Multigenerational Cohort Research Articles

Familial risk of dilated and hypertrophic cardiomyopathy: a national family study in Sweden.

This study aims to determine the familial incidence of dilated (DCM) and hypertrophic cardiomyopathy (HCM) in first-degree, second-degree, and third-degree relatives of affected individuals. In this population-based multigenerational cohort study, full-siblings, half-siblings, and cousin pairs born to Swedish parents between 1932 and 2015 were included, and register-based DCM and HCM diagnoses among relatives were ascertained. Adjusted odds ratios (ORs) for DCM and HCM were calculated for relatives of individuals with DCM and HCM compared with relatives of individuals without DCM and HCM for reference. Total study population included 6 334 979 subjects and consisted of 5 577 449 full-siblings, 1 321 414 half-siblings, and 3 952 137 cousins. Overall, 10 272 (0.16%) unique individuals were diagnosed with DCM and 3769 (0.06%) with HCM. Of these, 7716 (75.12%) and 2375 (63.01%) were males, respectively. Familial risk ORs for DCM were 5.35 [95% confidence intervals (CI): 4.85-5.90] for full-siblings, 2.68 (95% CI:1.86-3.87) for half-siblings, and 1.72 (95% CI:1.12-2.64) for cousins of affected individuals. The ORs for HCM were 42.44 (95% CI:37.66-47.82) for full-siblings, 32.70 (95% CI:21.32-50.15) for half-siblings, and 36.96 (95% CI:29.50-46.31) for cousins of affected individuals. In sex-stratified analysis, relatives of affected females were found more likely to be affected than were relatives of affected males, with stronger aggregation observed for HCM. Familial risk of HCM and DCM is high and associated with genetic resemblance, with strongest aggregations observed in relatives of affected females with HCM, whereas this association was distinctly attenuated for DCM. The finding of a Carter effect, more pronounced in HCM, suggests a multifactorial threshold model of inheritance.

Triceps skinfold thickness and body mass index and the risk of gestational diabetes mellitus: Evidence from a multigenerational cohort study

BackgroundPre-pregnancy obesity is a well-recognized risk factor for gestational diabetes mellitus (GDM). There is a continuity of obesity from childhood to adolescence and then adulthood. However, it is unknown whether early childhood obesity predicts GDM. MethodsWe investigated the prospective association of childhood triceps skinfold thickness and body mass index (BMI) with GDM risk among women from the Mater-University of Queensland Study of Pregnancy (MUSP), a multigenerational cohort study. A multiple logistic regression model was applied to estimate the odds of experiencing GDM by childhood skinfold thickness and BMI. ResultsOut of 552 women in the study for whom data were available on triceps skinfold thickness and BMI at average age 5 (range 3–7) years old, 52 (9.42%) developed GDM by average age 30 (range 28–33) years. We found that the risk of developing GDM was greater among women who had greater skinfold thickness but not greater BMI at age 5 years. Women who were classified as overweight or obese based on skinfold thickness at age 5 years had an increased odds ratio of GDM compared to women who had normal skinfold thickness. This association remained significant after adjustment for the potential confounders (OR 2.74; 95% confidence interval=1.28–5.86). ConclusionThe risk of developing GDM was associated with higher skinfold thickness at age 5 years.

No evidence of association between habitual physical activity and ECG traits: Insights from the electronic Framingham Heart Study

No evidence of association between habitual physical activity and ECG traits: Insights from the electronic Framingham Heart Study

Data Resource Profile: The Manitoba Multigenerational Cohort.

Families are important components of society; given their shared genetic and social environments, studying families can provide critical insight into health and social outcomes within family members and across generations. Few places in the world have high-quality linkages within families at a population level; one such location is Manitoba, Canada. The Manitoba Multigenerational Cohort (MMC) has been developed to facilitate health and social research using family-based designs. The MMC is derived from the Manitoba Health Insurance Registry (‘the Registry’)—a population-based registry of all individuals registered with Manitoba Health and Seniors Care (MHSC).1 The Registry is updated at the Manitoba Centre for Health Policy (MCHP) twice a year and is integrated with historical registry data to create a longitudinal population-based registry. Over 80 administrative and survey-based data sets are linkable at the individual level; these data sets make up the Manitoba Population Research Data Repository (‘ the Repository’) and are housed in a secure environment at the MCHP.

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.

Immune age and biological age as determinants of vaccine responsiveness among elderly populations: the Human Immunomics Initiative research program

The Human Immunomics Initiative (HII), a joint project between the Harvard T.H. Chan School of Public Health and the Human Vaccines Project (HVP), focuses on studying immunity and the predictability of immuneresponsiveness to vaccines in aging populations. This paper describes the hypotheses and methodological approaches of this new collaborative initiative. Central to our thinking is the idea that predictors of age-related non-communicable diseases are the same as predictors for infectious diseases like COVID-19 and influenza. Fundamental to our approach is to differentiate between chronological, biological and immune age, and to use existing large-scale population cohorts. The latter provide well-typed phenotypic data on individuals’ health status over time, readouts of routine clinical biochemical biomarkers to determine biological age, and bio-banked plasma samples to deep phenotype humoral immune responses as biomarkers of immune age. The first phase of the program involves 1. the exploration of biological age, humoral biomarkers of immune age, and genetics in a large multigenerational cohort, and 2. the subsequent development of models of immunity in relation to health status in a second, prospective cohort of an aging population. In the second phase, vaccine responses and efficacy of licensed COVID-19 vaccines in the presence and absence of influenza-, pneumococcal- and pertussis vaccines routinely offered to elderly, will be studied in older aged participants of prospective population-based cohorts in different geographical locations who will be selected for representing distinct biological and immune ages. The HII research program is aimed at relating vaccine responsiveness to biological and immune age, and identifying aging-related pathways crucial to enhance vaccine effectiveness in aging populations.

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.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Generation 2 questionnaire data capture May-July 2020.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 from the Bristol area (UK). ALSPAC has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. From 2012, ALSPAC has identified G1 participants who were pregnant (or their partner was) or had become parents, and enrolled them, their partners, and children in the ALSPAC-Generation 2 (ALSPAC-G2) study, providing a unique multi-generational cohort. At present, approximately 1,100 G2 children (excluding those in utero) from 810 G1 participants have been enrolled. In response to the COVID-19 pandemic, ALSPAC rapidly deployed two online questionnaires; one during the initial lockdown phase in 2020 (9 th April-15 th May), and another when national lockdown restrictions were eased (26 th May-5 th July). As part of this second questionnaire, G1 parents completed a questionnaire about each of their G2 children. This covered: parental reports of children's feelings and behaviour since lockdown, school attendance, contact patterns, and health. A total of 289 G1 participants completed this questionnaire on behalf of 411 G2 children. This COVID-19 G2 questionnaire data can be combined with pre-pandemic ALSPAC-G2 data, plus ALSPAC-G1 and -G0 data, to understand how children's health and behaviour has been affected by the pandemic and its management. Data from this questionnaire will be complemented with linkage to health records and results of biological testing as they become available. Prospective studies are necessary to understand the impact of this pandemic on children's health and development, yet few relevant studies exist; this resource will aid these efforts. Data has been released as: 1) a freely-available dataset containing participant responses with key sociodemographic variables; and 2) an ALSPAC-held dataset which can be combined with existing ALSPAC data, enabling bespoke research across all areas supported by the study.

Grandmaternal Perinatal Serum DDT in Relation to Granddaughter Early Menarche and Adult Obesity: Three Generations in the Child Health and Development Studies Cohort.

Serum DDTs during or just after pregnancy were associated with breast cancer in mothers (F0), and with breast cancer, mammographic density, and obesity in adult daughters (F1) in the Child Health and Development Studies multi-generational cohort in prior publications. Here, we investigate F0 perinatal serum DDT associations with granddaughters'(F2) measured obesity at a median age of 26 and self-reported age at menarche. F2 weight, height and waist circumference were measured by trained examiners. o,p'-DDT, p,p'-DDT and p,p'-DDE were measured in archived F0 perinatal serum. F0 DDT associations with F2 outcomes, accounting for F1 characteristics, were estimated in log-linear models adjusted for F0 and F1 body mass index (BMI), race, and menarche timing (N = 258 triads for obesity; N = 235 triads for early menarche). Interactions between F0 BMI and DDTs were estimated. F0 o,p'-DDT was associated with F2 obesity [Odds ratio (OR), 2.6; 95% confidence interval (CI), 1.3-6.7; tertile 3 vs. 1), among normal weight F0 (70%), but not among overweight and obese F0 (P interaction = 0.03), independent of other DDTs. F0 o,p'-DDT was also associated with F2 early menarche (OR, 2.1; 95% CI, 1.1-3.9, tertile 3 vs. 1) and this association was not modified by F0 BMI. Ancestral exposure to environmental chemicals, banned decades ago, may influence the development of earlier menarche and obesity, which are established risk factors for breast cancer and cardiometabolic diseases. Discovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention.See related commentary by Fenton and Boyles, p. 1459.

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.

Understanding utility essentials of e-learning management systems in higher education: a multi-generational cohort perspective

ABSTRACT This research aimed to explore the nuances of utility in components of e-learning systems by using a multi-generational undergraduate business school cohort programme and an e-learning utility-satisfaction evaluation model. Our empirical research demonstrates differences between the three generations for the utility of all the variables of the e-learning systems components, with varying differences in the relationships between Generations X, Y and Z. Furthermore, we show course development, learner support and user characteristics influence results demonstrability which has a high influence on overall satisfaction. We established nuances in the learning utility essentials in courses on e-learning systems for multi-generational cohorts; revealed the utility of learner support as a key differentiator and developed a model on utility-satisfaction with reasonable explanatory and predictive power. The model possesses the dual advantages of fewer constituent items and the connective capability to link utility to satisfaction to enable e-learning systems evaluation and ease of identifying areas for improvement in e-learning course delivery.

The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Generation 2 questionnaire data capture May-July 2020.

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 from the Bristol area (UK). ALSPAC has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. From 2012, ALSPAC has identified G1 participants who were pregnant (or their partner was) or had become parents, and enrolled them, their partners, and children in the ALSPAC-Generation 2 (ALSPAC-G2) study, providing a unique multi-generational cohort. At present, approximately 1,100 G2 children (excluding those in utero) from 810 G1 participants have been enrolled. In response to the COVID-19 pandemic, ALSPAC rapidly deployed two online questionnaires; one during the initial lockdown phase in 2020 (9 th April-15 th May), and another when national lockdown restrictions were eased (26 th May-5 th July). As part of this second questionnaire, G1 parents completed a questionnaire about each of their G2 children. This covered: parental reports of children's feelings and behaviour since lockdown, school attendance, contact patterns, and health. A total of 289 G1 participants completed this questionnaire on behalf of 411 G2 children. This COVID-19 G2 questionnaire data can be combined with pre-pandemic ALSPAC-G2 data, plus ALSPAC-G1 and -G0 data, to understand how children's health and behaviour has been affected by the pandemic and its management. Data from this questionnaire will be complemented with linkage to health records and results of biological testing as they become available. Prospective studies are necessary to understand the impact of this pandemic on children's health and development, yet few relevant studies exist; this resource will aid these efforts. Data has been released as: 1) a freely-available dataset containing participant responses with key sociodemographic variables; and 2) an ALSPAC-held dataset which can be combined with existing ALSPAC data, enabling bespoke research across all areas supported by the study.

Understanding satisfaction essentials of E-learning in higher education: A multi-generational cohort perspective

Despite the increasingly critical role of e-learning in higher education, there is limited understanding of the satisfaction essentials of multi-generational students' cohorts undertaking online courses. In this study, we examine the perceived value of educational experiences of multi-generational students' cohorts studying via an online learning management system (Moodle). The study analysed survey responses from multi-generational students (N = 611) on a core subject in an undergraduate business school programme. The results show that Generations X, Y and Z students produce different students' satisfaction levels in distinct components of the online programme; namely, course design, course delivery, course delivery environment and preference of the mode of delivery. Generations cohorts account for remarkable effects in the total satisfaction of students on the online learning programme. The results suggest that contextualising online teaching based on multi-generational students' cohort composition could be one strategy to enhance student learning experience and satisfaction.

Associations between preterm birth and low birth weight in parents and autism spectrum disorder (ASD) risk in their offspring: A population-based multigenerational cohort study in Denmark

Background: Fetal exposure risk factors are associated with increased ASD risk. New hypotheses regarding transgenerational risk for ASD have been proposed, but epidemiological evidence is still lacking. We evaluated whether parental preterm birth or low birth weight was associated with ASD risk in offspring.Methods: We conducted a nationwide register-based cohort study that included 230,174 mother-child and 157,926 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 the parental preterm (&lt;37 weeks) and low birth weight (&lt;2500 grams) status, with or without adjustment for grandmaternal sociodemographic factors. Mediation analyses were performed for selected parental and offspring health-related factors.Results: Offspring of mothers or fathers with adverse birth outcomes had about 31-43% higher risk for ASD (maternal preterm birth, OR=1.31, 95% CI= 1.12,1.55; maternal low birth weight, OR=1.35, 95% CI: 1.17,1.57; paternal preterm birth, OR=1.43, 95% CI=1.18, 1.73; paternal low birth weight, OR=1.38, 95% CI= 1.13, 1.70). Parents born very preterm (&lt;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 a small magnitude of indirect effect of parental social-mental and offspring perinatal risk factors on the child, especially for maternal birth outcome associations.Conclusions: Offspring of parents born with adverse outcomes had an elevated risk for ASD. Transgenerational risk for ASD through maternal and paternal factors should be considered in future research on ASD etiology.

Pediatric metabolic syndrome definitions impact prevalence and socioeconomic gradients

Abstract Background The choice of pediatric metabolic syndrome (MetS) definition influences prevalence estimates, but further implications, especially on the association with socioeconomic status (SES), are not well-known. This hampers a synthesis of the evidence to help guide the relevant stakeholders. For this reason, we aim to assess the impact of alternative definitions on the prevalence of MetS, the children that are identified, and the association between SES and MetS. Methods Data were used from the Lifelines Cohort Study, a prospective multigenerational cohort in the Netherlands. At baseline 9,754 children participated, of which 5,085 (52.1%) were included in the longitudinal analyses. We computed the prevalence of MetS according to five published definitions and measured the observed positive agreement between pairs of definitions, indicating the proportion of agreement across the average number of MetS cases. Logistic regression was used to assess the association between SES and MetS. All models were adjusted for age and sex; the longitudinal models were also adjusted for baseline MetS status. Results The prevalence rates of MetS varied between definitions (0.7-3.0% at baseline), but positive agreement between MetS definitions was generally fair to good ranging from 0.34 (95% confidence interval (CI) 0.28; 0.41) to 0.66 (95%CI 0.58; 0.75) at baseline. At both assessments, we found an inverse association between baseline SES and MetS, which ranged from 0.81 (95%CI 0.70; 0.93) to 0.92 (95%CI 0.86; 0.98) per definition in the longitudinal analyses with a mean follow-up (SD) of 3.0 (0.75) years. Conclusions Alternative definitions of MetS lead to differing prevalence estimates, and they agreed on 50% of the average number of cases of MetS. The alternative definitions also lead to similar socioeconomic gradients; regardless of which definition was used we concluded low SES was a risk factor for developing MetS. Key messages Evidence regarding different definitions of metabolic syndrome in children can be combined because the agreement among definitions is generally fair to good. As low socioeconomic status is a consistent risk factor for developing metabolic syndrome, preventive interventions should preferentially target children from low socioeconomic backgrounds.

Abstract IA11: Timing of environmental contributions to cancer in a multigenerational cohort

Abstract Transdisciplinary studies of environmental risk factors for cancer can discover paths to prevention. Using breast cancer as a case study, we review findings on the relation of a ubiquitous legacy environmental chemical, DDT, to breast cancer in three generations in the Child Health and Development Studies cohort. Although banned in the U.S. and in many places worldwide in the 1970s, the DDT story illustrates the potential role of legacy environmental chemicals in current cancer etiology. We demonstrate the importance of accounting for windows of susceptibility and induction time to cancer and provide evidence for multigenerational and transgenerational effects relevant to breast cancer risk in current generations. Findings provide proof of concept that the current environment may have lasting effects 60 years in the future. Findings support prudent management of current environmental exposures with known biologic toxicity. Waiting 60 years to understand human effects is too late to protect the public health and prevent cancer. The Child Health and Development Studies (CHDS) is a 60-year, prospective follow-up of 20,000 pregnancies that occurred in the 1960s and the resultant generations. The CHDS provides unique and valuable data to characterize how pregnancy and in utero exposures and responses contribute to disease risk in multiple generations. Maternal perinatal blood samples simultaneously provide the opportunity to measure the pregnancy exposome for Generation 1 mothers, the in utero exposome for Generation 2, and the germline exposome for Generation 3. In the CHDS we are also able to study the grandpaternal exposome in relation to granddaughters’ breast cancer risk factors, a design that estimates transgenerational effects via the paternal line. CHDS generations are tracked for place of residence, cancer risk factors, and cancer incidence to provide high quality of evidence avoiding errors of recall and accurate exposure assessment. We review breast cancer findings for Generation 1 (cohort mothers), Generation 2 (cohort daughters), and Generation 3 (cohort granddaughters). We describe perinatal DDT associations with breast cancer in mothers and daughters, with breast density in daughters, and with breast cancer risk factors in granddaughters. We show the results of next steps to uncover mechanisms, including DNA methylation patterns in breast cancer-related genes in the daughters’ generation associated with in utero DDT exposure, and the correlation of the maternal metabolome with DDT in mothers. We also compare the human, observational metabolomics data in maternal perinatal serum with parallel data from controlled experimental studies in mice designed to replicate the DDT dose and perinatal exposure in our human cohort. Along with DDT, we show findings on the relation of in utero exposure to PFASs, a class of chemicals of current concern that were also present in the 1960s. Along with grandmaternal associations, we also show early findings on some grandpaternal variables that are independently correlated with granddaughter breast cancer risk factors. We highlight findings based on high-resolution metabolomics data and exposome analyses in conjunction with epidemiologic data. These metabolomics data serve as important molecular footprints that result from gene and environmental interactions. We employ novel computational and statistical approaches to facilitate the interpretation of these high-dimensional data and integrative analysis, draw insights on the biologic effects of DDT and PFASs compounds, and explore the implication of findings on risk for breast cancer. Citation Format: Barbara A. Cohn. Timing of environmental contributions to cancer in a multigenerational cohort [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr IA11.

Adolescent and young adult mental health problems and infant offspring behavior: Findings from a prospective intergenerational cohort study

BackgroundParental depression and anxiety have been consistently linked to offspring behavior problems across childhood. However, many of the risks for these common mental health problems are established well before pregnancy. This study takes advantage of rare, prospective data to examine relations between parental mental health histories (from adolescence onwards) and next generation offspring behavior problems. MethodsData were drawn from a multi-generational cohort study that has followed Australians from infancy to adulthood since 1983, and 1171 of their offspring assessed prospectively from pregnancy. Generalized estimating equation models were used to estimate associations between parents’ depression/anxiety symptoms in adolescence and young adulthood and offspring behavior problems at 1 year. ResultsIn analyses of 648 mother-infant and 423 father-infant dyads, after adjustment for confounders and concurrent mental health problems, mean behavior problem scores in infants of mothers with a history of mental health problems in both adolescence and young adulthood were over half a standard deviation higher than those of mothers without problems during these periods, B = 2.19, 95% CI 1.21 – 3.17, β = 0.52. No association was observed for fathers. LimitationsWe only included infants born to participants aged 29–35 years and we assessed behavior problems via parent-report. ConclusionsA mother's history of persistent depression and anxiety from adolescence to young adulthood can predict higher levels of behavior problems in her infant. Findings support calls for greater policy and prevention focus on preconception and postnatal mental health, particularly a mother's early emotional health history, prior to parenthood.

Leukocyte Telomere Length Is Unrelated to Cognitive Performance Among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants

Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia. Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with generalized estimating equations, adjusting for sex, age, education, country, generation, and lymphocyte percentage. Older age and male gender were associated with shorter LTL, and LTL was significantly longer in family members than spouse controls (p < 0.005). LTL was not associated with working or episodic memory, semantic processing, and information processing speed for 1613 cognitively unimpaired individuals as well as 597 individuals with dementia or incipient dementia (p < 0.005), who scored significantly lower on all cognitive domains (p < 0.005). Within this unique LLFS cohort, a group of families assembled on the basis of exceptional survival, LTL is unrelated to cognitive ability for individuals with and without cognitive impairment. LTL does not change in the context of degenerative disease for these individuals who are biologically younger than the general population.

Association of Grandparental and Parental Age at Childbirth With Autism Spectrum Disorder in Children

Advanced parental age has been associated with autism spectrum disorders (ASDs) in children. However, little is known about the association between grandparental age at the time of birth of the parent and the risk of ASD in the grandchildren. To estimate the associations between parental and grandparental age and ASD risk in children. This population-based, multigenerational cohort study used data from Danish national health registries. A parental age cohort was constructed to evaluate the association between parental age and ASD in 1 476 783 singleton children born from 1990 to 2013, and a multigenerational cohort was also constructed including 362 438 fathers and 458 234 mothers born from 1973 to 1990 for whom information on grandparental age was available. Data analyses were conducted from November 1, 2018, through February 7, 2020. Parental age at childbirth and grandparental age at the time of the birth of the parent. Diagnoses of ASD in children were obtained from the Danish Psychiatric Central Register (1994-2017). Logistic regression analysis was used to estimate the associations between parental or grandparental age and ASD in children. Of the 1 476 783 children born from 1990 to 2013, 758 066 (51.3%) were male, and 27 616 (1.9%) had ASD (20 467 [74.1%] were male). Advanced paternal or maternal age over 30 years was monotonically associated with increased ASD risk, with odds ratios (ORs) of 1.56 (95% CI, 1.45-1.68) for maternal age 40 years and older and 1.57 (95% CI, 1.39-1.78) for paternal age 50 years and older, compared with parents aged 25 to 29 years. In the multigenerational cohort, 9364 grandchildren (1.7%) had ASD. This study found U-shaped associations, in that ASD risk was higher among grandchildren of younger (≤19 years) maternal grandmothers (OR, 1.68; 95% CI, 1.52-1.85), younger maternal grandfathers (OR, 1.50; 95% CI, 1.26-1.78), and younger paternal grandmothers (OR, 1.18; 95% CI, 1.04-1.34), and older (≥40 years) paternal grandmothers (OR, 1.40; 95% CI, 1.03-1.90) compared with the grandchildren of grandparents who were aged 25 to 29 years at the time of giving birth to the parents. These findings corroborate previous studies suggesting that advanced parental age is independently associated with increased ASD risk in children. This study also found that children with young maternal grandparents and children with young and old paternal grandparents had elevated ASD risk. Possible transmission of ASD risk across generations should be considered in etiological research on ASD.

The 3G Multigenerational Cohort of Nova Scotian women and their mothers and offspring.

The negative impact of exposures such as maternal obesity, excessive gestational weight gain, and hypertension in pregnancy on the health of the next generation has been well studied. Evidence from animal studies suggests that the effects of in utero exposures may persist into the second generation, but the epidemiological literature on the influence of pregnancy-related exposures across three generations in humans is sparse. This cohort was established to investigate associations between antenatal and perinatal exposures and health outcomes in women and their offspring. The cohort includes women who were born and subsequently had their own pregnancies in the Canadian province of Nova Scotia from 1980 onward. Intergenerational linkage of data in the Nova Scotia Atlee Perinatal Database was used to establish a population-based dynamic retrospective cohort. The cohort has prospectively collected information on sociodemographics, maternal health and health behaviours, pregnancy health and complications, and obstetrical and neonatal outcomes for two generations of women and their offspring. As of October 2018, the 3G cohort included 14978 grandmothers (born 1939-1986), 16766 mothers or cohort women (born 1981-2003), and 28638 children (born 1996-2018). The cohort women were generally younger than Nova Scotian women born after 1980, and as a result, characteristics associated with pregnancy at a younger age were more frequently seen in the cohort women; sampling weights will be created to account for this design effect. The cohort will be updated annually to capture future deliveries to women who are already in the cohort and women who become eligible for inclusion when they deliver their first child. The 3G Multigenerational Cohort is a population-based cohort of women and their mothers and offspring, spanning a time period of 38years, and provides the opportunity to study inter- and transgenerational associations across the maternal line.