Search

Objectives. We examined the relation between low birth weight and childhood family and neighborhood socioeconomic disadvantage and disease onset in adulthood. Methods. Using US nationally representative longitudinal data, we estimated hazard models of the onset of asthma, hypertension, diabetes, and stroke, heart attack, or heart disease. The sample contained 4387 children who were members of the Panel Study of Income Dynamics in 1968; they were followed up to 2007, when they were aged 39 to 56 years. Our research design included sibling comparisons of disease onset among siblings with different birth weights. Results. The odds ratios of having asthma, hypertension, diabetes, and stroke, heart attack, or heart disease by age 50 years for low-birth weight babies vs others were 1.64 (P<.01), 1.51 (P<.01), 2.09 (P<.01), and 2.16 (P<.01), respectively. Adult disease prevalence differed substantially by childhood socioeconomic status (SES). After accounting for childhood socioeconomic factors, we found a substantial hazard ratio of disease onset associated with low birth weight, which persisted for sibling comparisons. Conclusions. Childhood SES is strongly associated with the onset of chronic disease in adulthood. Low birth weight plays an important role in disease onset; this relation persists after an array of childhood socioeconomic factors is accounted for. [ABSTRACT FROM AUTHOR]

Using a life course framework, we examine the early life origins of the race gap in men's all-cause mortality. Using the National Longitudinal Survey of Older Men (1966-1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life socioeconomic conditions, particularly parental occupation and family structure, explain part of the race gap in mortality. Black men's higher rates of death are associated with lower socioeconomic standing in early life and living in homes lacking both biological parents. However these effects operate indirectly through adult socioeconomic achievement processes, as education, family income, wealth, and occupational complexity statistically account for the race gap in men's mortality. Our findings suggest that policy interventions to eliminate race disparities in mortality and health should address both childhood and adult socioeconomic conditions. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive aging is a lifelong process with implications for Alzheimer's disease and dementia. This study aims to fill major gaps in research on the natural history of and social disparities in aging-related cognitive decline over the life span. Methods: We conducted integrative data analysis of four large U.S. population-based longitudinal studies of individuals aged 12 to 105 followed over two decades and modeled age trajectories of cognitive function in multiple domains. Results: We found evidence for the onset of cognitive decline in the 4th decade of life, varying gender differences with age, and persistent disadvantage among non-Hispanic Blacks, Hispanics, and those without college education. We further found improvement in cognitive function across 20th century birth cohorts but widening social inequalities in more recent cohorts. Discussion: These findings advance an understanding of early life origins of dementia risk and invite future research on strategies for promoting cognitive health for all Americans. [ABSTRACT FROM AUTHOR]

Importance: Cardiometabolic disorders often occur concomitantly with psychosis and depression, contribute to high mortality rates, and are detectable from the onset of the psychiatric disorders. However, it is unclear whether longitudinal trends in cardiometabolic traits from childhood are associated with risks for adult psychosis and depression.Objective: To examine whether specific developmental trajectories of fasting insulin (FI) levels and body mass index (BMI) from early childhood were longitudinally associated with psychosis and depression in young adults.Design, Setting, and Participants: A cohort study from the Avon Longitudinal Study of Parents and Children, a prospective study including a population-representative British cohort of 14 975 individuals, was conducted using data from participants aged 1 to 24 years. Body mass index and FI level data were used for growth mixture modeling to delineate developmental trajectories, and associations with psychosis and depression were assessed. The study was conducted between July 15, 2019, and March 24, 2020.Exposures: Fasting insulin levels were measured at 9, 15, 18, and 24 years, and BMI was measured at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years. Data on sex, race/ethnicity, paternal social class, childhood emotional and behavioral problems, and cumulative scores of sleep problems, average calorie intake, physical activity, smoking, and alcohol and substance use in childhood and adolescence were examined as potential confounders.Main Outcomes and Measures: Psychosis risk (definite psychotic experiences, psychotic disorder, at-risk mental state status, and negative symptom score) depression risk (measured using the computerized Clinical Interview Schedule-Revised) were assessed at 24 years.Results: From data available on 5790 participants (3132 [54.1%] female) for FI levels and data available on 10 463 participants (5336 [51.0%] female) for BMI, 3 distinct trajectories for FI levels and 5 distinct trajectories for BMI were noted, all of which were differentiated by mid-childhood. The persistently high FI level trajectory was associated with a psychosis at-risk mental state (adjusted odds ratio [aOR], 5.01; 95% CI, 1.76-13.19) and psychotic disorder (aOR, 3.22; 95% CI, 1.29-8.02) but not depression (aOR, 1.38; 95% CI, 0.75-2.54). A puberty-onset major increase in BMI was associated with depression (aOR, 4.46; 95% CI, 2.38-9.87) but not psychosis (aOR, 1.98; 95% CI, 0.56-7.79).Conclusions and Relevance: The cardiometabolic comorbidity of psychosis and depression may have distinct, disorder-specific early-life origins. Disrupted insulin sensitivity could be a shared risk factor for comorbid cardiometabolic disorders and psychosis. A puberty-onset major increase in BMI could be a risk factor or risk indicator for adult depression. These markers may represent targets for prevention and treatment of cardiometabolic disorders in individuals with psychosis and depression. [ABSTRACT FROM AUTHOR]

Background A large part of the socioeconomic mortality gradient can be statistically accounted for by social patterning of adult health behaviours. However, this statistical explanation does not consider the early life origins of unhealthy behaviours and increased mortality risk. Methods Analysis is based on 2132 members of the MRC National Survey of Health and Development with mortality follow-up and complete data. Smoking behaviour was summarised by pack-years of exposure. Socioeconomic circumstances were measured in childhood (father's social class (age 4), maternal education (age 6)) and age 26 (education attainment, home ownership, head of household social class). We estimated the direct effect of early circumstances, the indirect effect through smoking and the independent direct effect of smoking on inequality in all-cause mortality from age 26 to 66. Results Mortality risk was higher in those with lower socioeconomic position at age 26, with a sex-adjusted HR (relative index of inequality) of 1.97 (95% CI 1.18 to 3.28). Smoking and early life socioeconomic indicators together explained 74% of the socioeconomic gradient in mortality (the gradient). Early life circumstances explained 47% of the gradient, 23.5% directly and 23.0% indirectly through smoking. The explanatory power of smoking behaviour for the gradient was reduced from 50.8% to 28% when early life circumstances were added to the model. Conclusions Early life socioeconomic circumstances contributed importantly to social inequality in adult mortality. Our life-course model focusing on smoking provides evidence that social inequalities in health will persist unless prevention strategies tackle the intergenerational transmission of disadvantage and risk. [ABSTRACT FROM AUTHOR]

Background: The legacy of structural and colonial violence has disrupted attachment which has led to the breakdown of healthy relationships within some Indigenous families and communities. A key component of re-establishing attachment is through addressing the effect of historical and on-going colonalism (e.g., intergenerational trauma, cultural connectedness) on individual, family, and community relationships. Methods: We conducted a descriptive environmental scan of web-based resources and complemented it with community reports from conversations with key Indigenous stakeholders, to identify and describe what programs are available to Indigenous youth within community settings that focus on fostering healthy relations. Qualitative descriptive summaries were used to synthesize information, summary statistics and frequencies described commonalities across programs, and pattern analysis identified patterns within the data based on demographic factors. In total, forty-seven programs were found across thirty-four organizations. Findings: Programs integrated cultivating healthy relationships by focusing on skill training (55%), Indigenous cultural education and activities (42%), and mentorship (25%). Programs described the relationships they focused on in broad terms such as healthy relationships, intergenerational relations, and relationships with the land. Programs differed based on gender and age; programs designed for girls focused on self-empowerment and those for boys on violence prevention training. Programs for younger youth aimed to foster positive identity, those for teenagers on relationship building, and those for older youth on promoting mental health. Conclusion: These findings highlight distinct features of healthy relationship programming for Indigenous youth in Canada and offers promising avenues in the future development of such programming based on age and gender. These findings may be of interest to healthcare service research or decision-makers looking to develop healthy relationship programs in Indigenous contexts to develop culturally-relevant and trauma-informed programming to address the effects of historical and on-going colonalism. [ABSTRACT FROM AUTHOR]

In recent years, population health research has focused on understanding the determinants of later-life health. Two strands of that work have focused on (1) international comparisons of later-life health and (2) assessing the early-life origins of disease and disability and the importance of life course processes. However, the less frequently examined intersection of these approaches remains an important frontier. The present study contributes to the integration of these approaches. We use the Health and Retirement Study family of data sets and a cohort dynamic approach to compare functional health trajectories across 12 high-income countries and to examine the role of life course processes and cohort dynamics in contributing to variation in those trajectories. We find substantial international variation in functional health trajectories and an important role of cohort dynamics in generating that variation, with younger cohorts often less healthy at comparable ages than the older cohorts they are replacing. We further find evidence of heterogeneous effects of life course processes on health trajectories. The results have important implications for future trends in morbidity and mortality as well as public policy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although previous studies suggest that exposure to traffic-related pollution during childhood increases the risk of childhood overweight or obesity (COWO), the role of early life exposure to fine particulate matter (aerodynamic diameter <2:5 lm; PM2.5) and its joint effect with the mother's prepregnancy body mass index (MPBMI) on COWO remain unclear. OBJECTIVES: The present study was conducted to examine the individual and joint effects of ambient PM2.5 exposures and MPBMI on the risk of COWO. METHODS: We estimated exposures to ambient PM2.5 in utero and during the first 2 y of life (F2YL), using data from the U.S. Environmental Protection Agency's (EPA's) Air Quality System matched to residential address, in 1,446 mother-infant pairs who were recruited at birth from 1998 and followed up prospectively through 2012 at the Boston Medical Center in Massachusetts. We quantified the individual and joint effects of PM2.5 exposure with MPBMI on COWO, defined as the child's age- and sex-specific BMI z-score ≥85th percentile at the last well-child care visit between 2 and 9 y of age. Additivity was assessed by estimating the reduced excess risk due to interaction. RESULTS: Comparing the highest and lowest quartiles of PM2.5, the adjusted relative risks (RRs) [95% confidence intervals (CIs)] of COWO were 1.3 (95% CI: 1.1, 1.5), 1.2 (95% CI: 1.0, 1.4), 1.2 (95% CI: 1.0, 1.4), 1.3 (95% CI: 1.1, 1.6), 1.3 (95% CI: 1.1, 1.5) and 1.3 (1.1, 1.5) during preconception; the first, second, and third trimesters; the entire period of pregnancy; and F2YL, respectively. Spline regression showed a dose-response relationship between PM2.5 levels and COWO after a threshold near the median exposure (10:46 μg=m³-10:89 μg=m³). Compared with their counterparts, children of obese mothers exposed to high levels of PM2.5 had the highest risk of COWO [RR ≥2:0, relative excess risk due to interaction (RERI) not significant]. CONCLUSIONS: In the present study, we observed that early life exposure to PM2.5 may play an important role in the early life origins of COWO and may increase the risk of COWO in children of mothers who were overweight or obese before pregnancy beyond the risk that can be attributed to MPBMI alone. Our findings emphasize the clinical and public health policy relevance of early life PM2.5 exposure. [ABSTRACT FROM AUTHOR]

Exposure to infectious diseases in early life has been linked to increased mortality risk in later life in high-disease settings, such as eighteenth- and nineteenth-century Europe. Less is known about the long-term effects of early-life disease exposure in milder disease environments. This study estimates heterogeneous effects from disease exposure in infancy on later-life mortality in twentieth-century Sweden, by socioeconomic status at birth and sex. Using historical population data for southern Sweden, we study 11,515 individuals who were born in 1905–1929 from age 1 until age 85. We measure exposure to disease using the local post–early neonatal mortality rate in the first 12 months after birth and apply flexible parametric survival models. For females, we find a negative effect on life expectancy (scarring) at ages 1–85 following high disease exposure in infancy, particularly for those born to unskilled workers. For males, we find no negative effect on later-life survival, likely because stronger mortality selection in infancy outweighs scarring. Thus, even as the incidence of infectious diseases declined at the start of the twentieth century, early-life disease exposure generated long-lasting negative but heterogeneous population health effects. [ABSTRACT FROM AUTHOR]

Suicide prevention efforts generally target acute precipitants of suicide, though accumulating evidence suggests that vulnerability to suicide is partly established early in life before acute precipitants can be identified. The aim of this systematic review was to synthesize evidence on early life vulnerability to suicide beginning in the prenatal period and extending through age 12. We searched PubMed, Embase, PsycNet, Web of Science, Scopus, Social Services Abstracts, and Sociological Abstracts for prospective studies published through January 2021 that investigated early life risk factors for suicide mortality. The search yielded 13,237 studies; 54 of these studies met our inclusion criteria. Evidence consistently supported the link between sociodemographic (e.g., young maternal age at birth, low parental education, and higher birth order), obstetric (e.g., low birth weight), parental (e.g., exposure to parental death by external causes), and child developmental factors (e.g., exposure to emotional adversity) and higher risk of suicide death. Among studies that also examined suicide attempt, there was a similar profile of risk factors. We discuss a range of potential pathways implicated in these associations and suggest that additional research be conducted to better understand how early life factors could interact with acute precipitants and increase vulnerability to suicide. [ABSTRACT FROM AUTHOR]

INTRODUCTION Maternal smoking during pregnancy disturbs fetal lung development, and induces in their offspring childhood respiratory diseases. Whether it has a continued impact on offspring adult lung health and exerts a casual effect of chronic respiratory diseases (CRDs), remains uncertain. We seek to determine the causal relationships between maternal smoking around birth and offspring adult CRDs, using summary data from previously described cohorts. METHODS Mendelian randomization (MR) study was used to analyze the genome-wide associations of maternal smoking around birth and offspring adult CRDs, including respiratory insufficiency, chronic obstructive pulmonary disease (COPD), related respiratory insufficiency, emphysema, COPD, COPD hospital admissions, early onset of COPD, later onset of COPD, asthma, idiopathic pulmonary fibrosis (IPF), lung cancer (LC), small cell lung carcinoma (SCLC), and lung squamous cell carcinoma (LUSC). RESULTS After removing single-nucleotide polymorphisms (SNPs) associated with smoking by the offspring, maternal smoking around birth was associated with increased risk of offspring adult respiratory diseases (OR=1.14; 95% CI: 1.013-1.284; p=0.030), respiratory insufficiency (OR=2.413; 95% CI: 1.039-5.603; p=0.040), COPD (OR=1.14; 95% CI: 1.013-1.284; p=0.003), and asthma (OR=1.336; 95% CI: 1.161-1.538; p<0.001). Besides, maternal smoking during pregnancy was associated with a greater risk of LUSC (OR=1.229; 95% CI: 0.992-1.523; p=0.059) than the risk of IPF (0R=1.001; 95% CI: 0.999-1.003; p=0.224), LC (0R=1.203; 95% CI: 0.964-1.501; p=0.103), or SCLC (OR=1.11; 95% CI: 0.77-1.601; p=0.577). CONCLUSIONS In this MR analysis, maternal smoking around birth caused a strong risk factor for the offspring to develop lung problems and CRDs in adulthood. The policy related to smoking cessation for mothers during pregnancy should be encouraged. [ABSTRACT FROM AUTHOR]

A longitudinal design was used to examine the psychometric properties of the Self-Efficacy for Diabetes Self-Management (SEDM) for children and adolescents with a diagnosis of type 1 diabetes (T1D). The SEDM was adapted to Spanish and the best factorial solution was selected to test the invariance of the measures of age and gender. Individuals between the ages of 10 and 19 years old with a diagnosis of T1D completed a self-reported questionnaire (167 at Time 1 [mean age = 14.49, SD = 2.76; 56.9% boys] and 122 at Time 2 [mean age = 14.77, SD = 2.58; 56.6% boys]). Two unifactorial solutions were tested. The psychometric properties of the scale were validated. The proposed validation obtained excellent reliability indices (χ2 (26) = 25.59, p > 0.49, RMSEA = 0.00, 95% CI [0.00, 0.07], CFI = 1.00, GFI = 0.96, AGFI = 0.92, TLI = 1.00, and CMIN = 0.98), and it appeared to be invariant for gender and for age groups. The Cronbach's α was 0.85. The test–retest reliability was high (r = 0.69 [p < 0.001]). Convergent, discriminant, and external validity were proven. The nine-item SEDM is a brief measure with satisfactory structural validity. From our knowledge, this study provides the first reliable tool to assess self-efficacy in the management of T1D for Spanish children and adolescents. [ABSTRACT FROM AUTHOR]

Objectives: Prior U.S. population studies have found that childhood adversity influences the quality of relationships in adulthood, with emerging research suggesting that this association might be especially strong for black men. We theorize psychosocial and behavioral coping responses to early life adversity and how these responses may link early life adversity to strain in men's relationships with their indeterminate partners and children across the life course, with attention to possible racial variation in these experiences and implications for later life well-being. Method: We analyze in-depth interviews with 15 black men and 15 white men. We use qualitative analysis techniques to connect childhood experiences to psychosocial processes in childhood and behavioral coping strategies associated with relationship experiences throughout adulthood. Results: Black men describe much stronger and more persistent childhood adversity than do white men. Findings further suggest that childhood adversity contributes to psychosocial processes (e.g., diminished sense of mastery) that may lead to ways of coping with adversity (e.g., self-medication) that are likely to contribute to relationship difficulties throughout the life span. Discussion: A life course perspective directs attention to the early life origins of cumulative patterns of social disadvantage, patterns that extend to later life. Our findings suggest psychosocial and behavioral pathways through which early life adversity may constrain and strain men's relationships, possibly contributing to racial inequality in family relationships across the life span. [ABSTRACT FROM AUTHOR]

Asthma is a common chronic disease without cure. Our understanding of asthma onset, pathobiology, classification, and management has evolved substantially over the past decade; however, significant asthma-related morbidity and excess healthcare use and costs persist. To address this important clinical condition, the NHLBI convened a group of extramural investigators for an Asthma Research Strategic Planning workshop on September 18-19, 2014, to accelerate discoveries and their translation to patients. The workshop focused on (1) in utero and early-life origins of asthma, (2) the use of phenotypes and endotypes to classify disease, (3) defining disease modification, (4) disease management, and (5) implementation research. This report summarizes the workshop and produces recommendations to guide future research in asthma. [ABSTRACT FROM AUTHOR]

Aim. To assess the incidence trends in type 1 diabetes among children and adolescents across Europe during the period from 1994 to 2022 using a systematic methodology. Materials and Methods. Cross‐sectional or follow‐up studies reporting population‐based incidence rates (IRs) of European children and adolescents diagnosed aged <15 years with type 1 diabetes were included. The Mantel‒Haenszel or DerSimonian and Laird random‐effects method was used to compute the pooled IR estimates and their 95% confidence intervals (CIs). Subgroup analyses were conducted by study year, biological sex, age group (0–4, 5−9, and 10–14 years), country, and European regions. Results. A total of 75 studies (219,331 children and adolescents aged 0–14 years) with data from 32 countries were included. Generally, a high overall rate of increase in type 1 diabetes incidence has been shown in most European countries from 1994 to 2022 in both sexes, with an overall increase from 10.85 (95% CI, 9.62–12.07) per 100,000 person‐years from 1994 to 2003 to 20.96 (95% CI, 19.26–22.66) per 100,000 person‐years from 2013 to 2022. Conclusions. There are substantial between‐country differences in the current levels and trends of IR in type 1 diabetes in European children and adolescents. Our data suggest a worrying upward trend in most European countries. [ABSTRACT FROM AUTHOR]

Early identification of children with neurodevelopmental abnormality is a major challenge, which is crucial for improving symptoms and preventing further decline in children with neurodevelopmental abnormality. This study focuses on developing a predictive model with maternal sociodemographic, behavioral, and medication-usage information during pregnancy to identify infants with abnormal neurodevelopment before the age of one. In addition, an interpretable machine-learning approach was utilized to assess the importance of the variables in the model. In this study, artificial neural network models were developed for the neurodevelopment of five areas of infants during the first year of life and achieved good predictive efficacy in the areas of fine motor and problem solving, with median AUC = 0.670 (IQR: 0.594, 0.764) and median AUC = 0.643 (IQR: 0.550, 0.731), respectively. The final model for neurodevelopmental abnormalities in any energy region of one-year-old children also achieved good prediction performance. The sensitivity is 0.700 (IQR: 0.597, 0.797), the AUC is 0.821 (IQR: 0.716, 0.833), the accuracy is 0.721 (IQR: 0.696, 0.739), and the specificity is 0.742 (IQR: 0.680, 0.748). In addition, interpretable machine-learning methods suggest that maternal exposure to drugs such as acetaminophen, ferrous succinate, and midazolam during pregnancy affects the development of specific areas of the offspring during the first year of life. This study established predictive models of neurodevelopmental abnormality in infants under one year and underscored the prediction value of medication exposure during pregnancy for the neurodevelopmental outcomes of the offspring. [ABSTRACT FROM AUTHOR]

This study investigated the sex-specific prevalence of smoking (past 30 days) and the associations with height among university/college students. 25,405 (11,579/14,826 males/females) college students in Xi'an China. A cross-sectional, self-administered survey. The male and female prevalence of smoking (past 30 days) was 32.9% and 7.4%, respectively. The prevalence of smoking of the male height groups ranged from 29.8% to 36.9%; only the ≥188 cm height group showed significantly higher prevalence than the reference group (i.e., 173–177cm; 33.0%). The female prevalence of smoking was 4.0–8.2% in the ≤170cm groups and increased to 12.3% in the 171–175 cm group and 36.1% in the ≥176 cm group, while it was 6.5% for the reference group (161–165 cm). This exploratory study firstly revealed the significantly higher prevalence of smoking among the "tallest" height groups, especially among females. Future studies are warranted to confirm such findings and explore related mechanisms. [ABSTRACT FROM AUTHOR]

To evaluate the effect of yoga on the frequency of MetS and its impact on cardiovascular risk markers in climacteric women. We recruited 84 sedentary women between 40 and 65 years diagnosed with MetS. Participants were randomly assigned to a 24-week yoga intervention or control group. We evaluated the frequency of MetS and changes in the individual components of MetS at baseline and after 24 weeks. We also assessed the impact of yoga practices on cardiovascular risk through the following markers: High-sensitivity C-reactive Protein (hs-CRP), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), and Atherogenic Index of Plasma (AIP). The frequency of MetS reduced significantly after 24 weeks of yoga practice (− 34.1%; p < 0.001). Statistical analysis showed that the frequency of MetS was significantly lower in the yoga group (65.9%; n = 27) than in the control group (93.0%; n = 40) after 24 weeks (p = 0.002). Regarding the individual components of MetS, yoga practitioners had statistically lower waist circumference, systolic blood pressure, triglycerides, HDLc, and glucose serum concentrations than the control group after 24 weeks. Yoga practitioners also had a significant decrease in hs-CRP serum concentrations (3.27 ± 2.95 mg/L vs. 2.52 ± 2.14 mg/L; p = 0.040) and a lower frequency of moderate or high cardiovascular risk (48.8% vs. 34.1%; p = 0.001) after 24 weeks of practice. The yoga group had LAP values significantly lower than the control group after the intervention period (55.8 ± 38.04 vs. 73.9 ± 40.7; p = 0.039). Yoga practice demonstrated to be an effective therapeutic to manage MetS and reduce cardiovascular risk in climacteric women. [ABSTRACT FROM AUTHOR]

Background: Chewing betel quid (BQ) – a preparation commonly containing areca nut and slaked lime wrapped in betel leaf – is entrenched in South Asia. Although BQ consumption during pregnancy has been linked to adverse birth outcomes, its effect on postnatal growth remains largely unexplored. Objective: We examined the associations of BQ use during pregnancy with children's height-for-age and body mass index-for-age z-scores (HAZ and BAZ, respectively) and fat and fat-free mass along with sex-based differences in association in rural Bangladesh. Methods: With a prospective cohort design, we assessed BQ use among mothers enrolled in the Preterm and Stillbirth Study, Matlab (n = 3140) with a structured questionnaire around early third trimester. Children born to a subset of 614 women (including 134 daily users) were invited to follow-up between October 2021 and January 2022. HAZ and BAZ were calculated from anthropometric assessment, and fat and fat-free mass were estimated using bioelectric impedance. Overall and sex-specific multiple linear regression models were fitted. Results: Growth data were available for 501 children (mean age 4.9 years): 43.3% of them were born to non-users, 35.3% to those using prior to or less-than-daily during the survey, and 21.3% to daily users. No statistically significant associations were observed after adjusting for sex, parity, maternal height and education, and household wealth. Conclusions: There was no effect of BQ use during pregnancy on postnatal growth in this study. Longitudinal studies following up those born to heavy users beyond childhood are warranted for capturing long-term implications of prenatal BQ exposure. PAPER CONTEXT: Main findings: In this cohort study, no association was observed between maternal betel quid use during pregnancy and children's growth around five years of age. Added knowledge: Although catch-up growth among those born to heavy users may have attenuated any negative impact of prenatal exposure to betel quid on postnatal growth, such catch-up growth often involves greater acquisition and a more centralized distribution of body fat and insulin resistance later in life; leading to a potential heightening of cardiometabolic risk. Global health impact for policy and action: Given that betel quid consumption during pregnancy remains socially acceptable across south and south-east Asia, this study highlights the need for following up those born to betel quid users beyond childhood for capturing long-term health implications of prenatal betel quid exposure [ABSTRACT FROM AUTHOR]

An influential literature on the Developmental Origins of Health and Disease (DOHaD) has documented that poor conditions in utero lead to higher risk of cardiovascular disease at older ages. Evidence from low-income countries (LICs) has hitherto been missing, despite the fact that adverse in utero conditions are far more common in LICs. We find that Malawians exposed in utero to the 1949 Nyasaland famine have better cardiovascular health 70 years later. These findings highlight the potential context specificity of the DOHaD hypothesis, with in utero adversity having different health implications among aging LIC individuals who were exposed to persistent poverty. [ABSTRACT FROM AUTHOR]

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the lower-middle São Francisco region. Methods: This is an analytical cohort and exploratory. Thirty children, were formed two groups, one of low birth weight children (LBW, n = 15) and another of normal weight (NBW = 15) were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves were measured at birth and the third and sixth months of life. Results: Weight gain during the 6 months of follow-up in newborns with a low birth weight was greater compared to newborns with a normal birth weight. All children who were born with a low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with a low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with a low birth weight. Conclusions: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with a low birth weight with greater adiposity in this group which may increase the risk of metabolic diseases in later life. [ABSTRACT FROM AUTHOR]

Background: Suboptimal rest-activity patterns in adolescence are associated with worse health outcomes in adulthood. Understanding sociodemographic factors associated with rest-activity rhythms may help identify subgroups who may benefit from interventions. This study aimed to investigate the association of rest-activity rhythm with demographic and socioeconomic characteristics in adolescents. Methods: Using cross-sectional data from the nationally representative National Health and Nutrition Examination Survey (NHANES) 2011–2014 adolescents (N = 1814), this study derived rest-activity profiles from 7-day 24-hour accelerometer data using functional principal component analysis. Multiple linear regression was used to assess the association between participant characteristics and rest-activity profiles. Weekday and weekend specific analyses were performed in addition to the overall analysis. Results: Four rest-activity rhythm profiles were identified, which explained a total of 82.7% of variance in the study sample, including (1) High amplitude profile; (2) Early activity window profile; (3) Early activity peak profile; and (4) Prolonged activity/reduced rest window profile. The rest-activity profiles were associated with subgroups of age, sex, race/ethnicity, and household income. On average, older age was associated with a lower value for the high amplitude and early activity window profiles, but a higher value for the early activity peak and prolonged activity/reduced rest window profiles. Compared to boys, girls had a higher value for the prolonged activity/reduced rest window profiles. When compared to Non-Hispanic White adolescents, Asian showed a lower value for the high amplitude profile, Mexican American group showed a higher value for the early activity window profile, and the Non-Hispanic Black group showed a higher value for the prolonged activity/reduced rest window profiles. Adolescents reported the lowest household income had the lowest average value for the early activity window profile. Conclusions: This study characterized main rest-activity profiles among the US adolescents, and demonstrated that demographic and socioeconomic status factors may shape rest-activity behaviors in this population. [ABSTRACT FROM AUTHOR]

Background Literature from the general population shows a consensus about the health benefits associated with breastfeeding for both mothers and children. However, studies investigating these issues in the context of homelessness and migration are rare. This research aimed to examine the relations of any breastfeeding duration with health outcomes among migrant mother–child dyads experiencing homelessness. Methods Data were collected among sheltered and mainly foreign-born mothers experiencing homelessness, and their children aged 6 months to 5 years, from the ENFAMS cross-sectional survey (n  = 481, 2013—Great Paris area). Any breastfeeding duration, along with various health outcomes of both the mother and her child, was ascertained by face-to-face questionnaires administered by trained interviewers to mothers (perceived physical and emotional health and maternal depression) or by trained psychologists to children (adaptive behaviours). Nurses measured weight and height [thus allowing them to calculate body mass index (BMI)] and haemoglobin concentration (mother–child dyad) and maternal blood pressure. Multivariable linear and modified Poisson regression analyses were performed to examine outcome-wide associations between any breastfeeding duration ≥6 months and the various mother–child outcomes. Results Any breastfeeding ≥6 months was associated with lower systolic blood pressure in mothers (B  = −0.40, 95% confidence interval = −0.68 to −0.12). No association was observed with the other outcomes. Conclusions The relevance of supporting breastfeeding to improve mothers' physical health holds true in the context of migration and homelessness. It is therefore important to support breastfeeding in these settings. Moreover, given the documented social complexity of breastfeeding practices, interventions should take mothers' socio-cultural heritage and the structural barriers they face into account. [ABSTRACT FROM AUTHOR]

Background: Macrosomia (birthweight ≥ 4 kg or ≥ 4.5 kg) is strongly associated with a predisposition to childhood obesity, which in turn is linked with adverse cardiometabolic health. Despite this, there is a lack of longitudinal investigation on the impact of high birthweight on cardiometabolic outcomes in youth. The preteen period represents an important window of opportunity to further explore this link, to potentially prevent cardiometabolic profiles worsening during puberty. Methods: This is a secondary analysis of 9–11-year-olds (n = 405) born to mothers in the ROLO longitudinal birth cohort study, who previously delivered an infant with macrosomia. Preteens were dichotomised into those born with and without macrosomia, using two common cut-off criteria (birthweight ≥ 4 kg (n = 208) and < 4 kg; ≥ 4.5 kg (n = 65) and < 4.5 kg). Cardiometabolic health was assessed using anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance (20-m shuttle run test), and non-fasting serum biomarkers for a subgroup (n = 213). Statistical comparisons between the two groups were explored using independent t-tests, Mann–Whitney U tests, and Chi-square tests. Crude and adjusted linear regression models investigated associations between macrosomia and preteen cardiometabolic outcomes. Results: In total, 29.3% (n = 119) of preteens had overweight/obesity based on their BMI z-score. Preteens born ≥ 4 kg had lower median (IQR) C3 concentrations (1.38 (1.22, 1.52) g/L vs. 1.4 (1.26, 1.6) g/L, p = 0.043) and lower median (IQR) ICAM-1 concentrations (345.39 (290.34, 394.91) ng/mL vs. 387.44 (312.91, 441.83) ng/mL, p = 0.040), than those born < 4 kg. Those born ≥ 4.5 kg had higher mean (SD) BMI z-scores (0.71 (0.99) vs. 0.36 (1.09), p = 0.016), and higher median (IQR) lean mass (24.76 (23.28, 28.51) kg vs. 23.87 (21.9, 26.79) kg, p = 0.021), than those born < 4.5 kg. Adjusted linear regression analyses revealed birthweight ≥ 4 kg was negatively associated with C3 concentration (g/L) (B = − 0.095, 95% CI = − 0.162, − 0.029, p = 0.005) and birthweight ≥ 4.5 kg was positively associated with weight z-score (B = 0.325, 95% CI = 0.018, 0.633, p = 0.038), height z-score (B = 0.391, 95% CI = 0.079, 0.703, p = 0.014), lean mass (kg) (B = 1.353, 95% CI = 0.264, 2.442, p = 0.015) and cardiorespiratory endurance (B = 0.407, 95% CI = 0.006, 0.808, p = 0.047). Conclusion: This study found no strong evidence to suggest that macrosomia is associated with adverse preteen cardiometabolic health. Macrosomia alone may not be a long-term cardiometabolic risk factor. Trial registration ISRCTN54392969 registered at www.isrctn.com. [ABSTRACT FROM AUTHOR]

We examined the effectiveness of a 26-week culture-inclusive intervention on reducing salivary stress biomarker levels, and perceived stress, depressive, and post-traumatic stress disorder (PTSD) symptoms measured using scales in 53 Indigenous women in Ontario, Canada. Statistical analyses compared the average biomarker levels, and the area under the curve (AUC) of biomarkers. Differences in biomarkers and mental health scale scores pre- and post-intervention were compared using mixed models with a random intercept. Interaction terms were included between the intervention and age, education, disability, and HIV status, individually, to test for sub-group differences. Cortisol AUC post-intervention was decreased compared to pre-intervention (β -1.29 µg/dL; 95%CI -2.35, -0.23). There was a slight decrease in perceived stress levels (aOR: -2.80; 95%CI -5.09, -0.50). The associations were stronger among women of younger age, higher education, and no disabilities. These interventions can be effective, but future interventions should target Indigenous population sub-groups to address individual needs. [ABSTRACT FROM AUTHOR]

Aim. Type 1 diabetes (T1D) is an autoimmune disease with heterogeneous risk factors. Metabolic perturbations in the pathogenesis of the disease are remarkable to illuminate the interaction between genetic and environmental factors and how islet immunity and overt diabetes develop. This review aimed to integrate the metabolic changes of T1D to identify potential biomarkers for predicting disease progression based on recent metabolomics and lipidomics studies with parallel methodologies. Methods. A total of 18 metabolomics and lipidomics studies of childhood T1D during the last 15 years were reviewed. The metabolic fingerprints consisting of 41 lipids and/or metabolite classes of subjects with islet autoantibodies, progressors of T1D, and T1D children were mapped in four-time dimensions based on a tentative effect-score rule. Results. From birth, high-risk T1D subjects had decreased unsaturated triacylglycerols, unsaturated phosphatidylcholines (PCs), sphingomyelins (SMs), amino acids, and metabolites in the tricarboxylic acid (TCA) cycle. On the contrary, lysophosphatidylcholines (LPCs) and monosaccharides increased. And LPCs and branched-chain amino acids (BCAAs) were elevated before the appearance of islet autoantibodies but were lowered after seroconversion. Choline-related lipids (including PCs, SMs, and LPCs), BCAAs, and metabolites involved in the TCA cycle were identified as consensus biomarkers potentially predicting the development of islet autoimmunity and T1D. Decreased LPCs and amino acids indicated poor glycemic control of T1D, while elevated lysophosphatidylethanolamines and saturated PCs implied good glycemic control. Further pathway analysis revealed that biosynthesis of aminoacyl-tRNA, BCAAs, and alanine, aspartate, and glutamate metabolism were significantly enriched. Moreover, established cohort studies and predictive statistical models of pediatric T1D were also summarized. Conclusion. The metabolic profile of high-risk T1D subjects and patients demonstrated significant changes compared with healthy controls. This integrated analysis provides a comprehensive overview of metabolic features and potential biomarkers in the pathogenesis and progression of T1D. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association. Study Design Data were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994–1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences. Study Results Higher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses. Conclusions Cognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic disease that is usually diagnosed in childhood, underscoring the importance of early disease control for overall wellbeing. Our aim was to design an explanatory model of subjective emotional wellbeing in children and adolescents with T1D. A longitudinal study was conducted at the Reina Sofia University Hospital in Cordoba (Spain). A total of 151 patients (mean age = 14.50, SD = 2.67; 41.1% girls) participated at T1, while 97 participated at T2 (mean age = 14.93, SD = 2.56; 39.2% girls). Participants completed a self-report questionnaire. Descriptive, reliability, correlation, path, and mediation analyses were performed. The explanatory model showed excellent fit indices [χ2 (10) = 8.62, p = 0.57, RMSEA = 0.00, 95% [0.00, 0.10], CFI = 1.00, GFI = 0.98, AGFI = 0.93, and TLI = 1.01]. The results showed significant and positive relationships between family social support and subjective emotional wellbeing and improved self-care skills. Self-efficacy presented a mediating role between family social support and subjective emotional wellbeing. Given that self-efficacy is a self-regulatory mechanism and a determinant of health, it is argued that future psychoeducational interventions could aim to improve self-efficacy to manage chronic diseases, to achieve greater emotional wellbeing in children and adolescents with T1D. [ABSTRACT FROM AUTHOR]

Indigenous women encounter increased stressful life experiences such as socioeconomic insecurities as well as inequities in health services and outcomes. These stress inequities, which stem from the historical and ongoing effects of settler colonialism, also worsen health outcomes for those women living with HIV. As a part of a broader research project on the impacts of stress-reducing interventions for indigenous women, this study examines the experiences of the women who facilitated the intervention. This research was conducted to evaluate the impacts of a biweekly stress-reducing intervention conducted in Thunder Bay, Ontario. The facilitators of the intervention participated in a focus group in 2019 where they detailed the reach, effectiveness, adoption, and implementation of the intervention. The results suggest that effective stress-reducing interventions should strive to be accessible and inclusive and that doing so can increase program engagement with the service organization hosting the intervention. Further, the results highlight the strengths and challenges of the intervention, including how it helped foster leadership skills and increased indigenous cultural learning among facilitators. These findings demonstrate the strength of community-led interventions and subsequent opportunities for facilitators to grow as leaders. Further, the study highlights how this style of intervention can also encourage participants to engage in other health and wellbeing programs offered by the community partner hosting the intervention. These findings suggest that interventions aimed at reducing stress among indigenous women facing socioeconomic insecurities, including those living with HIV, are both feasible and beneficial for participants, facilitators, and the nonprofit service organizations delivering them. [ABSTRACT FROM AUTHOR]

Aim: To examine the relationship between periodontitis as an independent effect of smoking and the development of chronic obstructive pulmonary disease (COPD) in Japanese people based on longitudinal data. Materials and Methods: We targeted 4745 people who underwent pulmonary function tests and dental check‐ups at baseline and 8 years later. The Community Periodontal Index was used to assess periodontal status. A Cox proportional hazard model was used to examine the relationship between the incidence of COPD and periodontitis and smoking. To clarify the interaction between smoking and periodontitis, interaction analysis was performed. Results: In a multivariable analysis, both periodontitis and heavy smoking had significant effects on COPD development. When periodontitis was analysed as a continuous value (number of sextants with periodontitis) and as a category (presence or absence of periodontitis) in the multivariable analyses after adjusting for smoking, pulmonary function and other variables, periodontitis had significantly higher hazard ratios (HRs) for the incidence of COPD; the HRs were 1.09 (1.01–1.17) and 1.48 (1.09–2.02), respectively. Interaction analysis showed no significant interaction between heavy smoking and periodontitis on COPD. Conclusions: These results suggest that periodontitis has no interaction with smoking but has an independent effect on developing COPD. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the health and economic outcomes of a universal early intervention for parents and children, the Salut Programme, from birth to when the child completed five years of age. Methods: This study adopted a retrospective observational design using routinely collected linked register data with respect to both exposures and outcomes from Västerbotten county, in northern Sweden. Making use of a natural experiment, areas that received care-as-usual (non-Salut area) were compared to areas where the Programme was implemented after 2006 (Salut area) in terms of: (i) health outcomes, healthcare resource use and costs around pregnancy, delivery and birth, and (ii) healthcare resource use and related costs, as well as costs of care of sick child. We estimated total cumulative costs related to inpatient and specialised outpatient care for mothers and children, and financial benefits paid to mothers to stay home from work to care for a sick child. Two analyses were conducted: a matched difference-in difference analysis using the total sample and an analysis including a longitudinal subsample. Results: The longitudinal analysis on mothers who gave birth in both pre- and post-measure periods showed that mothers exposed to the Programme had on average 6% (95% CI 3–9%) more full-term pregnancies and 2% (95% CI 0.03-3%) more babies with a birth weight ≥ 2500 g, compared to mothers who had care-as-usual. Savings were incurred in terms of outpatient care costs for children of mothers in the Salut area ($826). The difference-in-difference analysis using the total sample did not result in any significant differences in health outcomes or cumulative resource use over time. Conclusions: The Salut Programme achieved health gains, as a health promotion early intervention for children and parents, in terms of more full-term pregnancies and more babies with a birth weight ≥ 2500 g, at reasonable cost, and may lead to lower usage of outpatient care. Other indicators point towards positive effects, but the small sample size may have led to underestimation of true differences. [ABSTRACT FROM AUTHOR]

Summary: Background: Although the association between prenatal tobacco exposure and child obesity risk is well‐established, less is known about co‐exposure to tobacco and cannabis. Objective: Determine the relation between prenatal substance co‐exposure and obesity risk. Methods: In a diverse sample of pregnant women, we examined the association between prenatal substance exposure (tobacco‐only and co‐exposure) and child BMI (kg/m2) trajectories from birth to mid‐childhood (n = 262), overweight/obese status based on BMI percentiles from toddlerhood (24 months) to mid‐childhood (9–12 years), and adiposity outcomes at mid‐childhood (fat mass [kg], fat mass [%] and fat free mass [kg]; n = 128). Given that the major goal of this study was to examine the associations between prenatal substance exposure and child outcomes, we oversampled pregnant women for substance use (with tobacco as the primary focus). Results: Multilevel models demonstrated that children in both exposure groups had a steeper increase in BMI trajectory from birth to mid‐childhood and among co‐exposed children, girls had a steeper increase than boys. Odds ratio of having obesity by mid‐childhood was 12 times higher among those co‐exposed than non‐exposed. Co‐exposure led to significantly greater fat mass and fat mass % compared with no exposure, but exposure to only tobacco was no different than no exposure. Conclusions: Results highlight potentiating effects of cannabis exposure in the context of maternal tobacco use in pregnancy on obesity risk and the importance of multi‐method assessments of obesity. [ABSTRACT FROM AUTHOR]

Background. Ginsenoside Rg1 (Rg1) is one of the key bioactive components of the precious Traditional Chinese Medicine that has been used to treat diabetes in China. Ginsenosides have been reported to protect diabetics from tissue damage, inflammation, and insulin resistance. Type 1 diabetes (T1D) is an organ-specific autoimmune disease that occurred frequently among adolescents over the world, its development was related to inflammation and β-cells immunodeficiency. The aim of this study is to explore the biological mechanism of Rg1 on inflammation and autophagy of β-cells in T1D and its therapeutic potential. Methods. The model of T1D mice was established by injecting Streptozotocin (STZ) (55 mg/kg) or citric acids once a day for 5 days and from the fourth day of injection, mice were administered with Rg1 (20 mg/kg) or saline by gavage once a day for 12 days. Hematoxylin-eosin staining, immunofluorescence, ELISA, quantitative real-time PCR, and Western blot were used to observe the histopathological changes, inflammatory factor levels, and autophagy markers after administration of ginsenoside Rg1. Results. Compared to the T1D mice, Rg1 improved the weight (p < 0.05) and blood glucose (p < 0.01) of mice, advanced the injury and apoptosis of β-cells in islets (p < 0.01), and markedly inhibited the protein expression degrees of CD45, CXCL16, ox-LDL, and TF in the pancreas and spleens (p < 0.01), also activated the degrees of insulin in serum (p < 0.01). Besides, in T1D mice' pancreas and spleen, Rg1 markedly repressed the IL-1β, TNF-α, and NOS2 mRNA levels (p < 0.05 or p < 0.01), inhibited the CXCL16, NF-κB, and TF proteins (p < 0.05 or p < 0.01), while elevating the ratio of LC3 II/I (p < 0.01) and P62 (p < 0.05) protein level. Conclusions. This study proved that Rg1 protected mice against T1D possibly by improving islet injury and tissue inflammation, raising serum insulin, and tissue autophagy marker. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to study the associations between dietary intake of fatty acids in childhood and the risk of islet autoimmunity and type 1 diabetes (T1D). Methods: The prospective Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study included children with genetic susceptibility to T1D born between 1996 and 2004. Participants were followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Dietary intake of several fatty acids at the age of 3 months to 6 years was assessed 1–8 times per participant with a 3-day food record. Joint models adjusted for energy intake, sex, HLA genotype and familial diabetes were used to investigate the associations of longitudinal intake of fatty acids and the development of islet autoimmunity and T1D. Results: During the 6-year follow-up, 247 (4.4%) children of 5626 developed islet autoimmunity and 94 (1.7%) children of 5674 developed T1D. Higher intake of monounsaturated fatty acids (HR 0.63; 95% CI 0.47, 0.82), arachidonic acid (0.69; 0.50, 0.94), total n-3 fatty acids (0.64; 0.48, 0.84), and long-chain n-3 fatty acids (0.14; 0.04, 0.43), was associated with a decreased risk of islet autoimmunity with and without energy adjustment. Higher intake of total fat (0.73; 0.53, 0.98), and saturated fatty acids (0.55; 0.33, 0.90) was associated with a decreased risk of T1D only when energy adjusted. Conclusion: Intake of several fatty acids was associated with a decreased risk of islet autoimmunity or T1D among high-risk children. Our findings support the idea that dietary factors, including n-3 fatty acids, may play a role in the disease process of T1D. [ABSTRACT FROM AUTHOR]

Background/Objective. Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. Research Design and Methods. Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. Results. We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042. Conclusions. This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA. [ABSTRACT FROM AUTHOR]

Summary: Background: Childhood obesity has been associated with prenatal exposure to maternal hyperglycaemia, but we lack understanding about maternal insulin physiologic components that contribute to this association. Objectives: Evaluate the association between maternal insulin sensitivity during pregnancy and adiposity measures in childhood. Methods: In 422 mother–child pairs, we tested associations between maternal insulin sensitivity measures at ~26 weeks of pregnancy and child adiposity measures, including dual‐energy X‐ray absorptiometry body composition and anthropometry (body mass index and waist circumference) at ~5 years. We used linear regression analyses to adjust for maternal age, ethnicity, gravidity, first‐trimester body mass index, and child sex and age at mid‐childhood. Results: In early pregnancy, maternal mean age was 28.6 ± 4.3 years and median body mass index was 24.1 kg/m2. Lower maternal insulin sensitivity indices were correlated with greater child adiposity based on anthropometry measures and on dual‐energy X‐ray absorptiometry total and trunk % fat in univariate associations (r = −0.122 to −0.159). Lower maternal insulin sensitivity was specifically associated with higher dual‐energy X‐ray absorptiometry trunk % fat (n = 359 for Matsuda; β = −0.034 ± 0.013; p = 0.01) after adjustment for covariates, including maternal body mass index. Conclusions: Maternal insulin sensitivity during pregnancy may contribute to increased risk for higher offspring central adiposity in middle childhood. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fine particulate matter (PM2.5) has been found to be detrimental to respiratory health of children, but few studies have examined the effects of prenatal PM2.5 oxidative potential (OP) on lung function in infants and preschool children. OBJECTIVES: We estimated the associations of personal exposure to PM2.5  and OP during pregnancy on offspring objective lung function parameters and compared the strengths of associations between both exposure metrics. METHODS: We used data from 356 mother–child pairs from the SEPAGES cohort. PM filters collected twice during a week were analyzed for OP, using the dithiothreitol (DTT) and the ascorbic acid (AA) assays, quantifying the exposure of each pregnant woman. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple-breath washout (N2MBW) test, performed at 6 wk, and airwave oscillometry (AOS) performed at 3 y. Associations of prenatal PM2.5  mass and OP with lung function parameters were estimated using multiple linear regressions. RESULTS: In neonates, an interquartile (IQR) increase in OPDTTv (0.89nmol/min/m³) was associated with a decrease in functional residual capacity (FRC) measured by N2MBW  [β = -2.26 mL ; 95% confidence interval (CI): -4.68, 0.15]. Associations with PM2.5  showed similar patterns in comparison with OPDTTv  but of smaller magnitude. Lung clearance index (LCI) and TBFVL parameters did not show any clear association with the exposures considered. At 3 y, increased frequency-dependent resistance of the lungs (Rrs7-19) from AOS tended to be associated with higher OPDTTv  (β = 0.09hPa×s/L ; 95% CI: -0.06, 0.24) and OPAAv  (IQR = 1.14nmol/min/m³ ; β = 0.12hPa×s/L ; 95% CI: -0.04, 0.27) but not with PM2.5  (IQR = 6.9µg/m³ ; β = 0.02hPa×s/L ; 95% CI: -0.13, 0.16). Results for FRC and Rrs7-19 remained similar in OP models adjusted on PM2.5. DISCUSSION: Prenatal exposure to OPDTTv was associated with several offspring lung function parameters over time, all related to lung volumes. [ABSTRACT FROM AUTHOR]

Study Question: Can three-dimensional (3D) Power Doppler (PD) ultrasound and a skeletonization algorithm be used to assess first-trimester development of the utero-placental vascular morphology?Summary Answer: The application of 3D PD ultrasonography and a skeletonization algorithm facilitates morphologic assessment of utero-placental vascular development in the first trimester and reveals less advanced vascular morphologic development in pregnancies with placenta-related complications than in pregnancies without placenta-related complications.What Is Known Already: Suboptimal development of the utero-placental vasculature is one of the main contributors to the periconceptional origin of placenta-related complications. The nature and attribution of aberrant vascular structure and branching patterns remain unclear, as validated markers monitoring first-trimester utero-placental vascular morphologic development are lacking.Study Design, Size, Duration: In this prospective observational cohort, 214 ongoing pregnancies were included before 10 weeks gestational age (GA) at a tertiary hospital between January 2017 and July 2018, as a subcohort of the ongoing Rotterdam Periconception Cohort study.Participants/materials, Setting, Methods: By combining 3D PD ultrasonography and virtual reality, utero-placental vascular volume (uPVV) measurements were obtained at 7, 9 and 11 weeks GA. A skeletonization algorithm was applied to the uPVV measurements to generate the utero-placental vascular skeleton (uPVS), a network-like structure containing morphologic characteristics of the vasculature. Quantification of vascular morphology was performed by assigning a morphologic characteristic to each voxel in the uPVS (end-, vessel-, bifurcation- or crossing-point) and calculating total vascular network length. A Mann-Whitney U test was performed to investigate differences in morphologic development of the first-trimester utero-placental vasculature between pregnancies with and without placenta-related complications. Linear mixed models were used to estimate trajectories of the morphologic characteristics in the first trimester.Main Results and the Role Of Chance: All morphologic characteristics of the utero-placental vasculature increased significantly in the first trimester (P < 0.005). In pregnancies with placenta-related complications (n = 54), utero-placental vascular branching was significantly less advanced at 9 weeks GA (vessel points P = 0.040, bifurcation points P = 0.050, crossing points P = 0.020, total network length P = 0.023). Morphologic growth trajectories remained similar after adjustment for parity, conception mode, foetal sex and occurrence of placenta-related complications.Limitations, Reasons For Caution: The tertiary setting of this prospective observational study provides high internal, but possibly limited external, validity. Extrapolation of the study's findings should therefore be addressed with caution.Wider Implications Of the Findings: The uPVS enables assessment of morphologic development of the first-trimester utero-placental vasculature. Further investigation of this innovative methodology needs to determine its added value for the assessment of (patho-) physiological utero-placental vascular development.Study Funding/competing Interest(s): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest.Trial Registration Number: Registered at the Dutch Trial Register (NTR6854). [ABSTRACT FROM AUTHOR]

. Indian subcontinent exhibits considerable degree of ethnic heterogeneity in cardiovascular disease (CVD) risks. Given the importance of ethnicity, the present multi-ethnic study was conducted to find out the differences in body composition patterning and its influence on CVD risk variables.. Owing to considerable ethnic heterogeneity among Asian Indians the study was performed to determine the association of variability between body composition and CVD risk factors at the micro-level among different tribes by sex, province, and generation Nine tribes from three different states (provinces) were considered. Anthropometric measurements, body composition, adiposity, blood pressure, and fasting blood glucose was measured using standard technique. Body composition was measured using BIA method by means of body fat monitor. Mean differences of the body composition measures were analysed by ANOVA. Stepwise multiple regressions were done with CVD risk variables as dependent and body composition profiles as independent variables to find out the significant predictors. Those were then loaded for principal component factor analyses (PCFA).. Tribal subjects of both sexes and from both younger and older generations in Gujarat had significantly higher percentage body fat, subcutaneous fat-whole body, and subcutaneous fat-trunk as compared to tribal subjects of Odisha, and West Bengal, as well as significantly lower skeletal mass-whole body and skeletal mass-trunk. PCFA showed two components: (i) percentage body fat with muscle mass; and (ii) visceral fat with resting metabolism. These two components cumulatively explained 80–90% of the total variance associated with CVD risk variables, across the nine tribes.. Tribal subjects of Gujarat had higher CVD risks with significantly higher fat mass and lower muscle mass followed by the tribal subjects of Odisha, and West Bengal respectively. The younger generation are equally at risk as their older counterparts. The CVD risks are developing at a much faster rate resulting in a serious public health threat, even in traditional societies. Body composition measures could be considered as a better non-invasive technique for early intervention and proper risk management among the Asian Indians in general and tribal populations in particular. [ABSTRACT FROM AUTHOR]

Rationale: Randomized controlled trials only include a subset of patients with chronic obstructive pulmonary disease (COPD) fulfilling strict inclusion criteria. Thus, most patients with COPD in a real-world setting do not have the necessary evidence to support treatment effectiveness. Objectives: To test the hypotheses that most individuals with COPD in the general population are not represented in major clinical trials despite clinically significant disease with exacerbations and early death. Methods: In 105,630 adults from a Danish contemporary population-based cohort, we defined COPD as age 40 or more years, chronic respiratory symptoms, history of smoking exposure, and airflow limitation with FEV1/FVC < 0.70. Outcomes included acute exacerbations and all-cause mortality. Symptomatic smokers without COPD were used as a reference group. Measurements and Main Results: Of all, 7,516 (7%) and 16,079 (15%) were symptomatic smokers with and without COPD. Only 44% of those with COPD were eligible for major clinical trials when applying FEV1 < 80% predicted, smoking history of 10 or more pack-years, and no comorbid asthma as common inclusion criteria. During the median 8.9 years of follow-up, we observed 2,130 acute exacerbations and 3,973 deaths in symptomatic smokers. Compared with symptomatic smokers without COPD, multivariable-adjusted hazard ratios for exacerbations were 7.45 (95% confidence interval, 5.41-10.3) and 29.0 (21.1-39.8) in those with COPD, respectively, excluded and eligible for clinical trials. Corresponding hazard ratios for all-cause mortality were 1.21 (1.11-1.31) and 1.67 (1.54-1.81), respectively. Conclusions: More than half of individuals with COPD in the general population are excluded from major clinical trials; however, these individuals have a clinically significant disease with exacerbations and early death compared with symptomatic smokers without COPD. [ABSTRACT FROM AUTHOR]

Objective: This study tested the hypothesis, in a prospective cohort study design, that maternal saturated free fatty acid (sFFA) concentration during pregnancy is prospectively associated with offspring (newborn) hypothalamic (HTH) microstructure and to explore the functional relevance of this association with respect to early-childhood body fat percentage (BF%).Methods: In N = 94 healthy newborns (born mean 39.3 [SD 1.5] weeks gestation), diffusion-weighted magnetic resonance imaging was performed shortly after birth (25.3 [12.5] postnatal days), and a subgroup (n = 37) underwent a dual-energy x-ray absorptiometry scan in early childhood (4.7 [SD 0.7] years). Maternal sFFA concentration during pregnancy was quantified in fasting blood samples via liquid chromatography-mass spectrometry. Infant HTH microstructural integrity was characterized using mean diffusivity (MD). Multiple linear regression was used to test the association between maternal sFFA and HTH MD, accounting for newborn sex, age at scan, mean white matter MD, and image quality. Multiple linear regression models also tested the association between HTH MD and early-childhood BF%, accounting for breastfeeding status.Results: Maternal sFFA during pregnancy accounted for 8.3% of the variation in newborn HTH MD (β-std = 0.25; p = 0.006). Furthermore, newborn HTH MD prospectively accounted for 15% of the variation in early-childhood BF% (β-std = 0.32; p = 0.019).Conclusions: These findings suggest that maternal overnutrition during pregnancy may influence the development of the fetal hypothalamus, which, in turn, may have clinical relevance for childhood obesity risk. [ABSTRACT FROM AUTHOR]

Rationale: von Willebrand factor (vWF) mediates platelet adhesion during thrombosis. While chronic thromboembolic pulmonary hypertension (CTEPH) is associated with increased plasma levels of vWF, the role of this protein in CTEPH has remained enigmatic. Objectives: To identify the role of vWF in CTEPH. Methods: CTEPH-specific patient plasma and pulmonary endarterectomy material from patients with CTEPH were used to study the relationship between inflammation, vWF expression, and pulmonary thrombosis. Cell culture findings were validated in human tissue, and proteomics and chromatin immunoprecipitation were used to investigate the underlying mechanism of CTEPH. Measurements and Main Results: vWF is increased in plasma and the pulmonary endothelium of CTEPH patients. In vitro, the increase in vWF gene expression and the higher release of vWF protein upon endothelial activation resulted in elevated platelet adhesion to CTEPH endothelium. Proteomic analysis revealed that nuclear factor (NF)-κB2 was significantly increased in CTEPH. We demonstrate reduced histone tri-methylation and increased histone acetylation of the vWF promoter in CTEPH endothelium, facilitating binding of NF-κB2 to the vWF promoter and driving vWF transcription. Genetic interference of NFκB2 normalized the high vWF RNA expression levels and reversed the prothrombotic phenotype observed in CTEPH-pulmonary artery endothelial cells. Conclusions: Epigenetic regulation of the vWF promoter contributes to the creation of a local environment that favors in situ thrombosis in the pulmonary arteries. It reveals a direct molecular link between inflammatory pathways and platelet adhesion in the pulmonary vascular wall, emphasizing a possible role of in situ thrombosis in the development or progression of CTEPH. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is the end result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts, we propose therapeutic trials in two major groups of subjects: "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" patients with COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized controlled trials (RCTs). We highlight the need of RCTs focused on COPD in young patients or pre-COPD to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCT design, including potential outcomes such as lung function, patient-reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure, including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in 1) young adults with COPD and 2) those with pre-COPD at any age. [ABSTRACT FROM AUTHOR]

Purpose: Waterpipe tobacco smoking (WTS) is currently a serious and growing public health threat in the world, especially in adolescents and young women. The aim of the study was to explore sociocultural factors contributing to WTS among adolescents and young adult women in Iran. Methods: This qualitative study was conducted from August 2017 to January 2019 in Isfahan and Hamadan cities, Iran; it included 13–30-year-old females with experience of WTS. For data collection, in-depth semi-structured personal interviews were conducted at participants' preferred time and place. Concurrent with data collection, data were analysed through conventional content analysis. Results: The study participants described the various sociocultural factors contributing to WTS. These factors were categorized into four following main categories: waterpipe glamorization by its producers and sellers, media advertisement or silence, common sociocultural traditions, and governmental policies and regulations. Conclusion: A wide range of sociocultural factors affects WTS among Iranian adolescents and young adult women. Therefore, interdisciplinary multidimensional strategies are needed for WTS management and prevention among these at-risk groups. Public education, strict supervision of tobacco import, export, and selling, ample employment opportunities for young people and effective leisure time management are essential to reduce WTS.Abbreviation WTS: Waterpipe Tobacco Smoking; MPOWER: Monitor tobacco use and prevention policies, Protect people from tobacco smoke, Offer help to quit tobacco use, Warn about the dangers of tobacco, Enforce bans on tobacco advertising, promotion and sponsorship, Raise taxes on tobacco [ABSTRACT FROM AUTHOR]

Reversion of islet autoimmunity (IA) may point to mechanisms that prevent IA progression. We followed 199 individuals who developed IA during the Diabetes Autoimmunity Study in the Young. Untargeted metabolomics was performed in serum samples following IA. Cox proportional hazards models were used to test whether the metabolites (2,487) predicted IA reversion: two or more consecutive visits negative for all autoantibodies. We conducted a principal components analysis (PCA) of the top metabolites; |hazard ratio (HR) >1.25| and nominal P < 0.01. Phosphatidylcholine (16:0_18:1(9Z)) was the strongest individual metabolite (HR per 1 SD 2.16, false discovery rate (FDR)-adjusted P = 0.0037). Enrichment analysis identified four clusters (FDR P < 0.10) characterized by an overabundance of sphingomyelin (d40:0), phosphatidylcholine (16:0_18:1(9Z)), phosphatidylcholine (30:0), and l-decanoylcarnitine. Overall, 63 metabolites met the criteria for inclusion in the PCA. PC1 (HR 1.4, P < 0.0001), PC2 (HR 0.85, P = 0.0185), and PC4 (HR 1.28, P = 0.0103) were associated with IA reversion. Given the potential influence of diet on the metabolome, we investigated whether nutrients were correlated with PCs. We identified 20 nutrients that were correlated with the PCs (P < 0.05). Total sugar intake was the top nutrient. Overall, we identified an association between phosphatidylcholine, sphingomyelin, and carnitine levels and reversion of IA. [ABSTRACT FROM AUTHOR]

Prior research reveals that negative early-life experiences play a major role in the development of obesity in later life, but few studies identify mechanisms that alter the lifetime risk of obesity. This study examines the influence of negative childhood experiences on body mass index (BMI) and obesity (BMI ≥30) during older adulthood and the psychosocial and behavioral pathways involved. Using a nationally representative sample, we examine the influence of cumulative misfortune as well as five separate domains of misfortune on BMI and obesity. Results show that four of the five domains are associated with BMI and obesity either directly, indirectly, or both. The influence of cumulative misfortune on the outcomes is mediated by three adult factors: socioeconomic status, depressive symptoms, and physical activity. The mediators identified here provide targets for intervention among older adults to help offset the health risks of excess BMI attributable of early-life exposure to misfortune. [ABSTRACT FROM AUTHOR]

The fetal origins hypothesis suggests that health and nutrition shocks in utero are causally related to health deficits in old age. It has received considerable empirical support, both within epidemiology and economics but so far it has not been integrated into a life cycle theory of human aging and longevity. The present study shows that the health deficit model, based on the frailty index developed in gerontology, generates shock amplification consistent with the hypothesis. In order to discuss human health over the life cycle from conception to death, we develop a theory of ontogenetic growth and health in utero and during childhood, unify it with the health deficit model of adult aging, and discuss the transmission of early-life shocks to late-life health deficit accumulation. [ABSTRACT FROM AUTHOR]

Objective: To identify early life adversity (ELA) risk factors for earlier pubertal timing, itself a risk factor for poor cardiometabolic health, and to determine whether such ELA-related risk may be mediated by pre-pubertal body mass index (BMI).Methods: Subjects included 426 female participants in a prospective birth cohort study, the NICHD Study of Early Child Care and Youth Development. Survival analysis models were fit to examine ELA exposures, representing childhood socioeconomic status (SES), maternal sensitivity, mother-child attachment, and negative life events, along with child health indicators and covariates, in relation to pubertal timing outcomes, including age at menarche and ages at Tanner stage II for breast and pubic hair development.Results: Higher childhood SES emerged as an independent predictor of older age at menarche, showing each one standard deviation increase in childhood SES corresponded to a 1.3% increase in age at menarche (factor change = 1.013; 1.003-1.022; p < .01), but did not predict breast or pubic hair development (ps > .05). In mediation analyses, indirect (mediated) effects of mother-child attachment on the pubertal timing outcomes, via pre-pubertal BMI, were all statistically significant (ps < .05).Conclusions: Higher childhood SES predicted directly, and secure (vs. insecure) mother-child attachment predicted indirectly (via pre-pubertal BMI), later pubertal timing, suggesting these factors may protect girls from earlier pubertal development. By extension, clinical implications are that intervention strategies designed to lessen ELA- and pre-pubertal obesity-related risk may be effective in remediating life course pathways linking ELA, accelerated pubertal development, and cardiometabolic risk. [ABSTRACT FROM AUTHOR]