Early Life Risk Factors Research Articles

Disadvantage in early-life and persistent asthma in adolescents: a UK cohort study

ObjectiveTo determine how early-life risk factors explain socioeconomic inequalities in persistent asthma in adolescence.MethodsWe did a causal mediation analysis using data from 7487 children and young people in the UK...

Metabolic Reprogramming of Nasal Airway Epithelial Cells Following Infant Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2–3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.

The risk of respiratory tract infections and antibiotic use in a general population and among people with asthma.

AimThe aim of this study was to investigate occupational, environmental, early life and other risk factors associated with respiratory infections and antibiotics use in a general population and among asthmatic individuals.MethodThis study included 15 842 participants of the Respiratory Health in Northern Europe (RHINE) study aged 25–54 years from five Nordic countries, who answered a questionnaire covering respiratory outcomes, exposures, demographic characteristics and numbers of infections and courses of antibiotics in the last 12 months. Multiple logistic regression with and without adjustment for age, sex, smoking status, body mass index and centre were used to study the risk of infection and antibiotics in relation to asthma, and also the association between infection and antibiotics and occupations.ResultsIn the whole population, 11.6% reported having three or more respiratory infections, and 14.7% had used antibiotics because of respiratory tract infections within the last year. Asthmatic participants reported tripled odds for such infections (adjusted OR 2.98, 95% CI 2.53–3.52) and antibiotics use (adjusted OR 3.67, 95% CI 3.18–4.24) as compared to non-asthmatic participants. Both in the general and the asthmatic population, female sex, obesity and exposure to building dampness were associated with respiratory infections. Female sex and current smoking and living in Tartu were associated with antibiotic use. The use of antibiotics was doubled in people hospitalised for severe respiratory infection in childhood.ConclusionIn this study we identified several factors associated with increased respiratory infections and use of antibiotics in a general population and among asthmatic individuals. The frequency of respiratory infections and subsequent antibiotic treatment were increased among those with asthma.

Influence of early life risk factors and lifestyle on systemic vascular resistance in later adulthood: the cardiovascular risk in young Finns study

Purpose There are limited data available concerning the effects of lifetime risk factors and lifestyle on systemic hemodynamics, especially on systemic vascular resistance. The purpose of the study was to evaluate how lifetime cardiovascular risk factors (body mass index (BMI), high-density lipoprotein, low-density lipoprotein, triglycerides, systolic blood pressure, blood glucose) and lifestyle factors (vegetable consumption, fruit consumption, smoking and physical activity) predict systemic vascular resistance index (SVRI) and cardiac index (CI) assessed in adulthood. Materials and Methods Our study cohort comprised 1635 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3–18 years, females 54.3%) who had risk factor and lifestyle data available since childhood. Systemic hemodynamics were measured in 2007 (aged 30–45 years) by whole-body impedance cardiography. Results In the multivariable regression analysis, independent predictors of the adulthood SVRI were childhood BMI, blood glucose, vegetable consumption, smoking, and physical activity (p ≤ .046 for all). Vegetable consumption, smoking, and physical activity remained significant when adjusted for corresponding adult data (p ≤ .036 for all). For the CI, independent predictors in childhood were BMI, systolic blood pressure, vegetable consumption, and physical activity (p ≤ .044 for all), and the findings remained significant after adjusting for corresponding adult data (p ≤ .046 for all). The number of childhood and adulthood risk factors and unfavourable lifestyle factors was directly associated with the SVRI (p < .001) in adulthood. A reduction in the number of risk factors and unfavourable lifestyle factors or a favourable change in BMI status from childhood to adulthood was associated with a lower SVRI in adulthood (p < .001). Conclusion Childhood BMI, blood glucose, vegetable consumption, smoking and physical activity independently predict systemic vascular resistance in adulthood. A favourable change in the number of risk factors or BMI from childhood to adulthood was associated with lower vascular resistance in adulthood.

Spirometric phenotypes from early childhood to young adulthood: a Chronic Airway Disease Early Stratification study.

BackgroundThe prevalences of obstructive and restrictive spirometric phenotypes, and their relation to early-life risk factors from childhood to young adulthood remain poorly understood. The aim was to explore these phenotypes and associations with well-known respiratory risk factors across ages and populations in European cohorts.MethodsWe studied 49 334 participants from 14 population-based cohorts in different age groups (≤10, >10–15, >15–20, >20–25 years, and overall, 5–25 years). The obstructive phenotype was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) z-score less than the lower limit of normal (LLN), whereas the restrictive phenotype was defined as FEV1/FVC z-score ≥LLN, and FVC z-score <LLN.ResultsThe prevalence of obstructive and restrictive phenotypes varied from 3.2–10.9% and 1.8–7.7%, respectively, without clear age trends. A diagnosis of asthma (adjusted odds ratio (aOR=2.55, 95% CI 2.14–3.04), preterm birth (aOR=1.84, 1.27–2.66), maternal smoking during pregnancy (aOR=1.16, 95% CI 1.01–1.35) and family history of asthma (aOR=1.44, 95% CI 1.25–1.66) were associated with a higher prevalence of obstructive, but not restrictive, phenotype across ages (5–25 years). A higher current body mass index (BMI was more often observed in those with the obstructive phenotype but less in those with the restrictive phenotype (aOR=1.05, 95% CI 1.03–1.06 and aOR=0.81, 95% CI 0.78–0.85, per kg·m−2 increase in BMI, respectively). Current smoking was associated with the obstructive phenotype in participants older than 10 years (aOR=1.24, 95% CI 1.05–1.46).ConclusionObstructive and restrictive phenotypes were found to be relatively prevalent during childhood, which supports the early origins concept. Several well-known respiratory risk factors were associated with the obstructive phenotype, whereas only low BMI was associated with the restrictive phenotype, suggesting different underlying pathobiology of these two phenotypes.

Time trends of chronic immune diseases by year of birth in Danish registries.

Chronic immune diseases are often reported to be on the rise and are speculated to share early life risk factors. Here, we investigated year of birth as a common denominator for time trends using the consistent data source of the Danish National Patient Registry with 35years nationwide coverage. Observational nationwide birth cohort registry study, where persons born in Denmark since 1953 were investigated for chronic immune diseases per person years at risk. Outcomes were defined by inpatient hospitalizations in pre-chosen age bins by year of birth in 5year bins. A population of 3.8 million persons born in Denmark since 1953 was investigated for a total sum of 68 million person years in the ages 5-34years. We found increasing trends by year of birth for juvenile arthritis age 10-14, adult asthma age 20-24, inflammatory bowel diseases age 20-24, and multiple sclerosis age 25-29, whereas type 1 diabetes age 15-19 was declining until birth year mid 1980s followed by a subsequent increase. Childhood asthma age 5-9 inpatient hospitalizations were relatively stable over time. Nationwide introduction of measles, mumps, rubella vaccine in 1987 did not alter the trends. Hospitalization for the chronic immune diseases adult asthma, juvenile arthritis, inflammatory bowel diseases and multiple sclerosis showed a general increasing trend by birth year in recent 35years while diabetes 1 and childhood asthma seemed stable in this period. These results were not affected by the introduction of vaccinations against the major childhood viral infections.

Birth weight as destiny?

In 1989, Barker et al reported a correlation between lower birth weights and increased risk for death in adulthood from ischemic heart disease in men born between 1911-1930 in England (Lancet 1989;2:577-80. doi: https://doi.org/10.1016/s0140-6736(89)90710-1). Many subsequent studies have affirmed the relationship between birth weight and conditions such as diabetes, hypertension, and obesity. In this volume of The Journal of Pediatrics, Lilja et al report an association between birth weight and stroke in adulthood. The study used a large cohort of Swedish men born in 1945-1961 with recorded birth weight and body measurements until the age of young adult military conscription tests, linked to national disease and cause of death registers. The study found that lower birth weights were associated with an increased risk of stroke, regardless of body mass index in young adulthood. However, men who were overweight in young adulthood were at significantly higher risk. From a public health standpoint, it is important to learn how individuals can mitigate the risks associated with low birth weight and we need more studies such as this one that show how risk is increased or decreased along the lifespan. It is possible that birth weight is destiny, and that the baseline increase in risk incurred by the fetal environment cannot be decreased and disease risks can only be increased by postnatal health. To understand this, we need even deeper studies of how modifiable factors such as early diet and physical exercise interact with perinatal risk factors in both men and women. However, this needs to be studied prospectively with earlier outcomes, so we do not have to wait several more generations to start improving the long-term health of small newborn infants. Article page 162 ▸ Low Birth Weight as an Early-Life Risk Factor for Adult Stroke Among MenThe Journal of PediatricsVol. 237PreviewTo evaluate the association between birth weight and the risk of adult stroke in men, independent of body mass index (BMI) at young adult age. Full-Text PDF Open Access

Patterns of Atopic Eczema Disease Activity From Birth Through Midlife in 2 British Birth Cohorts

Atopic eczema is characterized by a heterogenous waxing and waning course, with variable age of onset and persistence of symptoms. Distinct patterns of disease activity such as early-onset/resolving and persistent disease have been identified throughout childhood; little is known about patterns into adulthood. This study aimed to identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, to examine whether early life risk factors and participant characteristics are associated with these subtypes, and to determine whether subtypes are associated with other atopic diseases and general health in mid-adulthood. This study evaluated members of 2 population-based birth cohorts, the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participant data were collected over the period between 1958 and 2016. Data were analyzed over the period between 2018 and 2020. Subtypes of atopic eczema were identified based on self-reported atopic eczema period prevalence at multiple occasions. These subtypes were the outcome in models of early life characteristics and an exposure variable in models of midlife health. Latent class analysis identified 4 subtypes of atopic eczema with distinct patterns of disease activity among 15 939 individuals from the NCDS (51.4% male, 75.4% White) and 14 966 individuals from the BCS70 (51.6% male, 78.8% White): rare/no (88% to 91%), decreasing (4%), increasing (2% to 6%), and persistently high (2% to 3%) probability of reporting prevalent atopic eczema with age. Sex at birth and early life factors, including social class, region of residence, tobacco smoke exposure, and breastfeeding, predicted differences between the 3 atopic eczema subtypes and the infrequent/no atopic eczema group, but only female sex differentiated the high and decreasing probability subtypes (odds ratio [OR], 1.99; 95% CI, 1.66-2.38). Individuals in the high subtype were most likely to experience asthma and rhinitis, and those in the increasing subtype were at higher risk of poor self-reported general (OR, 1.29; 95% CI, 1.09-1.53) and mental (OR 1.45; 95% CI, 1.23-1.72) health in midlife. The findings of this cohort study suggest that extending the window of observation beyond childhood may reveal clear subtypes of atopic eczema based on patterns of disease activity. A newly identified subtype with increasing probability of activity in adulthood warrants additional attention given observed associations with poor self-reported health in midlife.

1280Natural history, developmental trajectories, and determinants of eczema from infancy to 26 years of age

Abstract Background Eczema is a common inflammatory skin disease with varying developmental trajectories/patterns. This study sought to investigate eczema development from infancy to early adulthood by identifying distinct developmental trajectories that describe disease patterns over time and evaluate the role of early life risk factors. Methods The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed at birth, 1, 2, 4, 10, 18, and 26 years. At each assessment, eczema was ascertained based on established clinical criteria. Developmental trajectories of eczema between 1-or-2 and 26 years were identified separately for males and females by applying semiparametric mixture models. Associations were assessed by applying a modified Poisson regression to estimate adjusted risk ratios (aRR) and 95% confidence intervals (CI). Results In both males and females, the following eczema trajectories were identified: unaffected/transient (77.7% vs. 73.0%), mid-onset late-resolving (7.8% vs. 4.4%), late-onset (5.2% vs. 9.5%), and early-onset persistent (9.3% vs. 5.4%). In females, an additional trajectory was identified: early-onset early-resolving (7.7%). Among males, filaggrin gene (FLG) variants (aRR = 2.45, 95% CI: 1.34-4.46) and paternal eczema (2.66, 1.39-5.08) were associated with the early-onset persistent trajectory. Among females, maternal eczema (2.84, 1.42-5.70) and high birthweight (2.25, 1.08-4.69) were associated with the early-onset persistent trajectory. Conclusions Four and five trajectories represented eczema development among males and females, respectively, with different predisposing risk factors. Key messages Males and females may experience a different course of eczema and also sex-specific risk factors.

Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults.

Tree nut allergy may cause anaphylaxis. There are limited population-based studies on prevalence and early-life risk factors. We evaluated the prevalence of reported symptoms and allergic sensitization to tree nuts at age 24years in the BAMSE population-based cohort study and assessed early-life factors associated with the development of tree nut allergy. We estimated tree nut allergy prevalence, by analysing questionnaire data on tree nut ingestion and symptoms at age 12, 16 and 24years, and IgE sensitization at age 24years to hazelnut, walnut, pecan, cashew, pistachio, Brazil nut, almond extracts and allergen molecules Cor a 1, 9, 14 (hazelnut), Jug r 1 (walnut) and Ana o 3 (cashew). We evaluated eczema, asthma, food allergies, inherited risk of allergy and gender as potential early-life risk factors. Data were available for 2215/4089 (54%) BAMSE study participants, for estimation of the prevalence of tree nut sensitization (21.2%), tree nut allergy symptoms (9.8%) and combined sensitization and symptoms (7.9%, 2.1% for storage protein sensitization and symptoms, 4.3% for any sensitization and non-mild symptoms). Sixty-three per cent of sensitized individuals (295/470) were asymptomatic, but only 76/470 (16%) storage protein sensitized individuals. Egg allergy (ORadj 8.50 95% CI 2.15-33.6), eczema (ORadj 2.53 95% CI 1.21-5.32) and asthma (ORadj 5.59 95% CI 2.35-13.3)) at pre-school age were associated with future development of tree nut symptoms and storage protein sensitization. At age 24years, tree nut allergy was associated with current eczema and with markers of current asthma severity. Sensitization to storage proteins was more strongly associated with symptoms than sensitization to whole extract for all tree nuts evaluated. In this Swedish cohort, we found tree nut whole extract sensitization is common but usually asymptomatic. Storage protein sensitization is a more reliable indicator of tree nut symptoms. Tree nut allergy is associated with early onset, persistent and severe atopic disease.

Social change and cohort differences in group-based arrest trajectories over the last quarter-century

This article draws on official criminal histories for multiple birth cohorts spanning a 17-y difference in birth year to study how social change can alter our understanding of influential theories and policies about criminal offender groups. Arrest histories are linked to comprehensive longitudinal measurement on over 1,000 individuals originally from Chicago. Using group-based trajectory modeling, we investigated the magnitude and type of cohort differences in trajectories of arrest over the period 1995 to 2020. Our results show that trajectory group membership varies strongly by birth cohort. Membership in the nonoffender group is nearly 15 percentage points higher for cohorts born in the mid-1990s as compared to those born in the 1980s; conversely, older cohorts are more likely to be members of adolescent-limited and chronic-offender groups. Large cohort differences in trajectory group membership persist after controlling for a wide-ranging set of demographic characteristics and early-life risk factors that vary by cohort and that prior research has identified as important influences on crime. Not only does the effect of social change on cohort differentiation persist, but its magnitude is comparable to-indeed larger than-differences in trajectory group membership associated with varying levels of self-control or by whether individuals grew up in high-poverty households. These results suggest that changes in the broader social environment shared by members of the same birth cohort are as powerful in shaping their trajectory group membership as classic predictors identified in prior research, a finding that carries implications for crime-control policies that rely on prediction.

Risk factors for irreversible airway obstruction after infant bronchiolitis

BackgroundIncreasing evidence shows that environmental factors in childhood play a role in development of irreversible airway obstruction. We evaluated early-life and preschool-age risk factors for irreversible airway obstruction in adolescence after bronchiolitis in infancy. MethodsThis study is a secondary analysis of data collected during prospective long-term follow-up of our post-bronchiolitis cohort. Risk factor data were collected during hospitalisation and on follow-up visits at 5–7 and 10–13 years of ages. Lung function was measured from 103 participants with impulse oscillometry at 5–7 years of age and from 89 participants with flow-volume spirometry at 10–13 years of age. ResultsAsthma diagnosis at <12 months of age showed a significant association with irreversible airway obstruction at 10–13 years of age independently from current asthma. Irreversible airway obstruction was less frequent in children with variant than wild genotype of the Toll-like receptor 4(TLR4) rs4986790, but the significance was lost in logistic regression adjusted for current asthma and weight status. Higher post-bronchodilator respiratory system resistance at 5 Hz and lower baseline and post-bronchodilator reactance at 5 Hz by impulse oscillometry at 5–7 years of age were associated with irreversible airway obstruction at 10–13 years of age. ConclusionAsthma diagnosis during the first living year and worse lung function at preschool age increased the risk for irreversible airway obstruction at 10–13 years of age after bronchiolitis. TLR4 rs4986790 polymorphism may be protective for development of irreversible airway obstruction after bronchiolitis.

Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study.

We aimed to evaluate early-life epilepsy incidence, seizure types, severity, risk factors, and treatments among survivors of acute neonatal seizures. Neonates with acute symptomatic seizures born 7/2015-3/2018 were prospectively enrolled at nine Neonatal Seizure Registry sites. One-hour EEG was recorded at age three months. Post-neonatal epilepsy and functional development (Warner Initial Developmental Evaluation of Adaptive and Functional Skills - WIDEA-FS) were assessed. Cox regression was used to assess epilepsy-free survival. Among 282 infants, 37 (13%) had post-neonatal epilepsy by 24-months [median age of onset 7-months (IQR 3-14)]. Among those with post-neonatal epilepsy, 13/37 (35%) had infantile spasms and 12/37 (32%) had drug-resistant epilepsy. Most children with post-neonatal epilepsy had abnormal neurodevelopment at 24-months (WIDEA-FS >2SD below normal population mean for 81% of children with epilepsy vs 27% without epilepsy, RR 7.9, 95% CI 3.6-17.3). Infants with severely abnormal neonatal EEG background patterns were more likely to develop epilepsy than those with mild/moderate abnormalities (HR 3.7, 95% CI 1.9-5.9). Neonatal EEG with ≥3days of seizures also predicted hazard of epilepsy (HR 2.9, 95% CI 1.4-5.9). In an adjusted model, days of neonatal EEG-confirmed seizures (HR 1.4 per day, 95% CI 1.2-1.6) and abnormal discharge examination (HR 3.9, 95% CI 1.9-7.8) were independently associated with time to epilepsy onset. Abnormal (vs. normal) three-month EEG was not associated with epilepsy. In this multicenter study, only 13% of infants with acute symptomatic neonatal seizures developed post-neonatal epilepsy by age 24-months. However, there was a high risk of severe neurodevelopmental impairment and drug-resistant seizures among children with post-neonatal epilepsy. Days of EEG-confirmed neonatal seizures was a potentially modifiable epilepsy risk factor. An EEG at three months was not clinically useful for predicting epilepsy. These practice changing findings have implications for family counseling, clinical follow-up planning, and future research to prevent post-neonatal epilepsy.

Low Birth Weight as an Early-Life Risk Factor for Adult Stroke Among Men

To evaluate the association between birth weight and the risk of adult stroke in men, independent of body mass index (BMI) at young adult age. We included 35 659 men born between 1945 and 1961 from the BMI Epidemiology Study with data on birth weight together with BMI in childhood (8years) and young adulthood (20years). Information on stroke events (1184 first stroke events; 905 ischemic stroke [IS] events and 234 intracerebral hemorrhage [ICH] events) was retrieved from national registers in Sweden. Birth weight was inversely associated with the risk of stroke (IS, ICH and uncategorized together; hazard ratio [HR], 0.88 per SD increase, 95% CI, 0.84-0.93), IS, and ICH in a linear manner, independent of young adult BMI. This association was maintained when the analysis was restricted to individuals within the normal birth weight range only. Moreover, individuals with a birth weight in the lowest tertile followed by overweight at 20years had an 81% greater risk of stroke (HR, 1.81; 95% CI, 1.29; 2.54), compared with a reference group of individuals with birth weight in the middle tertile who were of normal weight at age 20years. We demonstrate an inverse association between birth weight and the risk of adult stroke, IS, and ICH independent of young adult BMI. These findings suggest that low birth weight should be included in assessments of stroke risk in adults.

Supernormal lung function and risk of COPD: A contemporary population-based cohort study.

BackgroundInvestigation of the natural history of chronic obstructive pulmonary disease (COPD) has led to the recognition that individuals with higher than normal lung function may have lower risk of developing COPD. We tested the hypothesis that individuals with supernormal lung function have lower risk of COPD.MethodsWe followed 108,246 adults from the Copenhagen General Population Study recruited between 2003 and 2015 for clinical COPD outcomes until 2018. A subset of 16,892 attended another examination approximately 10 years later, allowing to investigate lung function decline and COPD development (forced expiratory volume in 1 se (FEV1)/forced vital capacity (FVC)<0·70 and FEV1<80% predicted with chronic respiratory symptom). Supernormal lung function was defined as FEV1>upper limit of normal (ULN).FindingsAt baseline, 3944(4%) had supernormal lung function, 91,938(85%) normal lung function, and 12,364(11%) had below normal lung function. Individuals with baseline supernormal versus normal lung function had higher FEV1 decline but did not differ in FEV1/FVC decline. None had COPD at 10 years in those with supernormal lung function, while 3% had in those with normal lung function. Early-life risk factors associated with COPD development and smoking exposure in different stages of life were less common in individuals with supernormal lung function. Compared to individuals with normal lung function, multivariable adjusted hazard ratios in those with supernormal lung function were 0·19(95% confidence interval:0·08–0·46) for acute obstructive lung disease hospitalisations, 0·56(0·45–0·69) for pneumonia hospitalisations, and 0·81(0·72–0·91) for all-cause mortality.InterpretationSupernormal lung function is associated with lower risk of developing COPD.FundingHerlev and Gentofte Hospital and Lundbeck Foundation.

Early Life Microbial Exposure and Immunity Training Effects on Asthma Development and Progression.

Asthma is the most common inflammatory disease affecting the lungs, which can be caused by intrauterine or postnatal insults depending on the exposure to environmental factors. During early life, the exposure to different risk factors can influence the microbiome leading to undesired changes to the immune system. The modulations of the immunity, caused by dysbiosis during development, can increase the susceptibility to allergic diseases. On the other hand, immune training approaches during pregnancy can prevent allergic inflammatory diseases of the airways. In this review, we focus on evidence of risk factors in early life that can alter the development of lung immunity associated with dysbiosis, that leads to asthma and affect childhood and adult life. Furthermore, we discuss new ideas for potential prevention strategies that can be applied during pregnancy and postnatal period.

Medicinal Plants and Biogenic Metal Oxide Nanoparticles: A Paradigm Shift to Treat Alzheimer’s Disease

Alzheimer’s disease (AD) is the most prevalent form of dementia. Improving the amount of acetylcholine in the brain is an efficient way to treat the illness. The global incidence of dementia is estimated to be as high as 50 million, and it is expected to increase every 20 years until 2040, resulting in a costly burden of disease. Early-life risk factors for pathology include genes, chromosomal abnormalities, head injury, insulin resistance, and inflammation. Potentially modifiable risk factors including obesity, diabetes, hypertension, and smoking are associated with Alzheimer’s disease (AD) and represent promising targets for intervention. The drugs currently being used to manage AD have various drawbacks. The chemical inhibition of cholinesterase enzymes is an effective technique for treating signal related neuropathology, and possible sources of compounds with these properties are natural products and biogenic metal oxide nanoparticles. There is a potential source of AChE and BChE inhibitors in the abundance of plants in nature, and natural goods appear to offer useful medications and templates for the development of other compounds. This dissertation represents a review of the literature on species of medicinal plants and nanomaterial related plants tested for their inhibitory action of AChE and BChE. Plant species and the plant-mediated metal oxide nanoparticles referred to are possible cholinesterase inhibitors and can assist researchers in their study of natural products that may be beneficial in the treatment of AD.

Early Life Wheeze and Risk Factors for Asthma-A Revisit at Age 7 in the GEWAC-Cohort.

One third of all toddlers are in need of medical care because of acute wheeze and many of these children have persistent asthma at school age. Our aims were to assess risk factors for and the prevalence of asthma at age 7 in a cohort of children suffering from an acute wheezing episode as toddlers. A total of 113 children, included during an acute wheezing episode (cases), and 54 healthy controls were followed prospectively from early pre-school age to 7 years. The protocol included questionnaires, ACT, FeNO, nasopharyngeal virus samples, blood sampling for cell count, vitamin D levels, and IgE to food and airborne allergens. The prevalence of asthma at age 7 was 70.8% among cases and 1.9% among controls (p < 0.001). Acute wheeze caused by rhinovirus (RV) infection at inclusion was more common among cases with asthma at age 7 compared to cases without asthma (p = 0.011) and this association remained significant following adjustment for infection with other viruses (OR 3.8, 95% CI 1.4–10.5). Cases with asthma at age 7 had been admitted to hospital more often (p = 0.024) and spent more days admitted (p = 0.01) during the year following inclusion compared to cases without asthma. RV infection stands out as the main associated factor for wheeze evolving to persistent asthma. Cases who developed asthma also had an increased need of hospital time and care for wheeze during the year after inclusion.

Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

BackgroundCoexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan‐European, population‐based birth cohort study have been lacking. This study compares the prevalence and early‐life risk factors of these diseases in European primary school children.MethodsIn the prospective multicentre observational EuroPrevall‐iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC‐based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these.ResultsFrom 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family‐allergy‐score, odds ratio (OR) 1.50 (95% CI 1.32–1.70) per standard deviation; early‐life allergy symptoms, OR 2.72 (2.34–3.16) for each symptom; and caesarean birth, OR 1.35 (1.04–1.76). Female gender, OR 0.72 (0.58–0.90); older siblings, OR 0.79 (0.63–0.99); and day care, OR 0.81 (0.63–1.06) were protective factors.ConclusionAllergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early‐life factors are modifiable and may be considered for prevention strategies.

Association between early life circumstances and depressive symptoms among Chinese older adults: Results from China health and retirement longitudinal study: Early life circumstances and depression

BackgroundA growing body of literature suggests that early life circumstances can influence mental health throughout the lifespan. However, how these early life circumstances cumulatively contribute to depression in old age is not completely understood. The aim of this study was to examine the associations of eight factors with depression among community-dwelling older adults. MethodsData were from the China Health and Retirement Longitudinal Study. We included 8,239 community-dwelling individuals who were ≥60 years, completed the life history questionnaire, and had assessment of depression. An early life disadvantage index was established using risk factors that were significantly associated with depression. Logistic regression was used to examine the association of each early life risk factor and the index with depression. ResultsOf 8239 individuals included, 2,055 (24.9%) had depression. In bivariate analysis, each of eight early life risk factors was significantly associated with depression. Except for maternal and paternal education, all risk factors persisted to be associated with depression after multivariable adjustment. In the multivariable-adjusted model, a one-point higher in the early life disadvantage index (range: 0-6) was associated with a 45% (95% CI: 37%, 53%) higher odds of depression. LimitationsDepressive symptoms were measured in our study only by the CES-D scale. Some early life experiences might not be fully reliable due to recall bias. ConclusionThere was a strong association between early life environments and depressive symptoms among Chinese community-dwelling older adults. Adverse early life circumstances could contribute cumulatively to depression in old age.