The origins of unpredictability in life outcome prediction tasks.

Why are some life outcomes difficult to predict? We investigated this question through in-depth qualitative interviews with 40 families sampled from a multidecade longitudinal study. Our sampling and interviewing process was informed by the earlier efforts of hundreds of researchers to predict life outcomes for participants in this study. The qualitative evidence we uncovered in these interviews combined with a mathematical decomposition of prediction error led us to create a conceptual framework. Our specific evidence and our more general framework suggest that unpredictability should be expected in many life outcome prediction tasks, even in the presence of complex algorithms and large datasets. Our work provides a foundation for future empirical and theoretical work on unpredictability in human lives.

Adulthood adiposity affects cardiac structure and function in later life.

BACKGROUND AND AIMS: Excess adiposity is associated with poorer cardiac function and adverse left ventricular (LV) remodelling. However, its importance over the adult life course on future cardiac structure and systolic and diastolic function is unknown. METHODS: A total of 1690 participants in the National Survey of Health and Development birth cohort underwent repeated adiposity [body mass index (BMI)/waist-to-hip ratio (WHR)] measurements over adulthood and investigation, including echocardiography at age 60-64 years. The relationship between LV structure [LV mass (LVM), relative wall thickness, and LV internal diameter in diastole (LVIDd)] and function (diastolic: E/e', e', and left atrial volume indexed to body surface area; systolic: ejection fraction, S', and myocardial contraction fraction) was investigated using multivariable linear regression models. RESULTS: Increased BMI from age 20 years onwards was associated with greater LVM and LVIDd independent of confounders. Associations remained independent of current BMI for LVIDd and at age 26, 43, and 53 years for LVM. Increased BMI from 43 years onwards was associated with greater relative wall thickness, but not when BMI at age 60-64 years was accounted for. Increased BMI at age 26, 36, and 53 years and at 20 years onwards was associated with lower ejection fraction and myocardial contraction fraction, respectively, but not independently of BMI at 60-64 years. Higher BMI from 20 years onwards was associated with poorer diastolic function independent of confounders. Associations between BMI and left atrial volume indexed to body surface area persisted from 26 years onwards after adjustment for BMI at 60-64 years. Similar relationships were observed for WHR from age 43 years onwards. CONCLUSIONS: Higher adiposity (BMI/WHR) over adulthood is associated with evidence of adverse cardiac structure and function. Some of these associations are independent of adiposity in later life.

Overweight-years and cancer risk: A prospective study of the association and comparison of predictive performance with body mass index (Atherosclerosis Risk in Communities Study).

Excess body mass index (BMI) is associated with a higher risk of at least 13 cancers, but it is usually measured at a single time point. We tested whether the overweight-years metric, which incorporates exposure time to BMI ≥25 kg/m2 , is associated with cancer risk and compared this with a single BMI measure. We used adulthood BMI readings in the Atherosclerosis Risk in Communities (ARIC) study to derive the overweight-years metric. We calculated associations between the metric and BMI and the risk of cancers using Cox proportional hazards models. Models that either included the metric or BMI were compared using Harrell's C-statistic. We included 13,463 participants, with 3,876 first primary cancers over a mean of 19 years (SD 7) of cancer follow-up. Hazard ratios for obesity-related cancers per standard deviation overweight-years were 1.15 (95% CI: 1.05-1.25) in men and 1.14 (95% CI: 1.08-1.20) in women. The difference in the C-statistic between models that incorporated BMI, or the overweight-years metric was non-significant in men and women. Overweight-years was associated with the risk of obesity-related cancers but did not outperform a single BMI measure in association performance characteristics.

The health implications of cumulative exposure to contextual (dis)advantage: Methodological and substantive advances from a unique data linkage.

Deleterious neighborhood conditions are associated with poor health, yet the health impact of cumulative lifetime exposure to neighborhood disadvantage is understudied. Using up to five decades of residential histories for 4,177 adult participants in the Survey of Health of Wisconsin (SHOW) and spatio-temporally linked neighborhood conditions, we develop four operational approaches to characterizing cumulative neighborhood (dis)advantage over the life course. We estimated their associations with self-reported general health and compared to estimates using neighborhood (dis)advantage at time of study enrollment. When cumulative exposures were assessed with the most granular temporal scale (Approach 4), neighborhood transport constraints (OR = 1.21, 95% CI: 1.08, 1.36), residential turnover (OR = 1.20, 95% CI: 1.07, 1.34), education deficit (OR = 1.17, 95% CI: 1.04, 1.32), racial segregation (OR = 1.20, 95% CI: 1.04, 1.38) and median household income (OR = 0.85, 95% CI: 0.75, 0.97) were significantly associated with risk of fair or poor health. For composite neighborhood disadvantage, cumulative exposures had a stronger association (OR = 1.05, 95% CI: 1.02, 1.08) than the cross-sectional exposure (OR = 1.03, 95% CI: 1.01, 1.06). Single point-in-time neighborhood measures underestimate the neighborhood and health relationship, underscoring the importance of a life course approach to cumulative exposure measurement.

The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

Neighborhood eviction trajectories and odds of moderate and serious psychological distress during pregnancy among African American women.

African American mothers are unjustly burdened by both residential evictions and psychological distress. We quantified associations between trajectories of neighborhood evictions over time and the odds of moderate and serious psychological distress (MPD and SPD, respectively) during pregnancy among African American women. We linked publicly available data on neighborhood eviction filing and judgment rates to preconception and during-pregnancy addresses from the Life-course Influences on Fetal Environments (LIFE) Study (2009-2011; n = 808). Multinomial logistic regression-estimated odds of MPD and SPD during pregnancy that were associated with eviction filing and judgment rate trajectories incorporating preconception and during-pregnancy addresses (each categorized as low, medium, or high, with two 9-category trajectory measures). Psychological distress was measured with the Kessler Psychological Distress Scale (K6) (K6 scores 5-12 = MPD, and K6 scores ≥13 = SPD). MPD was reported in 60% of the sample and SPD in 8%. In adjusted models, higher neighborhood eviction filing and judgment rates, as compared with low/low rates, during the preconception and pregnancy periods were associated with 2- to 4-fold higher odds of both MPD and SPD during pregnancy among African American women. In future studies, researchers should identify mechanisms of these findings to inform timely community-based interventions and effective policy solutions to ensure the basic human right to housing for all. This article is part of a Special Collection on Mental Health.

Associations of Abnormal Maternal Glucose Regulation in Pregnancy with Offspring Adiposity, Insulin Resistance, and Adipokine Markers During Childhood and Adolescence.

OBJECTIVE: To examine the associations of abnormal maternal glucose regulation in pregnancy with offspring adiposity, insulin resistance, adipokine, and inflammatory markers during childhood and adolescence. STUDY DESIGN: Project Viva is a prospective prebirth cohort (n = 2128 live births) initiated from 1999 through 2002 in Eastern Massachusetts, US. During the second trimester of pregnancy, clinicians used 2-step oral glucose challenge testing to screen for gestational diabetes mellitus. In the offspring, we measured anthropometry, insulin resistance, adipokines, lipids, and inflammatory markers in mid-childhood (n = 1107), early adolescence (n = 1027), and mid-adolescence (n = 693). We used multivariable linear regression models and generalized estimating equations adjusted for child age and sex, and for maternal age, race/ethnicity, education, parity, and smoking during pregnancy; we further adjusted for prepregnancy body mass index (BMI). RESULTS: In mid-adolescence (17.1 [0.8] years of age), offspring of mothers with gestational diabetes mellitus (n = 27) had a higher BMI z-score (ß; 95% Cl; 0.41 SD; 0.00, 0.82), sum of skinfolds (8.15 mm; 2.48, 13.82), homeostatic model assessment for insulin resistance (0.81 units; 0.13, 1.50), leptin z-score (0.40 SD; 0.01, 0.78), and leptin/adiponectin ratio z-score (0.51 SD; CI 0.09, 0.93) compared with offspring of mothers with normoglycemia (multivariable-adjusted models). The associations with BMI, homeostatic model assessment for insulin resistance, and adiponectin seemed stronger in mid-adolescence compared with earlier time points. The associations were attenuated toward the null after adjustment for maternal prepregnancy BMI. CONCLUSION: Exposure to gestational diabetes mellitus is associated with higher adiposity, insulin resistance, and altered adipokines in mid-adolescence. Our findings suggest that the peripubertal period could be a key time for the emergence of prenatally programmed metabolic abnormalities.

Duration of Simultaneous Exposure to High-Risk and Lower-Risk Nephrotoxic Antimicrobials in the Neonatal Intensive Care Unit (NICU) and Future Adolescent Kidney Health.

OBJECTIVE: To determine whether greater duration of simultaneous exposure to antimicrobials with high nephrotoxicity risk combined with lower-risk antimicrobials (simultaneous exposure) in the neonatal intensive care unit (NICU) is associated with worse later kidney health in adolescents born preterm with very low birth weight (VLBW). STUDY DESIGN: Prospective cohort study of participants born preterm with VLBW (<1500 g) as singletons between January 1, 1992, and June 30, 1996. We defined simultaneous exposure as a high-risk antimicrobial, such as vancomycin, administered with a lower-risk antimicrobial on the same date in the NICU. Outcomes were serum creatinine, estimated glomerular filtration rate (eGFR), and first-morning urine albumin-creatinine ratio (ACR) at age 14 years. We fit multivariable linear regression models with days of simultaneous exposure and days of nonsimultaneous exposure as main effects, adjusting for gestational age, birth weight, and birth weight z-score. RESULTS: Of the 147 out of 177 participants who had exposure data, 97% received simultaneous antimicrobials for mean duration 7.2 days (SD 5.6). No participant had eGFR <90 ml/min/1.73 m2. The mean ACR was 15.2 mg/g (SD 38.7) and 7% had albuminuria (ACR >30 mg/g). Each day of simultaneous exposure was associated only with a 1.04-mg/g higher ACR (95% CI 1.01 to 1.06). CONCLUSIONS: Despite frequent simultaneous exposure to high-risk combined with lower-risk nephrotoxic antimicrobials in the NICU, there were no clinically relevant associations with worse kidney health identified in adolescence. Although future studies are needed, these findings may provide reassurance in a population thought to be at increased risk of chronic kidney disease.

Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis.

BACKGROUND: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status. METHODS: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms. RESULTS: Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years. CONCLUSIONS: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

Early life stress in relation with risk of overweight, depression, and their comorbidity across adulthood: findings from a British birth cohort.

BACKGROUND: Multimorbidity, known as the co-occurrence of at least two chronic conditions, has become of increasing concern in the current context of ageing populations, though it affects all ages. Early life risk factors of multimorbidity include adverse childhood experiences (ACEs), particularly associated with psychological conditions and weight problems. Few studies have considered related mechanisms and focus on old age participants. We are interested in estimating, from young adulthood, the risk of overweight-depression comorbidity related to ACEs while adjusting for early life confounders and intermediate variables. METHODS: We used data from the 1958 National Child Development Study, a prospective birth cohort study (N = 18 558). A four-category outcome (no condition, overweight only, depression only and, overweight-depression comorbidity) was constructed at 23, 33, and 42 years. Multinomial logistic regression models adjusting for intermediate variables co-occurring with this outcome were created. ACEs and sex interaction on comorbidity risk was tested. RESULTS: In our study sample (N = 7762), we found that ACEs were associated with overweight-depression comorbidity risk throughout adulthood (RRR [95% CI] at 23y = 3.80 [2.10-6.88]) though less overtime. Comorbidity risk was larger than risk of separate conditions. Intermediate variables explained part of the association. After full-adjustment, an association remained (RRR [95% CI] at 23y = 2.00 [1.08-3.72]). Comorbidity risk related to ACEs differed by sex at 42. CONCLUSION: Our study provides evidence on the link and potential mechanisms between ACEs and the co-occurrence of mental and physical diseases throughout the life-course. We suggest addressing ACEs in intervention strategies and public policies to go beyond single disease prevention.

Heterogeneity in glycaemic control in children and adolescents with type 1 diabetes: A latent class trajectory analysis of Danish nationwide data.

AIMS: Suboptimal glycaemic control in children and adolescents with type 1 diabetes is prevalent and associated with increased risk of diabetes-related complications and mortality later in life. First, we aimed to identify distinct glycated haemoglobin (HbA1c) trajectories in children and adolescents (2-19 years) with type 1 diabetes. Second, we examined their associations with clinical and socio-demographic factors. METHODS: Data were obtained from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) comprising all Danish children and adolescents diagnosed with type 1 diabetes from 1996 to 2019. Subgroups of distinct mean trajectories of HbA1c were identified using data-driven latent class trajectory modelling. RESULTS: A total of 5889 children (47% female) had HbA1c measured a median of 6 times (interquartile range 3-8) and contributing to 36,504 measurements. We identified four mean HbA1c trajectories, referred to as 'Stable but elevated HbA1c' (83%), 'Increasing HbA1c' (5%), 'Late HbA1c peak' (7%), and 'Early HbA1c peak' (5%). Compared to the 'Stable but elevated HbA1c' group, the three other groups presented rapidly deteriorating glycaemic control during late childhood or adolescence, had higher HbA1c at study entry, and included fewer pump users, higher frequency of inadequate blood glucose monitoring, more severe hypoglycaemic events, lower proportions with Danish origin, and worse educational status of parents. The groups also represented significant differences by healthcare region. CONCLUSIONS: Children and adolescents with type 1 diabetes experience heterogenous trajectories with different timings and magnitudes of the deterioration of HbA1c levels, although the majority follow on average a stable, yet elevated HbA1c trajectory. The causes and long-term health implications of these heterogenous trajectories need to be addressed.

Life course predictors of child emotional distress during the COVID-19 pandemic: Findings from a prospective intergenerational cohort study.

BACKGROUND: We examine precursors of child emotional distress during the COVID-19 pandemic in a prospective intergenerational Australian cohort study. METHODS: Parents (N = 549, 60% mothers) of 934 1-9-year-old children completed a COVID-19 specific module in 2020 and/or 2021. Decades prior, a broad range of individual, relational and contextual factors were assessed during parents' own childhood, adolescence and young adulthood (7-8 to 27-28 years old; 1990-2010) and again when their children were 1 year old (2012-2019). RESULTS: After controlling for pre-pandemic socio-emotional behaviour problems, COVID-19 child emotional distress was associated with a range of pre-pandemic parental life course factors including internalising difficulties, lower conscientiousness, social skills problems, poorer relational health and lower trust and tolerance. Additionally, in the postpartum period, pre-pandemic parental internalising difficulties, lower parental warmth, lower cooperation and fewer behavioural competencies predicted child COVID-19 emotional distress. CONCLUSIONS: Findings highlight the importance of taking a larger, intergenerational perspective to better equip young populations for future adversities. This involves not only investing in child, adolescent, and young adult emotional and relational health, but also in parents raising young families.

PrEP Method Switching: Will it Yield Greater Coverage of HIV Protection? Applying Lessons Learned from Family Planning to Guide Future Research in the Context of PrEP Choice.

PURPOSE OF REVIEW: Despite the growing availability of oral PrEP, coverage remains suboptimal. Through the introduction of additional PrEP methods, including vaginal rings and long-acting injectable formulations, health systems globally are on the cusp of offering PrEP methods that vary by route of administration, efficacy, and frequency of use. With PrEP choice, it will be important to explore PrEP use patterns to better understand how the ability to choose and switch products affects coverage and continuation. In this review, we draw parallels with family planning (FP) by summarizing how method choice and product switching affected contraceptive coverage globally, synthesize what is known about PrEP product switching, and outline evidence gaps to help guide future research on PrEP switching in the context of choice. RECENT FINDINGS: Decades of research in FP has demonstrated that product switching is common and can lead to more satisfaction and increases in contraceptive use. While research on PrEP product switching is nascent, findings suggest switching is common, and that providing more than one PrEP option can increase coverage. Key evidence gaps include understanding product switching in the context of full versus constrained choice, switching in the context of temporary need, and developing interventions that promote product switching for those who could benefit. Providing choice and allowing people to start, stop, and switch products according to their needs and desires is a core component of a rights-based approach to HIV prevention. More research is needed to better understand what drives use patterns, including switching, and how to leverage choice to improve coverage. Standard definitions -some of which have been proposed in this review-are needed to inform comparable measurement. Finally, there is a need to holistically frame PrEP use to acknowledge changes in need over the life course, thus making method switching a standard part of HIV prevention.

Childhood maltreatment and trajectories of cardiometabolic health across the reproductive life span among individuals with a first birth during the Coronary Artery Risk Development in Young Adults Study.

OBJECTIVE: Childhood adversity is associated with poor cardiometabolic health in adulthood; little is known about how this relationship evolves through childbearing years for parous individuals. The goal was to estimate differences in cardiometabolic health indicators before, during and after childbearing years by report of childhood maltreatment in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. METHODS: Including 743 individuals nulliparous at baseline (1985-1986) with one or more pregnancies >20 weeks during follow-up (1986-2022), we fit segmented linear regression models to estimate mean differences between individuals reporting or not reporting childhood maltreatment (physical or emotional) in waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, fasting glucose, and body mass index (BMI) prior to, during, and following childbearing years using generalized estimating equations, allowing for interaction between maltreatment and time within each segment, and adjusting for total parity, parental education, and race (Black or white, self-reported). RESULTS: Individuals reporting maltreatment (19%; 141) had a greater waist circumference (post-childbearing: +2.9 cm, 95% CI (0.7, 5.0), higher triglycerides [post-childbearing: +8.1 mg/dL, 95% CI (0.7, 15.6)], and lower HDL cholesterol [post-childbearing: -2.1 mg/dL, 95% CI (-4.7, 0.5)] during all stages compared to those not reporting maltreatment. There were not meaningful differences in blood pressure, fasting glucose, or BMI. Individuals who reported maltreatment did not report faster changes over time. CONCLUSION: Differences in some aspects of cardiometabolic health between individuals reporting versus not reporting childhood maltreatment were sustained across reproductive life stages, suggesting potentially persistent impacts of childhood adversity.

Adolescent behavioral problems, preterm/low birth weight children and adult life success in a prospective Australian birth cohort study.

BACKGROUND: Preterm and/or low birthweight (PT/LBW) is predictive of a range of adverse adult outcomes, including lower employment, educational attainment, and mental wellbeing, and higher welfare receipt. Existing studies, however, on PT/LBW and adult psychosocial risks are often limited by low statistical power. Studies also fail to examine potential child or adolescent pathways leading to later adult adversity. Using a life course framework, we examine how adolescent problem behaviors may moderate the association between PT/LBW and a multidimensional measure of life success at age 30 to potentially address these limitations. METHODS: We analyze 2044 respondents from a Brisbane, Australia cohort followed from birth in1981-1984 through age 30. We examine moderation patterns using obstetric birth outcomes for weight and gestation, measures of problem behaviors from the Child Behavioral Checklist at age 14, and measures of educational attainment and life success at 30 using multivariable normal and ordered logistic regression. RESULTS: Associations between PT/LBW and life success was found to be moderated by adolescent problem behaviors in six scales, including CBCL internalizing, externalizing, and total problems (all p < 0.01). In comparison, associations between LBW and educational attainment illustrate how a single-dimensional measure may yield null results. CONCLUSION: For PT/LBW, adolescent problem behaviors increase risk of lower life success at age 30. Compared to analysis of singular outcomes, the incorporation of multidimensional measures of adult wellbeing, paired with identification of risk and protective factors for adult life success as children develop over the lifespan, may further advance existing research and interventions for PT/LBW children.

Polygenic risk, childhood abuse and gene x environment interactions with depression development from middle to late adulthood: A U.S. national life-course study.

OBJECTIVE: Utilizing national longitudinal data, this study examines how polygenic depression risk and childhood abuse interactively influence the life-course development of depressive conditions from middle to late adulthood. METHOD: Data from 7512 participants (4323 females and 3189 males) of European ancestry aged 51-90, retrieved from the U.S. Health and Retirement Study (1992-2020), were analyzed. Childhood physical abuse and polygenic depression score were the primary predictors. Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression (CESD) scale, and clinical depression risk was a binary indicator. Growth-curve linear mixed and logit mixed-effects models were conducted for analysis. RESULTS: Increasing polygenic depression scores were associated with elevated CES-D levels and potential risks of clinical depression. Males experienced more detrimental effects of childhood abuse on depression development from ages 51 to 90 years. In contract, non-maltreated females generally exhibited higher depressive symptoms and clinical depression risk than males. A significant interactive effect was found between polygenic depression risk and childhood abuse among males. Higher depression levels and clinical risk were observed with increasing polygenic depression score among maltreated males, surpassing those of females with standardized polygenic score ≥0 from age 51 to 90 years. CONCLUSIONS: The interaction between childhood abuse and genetic factors significantly shaped lifelong depression trajectories in males, while the negative impact of abusive parenting remained constant regardless of polygenic depression risk among females. Individualized prevention and intervention strategies could be crucial in mitigating lifelong depression development, especially for high-genetic-risk males with a history of childhood physical abuse.

Heterogeneity in the risk of cardiovascular disease mortality after the hypertensive disorders of pregnancy across mothers' lifetime reproductive history.

BACKGROUND: Prior studies on maternal cardiovascular disease (CVD) mortality and hypertensive disorders of pregnancy (HDP) have focused only on a woman's first birth and have not accounted for successive affected pregnancies. OBJECTIVES: The objective of this study is to identify mothers' risk of CVD mortality considering lifetime reproductive history. METHODS: We used data from the Medical Birth Registry of Norway, the Norwegian Cause of Death Registry, and the Norwegian National Population Register to identify all mothers who gave birth from 1967 to 2020. Our outcome was mothers' CVD death before age 70. The primary exposure was the lifetime history of HDP. The secondary exposure was the order of HDP and gestational age at delivery of pregnancies with HDP. We used Cox regression models to estimate hazard ratio (HR) and 95% confidence interval (CI), adjusting for education, mother's age, and year of last birth. These models were stratified by the lifetime number of births. RESULTS: Among 987,378 mothers, 86,294 had HDP in at least one birth. The highest CVD mortality, relative to mothers without HDP, was among those with a pre-term HDP in their first two births, although this represented 1.0% of mothers with HDP (HR 5.12, 95% CI 2.66, 9.86). Multiparous mothers with term HDP in their first birth only had no increased risk of CVD relative to mothers without HDP (36.9% of all mothers with HDP; HR 1.12, 95% CI 0.95, 1.32). All other mothers with HDP had a 1.5- to 4-fold increased risk of CVD mortality. CONCLUSIONS: This study identified heterogeneity in the risk of CVD mortality among mothers with a history of HDP. A third of these mothers are not at higher risk compared to women without HDP, while some less common patterns of HDP history are associated with severe risk of CVD mortality.

Placental Abruption and Cardiovascular Event Risk (PACER): Design, data linkage, and preliminary findings.

BACKGROUND: Obstetrical complications impact the health of mothers and offspring along the life course, resulting in an increased burden of chronic diseases. One specific complication is abruption, a life-threatening condition with consequences for cardiovascular health that remains poorly studied. OBJECTIVES: To describe the design and data linkage algorithms for the Placental Abruption and Cardiovascular Event Risk (PACER) cohort. POPULATION: All subjects who delivered in New Jersey, USA, between 1993 and 2020. DESIGN: Retrospective, population-based, birth cohort study. METHODS: We linked the vital records data of foetal deaths and live births to delivery and all subsequent hospitalisations along the life course for birthing persons and newborns. The linkage was based on a probabilistic record-matching algorithm. PRELIMINARY RESULTS: Over the 28 years of follow-up, we identified 1,877,824 birthing persons with 3,093,241 deliveries (1.1%, n = 33,058 abruption prevalence). The linkage rates for live births-hospitalisations and foetal deaths-hospitalisations were 92.4% (n = 2,842,012) and 70.7% (n = 13,796), respectively, for the maternal cohort. The corresponding linkage rate for the live births-hospitalisations for the offspring cohort was 70.3% (n = 2,160,736). The median (interquartile range) follow-up for the maternal and offspring cohorts was 15.4 (8.1, 22.4) and 14.4 (7.4, 21.0) years, respectively. We will undertake multiple imputations for missing data and develop inverse probability weights to account for selection bias owing to unlinked records. CONCLUSIONS: Pregnancy offers a unique window to study chronic diseases along the life course and efforts to identify the aetiology of abruption may provide important insights into the causes of future CVD. This project presents an unprecedented opportunity to understand how abruption may predispose women and their offspring to develop CVD complications and chronic conditions later in life.

Updating the study protocol: Insight 46 - a longitudinal neuroscience sub-study of the MRC National Survey of Health and Development - phases 2 and 3.

BACKGROUND: Although age is the biggest known risk factor for dementia, there remains uncertainty about other factors over the life course that contribute to a person's risk for cognitive decline later in life. Furthermore, the pathological processes leading to dementia are not fully understood. The main goals of Insight 46-a multi-phase longitudinal observational study-are to collect detailed cognitive, neurological, physical, cardiovascular, and sensory data; to combine those data with genetic and life-course information collected from the MRC National Survey of Health and Development (NSHD; 1946 British birth cohort); and thereby contribute to a better understanding of healthy ageing and dementia. METHODS/DESIGN: Phase 1 of Insight 46 (2015-2018) involved the recruitment of 502 members of the NSHD (median age = 70.7 years; 49% female) and has been described in detail by Lane and Parker et al. 2017. The present paper describes phase 2 (2018-2021) and phase 3 (2021-ongoing). Of the 502 phase 1 study members who were invited to a phase 2 research visit, 413 were willing to return for a clinic visit in London and 29 participated in a remote research assessment due to COVID-19 restrictions. Phase 3 aims to recruit 250 study members who previously participated in both phases 1 and 2 of Insight 46 (providing a third data time point) and 500 additional members of the NSHD who have not previously participated in Insight 46. DISCUSSION: The NSHD is the oldest and longest continuously running British birth cohort. Members of the NSHD are now at a critical point in their lives for us to investigate successful ageing and key age-related brain morbidities. Data collected from Insight 46 have the potential to greatly contribute to and impact the field of healthy ageing and dementia by combining unique life course data with longitudinal multiparametric clinical, imaging, and biomarker measurements. Further protocol enhancements are planned, including in-home sleep measurements and the engagement of participants through remote online cognitive testing. Data collected are and will continue to be made available to the scientific community.

Clinical Staging for Personality Disorders in Older Adults.

OBJECTIVE: This scientific research aimed to investigate the feasibility of implementing a clinical staging (CS) model for personality disorders (PDs) in older adults. The CS model could provide valuable insights into the life course of personality pathology, prognosis, and treatment decisions for PDs in older adults. METHODS/DESIGN: The study employed an international Delphi methodology with three rounds and involved 21 experts. RESULTS: Consensus was achieved on 12 out of 17 statements, confirming the viability of a CS model for PDs in older adults. The proposed model incorporates the Alternative Model for PDs, criterion A, and integrates life course information, distinguishing between chronic PD, re-emergent PD, late-onset PD, and past PD. CONCLUSION: The findings suggest that international experts support the implementation of a CS model for PDs in older adults, considering both the severity of personality functioning and the retrospective life course of PD expression.