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Aims Pre-eclampsia increases women’s lifetime risk of cardiovascular disease (CVD). Little is known about the trajectory of CVD after pre-eclampsia, limiting the usefulness of this knowledge for informing screening, prevention, and interventions. We investigated when the risk of CVD increases after pre-eclampsia and how the risk changes over time since pregnancy. Methods and results This register-based study included 1 157 666 women with >1 pregnancy between 1978 and 2017. Cumulative incidences of acute myocardial infarction (AMI) and ischaemic stroke were estimated, as well as hazard ratios (HRs) by attained age and time since delivery. Up to 2% [95% confidence interval (CI): 1.46–2.82%] of women with pre-eclampsia in their first pregnancy had an AMI or stroke within two decades of delivery, compared with up to 1.2% (95% CI: 1.08–1.30%) of pre-eclampsia-free women; differences in cumulative incidences were evident 7 years after delivery. Ten years after delivery, women with pre-eclampsia had four- and three-fold higher rates of AMI (HR = 4.16, 95% CI: 3.16–5.49) and stroke (HR = 2.59, 95% CI 2.04–3.28) than women without pre-eclampsia; rates remained doubled >20 years later. Women with pre-eclampsia aged 30–39 years had five-fold and three-fold higher rates of AMI (HR = 4.88, 95% CI 3.55–6.71) and stroke (HR = 2.56, 95% CI 1.95–3.36) than women of similar age without pre-eclampsia. Conclusions Women with a history of pre-eclampsia have high rates of AMI and stroke at early ages and within a decade after delivery. The findings suggest that pre-eclampsia history could be useful in identifying women at increased risk of CVD and that targeted interventions should be initiated soon after delivery.

Background It has been suggested that the transiently increased infection risk following childcare enrolment is compensated by decreased infection risk later in childhood and adolescence. We investigated how childcare enrolment affected rates of antimicrobial-treated infections during childhood and adolescence. Methods In a register-based cohort study of all children born in Denmark 1997–2014 with available exposure information (n = 1 007 448), we assessed the association between childcare enrolment before age 6 years and infection risks up to age 20 years, using antimicrobial exposure as proxy for infections. Nationwide childcare and prescription data were used. We estimated infection rates and the cumulative number of infections using adjusted Poisson regression models. Results We observed 4 599 993 independent episodes of infection (antimicrobial exposure) during follow-up. Childcare enrolment transiently increased infection rates; the younger the child, the greater the increase. The resulting increased cumulative number of infections associated with earlier age at childcare enrolment was not compensated by lower infection risk later in childhood or adolescence. Accordingly, children enrolled in childcare before age 12 months had experienced 0.5–0.7 more infections at age 6 years (in total 4.5–5.1 infections) than peers enrolled at age 3 years, differences that persisted throughout adolescence. The type of childcare had little impact on infection risks. Conclusions Early age at childcare enrolment is associated with a modest increase in the cumulative number of antimicrobial-treated infections at all ages through adolescence. Emphasis should be given to disrupting infectious disease transmission in childcare facilities through prevention strategies with particular focus on the youngest children.

Childhood acute lymphoblastic leukaemia (ALL) is suggested to result from a dysregulated immune response to infections in children with a preleukaemic state. Childcare in early life supposedly may protect against childhood ALL by facilitating sufficient exposure to infections to stimulate and ensure normal maturation of the immune system. We assessed the association between childcare attendance before age two years and risk of childhood ALL in a register-based cohort study, including all children aged 2-14 years born in Denmark during 1991-2014 with available childcare information recorded in the Danish Childcare Database (n=1,116,185). Cox regression was used to estimate hazard ratios (HRs) comparing children enrolled in childcare and children not enrolled before age two years. Further, we assessed the association according to age at enrolment, type of childcare facility and specific ALL subtypes. During 10,460,811 person-years of follow-up, 460 children developed ALL at ages 2-14 years. Of these, 57 (12.4%) never attended childcare before age two years compared with 10.6% in the total cohort. Compared with homecare, childcare attendance before age two years was associated with a statistically non-significantly, marginally decreased risk of childhood ALL with adjusted HR = 0.87 (95% confidence interval (CI): 0.65-1.16). Risk estimates did neither vary statistically significantly by age at enrolment nor by type of childcare facility and also not between childhood ALL subtypes, including frequently prenatally initiated ALL subtypes. Results from this large, nationwide register-based study provided no evidence that childcare attendance in the first years of life protects against childhood ALL.

Background: Despite considerable research effort, causes of brain cancer are largely unknown. Male BC predominance and reduced brain cancer risk with increasing parity among women, however, support a favourable role of pregnancy. We set out to determine whether peripheral male origin microchimerism, namely the presence of circulating male origin cells, likely obtained via natural trafficking across the placenta during pregnancy, associates with reduced risk of brain cancer in women.Methods: Using a case-cohort design, we sampled 505 middle aged women randomly at baseline in the Diet, Cancer and Health cohort (controls), and 73 women with incident brain cancer diagnosed during follow-up in the Danish Cancer Registry (cases). Male origin microchimerism was determined by presence of Y chromosome sequences in female blood samples. Data was analysed using weighted proportional Hazards regression, yielding Hazard Ratios with 95% confidence intervals.Results: Compared with male origin microchimerism negative women, positive women had half the risk of developing brain cancer (Hazard Ratio=0.50 [0.33-0.77]). Sensitivity analyses support that our findings are unlikely due to bias or chance.Conclusion: Here, for the first time we demonstrate half the risk of brain cancer in male origin microchimerism positive compared with negative women. Our findings resemble those of previous studies of male origin microchimerism and other female cancers.

Increasing parity is associated with an increased risk of ischemic heart disease (IHD) and stroke in women. This is probably attributable to biological responses of pregnancy. Male cells of presumed fetal origin are commonly present in women years after pregnancy—a phenomenon termed male-origin microchimerism (MOM). In this study, we investigated whether MOM was associated with risk of IHD and ischemic stroke in women. We evaluated the association between MOM and ischemic events in a cohort of 766 Danish women enrolled in the Diet, Cancer and Health cohort during 1993–1997 when aged 50–64 years. Of these women, 545 (71.2%) tested positive for MOM through targeting of the Y chromosome (DYS14 DNA sequence) in their blood. Multiple Cox regression models were used to calculate hazard ratios with 95% confidence intervals. We found that MOM was associated with a significantly reduced rate of IHD (hazard ratio = 0.44, 95% confidence interval: 0.23, 0.83) but not ischemic stroke (hazard ratio = 0.80, 95% confidence interval: 0.46, 1.41). Our findings show that microchimerism positivity is associated with a lower rate of later IHD development in women. Although the underlying mechanisms are presently unknown, MOM may be relevant in women’s cardiovascular health. More studies are needed to confirm these findings.

Background Reduced risk of ovarian cancer is commonly ascribed to reduced exposure to endogenous hormones during pregnancy, using oral contraceptives or not using hormone replacement therapy. However, exposure to hormones alone account for less than half of all cases. Many women carry small amounts of male cells—known as male origin microchimerism—in their circulation and remarkable impacts of these cells on women’s health are being published. Here, we pursue the possibility that male origin microchimerism has a role in reducing ovarian cancer risk. Methods We conducted a prospective case-cohort study using blood samples and questionnaire data from 700 women participating in the Danish Diet, Cancer, and Health cohort. Blood samples were analysed for Y chromosome presence as a marker of male microchimerism. We evaluated the association between male microchimerism and ovarian cancer, using weighted Cox regression models reporting hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Results Male microchimerism was detected in 46% of cases and 65.9% of controls. Women testing positive for male microchimerism had a reduced hazard rate of ovarian cancer compared with women testing negative (HR = 0.44, 95% CI: 0.29-0.68). We found no evidence of interaction with measures of hormonal exposures (P = 0.50). Conclusions For the first time we report that women who test positive for male microchimerism in their circulation have reduced rates of ovarian cancer compared with women who test negative. Although the underlying mechanisms are presently unknown, we believe male microchimerism is potent in preventing ovarian cancer.

BACKGROUND: Many women carry male cells of presumed fetal origin-so-called male-origin microchimerism (MOM)-in their circulation and tissues. Studies have found reduced risks of hormone dependent cancers, including breast and ovarian cancer, among MOM-positive women. The aim of this study was to investigate the association between MOM and endometrial cancer.METHODS: We designed a prospective case-cohort study including 76 cases and 505 controls from the Diet, Cancer and Health cohort aged 50-64 years and cancer-free at enrolment in 1993-1997. We analyzed blood samples for the presence of Y-chromosome (DYS14). We examined the association between MOM and endometrial cancer in weighted Cox regression models. As a negative control outcome, we studied the association between MOM and injuries to test for spurious associations.RESULTS: We detected MOM in 65.9% controls and 54.0% cases. While we observed no overall association between MOM and endometrial cancer (HR=0.73, 95% CI: 0.47-1.15), we found a borderline significantly reduced rate of Type 1 endometrial cancer (HR=0.66, 95% CI: 0.39-1.00), but not other types of endometrial cancers (HR=1.00, 95% CI: 0.35-2.90). The reduced rate was not modified by hormonal exposure (P = 0.79). We found no association between MOM and risk of injuries (HR=0.96, 95% CI: 95% CI: 0.78-1.21).CONCLUSIONS: Our study suggests that MOM is inversely associated with Type 1 endometrial cancer, without evidence of an interaction with hormonal exposure. We encourage future research to confirm our findings.

STUDY QUESTION Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation? SUMMARY ANSWER The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years. WHAT IS KNOWN ALREADY The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment. STUDY DESIGN, SIZE, DURATION The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994–2016. PARTICIPANTS/MATERIALS, SETTING, METHODS Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18–46 years). Results are presented as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12–1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29–1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09–2.08). LIMITATIONS, REASONS FOR CAUTION Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation. WIDER IMPLICATIONS OF THE FINDINGS An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Although maternal use of hormones has been suspected of increasing the risk for childhood attention-deficit/hyperactivity disorder (ADHD), no study has examined hormonal contraception use in this context. We examined the association between maternal hormonal contraception use before or during pregnancy and ADHD risk in children. This nationwide population-based cohort study included 1,056,846 children born in Denmark between 1998 and 2014. Prescriptions for hormonal contraceptives redeemed by the mother was categorized as: no use, previous use (> 3 months before pregnancy), and recent use (≤ 3 months before or during pregnancy). Children were followed for ADHD, from birth until 31 December 2015. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During 9,819,565 person-years of follow-up (median: 9.2), ADHD was diagnosed or a prescription for ADHD medication redeemed for 23,380 children (2.2%). The adjusted HR for ADHD was higher in children of mothers who had previously (HR 1.23; 95% CI 1.18–1.28) or recently (HR 1.30; 95% CI 1.24–1.37) used hormonal contraception than in those of mothers with no use. The highest estimates were seen for use of non-oral progestin products with HRs of 1.90 (95% CI 1.59–2.26) for previous use, 2.23 (95% CI 1.96–2.54) for recent use, and 3.10 (95% CI 1.62–5.91) for use during pregnancy. Maternal use of hormonal contraception was associated with an increased risk for ADHD in the offspring; more pronounced for non-oral progestin-only than other products.

In previous studies, investigators have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. Our aim in this study was to explore the impact of relevant selection factors on the association between ART treatment and mortality and to explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994-2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until December 31, 2010. With adjustment for relevant confounders, the risk of death was lower among ART-treated women during the first 2 years after ART treatment (hazard ratio (HR) = 0.68, 95% confidence interval (CI): 0.63, 0.74), but there was no apparent difference after 10 years (HR = 0.92, 95% CI: 0.79, 1.07). Having children prior to ART treatment was associated with markedly reduced mortality (HR = 0.45, 95% CI: 0.38, 0.53), possibly due to better health among fertile women. While the frequencies of previous medical and psychiatric diagnoses among ART-treated and untreated women were similar, differences in disease severity could explain the reduced mortality among ART-treated women, as poor prognosis would make initiation of ART treatment unlikely. The survival advantage among ART-treated women is likely a selection phenomenon rather than a biological phenomenon.

Background It has been proposed that childhood vaccinations protect against acute lymphoblastic leukaemia (ALL) in children by modulation of future responses to common infections in childhood. However, the available studies provide inconsistent findings, and population-based cohort studies with longitudinal information on vaccinations are lacking. Methods In a register-based cohort of all children born in Denmark from 1 January 1990 to 31 December 2008, followed up until age 15 years or 31 December 2009 ( n = 1 225 404), we evaluated exposure to childhood vaccination and risk of childhood ALL, including information on ALL subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing vaccinated with unvaccinated children. Results Childhood ALL was diagnosed in 490 children during 10 829 194 person-years of follow-up. Neither the total number of vaccine doses received nor exposure to each vaccination given in childhood was associated with altered risk of ALL, including the following: (i) Haemophilus influenzae type b [HR, 1.04; 95% confidence interval (CI), 0.68-1.61]; ii) measles, mumps and rubella (HR, 1.01; 95% CI, 0.76-1.34); iii) whole-cell pertussis (HR, 1.10; 95% CI, 0.51-2.39); and iv) diphtheria, tetanus and inactivated polio (HR, 1.14; 95% CI, 0.42-3.13). Analyses conducted according to ALL subtypes defined by immunopheno- and karyotypes showed no association with childhood vaccination. Conclusions This nationwide cohort study provides no support of the proposed protective effect of childhood vaccination against childhood ALL.

BACKGROUND Previous studies show inconsistent associations between childcare and obesity. AIMS Our prior work demonstrated that childcare in infancy was associated with higher weight in a cohort of Danish children. Here, we extend this work and examine childcare through 6 years and body mass index (BMI) at age 7 years. MATERIALS AND METHODS We examined 24 714 children in the Danish National Birth Cohort who were also in the Childcare Database. We conducted multivariable linear regressions examining children prior to age 6, overall and by type (daycare, creche, age-integrated and kindergarten), and BMI z-score at 7 years, stratifying on maternal socio-occupational status. RESULTS A total of 19 760 (80.0%) children attended childcare before age 6. Childcare prior to age 6 was associated with BMI z-score at 7 years (0.004 units per each additional 6 months of care; 95% CI: 0.001, 0.008; p = 0.01). Childcare in a kindergarten was the only type of care associated with BMI (0.009 units; 95% CI: 0.003, 0.02; p = 0.01). For children of higher socio-occupational status mothers, childcare was associated with a 0.008 unit increase in BMI (95% CI: 0.004, 0.01; p > 0.001). CONCLUSIONS Childcare was weakly associated with later BMI. This relationship was more pronounced in children from higher socio-occupational status mothers and children in kindergarten care.

Objective In spite of the high incidence of cervical cancer in Greenland, no assessment has been made of the impact of organized cervical screening, introduced in 1998, in relation to occurrence of high-grade cervical lesions. The objectives of the present study were to estimate coverage of the screening program and to examine possible changes in cervical intraepithelial neoplasia (CIN3) incidence in Greenland during 1997–2011 according to calendar period and age. Methods Using nationwide registries, we calculated age-standardized incidence rates for all women born and living in Greenland. To investigate whether possible variation in the incidence of CIN3 were related to differences in screening coverage, we further estimated relative risks of CIN3 within two years of screening among women who participated in the screening program using log-linear binomial regression. Results Coverage of the screening program was low during 1997–2011 with the highest level of 54% observed in 2011. Peaks in CIN3 incidence of around 300 per 100,000 person-years were observed in 1999 and between 2009 and 2011, while the incidence was lower of approximately 100 per 100,000 person-years between 2000 and 2008. During 2009–2011, the highest incidence was found among women aged 25–34 years. Similar patterns of CIN3 risk according to calendar period and age groups were observed among screened women. Conclusions The great variations in CIN3 incidence and low screening coverage observed during 1997–2011 suggest that improvements in the Greenlandic screening program are warranted.

STUDY QUESTION Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION Women undergoing ART treatment during 1994–2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10–1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25–1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76–1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45–5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.

Natural acquisition of small amounts of foreign cells or DNA, referred to as microchimerism, occurs primarily through maternal-fetal exchange during pregnancy. Microchimerism can persist long-term and has been associated with both beneficial and adverse human health outcomes. Quantitative microchimerism data present challenges for statistical analysis, including a skewed distribution, excess zero values, and occasional large values. Methods for comparing microchimerism levels across groups while controlling for covariates are not well established. We compared statistical models for quantitative microchimerism values, applied to simulated data sets and 2 observed data sets, to make recommendations for analytic practice. Modeling the level of quantitative microchimerism as a rate via Poisson or negative binomial model with the rate of detection defined as a count of microchimerism genome equivalents per total cell equivalents tested utilizes all available data and facilitates a comparison of rates between groups. We found that both the marginalized zero-inflated Poisson model and the negative binomial model can provide unbiased and consistent estimates of the overall association of exposure or study group with microchimerism detection rates. The negative binomial model remains the more accessible of these 2 approaches; thus, we conclude that the negative binomial model may be most appropriate for analyzing quantitative microchimerism data.

I denne artikel præsenterer vi erfaringerne fra et projekt, der har til formål at styrke de studerendes danske, akademiske skrivefærdigheder på uddannelsen It og Sundhed på Københavns Universitet. Projektet bygger på antagelserne, at faglighed og formidlingskompetencer er tæt forbundet, og at sproglig bevidsthed inden for fagets kontekst er et fælles ansvar mellem underviser og studerende. Projektet er knyttet til bachelorkurset i Epidemiologiske metoder, og det er udviklet i samarbejde mellem kursuslederen og en sprogkonsulent i løbet af forårssemestrene 2014 og 2015. Gennem skriftlige afleveringer og formativ feedback på disse har de studerende haft mulighed for at arbejde med deres skriftlige formidling som forberedelse til den skriftlige eksamen i kurset og som styrkelse af deres akademiske skrivefærdigheder generelt. I artiklen beskriver vi baggrunden for projektet og erfaringerne med at udvikle og gennemføre det. Derudover diskuterer vi projektets udbytte samt udfordringerne med at sætte eksplicit fokus på fagets sproglige aspekt. På baggrund af de studerendes eva-luering og eksamensresultater konkluderer vi, at projektet har medvirket til at styrke deres akademiske skriftlighed. In this article, we report on experiences gained from a project designed to improve the Danish academic writing skills of students enrolled on the programme It & Health at the University of Copenhagen. Based on the assumptions that university disciplines and communicative competence are inextricably linked and that language awareness is a joint responsibility between teacher and students, the project focused explicitly on language use on the BSc course Introduction to Epidemiology. Through receiving formative feedback on written assignments, the students got the chance to reflect and work on their writing. This process acted both as preparation for their written exam and a way to improve their academic writing skills in general. The course coordinator worked with a language consultant to develop and refine the project during the spring semesters of 2014 and 2015. In this article, we describe the background to the initiative as well as the experiences of those involved. The learning outcomes are discussed, along with the challenges involved in integrating an explicit focus on language and feedback into students’ disciplinary writing. From the students’ evaluations and their exam results, we conclude that the project had a positive impact on improving the students’ academic writing skills.

Background: Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. Methods: We conducted a case–control study of 523 Danish women with endometrial cancer and 52 299controls during 1978–2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. Results: We observed no overall association between preeclampsia and endometrial cancer risk (OR=1.11 (95% CI 0.68–1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29–5.38)). Conclusions: Although we report no obvious association between preeclampsia and endometrial cancer, studying the subset of early-onset preeclampsia may prove fruitful in further understanding the aetiology of endometrial cancer.

Introduction In a preliminary case-control study, women with scleroderma more frequently reported having had hypertensive complications during pregnancy compared with healthy women. Material and methods To prospectively investigate this possible association, we conducted a nation-wide cohort analysis of a major hypertensive complication during pregnancy, namely preeclampsia, and later scleroderma. Analyses were based on Danish register-based birth and hospital contact data on preeclampsia and scleroderma. We followed 778,758 women from time of giving birth between 1978 and 2010 to end of follow-up, emigration, death, or scleroderma diagnosis, whichever occurred first. The association was evaluated by incidence rate ratios, obtained in Poisson regression models. Results We report that preeclampsia is associated with a 69% significantly increased risk of later developing scleroderma. Conclusions Though these findings do not impact clinical care directly, the association of preeclampsia with scleroderma underscores the significant relation of preeclampsia and other adverse pregnancy outcomes with later disease in women and should be included in patient counseling and education.

Background In parous women preeclampsia has been associated with reduced risk of developing breast cancer. Characteristics of births following preeclamptic pregnancies may help understand mechanisms involved in the breast cancer risk reduction inferred by preeclampsia. Methods We conducted a register-based cohort study of all Danish women giving birth during 1978–2010 (n = 778,701). The association between preeclampsia and breast cancer was evaluated overall and according to birth characteristics by means of incidence rate ratios (IRR) estimated in Poisson regression models. Results Compared with women with non-preeclamptic pregnancies only, women with one or more preeclamptic pregnancies were 19% significantly less likely to develop breast cancer (IRR = 0.81 [95% CI 0.72–0.93]). We found some indication of greater risk reduction in women with term births, one or more previous births, and in women giving birth to boys. These findings, however, did not reach statistical significance. Finally, risk reduction was slightly greater following milder forms of preeclampsia. Conclusion Our data is compatible with an approximately 20% reduction in risk of developing breast cancer following preeclampsia. Although we find some variability according to birth characteristics, the risk reduction inferred by preeclampsia seems applicable to most preeclamptic pregnancies.

BACKGROUND Studies have repeatedly demonstrated that blood donors experience lower mortality than the general population. While this may suggest a beneficial effect of blood donation, it may also r ...

BACKGROUND: Since the 1970s, Greenland has presented the highest reported incidence rates of the sexually transmitted infections (STIs) gonorrhoea and chlamydia in the Arctic regions.OBJECTIVE: This study aims to describe sex- and age-specific incidence rates of gonorrhoea and chlamydia from 1990 to 2012 in Greenland, and to evaluate if changes in case definitions, diagnostic procedures and implementation of STI interventions during the period coincide with rate changes.DESIGN: Gonorrhoea and chlamydia cases were identified from the national STI surveillance. For 1990-2008, STI cases were identified from weekly notified aggregated data. For 2009-2012, cases were identified in person-identifiable national registers. We used log-linear Poisson regression to calculate incidence rates (IRs) and incidence rate ratios (IRRs) with 95% confidence intervals (95% CI). Analyses were stratified according to sex, age and calendar period.RESULTS: Gonorrhoea and chlamydia incidence rates have increased since 1995 to reach 2,555 per 100,000 person-years (PY) for gonorrhoea and 6,403 per 100,000 PY for chlamydia in 2012. From 2006 to 2012, the incidence rates among young adults aged 15-19 years were 8,187 and 22,515 per 100,000 PY for gonorrhoea and chlamydia, respectively. Changes in surveillance reporting did not seem to influence the incidence rates for either disease, whereas a change in diagnostic test coincided with an increased incidence of chlamydia.CONCLUSION: Overall, the incidence of chlamydia in Greenland increased during the study period, whereas the incidence of gonorrhoea decreased until 1995 but increased thereafter. Young adults aged 15-24 years were at highest risk of infection. The increase in incidence rates was independent of changes in case definitions, whereas an observed increase in chlamydia incidence in 2005 coincided with a change in diagnostic test. None of the STI interventions launched after 1995 seemed to coincide with decreasing national incidence rates.

BACKGROUND: Maternal diabetes may be linked to childhood acute lymphoblastic leukaemia (ALL) in the offspring.METHODS: We assessed the association between maternal pregestational or gestational diabetes and offspring risk of childhood ALL in a register-based study, including all singletons born in Denmark during 1996-2015 (n=1 187 482).RESULTS: Adjusted hazard ratios of childhood ALL were 2.91 (95% confidence interval (CI): 1.30-6.51) for maternal pregestational diabetes and 1.75 (95% CI: 1.02-2.98) for maternal gestational diabetes. Paternal diabetes did not alter offspring ALL risk, and we found no association between offspring ALL and later maternal risk of diabetes.CONCLUSIONS: Regardless that absolute ALL risk among offspring of women with diabetes remains low, our findings suggest that characteristics of the diabetic intrauterine environment promote ALL development. This offers a setting for future research into the biological mechanisms underlying childhood ALL.

Fetal origin microchimerism (FMc) denotes the presence and persistence of fetal origin cells in the maternal organism. In all women fetal cells are acquired during pregnancy, and in some women FMc persists lifelong. The consequences of FMc on long-term maternal health including cancer are increasingly being investigated. In this review, we summarize available literature regarding associations between FMc and maternal cancer.

BACKGROUND/OBJECTIVES: Evidence suggests that the child care environment may be more obesogenic than the family home, and previous studies have found that child care use may be associated with obesity in children. Few studies, however, have focused on child care during infancy, which may be an especially vulnerable period. This study examined child care use in infancy and weight status at 12 months of age in a country where paid maternity leave is common and early child care is not as prevalent as in other developed countries.SUBJECTS/METHODS: We studied 27,821 children born to mothers participating in the Danish National Birth Cohort, a longitudinal study of pregnant women enrolled between 1997 and 2002, who were also included in the Childcare Database, a national record of child care use in Denmark. The exposure was days in child care from birth to 12 months. The outcomes were sex-specific body mass index (BMI) z-score and overweight/obesity (BMI ⩾ 85th percentile based on the World Health Organization classification) at 12 months. We conducted multivariable linear and logistic regression analyses examining child care use and weight outcomes.RESULTS: A total of 17,721 (63.7%) children attended child care during their first year of life. After adjustment for potential confounders, a 30-day increment of child care was associated with a modestly higher BMI z-score at 12 months (0.03 units; 95% confidence interval (CI) = 0.01, 0.05; P=0.003). Similarly, child care use was associated with increased odds of being overweight/obese at 12 months of age (odds ratio = 1.05; 95% CI = 1.01, 1.10; P=0.047).CONCLUSION: Child care in the first year of life was associated with slightly higher weight at 12 months, suggesting that child care settings may be important targets for obesity prevention in infancy.

Background During pregnancy, woman and fetus exchange small quantities of cells, and their persistence at later times is termed microchimerism. Microchimerism is known to substantially impact on women's later health. This study examined the survival of women according to male microchimerism status. Methods Male microchimerism presence, measured as Y chromosome in peripheral blood samples, was determined in 272 women from the large Danish Diet, Cancer and Health cohort when aged 50-64 years during 1993-97. Women were followed up for cause-specific death in national Danish registers until the end of 2009. Survival was analysed using Cox regression. Results A total of 190 women (70%) were male microchimerism positive. During follow-up 21 women died, of whom 11 (52%) were male microchimerism positive at enrolment and 10 were negative. Of the 21 deaths, 13 (62%) were due to cancer and 5 (24%) were due to cardiovascular disease. Male microchimerism presence was associated with a reduced hazard ratio of all-cause mortality of 0.42 (95% CI 0.17-1.03). The hazard ratio of death from cancer and cardiovascular disease was 0.24 (95% CI 0.08-0.79) and 1.66 (95% CI 0.18-15.48), respectively, among male microchimerism positive compared with negative women. Conclusions Although the biological mechanisms are not precisely known, male microchimerism presence in peripheral blood of women is associated with substantially improved survival in women. The results also indicate that the association with male microchimerism may vary between different causes of death.

Kamper-Jorgensen, M Rostgaard, K Glaser, S L Zahm, S H Cozen, W Smedby, K E Sanjose, S Chang, E T Zheng, T La Vecchia, C Serraino, D Monnereau, A Kane, E V Miligi, L Vineis, P Spinelli, J J McLaughlin, J R Pahwa, P Dosman, J A Vornanen, M Foretova, L Maynadie, M Staines, A Becker, N Nieters, A Brennan, P Boffetta, P Cocco, P Hjalgrim, H eng 5 ROI CA69269/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't England 2013/06/22 06:00 Ann Oncol. 2013 Sep;24(9):2245-55. doi: 10.1093/annonc/mdt218. Epub 2013 Jun 19.; International audience; BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Objective To investigate the independent and combined associations between female and male body mass index (BMI) on the probability of achieving a live birth after treatments with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) under adjustment for relevant covariates. Design Population-based cohort study. Setting Danish national registers. Patient(s) Patients with permanent residence in Denmark receiving IVF or ICSI treatment with use of autologous oocytes from January 1, 2006, to September 30, 2010. Intervention(s) None. Main Outcome Measure(s) Live birth. Analyses were adjusted for age and smoking at treatment initiation and results stratified by BMI groups and presented by IVF/ICSI treatment. Result(s) In total, 12,566 women and their partners went through 25,191 IVF/ICSI cycles with 23.7% ending in a live birth. Overweight and obese women with regular ovulation had reduced odds of live birth (adjusted OR 0.88, 95% CI 0.79–0.99 and adjusted OR 0.75, 95% CI 0.63–0.90, respectively) compared with normal-weight women. IVF-treated couples with both partners having BMI ≥25 kg/m 2 had the lowest odds of live birth (adjusted OR 0.73, 95% CI 0.48–1.11) compared with couples with BMI 2 . BMI showed no significant effect on chance of live birth after ICSI. Conclusion(s) Increased female and male BMI, both independently and combined, negatively influenced live birth after IVF treatments. With ICSI, the association with BMI was less clear.

Objective To study the association between birth weight and polycystic ovary syndrome (PCOS) in adult life in Danish women born 1973–1991. Design Register study. Setting Data were extracted from the Danish Medical Birth Register and the Danish National Patient Register (NPR). Patient(s) All female children born of Danish mothers in Denmark between 1973 and 1991 were included (n = 523,757) and followed for a total of 4,739,547 person-years at risk. Intervention(s) None. Main Outcome Measure(s) Information on birth weight was extracted from the Danish Medical Birth Register. The cohort was followed up in the NPR for PCOS diagnoses from age 15 years until the end of 2006. Furthermore, information on maternal diabetes diagnoses was extracted from the NPR. Result(s) The risk of PCOS was significantly increased in women with birth weight ≥4,500 g (incidence rate ratio, 1.57; 95% confidence interval 1.21–2.03) compared to women with birth weight 3,000–3,499 g. All women with birth weight ≥4,500 g were born large for gestational age and a birth weight of 4,500 g represented the 98.5th percentile of the birth weights. Women born of mothers diagnosed with diabetes were at increased risk of PCOS. In these women the risk of PCOS increased with decreasing birth weight. Conclusion(s) The risk of PCOS was increased in women born with birth weight ≥4,500 g. In women of diabetic mothers we found an increased risk of PCOS, which was inversely related to birth weight.

Male microchimerism, the presence of a small number of male cells, in women has been attributed to prior pregnancies. However, male microchimerism has also been reported in women with only daughters, in nulliparous women and prepubertal girls suggesting that other sources of male microchimerism must exist. The aim of the present study was to examine the presence of male microchimerism in a cohort of healthy nulliparous Danish girls aged 10-15 y using DNA extracted from cells from whole blood (buffy coats) and report the association with potential sources of male cells. A total of 154 girls were studied of which 21 (13.6%) tested positive for male microchimerism. There was a tendency that girls were more likely to test positive for male microchimerism if their mothers previously had received transfusion, had given birth to a son or had had a spontaneous abortion. Furthermore, the oldest girls were more likely to test positive for male microchimerism. However, less than half of microchimerism positivity was attributable to these factors. In conclusion, data suggest that male microchimerism in young girls may originate from an older brother either full born or from a discontinued pregnancy or from transfusion during pregnancy. We speculate that sexual intercourse may be important but other sources of male cells likely exist in young girls.

Background Detection of Y chromosome, thought to originate from previous pregnancies with a male fetus, is common in women. Lower concentrations have been reported in women with breast cancer than cancer-free women. Data in women with other types of cancer are sparse. The purpose of the study was to determine whether the lower concentrations predate cancer diagnosis, and whether a possible beneficial effect was specific to breast cancer. Methods We conducted a prospective case–cohort study of 50–64-year-old Danish women enrolled in the Diet, Cancer and Health cohort. Blood samples and questionnaire data were obtained during 1993–1997 when all women were cancer-free. In 2006 all women were followed up for incident breast and colon cancer in national registers. In blinded analyses, we analysed buffy coat DNA for Y chromosome ( DYS14 ) as a marker of male microchimerism. Results We detected male microchimerism in 70% of 272 cancer-free women, 40% of 89 women who later developed breast cancer, and 90% of 67 women who later developed colon cancer. The corresponding odds ratios were 0.30 (95% confidence interval (CI) 0.17–0.52) for breast, and 3.9 (95% CI 1.6–9.5) for colon cancer. Conclusion Detection of male microchimerism was strongly associated with reduced risk of developing breast cancer and also the increased risk of developing colon cancer. Confirmatory findings based on an improved study design, failure to identify important confounders and the strength of the associations lead us to believe that microchimerism may be highly relevant to later cancer development. However, the present study does not allow us to identify the underlying biological mechanisms.

OBJECTIVE: To establish a method of estimating the proportion of women with a subsequent live birth after a well-defined time period in an open cohort of women referred to a tertiary recurrent miscarriage clinic. METHODS: We performed a descriptive cohort study with register-based follow-up at a tertiary center for investigation and treatment of recurrent miscarriage in Denmark. All women with primary or secondary recurrent miscarriage referred to the clinic from 1986 to 2008 were included in the study (n987). Main outcome measures were age-specific and miscarriage-specific proportions of women with a live birth after the first consultation and similar hazard ratios compared with the prognosis in women aged 30–34 years with three miscarriages before the first consultation. RESULTS: Five years after the first consultation, 66.7% (95% confidence interval [CI] 63.7–69.7) had achieved a live birth, increasing to 71.1% (95% CI 68.0–74.2) 15 years after the first consultation. There was a significantly decreased chance of at least one subsequent live birth with increasing maternal age (log-rank P

Background: An infective, mostly viral basis has been found in different human cancers. To test the hypothesis of a possible infectious aetiology for central nervous system (CNS) tumours in children, we investigated the associations with proxy measures of exposure to infectious disease. Methods: In a large case–control study nested in the populations of Denmark, Norway, Sweden, and Finland of 4.4 million children, we studied the association of birth order and seasonal variation of birth with subsequent risk for CNS tumours. We identified 3983 children from the national cancer registries, and information on exposure was obtained from the high-quality national administrative health registries. We investigated the association between childcare attendance during the first 2 years of life and the risk for CNS tumours in a subset of Danish children with CNS tumours, using information from the Danish Childcare database. Results: We observed no association between birth order and risk of CNS tumours overall (odds ratio (OR) for second born or later born vs first born, 1.03; 95% confidence interval (CI), 0.96–1.10) or by histological subgroup, and children with CNS tumours did not show a seasonal variation of birth that was distinct from that of the background population. Childcare attendance compared with homecare showed a slightly increased OR (1.29; 95% CI, 0.90–1.86) for CNS tumours, with the highest risk observed in children attending a crèche. The strongest association was observed for embryonal CNS tumours. We found no effect of age at enrolment or duration of enrolment in childcare. Conclusion: These results do not support the hypothesis that the burden of exposure to infectious disease in early childhood has an important role in the aetiology of paediatric CNS tumours.

Aim: To estimate how risk of acute respiratory infection (ARI) hospitalization in children attending childcare facilities with a recently (within 1 month) hospitalized child is affected by gender, age and other characteristics. Methods: Population-based prospective cohort study of 436 434 Danish 0–5-year-old children attending childcare during 1989–2004. Information was collected from Danish registers. Main outcome measure was incidence rate ratios (IRRs) of in-patient hospitalization for ARI. Results: During 1 777 999 person-years of follow-up 42 681 hospitalizations for ARI occurred, of which 362 (1%) occurred within 1 month after another child was hospitalized for ARI in the facility. Children attending a facility with a recent ARI hospitalization had an increased risk of 42% (95% CI 27%;60%) compared with other children. The increased risk was higher in 0–2-year-old children than in 3–5-year-old children (55% vs 17%, p = 0.02) and if the latest hospitalized child was 0–2 years rather than 3–5 years (52% vs 19%, p = 0.04). The increased risk was similar in boys and girls, but was higher if the latest hospitalized child was a boy rather than a girl (52% vs 13%, p = 0.02). Conclusion: Although occurring infrequently, clustering of ARI hospitalizations involve 0–2-year-olds and boys as first hospitalized child relatively more often than would be expected.

Author(s): Edgren, Gustaf; Kamper-Jorgensen, Mads; Eloranta, Sandra; Rostgaard, Klaus; Custer, Brian; Ullum, Henrik; Murphy, Edward L; Busch, Michael P; Reilly, Marie; Melbye, Mads; Hjalgrim, Henrik; Nyren, Olof | Abstract: BackgroundDisquieting reports of increased complication and death rates after transfusions of red blood cells (RBCs) stored for more than 14 days prompted us to perform an observational retrospective cohort study of mortality in relation to storage time.Study design and methodsWe conducted a cohort study utilizing data on all recipients of at least one RBC transfusion in Sweden and Denmark between 1995 and 2002, as recorded in the Scandinavian Donations and Transfusions (SCANDAT) database. Relative risks of death in relation to storage time were estimated using Cox regression, adjusted for several possible confounding factors.ResultsAfter various exclusions, 404,959 transfusion episodes remained for analysis. The 7-day risk of death was similar in all exposure groups, but a tendency for a higher risk emerged among recipients of blood stored for 30 to 42 days (hazard ratio, 1.05; 95% confidence interval [CI], 0.97-1.12), compared to recipients of blood stored for 10 to 19 days. With 2-year follow-up, this excess remained at the same level (hazard ratio, 1.05; 95% CI, 1.02-1.08). No dose-response pattern was revealed and no differential effect was seen when the analyses were restricted to recipients of leukoreduced units only.ConclusionAlthough a small excess mortality was noted in recipients of the oldest RBCs, the risk pattern was more consistent with weak confounding than with an effect of the momentary exposure to stored RBCs. It seems, thus, that any excess mortality conferred by older RBCs in the combined Swedish and Danish transfusion recipient population is likely less than 5%, which is considerably smaller than in the hitherto largest investigation.

It has been proposed that exposure to infections and microbes protects against atopic diseases, but epidemiological data has so far been conflicting. We hypothesized that maternal exposure to infections and microbes before or during pregnancy would be of particular importance. To test this hypothesis, we studied the incidence of wheezing and atopic dermatitis (AD) in infants of mothers employed in child-care institutions - and thus presumably being highly exposed to infections and microbes - compared with infants of mothers not so employed. A total of 31471 mother-child pairs enrolled in the Danish National Birth Cohort were followed prospectively. Information on wheezing episodes, AD, maternal employment, and other variables were collected by interview at 12 and 30 wk of gestation, and 6 and 18 months of age, and by linkage to the Danish Medical Birth Register and the Child-care Database. The relative risk was estimated in Cox proportional hazard models. Analyses were stratified by sibling status (first born or not), as older siblings are likely to be a significant source of infectious agents. The adjusted relative risks of wheeze, recurrent wheeze and AD was 1.14 (95% CI: 0.96-1.37), 1.37 (95% CI: 1.05-1.77), and 1.03 (95% CI: 0.81-1.31), respectively, for first-born infants of mothers employed in child-care institutions compared with infants of mothers not so employed. There was no effect of maternal employment in child-care institutions among infants with older siblings. In conclusion, the results did not support the hypothesis that maternal microbial exposure before or during pregnancy as reflected by maternal employment in child-care institutions protects the offspring against infant wheeze and AD.

Childcare in the first 2 years of life reduces the risk of childhood acute lymphoblastic leukemia

Background. Denmark’s systems of registry-based data offer a unique opportunity to examine, on a population basis, risk factors for invasive pneumococcal disease (IPD) relating to perinatal and crowding exposures among children. The main objective of this study was to identify the role of familial and day care factors in the risk of IPD among unvaccinated infants and children. Methods. A total of 1381 children aged 0–5 years old who experienced IPD were identified from a national surveillance program of IPD in Denmark. Risk factors were assessed in a matched, nested, case-control study that assigned 10 population control subjects to every case patient. Exposure information was obtained from several population-based, person-identifiable Danish registries. Results. Preterm birth and low birth weight significantly increased the risk of IPD among infants. In infants 0–5 months of age, the risk of IPD was high among infants who had older siblings, compared with infants of the same age who had no older siblings (adjusted rate ratio [aRR], 3.38; 95% confidence interval, 2.11–5.42), whereas the aRR was low (aRR, 0.56; 95% confidence interval, 0.47–0.65) in children aged 6–23 months. Day care attendance, compared with home care, increased the aRR of IPD 0–2 months after enrollment in a day care program (aRR, 2.28; 95% confidence interval, 1.73–3.00), whereas the aRR was 0.70; (95% confidence interval, 0.46–1.06) 6 months after enrollment in children aged 6–23 months. Conclusions. During infancy (age, 0–6 months), risk of IPD is associated with low birth weight, presumably because of lower levels of passively acquired maternal antibody. During early childhood, exposure to other young children (either siblings or through day care attendance) is clearly associated with IPD, but natural exposure appears to occur rapidly and confer durable immunity. Invasive pneumococcal disease (IPD) is a serious health problem worldwide, causing substantial morbidity and mortality [1–3]. In many countries, including Denmark, Streptococcus pneumoniae (pneumococcus) is the most common cause of meningitis and is a leading cause of bacteremia [4, 5]. Even so, the incidence of IPD is low and, although a pneumococcal vaccine is

The aim of this study is to identify the risk factors for hospitalization for respiratory syncytial virus (RSV) infection in Danish children.This is a population-based cohort study with follow-up till 24 months of age. A total of 421,943 Danish children were divided into 5 groups based on gestational age (23-32, 33-35, 36, 37-41 and 42-45 weeks).In adjusted Cox regression models, chronic disease, asthma hospitalization before the RSV infection and siblings were associated with an increased risk of hospitalization for RSV infection in all children independent of gestational age. Plurality was associated with a decreased risk in children born between 23 and 36 weeks of gestation, whereas young maternal age, maternal asthma, single parenthood, maternal smoking, being born small for gestational age, Caesarian section, male gender and day care were associated with an increased risk of hospitalization for RSV infection in term children. In postterm children, young maternal age, male sex, being born small for gestational age and maternal smoking were associated with an increased risk of hospitalization for RSV. Asthma hospitalization before the RSV infection and siblings were associated with the highest measures of increased risk of hospitalization for RSV infection independent of gestational age.By 5 groups of gestational age, we provide estimates of the effects of 12 different factors, which can be regarded as add-on risk factors to those already known to increase the risk of hospitalization for RSV infection. Our study may help clinicians to precisely assess the risk profile in the individual child.

Item does not contain fulltext BACKGROUND: During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS: European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS: In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION: This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Studies have repeatedly demonstrated that blood donors experience lower mortality than the general population. While this may suggest a beneficial effect of blood donation, it may also reflect the selection of healthy persons into the donor population. To overcome this bias, we investigated the relation between blood donation frequency and mortality within a large cohort of blood donors. In addition, our analyses also took into consideration the effects of presumed health differences linked to donation behavior.Using the Scandinavian Donation and Transfusion database (SCANDAT), we assessed the association between annual number of donations in 5-year windows and donor mortality by means of Poisson regression analysis. The analyses included adjustment for demographic characteristics and for an internal healthy donor effect, estimated among elderly donors exempted from continued donation because of age criteria.Statistical analyses included 1,182,495 donors of whom 15,401 died during 9,526,627 person-years of follow-up. Analyses adjusted only for demographic characteristics showed a 18.6% reduction in mortality per additional annual donation (95% confidence interval [CI], 16.8%-20.4%). After additional adjustment for the internal healthy donor effect, each additional annual donation was associated with a 7.5% decreased mortality risk 7.5% (95% CI, 5.7%-9.4%).We observed an inverse relationship between donation frequency and mortality. The magnitude of the association was reduced after adjustment for an estimate of self-selection in the donor population. Our observations indicate that repeated blood donation is not associated with premature death, but cannot be interpreted as conclusive evidence of a beneficial health effect.

OBJECTIVES. It is well known that children attending childcare have a higher risk of acute respiratory infections compared with children in home care; however, knowledge is sparse regarding how the excess risk of acute respiratory infection varies with age, time since enrollment, and other factors.METHODS. A national register-based study of 138821 inpatient admissions to hospital for acute respiratory infection during 3982925 person-years of follow-up in Danish children aged 0 to 5 years. Data on child and family characteristics, childcare attendance, and hospitalizations were obtained from Danish registries. The outcome of the study was inpatient admissions to hospital for acute respiratory infection. Incidence rate ratios were estimated using Poisson regression.RESULTS. In children CONCLUSIONS. The increased risk of acute respiratory infection was most pronounced among 0- to 2-year-old children living with no other children during the first 6 months of enrollment. Our findings may suggest that it would be optimal to postpone enrollment into childcare until after 1 year of age.

Aim: To study temporal trends in the incidence of hospitalisations due to infection in children in Denmark. Methods: A national register based cohort of 1 892 711 Danish children aged 0–5 years were studied from 1980 to 2001. Child and family characteristics were identified in the Danish Civil Registration System; hospitalisations were identified in the Danish National Patient Registry. Annual incidence rates were estimated using log-linear Poisson regression. Results: During the studied period, the incidence of hospitalisations from infection increased by 62% in 0–5 year old children. The increase was mainly due to a sevenfold increase in the incidence of infections leading to short term hospitalisation in children aged 0–1 years. Since the increase in incidence was contrasted with a decrease in duration of hospitalisation, no further strain was put on the health services in Denmark. Conclusion: During the last two decades, the incidence of short term hospitalisations due to infections increased markedly among the youngest children. However, the strain on the health services remained constant. The observed increase in the incidence of short term hospitalisations among the youngest children may reflect changes in hospitalisation practices and utilisation, rather than an increase in incidence of infections.