Multigenerational Study Research Articles

Understanding the potential and pitfalls of digital phenotypes to measure population mental health and wellbeing

BackgroundDigital phenotypes such as social media data are increasingly being used to infer supposed trends in population mental health and wellbeing. These methods are attractive for their potential scale and timeliness. However, many methodological aspects need investigation to establish if these approaches could be applied successfully. We aim to explore these challenges by linking digital phenotypes to high-quality epidemiological data in a birth cohort study. MethodsWe retrospectively linked social media data from Twitter for 661 consenting participants in the Avon Longitudinal Study of Parents and Children, a multigenerational population cohort study. Participants volunteered their Twitter usernames, after a series of focus groups with 14 cohort participants about the acceptability of social media data linkage. Twitter data were used to test the effectiveness of inferring mental health and wellbeing from a range of sentiment analysis algorithms in combination with behavioural and temporal features. These methods were evaluated with participant-level survey data collected during the COVID-19 pandemic (April 9, 2020, to July 3, 2020), including with the Warwick Edinburgh Mental Wellbeing Scale, the General Anxiety Disorder-7 scale, and the Mood and Feelings Questionnaire. Ethical approval for the study was obtained from the Avon Longitudinal Study of Parents and Children Ethics and Law Committee, and informed consent was obtained from participants. FindingsTwitter provides a specific Application Programming Interface for academic research, granting free access to the full history archive and thus enabling the collection of data from cohorts. The focus groups determined that data linkage with Twitter and subsequent sharing is acceptable when data are anonymised. However, publicly available data such as Twitter data can be easily identifiable, and we are therefore exploring methods that would preserve privacy more effectively for data sharing. Our initial results show that temporal features have a key influence on the sensitivity and specificity of a model for the inference of wellbeing, anxiety, and depression when used in combination with textual and behavioural features. This influence varies depending on the specific outcome measure. Ongoing analyses will establish whether extrapolating successful models to alternative population samples is possible. InterpretationEarly results suggest that different mental health and wellbeing outcomes require individual models with uniquely tuned features. Cohort studies are a rich source of training data, but attention must be given to adequate anonymisation practices. FundingThis work was supported by the Health Foundation, the Alan Turing Institute, a Philip Leverhulme Prize to CMAH, and the Medical Research Council.

Effects of the endocrine disruptor 4-nonylphenol on the demography of rotifers Plationus patulus and Brachionus havanaensis: a multigenerational study

The emerging contaminant 4-nonylphenol is an active ingredient in many surfactants. Though 4-nonylphenol has been reported in Mexican waterbodies, no stringent law is available to establish its permissible limits. Most ecotoxicological assays using zooplankton species are based on previously unexposed populations, and multigenerational experiments are rare. Plationus patulus and Brachionus havanaensis are widely distributed species in Mexico and have been used in ecotoxicological assessments. In this work, the median lethal concentration of 4-nonylphenol (LC50, 24 h) for both rotifer species was derived. Based on our acute toxicity data (24 h LC50 of 4-nonylphenol for P. patulus and B. havanaensis were 500 and 250 µg L−1, respectively), three sublethal concentrations (µg L−1) (7.81, 15.82 and 31.25 for B. havanaensis and 15.62, 31.25 and 62.5 for P. patulus) were used in the life table demography tests for two successive generations (F0 and F1) of either rotifer species. Regardless of the concentrations used, 4-nonylphenol had an adverse effect on both rotifer species over two successive generations. P. patulus was more sensitive than B. havanaensis in chronic toxicity tests. F1 generation of both rotifer species was far more adversely affected than the F0 in all toxicant treatments.

Social mobility, adolescents’ psycho-social dispositions, and parenting

Psycho-social dispositions and parental influence are central in early status attainment models. We apply the Social Structure and Personality framework to investigate the contributions of adolescents’ psycho-social dispositions to social mobility, and then the contributions of parents’ socioeconomic status (SES) and parenting to adolescents’ psycho-social dispositions. The Kaplan Longitudinal and Multigenerational Study includes data on two generations of respondents: the first-generation of respondents was observed from seventh grade in 1971 until midlife, and the second-generation, their children, was observed from adolescence to young adulthood. We find that upward social mobility is inhibited by poor psycho-social dispositions, particularly by negative self-feelings. SES, in turn, also affects psycho-social dispositions. Family income is more relevant (i.e., variance explained) than parental education for adolescents’ locus of control, while parental education is more relevant for adolescents’ negative self-feelings. Finally, our findings indicate that parenting can disrupt the cycle of social reproduction, with lower SES adolescents exhibiting lower levels of negative self-feelings if their parents are more attached or less authoritarian.

Socioeconomic origin, future expectations, and educational achievement: A longitudinal three-generation study of the persistence of family advantage.

Expectations about the future direct effort in goal-oriented action and may influence a range of life course outcomes, including educational attainment. Here we investigate whether such expectations are implicated in the dynamics underlying the persistence of educational advantage across family generations, and whether such dynamics have changed in recent decades in view of historical change. Focusing on the role of domain-specific (educational) and general (optimism and control) expectations, we examine parallels across parent-child cohorts in (a) the relationships between parental socioeconomic status (SES) and children's future expectations and (b) the associations between children's future expectations and their academic achievement. We estimate structural equation models using data from the prospective multigenerational Youth Development Study (N = 422 three-generation triads [G1-G2-G3]; G1 Mage in 1988 = 41.0 years, G2 Mage in 1989 = 14.7 years, G3 Mage in 2011 = 15.8 years; G2 White in 1989 = 66.4%, G3 White in 2011 = 64.4%; G1 mean annual household income, converted to 2008 equivalents = $41,687, G2 mean annual household income in 2008 dollars = $42,962; G1 mode of educational attainment = high school, G2 mode of educational attainment = some college). We find intergenerational similarity in the relationships between parental educational attainment and children's future expectations. Children's educational expectations strongly predicted their academic achievement in the second generation, but not in the third generation. With educational expansion, the more recent cohort had higher educational expectations that were less strongly related to achievement. Overall, the findings reveal dynamics underlying the persistence of educational success across generations. The role of future expectations in this intergenerational process varies across historical time, confirming a central conclusion of life span developmental psychology and life course sociological research that individual functioning is influenced by sociocultural contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Collaborative Research: Partnering with the community to improve the science and its impact

BACKGROUND AND AIM: The Michigan PBB Research Registry consists of ~7,000 people exposed to polybrominated biphenyls (PBB) following its accidental introduction into Michigan’s animal feed. After nearly forty years, the PBB Registry was transferred to Emory University, allowing the research team to engage this community. METHODS: Community engagement (CE) activities were initiated with goals of disseminating research findings to those affected, responding to educational needs, incorporating community input, and facilitating research participation. CE methods include community meetings, where research results are shared with the affected community and questions/concerns are addressed and documented. At the first community meeting, we asked for volunteers for the Citizens Advisory Board (CAB) to guide us in research and engagement efforts. The CAB joined forces with the Pine River Superfund Citizen Task Force, a community advisory group focused on the remediation of the Superfund sites left from the PBB manufacturer, and the Mid-Michigan District Health Department. RESULTS:These efforts have evolved into a community-research partnership, where the community identified research questions, helped develop the research approach, and is an integral part of research decision-making. This partnership has led to significant changes in outreach activities, research protocols, and research priorities: community health concerns were added to surveys, the age range for participation was expanded, and chemical workers/family who were removed from the Registry (1990s) due to multiple exposures were re-enrolled with exposome methods to evaluate their complex exposures. Community concerns regarding multi-generational effects and continued high-levels of PBB body burden led to a multi-generational epigenetics study, a clinical trial aimed at accelerating PBB elimination, and an oral history study documenting the lived experience of those affected using qualitative methods. This work will be translated in an online continuing medical education course for healthcare providers. CONCLUSIONS:The community-research partnership has enhanced the science and its relevancy and potential benefit to the impacted community. KEYWORDS: Community-engaged research, science communication, exposome, environmental epidemiology, environmental justice

Biochemical and physiological responses of the water flea Moina macrocopa to microplastics: a multigenerational study

Biochemical and physiological responses of the water flea Moina macrocopa to microplastics: a multigenerational study

Prenatal tobacco exposure and the risk of conduct disorder symptoms in offspring at the age of 14 years: Findings from the Raine Study

BackgroundEmerging epidemiological evidence suggests that offspring born to mothers who smoked tobacco during pregnancy may have elevated risk of developing conduct disorder (CD) symptoms. We examined associations between maternal and paternal tobacco smoking during pregnancy and CD symptoms in offspring at the age of 14 years. MethodsWe obtained data from the Raine Study, a multi-generational cohort study based in Western Australia. DSM-oriented scale of the Child Behavior Checklist (CBCL) was used to measure CD symptoms in offspring. Negative binomial regression was used to estimate the rate ratio (risks) (RR) of CD symptoms in offspring. We also produced the E-values to investigate the extent of unmeasured confounding. Paternal smoking during pregnancy was used as a proxy for environmental tobacco smoke exposure. ResultsComplete data were available for 1747 mother-offspring and 1711 father-offspring pairs. After adjusting for potential confounders, we found elevated risks (rates) of CD symptoms in offspring born to mothers smoking tobacco during the first trimester [RR 1.52 (95 % CI: 1.24–1.87)], third trimester [RR 1.36 (95 % CI: 1.09–1.69)] and during both trimesters of pregnancy [RR 1.50 (95 % CI: 1.19–1.90)]. The rates of CD symptoms in offspring increased with the level of exposure to maternal smoking during pregnancy. However, we noted insufficient statistical evidence for an association between paternal smoking during pregnancy and CD symptoms in offspring. ConclusionThe associations we found for maternal but not paternal smoking may suggest a biological mechanism for intrauterine tobacco exposure on the risk of CD symptoms in offspring. Early interventions assisting pregnant mothers to quit tobacco smoking, or avoid smoking initiation, have potential to contribute health benefits to both mothers and their offspring.

Intergenerational transmission of out-of-home care and the role of mental health problems: Findings from Stockholm birth cohort multigenerational study

Out-of-home care (OHC) experiences are associated with poor long-term outcomes throughout life. However, the continuity of OHC over generations is not fully explored, and the influence of mental health problems (MHP) and socioeconomic conditions on such transmission is still unclear. We therefore assessed the extent to which MHP affect the intergenerational transmissions of OHC as well as whether there are differential patterns depending on the socioeconomic conditions of the family of origin. We used a prospective data from the Stockholm Birth Cohort Multigenerational Study (SBC Multigen) on 11,333 cohort members (Generation 1; G1), their parents (Generation 0; G0), and 24,905 children (Generation 2; G2). Multivariate regressions and path models were used to examine the associations between OHC and MHP across generations; stratified analysis by occupational class in G0 was performed to explore potentially differential patterns. Our findings support the existence of an intergenerational transmission of OHC, particularly in the working class group (OR 4.70); MHP was only transmitted across generations in this group (OR 1.51). While the results indicated a stronger role of MHP among the middle/upper class (OR 5.59) compared to working class (OR 3.52) in part of the pathway (MHP G1→OHC G2), this patter was not consistent throughout the whole pathway (e.g. OHC G1→MHP G1). We conclude that there is a tendency for OHC and MHP experiences to continue across generations, particularly among families with more disadvantageous socioeconomic conditions. MHP seem to play an important role in the transmission of OHC irrespective of socioeconomic conditions.

Involving elderly research participants in the co-design of a future multi-generational cohort study

BackgroundIt has been proposed that the existing ASPirin in Reducing Events in the Elderly Extension observational cohort study (ASPREE-XT) would provide a platform for a future multigenerational research study (MGRS). An advert was sent to 14,268 participants (aged 74 years and older, from Australia, and located in both metropolitan and rural locations) to invite them to share views and preferences about being involved in the co-design of a future MGRS, as their preferences were not known. The objective of this article is to report as a case study the process of involving study participants and how this impacted the co-design of a proposed multi-generational research study, using a novel standardised reporting tool.MethodsWe used participatory action research to involve elderly research participants in the co-design of a proposed multi-generational cohort study between 2017 and 2019 using newsletters, telephone interviews and an in-person workshop. We used the novel ‘Standardised Data on Initiatives Alpha Version 0.1’ (STARDIT 0.1) to plan and report how participant involvement activities positively impacted the study design.ResultsFifty-nine ASPREE-XT participants were interviewed by telephone and 18 participants attended a face-to-face event. Involving participants positively impacted the proposed study design by improving the research objectives, developing protocols, influencing funding decisions and improving ethics applications. Learning points included the importance of maintaining the ideals of ASPREE-XT (respect, quality and transparency); research participants’ preference for the option of receiving results (including genetic results); participants’ need for involvement in decisions about recruitment, data access, governance and other ethical issues; and the preference for different communication methods, including both face-to-face and online methods. Data from the process indicated it was highly valued by all stakeholders, including research participants, study staff and lead investigators. Involvement of participants was described by a lead study investigator of ASPREE-XT as “enormously helpful”.ConclusionsThis case study demonstrates that including participants in the design of a research study positively impacted the study design, participants and researchers. Using a standardised reporting tool to describe the methods and impacts provides a way for learning from this case study to inform future research studies planning to involve people.

Multigenerational Exposure to Nano‐TiO2 Induces Ageing as a Stress Response Mitigated by Environmental Interactions

Despite their ubiquity in personal care products, the health implications of titanium dioxide (TiO2) nanomaterials (NMs) are under strenuous investigation for their potential as a carcinogen, whereas other evidence has shown links with premature ageing. Both potential hazards are manifested after chronic exposure. To explore the chronic effects of TiO2 NMs in the environment, a multigenerational study using the model test species Daphnia magna is conducted. Phenotypical characteristics associated with ageing are observed (loss or shortening of tails and lipid accumulation) with increased expression of highly conserved key stress response genes involved in inflammatory responses and oxidative stress. These responses are visible in continuously exposed daphnids over four generations and in daphnids removed from maternal exposure even three generations later. However, exposure to the “aged” variants of these NMs at the same concentrations significantly reduced these effects, and exposure in medium containing natural organic matter is less severe than in salt‐only medium.

The risk of anxiety symptoms in young adult offspring of parents with mental health problems: Findings from the raine study

IntroductionPrevious research has suggested that offspring of parents with mental health problems, including depression and anxiety, are at an increased risk of developing anxiety disorders. Few studies have investigated this relationship in young adults.ObjectivesTo investigate the risk of anxiety symptoms in young adult offspring of parents with mental health problemsMethodsWe used data from the 1989-1991 cohort of the Western Australian Pregnancy (Raine) Study, which is a multi-generational birth cohort study following mothers and their offspring from pregnancy to 28 years of age. The Depression, Anxiety, and Stress Scale (DASS) was used to assess maternal anxiety and depression whereas a self-reported questionnaire was used to assess paternal emotional problems. Anxiety symptoms among offspring at age 20 were measured by using the short form of the Depression, Anxiety, and Stress Scale (DASS 21). A multivariable negative binomial regression model was used to quantify the associations.ResultsAfter adjustment, maternal anxiety [RR 1.60 (95% CI 1.11-2.32)] and paternal emotional problems [RR 1.32 (95%CI 1.03-1.68)] were associated with an increased risk of anxiety in offspring at age 20 years. Conversely, maternal depressive symptoms [RR 1.04 (95%CI 0.84-1.32)] were not associated with an increased risk of anxiety in offspring.ConclusionsThe present study suggests that maternal anxiety and paternal emotional problems were associated with an increased risk of anxiety in young adult offspring. However, maternal depressive symptoms were not associated with an increased risk of anxiety in the offspring. The findings suggest the potential for targeted screening and intervention of anxiety problems in the offspring.DisclosureNo significant relationships.

Parental death in childhood and pathways to increased mortality across the life course in Stockholm, Sweden: A cohort study.

BackgroundPrevious studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63.Methods and findingsA cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality.Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study.ConclusionsOur findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.

Does time heal all wounds? Life course associations between child welfare involvement and mortality in prospective cohorts from Sweden and Britain.

Child welfare involvement reflects childhood adversity and is associated with increased adult mortality, but it remains unclear how this association changes over the life course. Drawing on the Stockholm Birth Cohort Multigenerational Study (Sweden) and the National Childhood Development Study (Great Britain) this study examines whether inequalities within these cohorts diverge or converge. Involvement with child welfare services (ICWS) is divided into two levels (‘child welfare contact’ and ‘out-of-home care’). For each cohort, we quantify absolute health inequalities as differences in cumulative probabilities of death (18–58 years) and temporary life expectancy; and relative inequalities as hazard ratios in ten-year intervals and ratios of lifetime lost. Persistently, ICWS was associated with premature mortality. The strength of the association varied by age, sex and level of ICWS. Consistently across both countries, the most robust relationship was between out-of-home care and mortality, with statistically significant age-specific hazard ratios ranging between 1.8 and 3.4 for males and 1.8–2.1 for females. Child welfare contact that did not result in out-of-home placement showed less consistent results. Among females the mortality gap developed later compared to males. Estimates attenuate after controlling for family socioeconomic and other background variables but patterns remain intact. Our results show that absolute inequalities widen with increasing age, while relative inequalities might peak in early adulthood and then stabilize in midlife. The relative disadvantage among looked-after children in early adulthood is heightened by overall low rates of mortality at this age. Absolute inequality increases with age, highlighting the weight of the accumulation of disadvantage in mortality over time. The bulk of excess deaths that could be attributed to ICWS occurs from midlife onwards. Mechanisms that uphold the disadvantage after childhood experiences require further exploration. This study highlights that the association between out-of-home care and premature mortality seems to transcend welfare systems.

Early life programming of adult ischemic heart disease within and across generations: The role of the socioeconomic context.

The developmental origins of ischemic heart disease (IHD) have been widely documented but little is known about their persistence across more than one generation. This study aimed to investigate whether the effects of early life disadvantages on adult IHD have changed between generations and are mediated by adult socioeconomic circumstances, and further explore the transgenerational effects of grandparental and parental exposures to disadvantaged circumstances on adult offspring's IHD. We used register-based data from the Uppsala Multigenerational Study, Sweden. The study populations were the parents born 1915-1929 and their offspring born 1932-1972 with available obstetric data. The offspring were further linked to grandparents who had their socioeconomic and demographic data recorded. The outcome was incident IHD assessed at ages 32-75 during a follow-up from January 1, 1964 till December 31, 2008. The exposures included birthweight standardized-for-gestational age, ponderal index, gestational length, and parental socioeconomic position (SEP). Education and income were analyzed as mediators. Potential transgenerational associations were explored by linking offspring IHD to parents' standardized birthweight and gestational length, grandparental SEP, and to grandmothers' age, parity, and marital status at parental birth. All associations were examined in Cox proportional hazard regression models. Lower standardized birthweight and lower parental SEP were found to be associated with higher IHD rates in both generations, with no evidence of effect modification by generation. Education and income did not mediate the association between standardized birthweight and IHD. Disadvantaged grandparental SEP, younger and older childbearing ages of grandmothers, and paternal preterm birth affected offspring's IHD independent of parental education, income, or IHD history. The findings point to similar magnitudes of IHD inequalities by early life disadvantages across two historical periods and the existence of transgenerational effects on IHD. Epigenetic dysregulation involving the germline is a plausible candidate mechanism underlying the transgenerational associations that warrant further research.

Dissociating disorders of depression, anxiety, and their comorbidity with measures of emotional processing: A joint analysis of visual brain potentials and auditory perceptual asymmetries

In a multigenerational study of families at risk for depression, individuals with a lifetime history of depression had: 1) abnormal perceptual asymmetry (PA; smaller left ear/right hemisphere [RH] advantage) in a dichotic emotion recognition task, and 2) reduced RH late positive potential (P3RH) during an emotional hemifield task. We used standardized difference scores for processing auditory (PA sad-neutral) and visual (P3RH negative-neutral) stimuli for 112 participants (52 men) in a logistic regression to predict history of depression, anxiety or comorbidity of both. Whereas comorbidity was separately predicted by reduced PA (OR = 0.527, p = .042) or P3RH (OR = 0.457, p = .013) alone, an interaction between PA and P3RH (OR = 2.499, p = .011) predicted depressive disorder. Follow-up analyses revealed increased probability of depression at low (lack of emotional differentiation) and high (heightened reactivity to negative stimuli) levels of both predictors. Findings suggest that reduced or heightened right-lateralized emotional responsivity to negative stimuli may be uniquely associated with depression.

Associations of maternal and paternal mental health problems with offspring anxiety at age 20 years: Findings from a population-based prospective cohort study

Epidemiological studies indicate that children of parents with mental health problems are at an increased risk of developing anxiety disorders. Few studies have investigated this relationship in young adults. Participants were from the Raine Study, which is a multi-generational birth cohort study in Australia. Maternal anxiety and depression in late childhood were assessed using the Depression, Anxiety, and Stress Scale (DASS-42), and paternal lifetime mental health problems were assessed using a self-reported questionnaire. The short form of DASS-42 (DASS-21) was used to assess anxiety symptoms among offspring at age 20. Negative binomial regression model was used to quantify the association. Data were available for 1,220 mother-offspring and 1,190 father-offspring pairs. After adjusting for potential confounders, we found an increased risk of anxiety in young adult offspring exposed to maternal anxiety in late childhood and paternal lifetime mental health problems. However, we observed no increased risks of anxiety in offspring exposed to maternal depressive symptoms. Our sensitivity analysis based on the log-binomial model (binary outcome) as well as the linear model (log-transformed data) confirmed the robustness of the main results. Our findings suggest there can be value to consider and apply targeted screening and intervention programs of anxiety in the young adult offspring with parental mental health problems.

Inequality in hospitalization due to non-communicable diseases in Sweden: Age-cohort analysis of the Uppsala Birth Cohort Multigenerational Study.

We aimed to investigate cohort differences in age trajectories of hospitalization due to non-communicable conditions, and if these varied by paternal socioeconomic position. We used the Uppsala Birth Cohort Multigenerational Study—including virtually complete information on medical diagnoses.Our sample constituted 28,448 individuals (103,262 observations). The outcome was five-year prevalence of hospitalization due to major non-communicable conditions in 1989–2008. The exposures were age (19–91), year-of-birth (1915–1929; 1938–1972), gender (man vs woman), and parental socioeconomic position (low, medium, and high). We used multilevel logit models to examine associations between exposures and the hospitalization outcome.Younger cohorts had a higher prevalence of hospitalization at overlapping ages than those born earlier, with inter-cohort differences emerging from early-adulthood and increasing with age. For instance, at age 40 predicted probability of hospitalization increased across birth-cohorts—from 1.2% (born in 1948-52) to 2.0% (born in 1963-67)—whereas at age 50 it was 2.9% for those born in 1938-42 compared with 4.6% among participants born in 1953-57. Those with medium and low socioeconomic position had 13.0% and 20.0% higher odds of experiencing hospitalization during the observation period, respectively—when age, year-of-birth and gender were accounted for.We found that no progress was made in reducing the socioeconomic inequalities in hospitalization across cohorts born between 1915 and 1972. Hence, more effective policies and interventions are needed to reduce the overall burden of morbidity—particularly among the most vulnerable.

Associations of parental birth characteristics with autism spectrum disorder (ASD) risk in their offspring: a population-based multigenerational cohort study in Denmark

Fetal exposure risk factors are associated with increased autism spectrum disorder (ASD) risk. New hypotheses regarding multigenerational risk for ASD have been proposed, but epidemiological evidence is largely lacking. We evaluated whether parental birth characteristics, including preterm birth and low birthweight, were associated with ASD risk in offspring. We conducted a nationwide register-based cohort study that included 230174 mother-child and 157926 father-child pairs in Denmark. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for offspring ASD according to parental preterm (<37 weeks) and low birthweight (<2500 g) status, with or without adjustment for certain grandmaternal sociodemographic factors. Mediation analyses were performed for selected parental and offspring health-related factors. Offspring of mothers or fathers with adverse birth characteristics had about 31-43% higher risk for ASD (maternal preterm birth, OR = 1.31, 95% CI= 1.12, 1.55; maternal low birthweight, OR = 1.35, 95% CI: 1.17,1.57; paternal preterm birth, OR = 1.43, 95% CI = 1.18, 1.73; paternal low birthweight, OR = 1.38, 95% CI= 1.13, 1.70). Parents born very preterm (<32 weeks) marked a nearly 2-fold increase in ASD risk in their children. These associations were slightly attenuated upon adjustment for grandmaternal sociodemographic factors. Mediation analyses suggested that parental social-mental and offspring perinatal factors might explain a small magnitude of the total effect observed, especially for maternal birth characteristic associations. Offspring of parents born with adverse characteristics had an elevated risk for ASD. Transmission of ASD risk through maternal and paternal factors should be considered in future research on ASD aetiology.

Mechanisms of Racial and Ethnic Differences in Cognitive Aging

Racial and ethnic disparities in age-related cognitive function and dementia risk in the US are well recognized. However, the psychosocial drivers of these disparities and underlying mechanisms are less well studied. This symposium will highlight novel research regarding our current understanding of racial/ethnic differences in brain and cognitive aging and the underlying mechanisms of the disparities. Frist, two papers will describe results regarding racial/ethnic differences in cognitive function and brain aging markers. Few studies have assessed racial/ethnic differences in cognitive function across age groups. Indira Turney will utilize data from a multigenerational study to explore how age impacts racial/ethnic differences in cognitive function. Underlying brain mechanisms of racial/ethnic differences in cognitive outcomes are also not well defined. Sara Godina will present a systematic review of racial/ethnic differences in structural markers of brain aging and neuropathology. Second, three papers will explore how various risk factors may explain the racial/ethnic disparities in cognitive outcomes. Melissa Lamar will demonstrate the differential associations of various blood pressure indicators with cognitive change among black older adults. B. Gwen Windham will present data from two studies that illustrate differential effects of common risk factors by race and region, highlighting inherent difficulties in race-place disparity research. Finally, Laura Zahodne will present results on how psychosocial factors, beyond socioeconomic status, contribute to racial/ethnic disparities in cognitive function. Jen Manly will lead a discussion on the implications of these results for the future of dementia prevention efforts for an increasingly diverse older US population.

Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet.

Bisphenol S is an endocrine disruptor exhibiting metabolic disturbances, especially following perinatal exposures. To date, no data are available on the obesogen effects of BPS in a mutligenerational issue. We investigated obesogen effects of BPS in a multigenerational study by focusing on body weight, adipose tissue and plasma parameters in male and female mice. Pregnant C57BL6/J mice were exposed to BPS (1.5μg/kgbw/day ie a human equivalent dose of 0.12μg/kgbw/day) by drinking water from gestational day 0 to post natal day 21. All offsprings were fed with a high fat diet during 15 weeks. Body weight was monitored weekly and fat mass was measured before euthanasia. At euthanasia, blood glucose, insuline, triglyceride, cholesterol and no esterified fatty acid plasma levels were determined and gene expressions in visceral adipose tissue were assessed. F1 males and females were mated to obtain the F2 generation. Likewise, the F2 mice were cross-bred to obtain F3. The same analyses were performed. In F1 BPS induced an overweight in male mice associated to lipolysis gene expressions upregulation. In F1 females, dyslipidemia was observed. In F2, BPS exposure was associated to an increase in body weight, fat and VAT masses in males and females. Several plasma parameters were increased but with a sex related pattern (blood glucose, triglycerides and cholesterol in males and NEFA in females). We observed a down-regulation in mRNA expression of gene involved in lipogenesis and in lipolysis for females but only in the lipogenesis for males. In F3, a decrease in VAT mass and an upregulation of lipogenesis gene expression occurred only in females. BPS perinatal exposure induced sex-dependent obesogen multigenerational effects, the F2 generation being the most impacted. Transgenerational disturbances persisted only in females.