Application of life course trajectory methods to public health data: A comparison of sequence analysis and group-based multi-trajectory modeling for modelling childhood adversity trajectories.

There is increasing awareness of the importance of modelling life course trajectories to unravel how social, economic and health factors relate to health over time. Different methods have been developed and applied in public health to classify individuals into groups based on characteristics of their life course. However, the application and results of different methods are rarely compared. We compared the application and results of two methods to classify life course trajectories of individuals, i.e. sequence analysis and group-based multi-trajectory modeling (GBTM), using public health data. We used high-resolution Danish nationwide register data on 926,160 individuals born between 1987 and 2001, including information on the yearly occurrence of 7 childhood adversities in 2 dimensions (i.e. family poverty and family dynamics). We constructed childhood adversity trajectories from 0 to 15 years by applying (1) sequence analysis using optimal matching and cluster analysis using Ward's method and (2) GBTM using logistic and zero-inflated Poisson regressions. We identified 2 to 8 cluster solutions using both methods and determined the optimal solution for both methods. Both methods generated a low adversity, a poverty, and a consistent or high adversity cluster. The 5-cluster solution using sequence analysis additionally included a household psychiatric illness and a late adversity cluster. The 4-group solution using GBTM additionally included a moderate adversity cluster. Compared with the solution obtained through sequence analysis, the solution obtained through GBTM contained fewer individuals in the low adversity cluster and more in the other clusters. We find that the two methods generate qualitatively similar solutions, but the quantitative distributions of children over the groups are different. The method of choice depends on the type of data available and the research question of interest. We provide a comprehensive overview of important considerations and benefits and drawbacks of both methods.

Childhood adversity and the risk of gestational diabetes: A population-based cohort study of nulliparous pregnant women.

AIMS: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications, and though it may be linked to childhood adversity, the effect of different types of adversity remains unclear. Childhood adversity is linked to a younger maternal age, which may hide the overall impact of adversity on GDM risk. We therefore aimed to explore the association between different types of childhood adversity and GDM while accounting for the potential impact of maternal age. METHODS: We used Danish nation-wide register data, including 208,207 women giving birth for the first time from 2004 to 2018. Five adversity groups were used to examine the effect of childhood adversity on GDM risk: (1) low (referent group), (2) early life material deprivation, (3) persistent deprivation, (4) loss or threat of loss within the family and (5) high adversity. RESULTS: 5375 women were diagnosed with GDM in the study population (2.6% absolute risk). Compared to women who experienced low adversity, the other adversity groups had a higher GDM risk (absolute difference [%]) directly; early material deprivation (0.64% [95% CI 0.44; 0.84]), persistent deprivation (0.63% [0.41; 0.86]), loss or threat of loss (0.73% [0.42; 1.05]) and high adversity (0.80% [0.32; 1.27]). The indirect effect of maternal age attenuated the total effect of childhood adversity on GDM by an absolute difference of 0.25%-0.46%. CONCLUSIONS: Experiencing childhood adversity to any extent is associated with a higher risk of GDM. Interventions aimed at preventing childhood adversity may have a positive effect in reducing GDM burden and the associated health risks.

Early childhood adversity and body mass index in childhood and adolescence: linking registry data on adversities with school health records of 53,401 children from Copenhagen.

OBJECTIVE: We examined whether childhood adversity experienced in early childhood (0-5 years) is related to body mass index (BMI) in childhood (6-7 years) and adolescence (12-15 years). METHODS: This study combined data from the nationwide register-based DANLIFE study on childhood adversities with data on height and weight of school children in Copenhagen. Data were available for 53,401 children born in Denmark between 1980 and 1996. Children were divided into groups of early childhood adversity by applying group-based multi-trajectory modelling using their yearly count of childhood adversity in three dimensions (i.e., material deprivation, loss or threat of loss, and family dynamics) from 0-5 years. Direct and total associations between the early childhood adversity groups and BMI z-scores in childhood and adolescence were estimated using sex-stratified structural equation models. RESULTS: Five exclusive and exhaustive groups of early childhood adversity were identified, which were characterized by low adversity (51%), moderate material deprivation (30%), high material deprivation (14%), loss or threat of loss (3%) and high adversity (2%). Boys and girls exposed to moderate or high material deprivation and loss or threat of loss had a slightly higher BMI z-score, especially in adolescence, compared with those in the low adversity group, with the strongest association found for girls in the loss or threat of loss group (b (95% CI) = 0.18 (0.10, 0.26)). Additionally, boys in the high adversity group had a slightly lower BMI z-score in childhood than boys in the low adversity group (b (95% CI) = -0.12 (-0.22, -0.02)). CONCLUSIONS: Whereas associations with BMI were found for children and adolescents exposed to material deprivation, loss or threat of loss, and high adversity, the effect sizes were generally small. Contrary to prevailing hypotheses, weight changes in childhood is probably not a major explanatory mechanism linking early childhood adversity with later-life morbidity.

Saving time and money in biomedical publishing: the case for free-format submissions with minimal requirements.

BACKGROUND: Manuscript preparation and the (re)submission of articles can create a significant workload in academic jobs. In this exploratory analysis, we estimate the time and costs needed to meet the diverse formatting requirements for manuscript submissions in biomedical publishing. METHODS: We reviewed 302 leading biomedical journals' submission guidelines and extracted information on the components that tend to vary the most among submission guidelines (the length of the title, the running title, the abstract, and the manuscript; the structure of the abstract and the manuscript, number of items and references allowed, whether the journal has a template). We estimated annual research funding lost due to manuscript formatting by calculating hourly academic salaries, the time lost to reformatting articles, and quantifying the total number of resubmissions per year. We interviewed several researchers and senior journal editors and editors-in-chief to contextualize our findings and develop guidelines that could help both biomedical journals and researchers work more efficiently. RESULTS: Among the analyzed journals, we found a huge diversity in submission requirements. By calculating average researcher salaries in the European Union and the USA, and the time spent on reformatting articles, we estimated that ~ 230 million USD were lost in 2021 alone due to reformatting articles. Should the current practice remain unchanged within this decade, we estimate ~ 2.5 billion USD could be lost between 2022 and 2030-solely due to reformatting articles after a first editorial desk rejection. In our interviews, we found alignment between researchers and editors; researchers would like the submission process alignment between researchers and editors; researchers would like the submission process to be as straightforward and simple as possible, and editors want to easily identify strong, suitable articles and not waste researchers' time. CONCLUSIONS: Based on the findings from our quantitative analysis and contextualized by the qualitative interviews, we conclude that free-format submission guidelines would benefit both researchers and editors. However, a minimum set of requirements is necessary to avoid manuscript submissions that lack structure. We developed our guidelines to improve the status quo, and we urge the publishers and the editorial-advisory boards of biomedical journals to adopt them. This may also require support from publishers and major international organizations that govern the work of editors.

Childhood adversity and risk of type 2 diabetes in early adulthood: results from a population-wide cohort study of 1.2 million individuals.

AIMS/HYPOTHESIS: To examine whether childhood adversity is related to development of type 2 diabetes in early adulthood (16 to 38 years) among men and women. METHODS: We used nationwide register data of 1,277,429 individuals born in Denmark between 1 January 1980 and 31 December 2001, who were still resident in Denmark and without diabetes at age 16 years. Individuals were divided into five childhood adversity groups based on their yearly exposure to childhood adversities (from age 0-15 years) across three dimensions: material deprivation, loss or threat of loss, and family dynamics. We estimated HR and hazard differences (HD) for type 2 diabetes according to the childhood adversity groups using Cox proportional hazards and Aalen additive hazards models. RESULTS: During follow-up from age 16 to 31 December 2018, 4860 individuals developed type 2 diabetes. Compared with the low adversity group, the risk of type 2 diabetes was higher in all other childhood adversity groups among both men and women. For example, the risk was higher in the high adversity group characterised by high rates of adversity across all three dimensions among men (HR 2.41; 95% CI 2.04, 2.85) and women (1.58; 1.31, 1.91), translating into 36.2 (25.9, 46.5) additional cases of type 2 diabetes per 100,000 person-years among men and 18.6 (8.2, 29.0) among women. CONCLUSIONS/INTERPRETATION: Individuals who experienced childhood adversity are at higher risk of developing type 2 diabetes in early adulthood. Intervening upon proximal determinants of adversity may help reduce the number of type 2 diabetes cases among young adults.

Cancer burden among adolescents and young adults in relation to childhood adversity: a nationwide life-course cohort study of 1.2 million individuals.

Background: Childhood adversity such as poverty, loss of a parent, and dysfunctional family dynamics may be associated with exposure to environmental and behavioral hazards, interfere with normal biological functions, and affect cancer care and outcomes. To explore this hypothesis, we assessed the cancer burden among young men and women exposed to adversity during childhood. Methods: We undertook a population-based study using Danish nationwide register data on childhood adversity and cancer outcomes. Children who were alive and resident in Denmark until their 16th birthday were followed into young adulthood (16-38 years). Group-based multi-trajectory modelling was used to categorize individuals into five distinct groups: low adversity, early material deprivation, persistent material deprivation, loss/threat of loss, and high adversity. We assessed the association with overall cancer incidence, mortality, and five-year case fatality; and cancer specific outcomes for the four most common cancers in this age group in sex-stratified survival analyses. Findings: 1,281,334 individuals born between Jan 1, 1980, and Dec 31, 2001, were followed up until Dec 31, 2018, capturing 8229 incident cancer cases and 662 cancer deaths. Compared to low adversity, women who experienced persistent material deprivation carried a slightly lower risk of overall cancer (hazard ratio (HR) 0.90; 95% CI 0.82; 0.99), particularly due to malignant melanoma and brain and central nervous system cancers, while women who experienced high adversity carried a higher risk of breast cancer (HR 1.71; 95% CI 1.09; 2.70) and cervical cancer incidence (HR 1.82; 95% CI 1.18; 2.83). While there was no clear association between childhood adversity and cancer incidence in men, those men who had experienced persistent material deprivation (HR 1.72; 95% CI 1.29; 2.31) or high adversity (HR 2.27; 95% CI 1.38; 3.72) carried a disproportionate burden of cancer mortality during adolescence or young adulthood compared to men in the low adversity group. Interpretation: Childhood adversity is associated with a lower risk of some subtypes of cancer and a higher risk of others, particular in women. Persistent deprivation and adversity are also associated with a higher risk of adverse cancer outcomes for men. These findings may relate to a combination of biological susceptibility, health behaviors and treatment-related factors. Funding: None.

Out-of-home care placement and mortality rate in early adulthood: identifying vulnerable subgroups in a nationwide cohort study.

Out-of-home care has been linked to excess mortality across the lifespan. We examined whether this association is modified by the age at first out-of-home care placement and the number of placements. In this population-based cohort study, we used register data covering all children born in Denmark between 1 and 1980 and 31 December 1999, totalling 1,111,193 individuals followed until 31 December 2018. We divided participants according to sex, out-of-home care status, age at first placement, and the number of placements. We estimated adjusted hazard ratios and hazard differences per 10,000 person-years for all-cause mortality and mortality due to suicide, accidents, and cancer between ages 18 and 39. 53,015 (4.8%) of the participants were placed in out-of-home care before age 18. The adjusted hazard ratio for all-cause mortality was 3.4 (95% CI 3.1-3.7) for males and 4.7 (4.0-5.4) for females, corresponding to 20.6 (19.0-22.2) and 10.3 (9.1-11.5) additional deaths per 10,000 individuals annually among males and females, respectively. Associations did not vary substantially according to age at first placement or the number of placements. Both males and females with a history of out-of-home care were more likely to die from suicide, accidents, and cancer compared with their peers. We show a markedly higher all-cause and cause-specific mortality among children who have been placed in out-of-home care, but contrary to our hypothesis, age at first placement and the number of placements did not modify this relation. These results warrant further investigation into potential target points for interventions that may prevent premature mortality in this group of disadvantaged individuals.

Childhood adversity and cardiovascular disease in early adulthood: a Danish cohort study.

AIMS: To examine the effect of childhood adversity on the development of cardiovascular disease (CVD) between ages 16 and 38, specifically focusing on ischaemic heart disease and cerebrovascular disease. METHODS AND RESULTS: Register data on all children born in Denmark between 1 January 1980 and 31 December 2001, who were alive and resident in Denmark without a diagnosis of CVD or congenital heart disease until age 16 were used, totalling 1 263 013 individuals. Cox proportional hazards and Aalen additive hazards models were used to estimate adjusted hazard ratios (HRs) and adjusted hazard differences of CVD from ages 16 to 38 in five trajectory groups of adversity experienced between ages 0 and 15. In total, 4118 individuals developed CVD between their 16th birthday and 31 December 2018. Compared with those who experienced low levels of adversity, those who experienced severe somatic illness and death in the family (men: adjusted HR: 1.6, 95% confidence interval: 1.4-1.8, women: 1.4, 1.2-1.6) and those who experienced very high rates of adversity across childhood and adolescence (men: 1.6, 1.3-2.0, women: 1.6, 1.3-2.0) had a higher risk of developing CVD, corresponding to 10-18 extra cases of CVD per 100 000 person-years in these groups. CONCLUSIONS: Individuals who have been exposed to childhood adversity are at higher risk of developing CVD in young adulthood compared to individuals with low adversity exposure. These findings suggest that interventions targeting the social origins of adversity and providing support for affected families may have long-term cardio-protective effects.

The effect on women's health of extending parental leave: a quasi-experimental registry-based cohort study.

BACKGROUND: Parental leave policies have been hypothesized to benefit mothers' mental health. We assessed the impact of a 6-week extension of parental leave in Denmark on maternal mental health. METHODS: We linked individual-level data from Danish national registries on maternal sociodemographic characteristics and psychiatric diagnoses. A regression discontinuity design was applied to study the increase in parental leave duration after 26 March 1984. We included women who had given birth between 1 January 1981 and 31 December 1987. Our outcome was a first psychiatric diagnosis following the child's birth, ascertained as the first day of inpatient hospital admission for any psychiatric disorder. We presented cumulative incidences for the 30-year follow-up period and reported absolute risk differences between women eligible for the reform vs not, in 5-year intervals. RESULTS: In all, 291 152 women were followed up until 2017, death, emigration or date of first psychiatric diagnosis. The median follow-up time was 29.99 years, corresponding to 10 277 547 person-years at risk. The cumulative incidence of psychiatric diagnoses at 30 years of follow-up was 59.5 (95% CI: 57.4 to 61.6) per 1000 women in the ineligible group and 57.5 (95% CI: 55.6 to 59.4) in the eligible group. Eligible women took on average 32.85 additional days of parental leave (95% CI: 29.20 to 36.49) and had a lower probability of having a psychiatric diagnosis within 5 years [risk difference (RD): 2.4 fewer diagnoses per 1000 women, 95% CI: 1.5 to 3.2] and up to 20 years after the birth (RD: 2.3, 95% CI: 0.4 to 4.2). In subgroup analyses, the risk reduction was concentrated among low-educated, low-income and single women. CONCLUSIONS: Longer parental leave may confer mental health benefits to women, in particular to those from disadvantaged backgrounds.

Prevalence of Patients Receiving Urate-Lowering Medicine in Greenland and Denmark: A Cross-Sectional Case-Control Study.

This study estimates the age- and sex-specific prevalence of patients receiving urate-lowering therapy (ULT) in Greenland and compares the results with estimates in Denmark. Characteristics of patients receiving ULT in Greenland were compared to age- and sex-matched controls. The study was designed as a cross-sectional case−control study based on nationwide data from medical and population registers in Greenland and Denmark. The prevalence of patients receiving ULT was significantly lower in Greenland (0.55%) compared to Denmark (1.40%) (p < 0.001). In both countries, the prevalence increased with age and was higher among men compared to women. In Greenland, patients receiving ULT were more often overweight, and more frequently received blood glucose-, lipid-, and blood pressure-lowering medicine including diuretics compared to age- and sex-matched controls. The prevalence of patients receiving ULT was significantly lower in Greenland compared to Denmark. Common life-style related risk factors for hyperuricemia and gout were observed frequently among ULT-treated patients compared to controls. Along with an increasing prevalence of lifestyle-related diseases in Greenland, the prevalence of patients receiving ULT may increase in the years to come. More focus on detection and management of hyperuricemia and gout in Greenland is warranted to improve quality of health care.

Mediation of the parental education gradient in early adult mortality by childhood adversity: a population-based cohort study of more than 1 million children.

BACKGROUND: Children born into disadvantaged socioeconomic circumstances are more likely to experience both adversity during childhood and premature mortality. The aim of this study was to investigate how much of the parental education gradient in early adult mortality is explained by exposure to childhood adversity. METHODS: We used data from the nationwide register-based Danish Life Course cohort study. Our sample consisted of all individuals born between Jan 1, 1980, and Dec 31, 2001, who did not emigrate or die before age 16 years, and for whom information on parental education level was available. These individuals were followed up for mortality from age 16 years until Dec 31, 2018. Highest attained parental education level at birth was divided into low (≤9 years), medium (10-12 years), and high (>12 years) according to years in education. Individuals were assigned to one of five childhood adversity trajectory groups based on their annual exposure between age 0 and 16 years to a broad selection of adversities in three dimensions: material deprivation, loss or threat of loss in the family, and family dynamics. Childhood abuse was not included. The association between parental education level and mortality was assessed with a Cox proportional hazards model. To assess the magnitude of mediation of this association by childhood adversity, we used counterfactual mediation analysis and an Aalen additive hazards model. Analyses were unadjusted and adjusted for parental origin and parental ages at birth. FINDINGS: Our sample consisted of 1 278 156 individuals followed up from birth until age 16-38 years. The sample comprised 655 633 (51·3%) men and 622 523 (48·7%) women, and 1 243 981 (97·3%) participants were of European descent. During follow-up, 5387 deaths were registered. Compared with the high parental education group, we calculated a total effect equal to 8·7 additional deaths (95% CI 6·6-10·9) per 100 000 person-years in the medium parental education group and 31·9 (28·5 to 35·2) per 100 000 person-years in the low parental education group. Mediation through childhood adversity trajectories accounted for 41·5% (95% CI 8·0-67·5) of the additional deaths in the medium parental education group and 46·4% (32·9-58·8) of the additional deaths in the low parental education group. The results were similar when adjusting the analyses for sociodemographic factors. INTERPRETATION: The experience of childhood adversity seems to be an important mediator of the association between parental education and mortality in early adulthood. Interventions reducing the exposure to childhood adversity might thus reduce the parental education gradient in early adult mortality. FUNDING: Netherlands Organisation for Health Research and Development.

Hospitalisation patterns among children exposed to childhood adversity: a population-based cohort study of half a million children.

BACKGROUND: Children who are exposed to adversities might be more susceptible to disease development during childhood and in later life due to impaired physiological and mental development. To explore this hypothesis, we assessed hospitalisation patterns through childhood and into adult life among those exposed to different trajectories of adversities during childhood. METHODS: For this population-based cohort study, we used annually updated data from Danish nationwide registers covering more than half a million children (aged 0-15 years) born between 1994 and 2001. Children who were alive and resident in Denmark on their 16th birthday were included in the analysis. Cluster analysis was used to divide children into five distinct trajectories according to their experience of childhood adversities, including poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics. To describe comprehensively the disease patterns experienced by these groups of children, we assessed the associations of each adversity trajectory with hospital admission patterns according to the entire spectrum of disease diagnoses in the International Classification of Diseases 10th edition, from birth to 24 years of age, using survival models. FINDINGS: 508 168 children born between Jan 1, 1994, and Dec 31, 2001, were followed up until Dec 31, 2018, capturing more than 3·8 million hospital admissions from birth to early adulthood. Hospitalisation rates were consistently higher in all four adversity groups compared with the low adversity group. The high adversity group (14 577 children, 3%), who were exposed to adversities of deprivation, family loss, and negative family dynamics, had a markedly higher rate of hospitalisations across all ages. For example, we observed 243 additional hospital admissions per 1000 person-years (95% CI 238-248) in the high versus low adversity group for those aged 16-24 years. These associations were particularly strong for diagnoses related to injuries, unspecified symptoms, and factors influencing health service contacts (eg, health screening and observation). They also covered a considerable burden of respiratory and infectious diseases, congenital malformations, diseases of the nervous system (especially in early life), mental and behavioural diagnoses, and diagnoses related to pregnancy and childbirth in early adult life. INTERPRETATION: The close linkage between childhood adversities and poor lifelong health outcomes highlights a need for public health and policy attention on improving the socioeconomic circumstances children are born into to prevent the early emergence of health inequalities. FUNDING: None.

Childhood adversity trajectories and PTSD in young adulthood: A nationwide Danish register-based cohort study of more than one million individuals.

We examine the association between trajectories of childhood adversities and Post-Traumatic Stress Disorder (PTSD) using a register-based Danish cohort. The DANish LIFE Course (DANLIFE) cohort includes and prospectively follows all individuals born in Denmark from 1980. We estimated the rate of PTSD diagnosed from age 16, according to childhood adversity trajectories from age 0 to 16 (n = 1 277 548). Trajectories were previously defined into 5 groups: Low Adversity, Early Life Material Deprivation, Persistent Material Deprivation, Loss or Threat of Loss, And High Adversity. We then estimated adjusted relative hazard ratios (aHR), and absolute hazards differences of PTSD according to childhood adversity trajectories in adjusted survival analysis. All analyses were stratified by sex. Individuals were followed for a median of 10·1 years a fter their 16th birthday, and 4966 individuals were diagnosed with PTSD. Compared with the low adversity group, children exposed to childhood adversity were more likely to be diagnosed with PTSD. The aHR for PTSD varied from 1·4 (95% CI: 1·3-1·5) in the Early Life Material Deprivation group, to 3·7 (3·3-4·1) in the High Adversity group, which corresponds to 8·3 extra cases of PTSD per 10 000 person years. The relative associations were comparable in men and women, but approximately twice as many women compared with men were affected. We report a clear association between exposure to childhood adversities and PTSD in young adulthood. The highest burden was among women in the high adversity group.

Trajectories of Childhood Adversity and Type 1 Diabetes: A Nationwide Study of One Million Children.

OBJECTIVE: Experiencing adversities in childhood may increase the risk of type 1 diabetes through hyperactivation of the stress response system, but the empirical evidence is conflicting. We aim to describe the age-specific incidence of type 1 diabetes for males and females separately in five predefined groups covering the most common trajectories of adversity among Danish children. RESEARCH DESIGN AND METHODS: We included all 1,081,993 children without parental type 1 diabetes born in Denmark from 1980 to 1998. We used register data to estimate age-specific incidence rates of type 1 diabetes in five trajectory groups of adversity characterized by 1) low adversity, 2) early life material deprivation, 3) persistent material deprivation, 4) loss or threat of loss in the family, and 5) cumulative high adversity. All analyses were stratified by sex. RESULTS: In total, 5,619 people developed type 1 diabetes before 2016. We found only minor differences when comparing the incidence rates of type 1 diabetes between the trajectory groups. The only clear exceptions were in the high versus low adversity group, in which males had a higher incidence of type 1 diabetes in childhood (<11 years [incidence rate ratio (IRR) 1.78 (95% CI 1.31-2.42)]) and females had a higher incidence in early adulthood (≥16 years [IRR 2.19 (95% CI 1.57-3.07)]). CONCLUSIONS: Childhood adversities were generally not associated with age-specific incidence of type 1 diabetes except among those exposed to a very high and increasing annual rate of childhood adversities. Differences between highly exposed males and females seem to depend on age at onset of type 1 diabetes.

Accumulation of childhood adversities and type 1 diabetes risk: a register-based cohort study of all children born in Denmark between 1980 and 2015.

BACKGROUND: Previous studies have indicated an association between childhood adversities and type 1 diabetes but have been underpowered and limited by selection. We aim to quantify the effect of accumulation of childhood adversities on type 1 diabetes risk, and to assess whether the effect differs between males and females in a large and unselected population sample. METHODS: We used register-based data covering all children born in Denmark between 1980 and 2015, totalling >2 million children. We specified a multi-state model to quantify the effect of accumulation of childhood adversities on type 1 diabetes risk. The effects of specific childhood adversities on type 1 diabetes were estimated using proportional hazards models. RESULTS: Accumulation of childhood adversities had a quantitatively small effect on type 1 diabetes risk among females [adjusted hazard ratio (HR) per adversity increase: 1.07; 95% confidence interval (CI): 1.02-1.11], but not among males (adjusted HR per adversity increase: 0.99; 95% CI: 0.97-1.03). Females exposed to extreme numbers (7+) of adversities had two times higher risk of type 1 diabetes compared with unexposed females (adjusted HR: 2.06; 95% CI: 1.10-3.86). CONCLUSIONS: In an unselected total population sample, we generally find no or negligible effects of childhood adversities on type 1 diabetes risk, which may be reassuring to persons with type 1 diabetes who are concerned that personal trauma contributed to their disease. There is a very small group of females exposed to a high degree of adversity who may have a higher risk of type 1 diabetes and this group needs further attention.

Trajectories of childhood adversity and mortality in early adulthood: a population-based cohort study.

BACKGROUND: Childhood is a sensitive period with rapid brain development and physiological growth, and adverse events in childhood might interfere with these processes and have long-lasting effects on health. In this study, we aimed to describe trajectories of adverse childhood experiences and relate these to overall and cause-specific mortality in early adult life. METHODS: For this population-based cohort study, we used unselected annually updated data from Danish nationwide registers covering more than 1 million children born between 1980 and 1998. We distinguished between three different dimensions of childhood adversities: poverty and material deprivation, loss or threat of loss within the family, and aspects of family dynamics such as maternal separation. We used a group-based multi-trajectory clustering model to define the different trajectories of children aged between 0 and 16 years. We assessed the associations between these trajectories and mortality rates between 16 and 34 years of age using a Cox proportional hazards model and an Aalen hazards difference model. FINDINGS: Between Jan 1, 1980 and Dec 31, 2015, 2 223 927 children were included in the Danish Life Course cohort. We excluded 1 064 864 children born after 1998, 50 274 children who emigrated before their 16th birthday, and 11 161 children who died before their 16th birthday, resulting in a final sample of 1 097 628 children. We identified five distinct trajectories of childhood adversities. Compared with children with a low adversity trajectory, those who had early-life material deprivation (hazard ratio 1·38, 95% CI 1·27-1·51), persistent deprivation (1·77, 1·62-1·93), or loss or threat of loss (1·80, 1·61-2·00) had a moderately higher risk of premature mortality. A small proportion of children (36 081 [3%]) had multiple adversities within all dimensions and throughout the entire childhood. This group had a 4·54 times higher all-cause mortality risk (95% CI 4·07-5·06) than that of children with a low adversity trajectory, corresponding to 10·30 (95% CI 9·03-11·60) additional deaths per 10 000 person-years. Accidents, suicides, and cancer were the most common causes of death in this high adversity population. INTERPRETATION: Almost half of Danish children in our study experienced some degree of adversity, and this was associated with a moderately higher risk of mortality in adulthood. Among these, a small group of children had multiple adversities across social, health, and family-related dimensions. This group had a markedly higher mortality risk in early adulthood than that of other children, which requires public health attention. FUNDING: None.

Cohort profile: the DANish LIFE course (DANLIFE) cohort, a prospective register-based cohort of all children born in Denmark since 1980.

PURPOSE: The DANish LIFE course (DANLIFE) cohort is a prospective register-based study set up to investigate the complex life course mechanisms linking childhood adversities to health and well-being in childhood, adolescence and young adulthood including cumulative and synergistic actions and potentially sensitive periods in relation to health outcomes. PARTICIPANTS: All children born in Denmark in 1980 or thereafter have successively been included in the cohort totalling more than 2.2 million children. To date, the study population has been followed annually in the nationwide Danish registers for an average of 16.8 years with full data coverage in the entire follow-up period. The information is currently updated until 2015. FINDINGS TO DATE: DANLIFE provides information on a wide range of family-related childhood adversities (eg, parental separation, death of a parent or sibling, economic disadvantage) with important psychosocial implications for health and well-being in childhood, adolescence and young adulthood. Measurement of covariates indicating demographic (eg, age, sex), social (eg, parental education) and health-related factors (eg, birth weight) has also been included from the nationwide registers. In this cohort profile, we provide an overview of the childhood adversities and covariates included in DANLIFE. We also demonstrate that there is a clear social gradient in the exposure to childhood adversities confirming clustering of adverse experiences within individuals. FUTURE PLANS: DANLIFE provides a valuable platform for research into early life adversity and opens unique possibilities for testing new research ideas on how childhood adversities affect health across the life course.

Potential exposure to endocrine disrupting chemicals and selected adverse pregnancy outcomes: a follow-up study of pregnant women referred for occupational counselling.

BACKGROUND: Experimental evidence indicates that fetal exposure to xenobiotics with the potential to interfere with the endogenous steroid hormone regulation of fetal development may reduce birth weight. However, epidemiological studies are limited. The aim of the study was to investigate whether potential occupational exposure to endocrine disrupting chemicals (EDC) of the mother during pregnancy is associated with preterm birth and low birth weight. METHODS: Pregnant women referred to an Occupational Health Clinic (OHC) in two Danish regions (Copenhagen or Aarhus) between 1984 and 2010, suspected of being exposed to occupational reproductive hazards were included in the study. A job exposure matrix enabled estimation of potential occupational exposure to EDC on the basis of job title. Births by women potentially exposed to EDC (n = 582) were compared to births by women referred to an OHC on the suspicion of other exposures than EDC (n = 620), and to a sample of births by all occupationally active women in the same geographical regions (n = 346,544), including 1,077 births of the referred women's non-referred pregnancies. RESULTS: No indications of reduced birth weight or increased risk of preterm birth were found among women potentially exposed to EDC. Women potentially exposed to EDC had children with a higher birth weight compared to the sample of occupationally active women but not compared to other women referred to an OHC. CONCLUSIONS: Potential maternal exposure to EDC at Danish workplaces is not related to low birth weight or preterm birth among women referred to occupational counselling. Occupational exposures might be too weak on the average to cause these adverse effects or counselling at the OHCs is effective in preventing them.

Measuring and modeling the oxygen profile in a nitrifying Moving Bed Biofilm Reactor.

In this paper we determine the oxygen profile in a biofilm on suspended carriers in two ways: firstly by microelectrode measurements and secondly by a simple mathematical model. The Moving Bed Biofilm Reactor is well-established for wastewater treatment where bacteria grow as a biofilm on the protective surfaces of suspended carriers. The flat shaped BiofilmChip P was developed to allow good conditions for transport of substrates into the biofilm. The oxygen profile was measured in situ the nitrifying biofilm with a microelectrode and it was simulated with a one-dimensional mathematical model. We extended the model by adding a CSTR equation, to connect the reactor to the biofilm through the boundary conditions. We showed the dependence of the thickness of the mass transfer boundary layer on the bulk flow rate. Finally, we estimated the erosion parameter lambda to increase the concordance between the measured and simulated profiles. This lead to a simple empirical relationship between lambda and the flow rate. The data gathered by in situ microelectrode measurements can, together with the mathematical model, be used in predictive modeling and give more insight in the design of new carriers, with the ambition of making process operation more energy efficient.