Latent class trajectories of socioeconomic position over four time points and mortality: the Uppsala Birth Cohort Study.

BACKGROUND: The study assessed socioeconomic position (SEP) over four time points and employed a latent class analysis (LCA) to explore the associations between longitudinal SEP trajectories and late-life mortality. METHODS: We analyzed a cohort of 11 336 members born at the Uppsala University Hospital, Sweden during 1915-29 and followed up for mortality during 1980-2008. SEP was measured at birth, age 10, mid-adulthood and late adulthood. LCA was used to identify SEP trajectories, which were linked to all-cause and cause-specific mortality through Cox proportional hazard regression models. RESULTS: The age and birth cohort adjusted hazard ratio (HR) of all-cause mortality among the upwardly mobile from middle vs. stable low SEP was 28% lower in men [HR: 0.72; 95% confidence interval (95% CI): 0.65, 0.81] and 30% lower in women (HR: 0.70; 95% CI: 0.62, 0.78). The corresponding HR of cardiovascular mortality was 30% lower in men (HR: 0.70; 95% CI: 0.60, 0.82) and 31% lower in women (HR: 0.69; 95% CI: 0.58, 0.83). Upward mobility was also associated with decreased HR of mortality from respiratory diseases and injuries among men and from cancer, respiratory diseases, injuries and mental disorders among women. The upwardly mobile were similar to the stable high group in terms of their HRs of mortality from all-causes and cardiovascular, cancer and mental diseases. CONCLUSIONS: Upward mobility appeared to be protective of mortality from a wide range of causes. Interventions aiming to prevent deaths can benefit from creating optimal conditions earlier in the life course, letting disadvantaged children maximize their socioeconomic and health potentials.

A divisive hierarchical clustering methodology for enhancing the ensemble prediction power in large scale population studies: the ATHLOS project.

The ATHLOS cohort is composed of several harmonized datasets of international groups related to health and aging. As a result, the Healthy Aging index has been constructed based on a selection of variables from 16 individual studies. In this paper, we consider additional variables found in ATHLOS and investigate their utilization for predicting the Healthy Aging index. For this purpose, motivated by the volume and diversity of the dataset, we focus our attention upon data clustering, where unsupervised learning is utilized to enhance prediction power. Thus we show the predictive utility of exploiting hidden data structures. In addition, we demonstrate that imposed computation bottlenecks can be surpassed when using appropriate hierarchical clustering, within a clustering for ensemble classification scheme, while retaining prediction benefits. We propose a complete methodology that is evaluated against baseline methods and the original concept. The results are very encouraging suggesting further developments in this direction along with applications in tasks with similar characteristics. A straightforward open source implementation for the R project is also provided (https://github.com/Petros-Barmpas/HCEP). Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-022-00171-1.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Development of a common scale for measuring healthy ageing across the world: results from the ATHLOS consortium.

BACKGROUND: Research efforts to measure the concept of healthy ageing have been diverse and limited to specific populations. This diversity limits the potential to compare healthy ageing across countries and/or populations. In this study, we developed a novel measurement scale of healthy ageing using worldwide cohorts. METHODS: In the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) project, data from 16 international cohorts were harmonized. Using ATHLOS data, an item response theory (IRT) model was used to develop a scale with 41 items related to health and functioning. Measurement heterogeneity due to intra-dataset specificities was detected, applying differential item functioning via a logistic regression framework. The model accounted for specificities in model parameters by introducing cohort-specific parameters that rescaled scores to the main scale, using an equating procedure. Final scores were estimated for all individuals and converted to T-scores with a mean of 50 and a standard deviation of 10. RESULTS: A common scale was created for 343 915 individuals above 18 years of age from 16 studies. The scale showed solid evidence of concurrent validity regarding various sociodemographic, life and health factors, and convergent validity with healthy life expectancy (r = 0.81) and gross domestic product (r = 0.58). Survival curves showed that the scale could also be predictive of mortality. CONCLUSIONS: The ATHLOS scale, due to its reliability and global representativeness, has the potential to contribute to worldwide research on healthy ageing.

Education and wealth inequalities in healthy ageing in eight harmonised cohorts in the ATHLOS consortium: a population-based study.

BACKGROUND: The rapid growth of the size of the older population is having a substantial effect on health and social care services in many societies across the world. Maintaining health and functioning in older age is a key public health issue but few studies have examined factors associated with inequalities in trajectories of health and functioning across countries. The aim of this study was to investigate trajectories of healthy ageing in older men and women (aged ≥45 years) and the effect of education and wealth on these trajectories. METHODS: This population-based study is based on eight longitudinal cohorts from Australia, the USA, Japan, South Korea, Mexico, and Europe harmonised by the EU Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. We selected these studies from the repository of 17 ageing studies in the ATHLOS consortium because they reported at least three waves of collected data. We used multilevel modelling to investigate the effect of education and wealth on trajectories of healthy ageing scores, which incorporated 41 items of physical and cognitive functioning with a range between 0 (poor) and 100 (good), after adjustment for age, sex, and cohort study. FINDINGS: We used data from 141 214 participants, with a mean age of 62·9 years (SD 10·1) and an age range of 45-106 years, of whom 76 484 (54·2%) were women. The earliest year of baseline data was 1992 and the most recent last follow-up year was 2015. Education and wealth affected baseline scores of healthy ageing but had little effect on the rate of decrease in healthy ageing score thereafter. Compared with those with primary education or less, participants with tertiary education had higher baseline scores (adjusted difference in score of 10·54 points, 95% CI 10·31-10·77). The adjusted difference in healthy ageing score between lowest and highest quintiles of wealth was 8·98 points (95% CI 8·74-9·22). Among the eight cohorts, the strongest inequality gradient for both education and wealth was found in the Health Retirement Study from the USA. INTERPRETATION: The apparent difference in baseline healthy ageing scores between those with high versus low education levels and wealth suggests that cumulative disadvantage due to low education and wealth might have largely deteriorated health conditions in early life stages, leading to persistent differences throughout older age, but no further increase in ageing disparity after age 70 years. Future research should adopt a lifecourse approach to investigate mechanisms of health inequalities across education and wealth in different societies. FUNDING: European Union Horizon 2020 Research and Innovation Programme.

Alcohol Drinking and Health in Ageing: A Global Scale Analysis of Older Individual Data through the Harmonised Dataset of ATHLOS.

We investigated the relation between alcohol drinking and healthy ageing by means of a validated health status metric, using individual data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project. For the purposes of this study, the ATHLOS harmonised dataset, which includes information from individuals aged 65+ in 38 countries, was analysed (n = 135,440). Alcohol drinking was reflected by means of three harmonised variables: alcohol drinking frequency, current and past alcohol drinker. A set of 41 self-reported health items and measured tests were used to generate a specific health metric. In the harmonised dataset, the prevalence of current drinking was 47.5% while of past drinking was 26.5%. In the pooled sample, current alcohol drinking was positively associated with better health status among older adults ((b-coef (95% CI): 1.32(0.45 to 2.19)) and past alcohol drinking was inversely related (b-coef (95% CI): -0.83 (-1.51 to -0.16)) with health status. Often alcohol consumption appeared to be beneficial only for females in all super-regions except Africa, both age group categories (65-80 years old and 80+), both age group categories, as well as among all the financial status categories (all p < 0.05). Regional analysis pictured diverse patterns in the association for current and past alcohol drinkers. Our results report the need for specific alcohol intake recommendations among older adults that will help them maintain a better health status throughout the ageing process.

Pain rates in general population for the period 1991-2015 and 10-years prediction: results from a multi-continent age-period-cohort analysis.

BACKGROUND: Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. METHODS: We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content "self-reported pain experienced at the time of the interview", with a dichotomous (yes or no) modality. RESULTS: Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. CONCLUSIONS: Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.

Psychiatric comorbidity among women with endometriosis: nationwide cohort study in Sweden.

BACKGROUND: Endometriosis is a common gynecologic condition affecting women of reproductive age. It has been linked with greater rates of depression and anxiety in small, cross-sectional, and clinical studies. Other studies have reported that women with endometriosis have increased risk of bipolar disorder. These reports suggest that psychiatric disorders might be more common among women with endometriosis, contributing to increased burden of mental ill-health in this population of women. However, this hypothesis has not been adequately studied. OBJECTIVES: In this population-based study, we investigated the overall psychiatric comorbidity among women with endometriosis, and the role of familial liability. STUDY DESIGN: Several Swedish national registers were linked and used to follow all women born in Sweden in 1973-1990 for diagnosed psychiatric disorders and endometriosis from age 14 years until year 2016. Sibling comparison analyses were performed in a subsample of 173,650 families. RESULTS: After adjustment for birth characteristics and education, women with endometriosis had an increased risk of being later diagnosed with depressive-, anxiety and stress-related disorders, alcohol/drug dependence, and attention-deficit hyperactivity disorder compared with the general population and with their sisters without endometriosis. The adjusted hazard ratios ranged from 1.56 (95% confidence interval, 1.29-1.88) for depressive disorders to 1.98 (95% confidence interval, 1.34-2.93) for attention-deficit hyperactivity disorder in the sibling analysis. Also, women with previous affective psychotic disorders, depressive-, anxiety and stress-related disorders, eating disorders, personality disorders, and attention-deficit hyperactivity disorder were more likely to be later diagnosed with endometriosis. The adjusted hazard ratios ranged from 1.51 (95% confidence interval, 1.30-1.76) for depressive disorders to 1.93 (95% confidence interval, 1.47-2.52) for personality disorders. CONCLUSION: These findings reveal a high degree of comorbidity between endometriosis and many psychiatric disorders that was not entirely explained by shared familial confounding. Clinical practice may consider psychosocial support to women with endometriosis and treating them from a multidisciplinary perspective.

Early-life social and health determinants of adult socioeconomic position: associations and trends across generations.

BACKGROUND: Social and biological circumstances at birth are established predictors of adult socioeconomic position (SEP). This study aims to assess the trends in these associations across two generations and examine the effects of parental early-life characteristics on descendants' adult SEP. METHODS: We studied men and women born in the Uppsala University Hospital 1915-1929 (G1) and their offspring born 1932-1960 (G2). Data were collected in archives and routine registers. Adult SEP was assessed as an aggregate measure combining education and occupation. The exposures were family SEP, mother's marital status, mother's parity, mother's age, standardised birth weight, gestational length and birth multiplicity. Linear regression was used to examine the associations across generations. RESULTS: The difference in adult SEP between low and high family SEP at birth was 15.8 (95% CI: 13.3 to 18.3) percentage points smaller in G2 compared with G1, although a considerable difference was still evident in G2. The associations of adult SEP with small birth weight for gestational age, post-term birth and high parity were stable between the generations: the generational differences in adjusted coefficients were 1.5 (95% CI: -1.1 to 4.1), 0.6 (-1.7 to 2.9) and 1.8 (-0.2 to 3.8) percentage points, respectively. The association between grandparental and grandchildren's SEPs was largely explained by parental socioeconomic conditions. Father's preterm birth was independently associated with offspring's SEP. CONCLUSION: The stability of the associations between early-life biological disadvantages and adult SEP and the persistent, although attenuated, association between early-life and adult SEPs necessitates increased policy attention to both social and health conditions at birth.

2009 IOM guidelines for gestational weight gain: how well do they predict outcomes across ethnic groups?

Objective: To determine whether the Institute Of Medicine's (IOM) 2009 guidelines for weight-gain during pregnancy are predictive of maternal and infant outcomes in ethnic minority populations.Methods: We designed a population-based study using administrative data on 181,948 women who delivered live singleton births in Washington State between 2006-2008. We examined risks of gestational hypertension, preeclampsia/eclampsia, cesarean delivery, and extended hospital stay in White, Black, Native-American, East-Asian, Hispanic, South-Asian and Hawaiian/Pacific islander women according to whether they gained more or less weight during pregnancy than recommended by IOM guidelines. We also examined risks of neonatal outcomes including Apgar score <7 at 5 min, admission to NICU, requirement for ventilation, and a diagnosis of small or large for gestational age at birth.Results: Gaining too much weight was associated with increased odds for gestational hypertension (adjusted OR (aOR) ranged between 1.53-2.22), preeclampsia/eclampsia (aOR 1.44-1.81), cesarean delivery (aOR 1.07-1.38) and extended hospital stay (aOR 1.06-1.28) in all ethnic groups. Gaining too little weight was associated with decreased odds for gestational hypertension and delivery by cesarean section in Whites, Blacks and Hispanics. Gaining less weight or more weight than recommended was associated with increased odds for small for gestational age and large for gestational age infants respectively, in all ethnic groups.Conclusions: Adherence to the 2009 IOM guidelines for weight gain during pregnancy reduces risk for various adverse maternal outcomes in all ethnic groups studied. However, the guidelines were less predictive of infant outcomes with the exception of small and large for gestational age.Abbreviations: GWG: Gestational weight gain; IOM/NRC; Institute of Medicine and National Research Council; NICU: Neonatal intensive care need for ventilation; SGA: Small for gestational age; LGA: Large for gestational age; BERD: Birth Events Records Database; CHARS: Comprehensive Hospital Discharge Abstract Reporting System; ICD: International Classification of Disease; LMP: Last menstrual period; OR: Odds ratio.

Associations of perinatal characteristics with endometriosis: a nationwide birth cohort study.

BACKGROUND: Perinatal characteristics are associated with subsequent risk of several chronic diseases. Previous studies regarding endometriosis were based on small samples and retrospective data and were limited by unmeasured confounding bias, leading to conflicting and inconclusive findings. We investigated the associations of maternal and birth characteristics with risk of endometriosis among Swedish women of reproductive age. METHODS: This total-population register-based cohort study consisted of 628 312 singleton women born in Sweden between 1973 and 1987, who were followed for diagnosed endometriosis from age 15 years until the end of 2012. Multivariable Cox regression was applied to examine associations with perinatal characteristics. Residual unmeasured confounding was assessed through within-family and E-value analyses. RESULTS: During follow-up, 8262 women received an endometriosis diagnosis. There were clear dose-response/linear associations of endometriosis with lower maternal education, endometriosis in the mother [adjusted hazard ratio (aHR): 2.24, 95% confidence interval (CI): 2.04-2.46], maternal smoking during pregnancy (aHR: 1.18, 95% CI: 1.04-1.33 for moderate smoker and aHR: 1.36, 95% CI: 1.18-1.57 for heavy smoker vs non-smoker), lower birthweight, and lower birthweight-for-gestational age (aHR: 0.93 per standard deviation increase, 95% CI: 0.91-0.95). Within-family and E-value analyses suggested that these perinatal characteristics are robust predictors of the incidence of endometriosis. We also found that an estimated 26% of the association between maternal smoking and early-onset endometriosis could be explained by birthweight-for-gestational age. CONCLUSION: This study finds support for fetal origins of endometriosis, in that exposure to adverse environment or restricted development during the perinatal period may increase the risk. Further research is needed to provide an understanding of the underlying mechanisms.

Social and Psychological Predictors of Body Mass Index among South Africans 15 Years and Older: SANHANES-1.

This study investigated how psychological distress and the proxies for social position combine to influence the risk of both underweight and overweight in South Africans aged 15 years and older. This was a cross-sectional study that included 2254 men and 4170 women participating in the first South African National Health and Nutrition Examination Survey (SANHANES-1). An analysis exploring the associations of social and mental health characteristics with body mass index (BMI) was conducted using binary and multinomial logistic regressions. Results suggested that, overall, women had a higher risk of overweight/obesity compared to men (age-adjusted odds ratio [AOR] 4.65; 95% confidence intervals [CI] 3.94-5.50). The gender effect on BMI was smaller in non-African participants (AOR 3.02; 95% CI 2.41-3.79; p-value for interaction = 0.004). Being employed and having a higher level of education were associated with higher risks of overweight and obesity and a lower risk of underweight. Being single or without a spouse and poor mental health were found to increase the odds of being underweight, especially in men. To conclude, there are strong social gradients and important gender and ethnic differences in how BMI is distributed in the South African population.

Short-term and long-term case-fatality rates for myocardial infarction and ischaemic stroke by socioeconomic position and sex: a population-based cohort study in Sweden, 1990-1994 and 2005-2009.

OBJECTIVE: Case-fatality rates (CFRs) for myocardial infarction (MI) and ischaemic stroke (IS) have decreased over time due to better prevention, medication and hospital care. It is unclear whether these improvements have been equally distributed according to socioeconomic position (SEP) and sex. The aim of this study is to analyse differences in short-term and long-term CFR for MI and IS by SEP and sex between the periods 1990-1994 to 2005-2009 for the entire Swedish population. DESIGN: Population-based cohort study based on Swedish national registers. METHODS: We used logistic regression and flexible parametric models to estimate short-term CFR (death before reaching the hospital or on the disease event day) and long-term CFR (1 year case-fatality conditional on surviving short-term) across five distinct SEP groups, as well as CFR differences (CFRDs) between SEP groups for both MI and IS from 1990-1994 to 2005-2009. : Result S: Overall short-term CFR for both MI and IS decreased between study periods. For MI, differences in short-term and long-term CFR between the least and most favourable SEP group were generally stable, except in long-term CFR among women; intermediate SEP groups mostly managed to catch up with the most favourable SEP group. For IS, short-term CFRD generally decreased compared with the most favourable group; but long-term CFRD were mostly stable, except for an increase for older subjects. CONCLUSION: Despite a general decline in CFR for MI and IS across all SEP groups and both sexes as well as some reductions in CFRD, we found persistent and even increasing CFRD among the least advantaged SEP groups, older patients and women. We speculate that targeted prevention rather than treatment strategies have the potential to reduce these inequalities.

Early life socioeconomic position and mortality from cardiovascular diseases: an application of causal mediation analysis in the Stockholm Public Health Cohort.

OBJECTIVE: We aimed to quantify the mediating impact of adult social and behavioural mechanisms in the association between childhood socioeconomic position (SEP) and cardiovascular disease (CVD) mortality by employing a weighting approach to mediation analysis. DESIGN: Prospective cohort study. SETTING: Stockholm County, Sweden. PARTICIPANTS: 19 720 individuals who participated in the Stockholm Public Health Cohort survey in 2002 and were older than 40 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was CVD mortality. Non-CVD mortality was additionally analysed for comparison. METHODS: Study subjects were followed in routine registers from 2002 to 2011 for mortality. Data on father's SEP and adult social and behavioural factors came from questionnaire survey. The inverse odds weighting method was used to estimate the total effect, the natural direct effect and the natural indirect effect (NIE) in Poisson regression models. All results were adjusted for gender, age, country of birth and marital status. Multiple imputation was used to handle missing data. RESULTS: The total effect of manual versus non-manual father's SEP on CVD mortality was estimated as an incidence rate ratio (IRR) of 1.24 (95% CI 1.09 to 1.41). When the social and behavioural factors were accounted for, the IRR for the NIE was 1.09 (95% CI 1.04 to 1.14), suggesting a mediation of 44% of the total effect. As for non-CVD mortality, father's manual SEP was associated with 1.15 fold excess risk (IRR: 1.15; 95% CI 1.04 to 1.27) of which the effect represented by the whole set of mediators was 1.06 (95% CI 1.01 to 1.10). CONCLUSION: Adult social and behavioural factors had a considerable mediating effect on the early life social origin of mortality from CVDs and other causes. Future research employing causal mediation analysis may nevertheless have to consider additional factors for a fuller understanding of the mechanisms.

Academic performance, externalizing disorders and depression: 26,000 adolescents followed into adulthood.

BACKGROUND: The incidence of major depression among adults has been shown to be socially differentiated, and there are reasons to seek explanations for this before adulthood. In this cohort study, we examined whether academic performance in adolescence predicts depression in adulthood, and the extent to which externalizing disorders explain this association. METHODS: We followed 26,766 Swedish women and men born 1967-1982 from the last year of compulsory school, at age about 16, up to 48 years of age. We investigated the association between grade point average (GPA, standardized by gender) and first diagnosis of depression in national registers of in- or out-patient psychiatric care. We used Cox proportional hazards models, adjusting for lifetime externalizing diagnoses and potential confounders including childhood socioeconomic position and IQ. RESULTS: During follow-up, 7.0% of the women and 4.4% of the men were diagnosed with depression. A GPA in the lowest quartile, compared with the highest, was associated with an increased risk in both women (hazard ratio 95% confidence interval 1.7, 1.3-2.1) and men (2.9, 2.2-3.9) in models controlling for potential confounders. Additional control for externalizing disorders attenuated the associations, particularly in women. CONCLUSIONS: The findings suggest that poor academic performance is associated with depression in young adulthood and that the association is partly explained by externalizing disorders. Our results indicate the importance of early detection and management of externalizing disorders among children and adolescents.

Developmental origins of endometriosis: a Swedish cohort study.

BACKGROUND: Endometriosis is a chronic condition affecting women of reproductive age and is associated with multiple health burdens. Yet, findings regarding its 'developmental origins' are inconsistent. We aimed to investigate the associations of birth characteristics with endometriosis. We also explored potential mediation by adult social and reproductive factors. METHODS: This cohort study consisted of 3406 women born in Uppsala, Sweden, between 1933 and 1972. We used data from archived birth records and endometriosis diagnoses at ages 15-50 recorded in the national patient registers. Socioeconomic and reproductive characteristics were obtained from routine registers. HRs were estimated from Cox regression. RESULTS: During the follow-up, 111 women have been diagnosed with endometriosis, and most cases are external endometriosis (ie, outside the uterus, n=91). Lower standardised birth weight for gestational age was associated with increased rate of endometriosis (HR 1.35 per standard deviation decrease; 95% CI 1.08 to 1.67). This increased rate was also detected among women with fewer number of live births (HR 2.38; 95% CI 1.40 to 4.07 for one child vs ≥2 children; HR 6.09; 95% CI 3.88 to 9.57 for no child vs ≥2 children) and diagnosed infertility problem (HR 2.00; 95% CI 1.10 to 3.61) prior to endometriosis diagnosis. All the observed associations were stronger for external endometriosis. However, no evidence was found that number of births was the mediator of the inverse association between standardised birth weight and endometriosis. CONCLUSION: This study supports the developmental origins theory and suggests that exposure to growth restriction during the fetal period is associated with increased risk of endometriosis during reproductive years.