Risk in Communities Study

Introduction: Engagement in leisure-time physical activity (PA) levels recommended by the American Heart Association (AHA) is inversely associated with both ischemic and hemorrhagic stroke risk. PA levels fluctuate over the lifecourse, but the association between changes in PA from mid- to late-life and stroke risk is unknown. Hypothesis: Participants who maintained ideal levels of PA or increased their PA across 6 years will have lower ischemic and hemorrhagic stroke risk relative to those who had persistently poor PA. Methods: We included 11,658 participants of the Atherosclerosis Risk in Communities study without a history of CHD or stroke at visit 3 (1993-1995). Leisure-time PA was assessed using the modified Baecke questionnaire at visits 1 and 3 and categorized according to the AHA guidelines for PA (ideal, intermediate, or poor). All adjudicated definite and probable incident ischemic and hemorrhagic strokes between visit 3 and end of year 2013 were included. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for ischemic and hemorrhagic stroke by categories of PA at visits 1 and 3. Those with poor PA at both visits were the referent group. We adjusted for age, sex, race/center, smoking, alcohol consumption, hypertension, diabetes mellitus, LDL, HDL, triglycerides, and body mass index. Results: During a median of 18.7 years of follow-up, 640 incident ischemic strokes and 76 hemorrhagic strokes occurred. In adjusted analyses, participants with ideal PA at both visits had a significantly lower ischemic stroke risk (HR=0.75 (0.59, 0.96)) but not significantly lower hemorrhagic stroke risk (HR=1.27 (0.65, 2.48)). Those whose PA levels increased from poor to ideal also had lower ischemic stroke risk (HR=0.74 (0.54, 1.03)) but not hemorrhagic stroke risk (HR=0.74 (0.28, 2.02)). Conclusion: Increasing PA between visit 1 and visit 3 was associated with lower ischemic stroke risk. Increasing PA may be an important component of stroke prevention.

Abstract 74: Relationship Between Preeclampsia and Subsequent Stroke: A Secondary Analysis of the Framingham Heart Study

Introduction: Although prior studies have examined the later-life risk of stroke in women with a history of preeclampsia, they have relied on claims data or epidemiological studies with poorly detailed risk factor or outcome data. The Framingham Heart Study (FHS) is a landmark epidemiological study that began in 1948 and followed participants aged 30-59 at baseline until death. The study enrolled 5,209 residents of Framingham, Massachusetts, almost half of which were female. The adjudicated outcome of stroke was ascertained during follow-up visits until 2015, death, or loss to follow-up. Methods: We examined a cohort of 2,136 women from FHS for an association of preeclampsia with stroke occurrence. With each subject having their own unique history of exposures and treatments that vary over time, standard approaches of adjusting for confounding are biased when time-dependent confounders exist. Using a marginal structural model, the effects of possible time-dependent confounders were controlled for using inverse-probability-of-treatment weighted estimators. At each of the study visits, potential confounders were evaluated. Variables controlled for, across the study visits, included age, blood pressure, cholesterol, weight, glucose, treatment for hypertension, treatment for hyperlipidemia, and smoking. Results: Two hundred women (9.4%) had preeclampsia and 380 women (17.8%) had strokes. As compared with the 1,936 women who did not have a history with preeclampsia, the 200 women with a history of preeclampsia had a significantly higher risk of stroke (adjusted Hazard Ratio, 2.29; 95% CI, 1.13 - 4.63) when controlling for time-dependent confounders. Conclusion: A history of preeclampsia is associated with a significantly increased risk of a future stroke. Prior approaches to analyses of this nature have not fully emphasized the importance of controlling for time-dependent confounders with methods such as marginal structural modeling. We plan on analyzing the mediators of the observed association to determine which risk factors might prove beneficial for disease-modifying treatment in midlife.

Promoting Healthy Lifestyle in High School Students: Determination of the Lifestyle Status through the Healthy Lifestyle Screen (HLS) Assessment.

BackgroundHealthy lifestyle behaviors have given emphasis as an important characteristic in health promotion and to prevent diseases. Individuals who practiced healthy lifestyle behaviors in the early stage of life can withstand health risks in later life. To this end, researchers conducted a healthy lifestyle assessment as the initial step in school-based programs promoting healthy lifestyle and wellness among high school students. The aim of this study was to determine the lifestyle status among students and further assess lifestyle components that could affect them.MethodsData were collected from 380 high school students from grades eighth (n = 192) and tenth (n = 188). The Healthy Lifestyle Screen (HLS) was utilized to assess the lifestyle condition of the subjects of this study and it has components consisting dietary behavior, exercise or physical activity, water intake, sunshine exposure, temperance or self-control, quality of air, quality of rest or sleep, trust of which the higher score denotes healthier lifestyle.ResultsThe results showed that respondents of the study are in the unstable lifestyle status as they obtained low mean sub-scale scores on lifestyle components such as water, rest and exercise. Lifestyle components included in HLS showed significant differences comprising the physical/mental, behavioral and environmental aspects (p < 0.001) associated with the general characteristics of the high school students.ConclusionFindings of this study showed the necessity in assessing the lifestyle status as an initial step for promoting, maintaining and establishing a well-balanced life and preventing the increase of health-risk behaviors and thus, highlighted the need of transforming healthy lifestyle behaviors among students through school-based intervention programs.

Hypertensive Complications of Pregnancy and Risk of Venous Thromboembolism.

Hypertension during pregnancy and preeclampsia are associated with increased arterial thrombotic risk in later life. Whether these complications are associated with risk of venous thromboembolism (VTE) on the short term after pregnancy and on the long term, that is, outside pregnancy, is largely unknown. We conducted a nationwide cohort study in women with at least 1 pregnancy and their first VTE risk by linking the Dutch perinatal registry (Perined) to anticoagulation clinics. We used Cox proportional hazard models to estimate hazard ratios (HRs) and corresponding 95% CI for VTE risk in women with hypertension during pregnancy, women with preeclampsia, compared with women with uncomplicated pregnancies (reference). A total of 1 919 918 women were followed for a median of 13.7 (interquartile range, 7.6–19.2) years for a total of 24 531 118 person-years in which 5759 first VTEs occurred; incidence rate: 2.3 (95% CI, 2.3–2.4) per 10 000 person-years. In the first pregnancy and 3-month postpartum period, VTE risk was higher in women with hypertension, HR, 2.0 (95% CI, 1.7–2.4), and highest among women with preeclampsia, HR, 7.8 (95% CI, 5.4–11.3), versus the reference group. On the long term, women with hypertension during pregnancy and preeclampsia had a higher VTE risk: HR, 1.5 (95% CI, 1.4–1.6) and HR, 2.1 (95% CI, 1.8–2.4), respectively, versus the reference group. When excluding events during pregnancy and postpartum, these HRs were 1.4 (95% CI, 1.3–1.5) and 1.6 (95% CI, 1.4–2.0), respectively. In conclusion, hypertension during pregnancy and preeclampsia are associated with an increased VTE risk during pregnancy and postpartum period and in the 13 years after.

The Gut Microbiome in Child Malnutrition.

Undernutrition affects almost 25% of all children under the age of 5 worldwide and underlies almost half of all child deaths. Child undernutrition is also associated with long-term growth deficits, in addition to reduced cognitive potential, reduced economic potential, and elevated chronic disease risk in later life. Dietary interventions alone are insufficient to comprehensively reduce the burden of child undernutrition and fail to address the persistent infectious burden of the disease. Although the role of infections is well recognized in the pathogenesis of undernutrition, an emerging body of evidence suggests that commensal microbial communities, known as the microbiome, also play an important role. The gut microbiome regulates energy harvesting from nutrients, growth hormone signaling, colonization resistance, and immune tolerance against pathogens, amongst other pathways critically associated with healthy child growth. Hence, disturbance of the normal gut microbial ecosystem via undernourished diets or unhygienic environments, especially in the early phases of life, may perturb these critical pathways associated with child growth, thereby contributing to child undernutrition. Here we discuss the emerging evidence for the role of the gut microbiome in child undernutrition and the potential for novel gut microbiota-targeted treatments to restore healthy child growth.

Statins Reverse Postpartum Cardiovascular Dysfunction in a Rat Model of Preeclampsia.

Preeclampsia is associated with increased cardiovascular long-term risk; however, the underlying functional and structural mechanisms are unknown. We investigated maternal cardiac alterations after preeclampsia. Female rats harboring the human angiotensinogen gene [TGR(hAogen)L1623] develop a preeclamptic phenotype with hypertension and albuminuria during pregnancy when mated with male rats bearing the human renin gene [TGR(hRen)L10J] but behave physiologically normal before and after pregnancy. Furthermore, rats were treated with pravastatin. We tested the hypothesis that statins are a potential therapeutic intervention to reduce cardiovascular alterations due to simulated preeclamptic pregnancy. Although hypertension persists for only 8 days in pregnancy, former preeclampsia rats exhibit significant cardiac hypertrophy 28 days after pregnancy observed in both speckle tracking echocardiography and histological staining. In addition, fibrosis and capillary rarefaction was evident. Pravastatin treatment ameliorated the remodeling and improved cardiac output postpartum. Preeclamptic pregnancy induces irreversible structural changes of cardiac hypertrophy and fibrosis, which can be moderated by pravastatin treatment. This pathological cardiac remodeling might be involved in increased cardiovascular risk in later life.

LONELINESS AND SUICIDE IDEATION IN OLDER ADULTS: A LONGITUDINAL INVESTIGATION

Older adults have the highest rates of suicide globally, necessitating theory and research investigating suicide and its prevention in later-life. The experience of loneliness is significantly associated with depression, hopelessness, negative health outcomes, and mortality among older adults. Yet, relatively little research has focused on the role of loneliness in conferring suicide risk in later life. The purpose of the present study was thus to investigate the potential associations between loneliness and suicide ideation and behavior in a sample of community-residing older adults recruited into a larger two-year longitudinal study of psychological risk and resiliency to later-life suicide ideation. We specifically recruited 173 adults, 65 years or older, from community locations in a medium-sized Canadian city, for a study on “healthy aging.” Participants completed measures of positive and negative psychological variables, including depression, loneliness, and suicide ideation at a baseline assessment, and again at 2-4 week, 6-12 month, and 1-2 year follow-up points. Findings indicated that loneliness (UCLA Loneliness Scale) was significantly positively associated with concurrent depression and suicide ideation, negatively associated with psychological well-being and perceived social support, and differentiated between participants who endorsed or denied having ever engaged in suicide behavior. Baseline loneliness also explained significant variability in the onset of suicide ideation over a 1-2 year period of follow-up, controlling for age, sex, and baseline depression and suicide ideation. These findings will be discussed in the context of the need for increased focus on psychosocial factors when assessing and intervening to reduce suicide risk in older adults.

LIFE COURSE ORIGINS OF FRAILTY IN LATER LIFE

Frailty, generally characterized as a clinical state of increased vulnerability resulting from age-related decline in reserve and function across multiple physiologic systems, has been gaining attention in recent years due to its high correlates with a number of poor health outcomes including falls, hospitalization, and mortality. Similar to other adult health outcomes, research on the etiology of frailty has begun to move from proximal risk factors only to those more distal in time. This research uses data from the Health and Retirement study (2004-2016) to examine whether childhood exposures predict developing frailty in later life. A series of ordinal logistic regression models were estimated to test whether six domains of childhood exposures (socioeconomic status, infectious disease, chronic disease, impairments, risky adolescent behavior, and risky parental behavior) were associated with frailty, composed of five components: unintentional weight loss, weakness, slowness, exhaustion, and low energy expenditure (Fried et al., 2001). After adjusting for demographic factors, experiencing multiple SES misfortunes or risky adolescent behaviors in childhood are associated with higher odds of frailty in later life (OR= 1.24 and 2.37, respectively), while experiencing any infectious diseases is associated with lower odds of frailty (OR= 0.67 and 0.72). After further adjusting for adult characteristics, experiencing 2 or more chronic diseases in childhood is associated with a 1.35 higher odds of incident frailty over an 8-year period. These results reveal some of the early exposures that may raise frailty risk in later life but also the mid-life factors that mediate those risks.

GENDER DIFFERENCES IN THE PREVALENCE AND INCIDENCE OF COGNITIVE IMPAIRMENT: DOES IMMIGRATION MATTER?

Using two waves of the PINE data, this study examined gender difference in the associations between immigration-related factors and cognitive impairment (CI). CI was assessed by the Chinese Mini-Mental State Examination (C-MMSE). CI prevalence was determined by C-MMSE < 18 at baseline; incidence was the percentage of the respondents whose C-MMSE > 18 at baseline but dropped below 18 at Wave 2. We found 7.62% CI prevalence and 5.12% incidence rate. Women were more likely than men to have CI, consisting of 77.06% and 75.20% among persons with CI at two time points. Older Chinese women were generally disadvantaged in cognition and overall health compared with older men. Yet immigration experience does not link to CI for both men and women after controlling the well-established effects of age and education. Future research needs to investigate what biological and contextual factors earlier in life are predictive of late-life CI risk.