Mads Kamper-Jørgensen

Duration of red blood cell storage and survival of transfused patients (CME)

BACKGROUND: Disquieting 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.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

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.

The influence of female and male body mass index on live births after assisted reproductive technology treatment: a nationwide register-based cohort study

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 <25 kg/m(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.

Duration of red blood cell storage and survival of transfused patients

BACKGROUND: Disquieting 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.

Prognosis for Live Birth in Women With Recurrent Miscarriage What Is the Best Measure of Success

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 (n=987). 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<.01) and increasing number of miscarriages (log-rank P<.01) at first consultation. CONCLUSION: Approximately two thirds of women with recurrent miscarriage referred to a tertiary center succeed in having at least one live birth within 5 years after their first consultation. Our study allows for a descriptive overview of the course of live birth outcome in women with recurrent miscarriage, but not for evaluation of the effect of treatment. LEVEL OF EVIDENCE: III

Opposite effects of microchimerism on breast and colon cancer

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.

Clustered tuberculosis in a low burden country: nationwide genotyping through 15 years.

ABSTRACT Molecular genotyping of Mycobacterium tuberculosis has proved to be a powerful tool in tuberculosis surveillance, epidemiology, and control. Based on results obtained through 15 years of nationwide IS6110 restriction fragment length polymorphism (RFLP) genotyping of M. tuberculosis cases in Denmark, a country on the way toward tuberculosis elimination, we discuss M. tuberculosis transmission dynamics and point to areas for control interventions. Cases with 100% identical genotypes (RFLP patterns) were defined as clustered, and a cluster was defined as cases with an identical genotype. Of 4,601 included cases, corresponding to 76% of reported and 97% of culture-verified tuberculosis cases in the country, 56% were clustered, of which 69% were Danes. Generally, Danes were more often in large clusters (≥50 persons), older (mean age, 45 years), and male (male/female ratio, 2.5). Also, Danes had a higher cluster frequency within a 2-year observation window (60.8%), and higher clustering rate of new patterns over time, compared to immigrants. A dominant genotype, cluster 2, constituted 44% of all clustered and 35% of all genotyped cases. This cluster was primarily found among Danish males, 30 to 59 years of age, often socially marginalized, and with records of alcohol abuse. In Danes, cluster 2 alone was responsible for the high cluster frequency level. Immigrants had a higher incidence of clustered tuberculosis at a younger age (0 to 39 years). To achieve tuberculosis elimination in Denmark, high-risk transmission environments, like the cluster 2 enviornment in Danes, and specific transmission chains in immigrants in the capital area, e.g., homeless/socially marginalized Somalis/Greenlanders, often with alcohol abuse, must be targeted, including groups with a high risk of reactivation.

Blood donation and blood donor mortality after adjustment for a healthy donor effect

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.

Birth weight and polycystic ovary syndrome in adult life: a register-based study on 523,757 Danish women born 1973–1991

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.

Preeclampsia and breast cancer: The influence of birth characteristics

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.