Effectiveness evaluation of an antenatal care intervention addressing disparities to improve perinatal outcomes in Denmark: A nationwide register-based analysis of a cluster randomised controlled trial (MAMAACT).

OBJECTIVE: To evaluate whether MAMAACT, an antenatal care (ANC) intervention, aimed at reducing ethnic and social disparities in perinatal mortality, affected perinatal health outcomes. DESIGN: Cluster randomised controlled trial. SETTING: Nineteen of 20 maternity wards in Denmark. POPULATION: All newborn children within a pre-implementation period (2014-2017) or an implementation period (2018-2019) (n = 188 658). INTERVENTION: A 6-h training session for midwives in intercultural communication and cultural competence, two follow-up dialogue meetings, and health education materials for pregnant women on warning signs of pregnancy complications in six languages. METHODS: Nationwide register-based analysis of the MAMAACT cluster randomised controlled trial. Mixed-effects logistic regression models were used to estimate the change in outcomes from pre- to post-implementation in the intervention group relative to the control group. Results were obtained for the overall study population and for children born to immigrants from low- to middle-income countries, separately. Models were adjusted for confounders selected a priori. MAIN OUTCOME MEASURES: A composite perinatal mortality and morbidity outcome, including stillbirths, neonatal deaths, Apgar score <7, umbilical arterial pH < 7.0, admissions to a neonatal intensive care unit (NICU) >48 h, and NICU admissions for mechanical ventilation. Additional outcomes were the individual measures. RESULTS: The intervention increased the risk of the composite outcome (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 0.99-1.34), mainly driven by differences in NICU admission risk (composite outcome excluding NICU, aOR 0.98, 95% CI 0.84-1.14). The intervention slightly increased the risk of low Apgar score and decreased the risk of low arterial pH, reflecting, however, small differences in absolute numbers. Other outcomes were unchanged. CONCLUSIONS: Overall, the MAMAACT intervention did not improve the composite perinatal mortality and morbidity outcome (when excluding NICU admissions). The lack of effects may be due to contextual factors including organisational barriers in ANC hindering the midwives from changing practices.

Preterm birth after the introduction of COVID-19 mitigation measures in Norway, Sweden, and Denmark: a registry-based difference-in-differences study.

BACKGROUND: Although some studies have reported a decrease in preterm birth following the start of the COVID-19 pandemic, the findings are inconsistent. OBJECTIVE: This study aimed to compare the incidences of preterm birth before and after the introduction of COVID-19 mitigation measures in Scandinavian countries using robust population-based registry data. STUDY DESIGN: This was a registry-based difference-in-differences study using births from January 2014 through December 2020 in Norway, Sweden, and Denmark. The changes in the preterm birth (<37 weeks) rates before and after the introduction of COVID-19 mitigation measures (set to March 12, 2020) were compared with the changes in preterm birth before and after March 12 from 2014 to 2019. The differences per 1000 births were calculated for 2-, 4-, 8-, 12-, and 16-week intervals before and after March 12. The secondary analyses included medically indicated preterm birth, spontaneous preterm birth, and very preterm (<32 weeks) birth. RESULTS: A total of 1,519,521 births were included in this study. During the study period, 5.6% of the births were preterm in Norway and Sweden, and 5.7% were preterm in Denmark. There was a seasonal variation in the incidence of preterm birth, with the highest incidence during winter. In all the 3 countries, there was a slight overall decline in preterm births from 2014 to 2020. There was no consistent evidence of a change in the preterm birth rates following the introduction of COVID-19 mitigation measures, with difference-in-differences estimates ranging from 3.7 per 1000 births (95% confidence interval, -3.8 to 11.1) for the first 2 weeks after March 12, 2020, to -1.8 per 1000 births (95% confidence interval, -4.6 to 1.1) in the 16 weeks after March 12, 2020. Similarly, there was no evidence of an impact on medically indicated preterm birth, spontaneous preterm birth, or very preterm birth. CONCLUSION: Using high-quality national data on births in 3 Scandinavian countries, each of which implemented different approaches to address the pandemic, there was no evidence of a decline in preterm births following the introduction of COVID-19 mitigation measures.

Advanced paternal age and childhood cancer in offspring: A nationwide register-based cohort study.

Cancer initiation is presumed to occur in utero for many childhood cancers and it has been hypothesized that advanced paternal age may have an impact due to the increasing number of mutations in the sperm DNA with increasing paternal age. We examined the association between paternal age and specific types of childhood cancer in offspring in a large nationwide cohort of 1,904,363 children born in Denmark from 1978 through 2010. The children were identified in the Danish Medical Birth Registry and were linked to information from other national registers, including the Danish Cancer Registry. In total, 3,492 children were diagnosed with cancer before the age of 15 years. The adjusted hazard ratio of childhood cancer according to paternal age was estimated using Cox proportional hazards regressions. We found a 13% (95% confidence interval: 4-23%) higher hazard rate for every 5 years advantage in paternal age for acute lymphoblastic leukemia, while no clear association was found for acute myeloid leukemia (hazard ratio pr. 5 years = 1.02, 95% confidence interval: 0.80-1.30). The estimates for neoplasms in the central nervous system suggested a lower hazard rate with higher paternal age (hazard ratio pr. 5 years = 0.92, 95% confidence interval: 0.84-1.01). No clear associations were found for the remaining childhood cancer types. The findings suggest that paternal age is moderately associated with a higher rate of childhood acute lymphoblastic leukemia, but not acute myeloid leukemia, in offspring, while no firm conclusions could be made for other specific cancer types.

Cardiovascular Disease in Relation to Placental Abruption: A Population-Based Cohort Study from Denmark.

BACKGROUND: Cardiovascular (CVD) complications stemming from vascular dysfunction have been widely explored in the setting of preeclampsia. However, the impact of abruption, a strong indicator of microvascular disturbance, on the risk of CVD mortality and morbidity remains poorly characterised. METHODS: We designed a cohort analysis of 828 289 women who delivered singletons in Denmark between 1978 and 2010. We linked the National Patient Registry and the Registry of Causes of Death to the Danish Birth Registry to ascertain CVD events. We estimated CVD risks in relation to abruption from Cox proportional hazards regression following adjustments for confounders. RESULTS: With 13 231 562 person-years of follow-up of women with at least one delivery, 11 829 pregnancies were complicated by abruption. The median (interquartile range) follow-up in the non-abruption and abruption groups was 16 (8, 24) and 18 (10, 25) years, respectively. CVD mortality rates in women with and without abruption were 0.9 and 0.3 per 10 000 person-years, respectively (adjusted hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.5, 5.0). The corresponding CVD morbidity complication rates were 16.7 and 10.0 per 10 000 person-years, respectively (HR 1.5, 95% CI 1.4, 1.8). The increased risks were evident for ischaemic heart disease, acute myocardial infarction, hypertensive heart disease, non-rheumatic valvular disease, and congestive heart failure. CONCLUSIONS: This study shows increased hazards of CVD morbidity and mortality in relation to abruption. A better understanding of the pathogenesis of distorted placental microvasculature is needed as this appears to be a harbinger of CVD later in life.

Focused breastfeeding counselling improves short- and long-term success in an early-discharge setting: A cluster-randomized study.

Length of postnatal hospitalization has decreased and has been shown to be associated with infant nutritional problems and increase in readmissions. We aimed to evaluate if guidelines for breastfeeding counselling in an early discharge hospital setting had an effect on maternal breastfeeding self-efficacy, infant readmission and breastfeeding duration. A cluster randomized trial was conducted and assigned nine maternity settings in Denmark to intervention or usual care. Women were eligible if they expected a single infant, intended to breastfeed, were able to read Danish, and expected to be discharged within 50 hr postnatally. Between April 2013 and August 2014, 2,065 mothers were recruited at intervention and 1,476 at reference settings. Results show that the intervention did not affect maternal breastfeeding self-efficacy (primary outcome). However, less infants were readmitted 1 week postnatally in the intervention compared to the reference group (adjusted OR 0.55, 95% CI 0.37, -0.81), and 6 months following birth, more infants were exclusively breastfed in the intervention group (adjusted OR 1.36, 95% CI 1.02, -1.81). Moreover, mothers in the intervention compared to the reference group were breastfeeding more frequently (p < .001), and spend more hours skin to skin with their infants (p < .001). The infants were less often treated for jaundice (p = 0.003) and there was more paternal involvement (p = .037). In an early discharge hospital setting, a focused breastfeeding programme concentrating on increased skin to skin contact, frequent breastfeeding, good positioning of the mother infant dyad, and enhanced involvement of the father improved short-term and long-term breastfeeding success.

Use of azathioprine and corticosteroids during pregnancy and birth outcome in women diagnosed with inflammatory bowel disease.

BACKGROUND: The aim of this study was to describe prescription patterns for azathioprine and corticosteroids for pregnant women with inflammatory bowel diseases (IBD) before, during, and after pregnancy and to describe pregnancy outcomes. METHODS: A cohort composed of all singleton pregnancies in Danish registries from 1996 to 2009 was divided by maternal IBD status: Crohn's disease (CD, n = 827), ulcerative colitis (UC, N = 1361), or no IBD diagnosis (background population, n = 814,231). The number of women with a prescription for azathioprine, local and systemic steroids within a 3-month period was computed for each of the pregnancy trimesters and the year before and after pregnancy. Outcomes of interest were stillbirth, perinatal mortality, low birth weight (LBW), preterm birth, and small for gestational age (SGA). RESULTS: Number of prescriptions for azathioprine decreased just before and during pregnancy and increased after birth. Number of prescriptions for local and systemic corticosteroids decreased approximately 30% compared with before pregnancy and increased in the second trimester. There was an increased risk among mothers with IBD of LBW (adjusted odds ratio [adjOR]: CD: 2.25 [95% confidence interval {CI}, 1.74-2.91], UC: 1.81 [95% CI, 1.42-2.30]), preterm birth (adjOR: CD: 2.54 [95% CI, 2.04-3.15], UC: 1.86 [95% CI, 1.52-2.27]), and SGA (adjOR: CD: 1.99 [95% CI, 1.26-3.15], UC: 1.80 [95% CI, 1.18-2.75]). CONCLUSION: Use of azathioprine and corticosteroids was often reduced or discontinued before or during early pregnancy followed by an increased use of corticosteroids later in pregnancy. Women diagnosed with IBD and with prescriptions for azathioprine and/or corticosteroids, have an increased risk of LBW, pre-term birth, and SGA. Birth Defects Research (Part A) 106:494-499, 2016. © 2016 Wiley Periodicals, Inc.

Use of asthma medication during pregnancy and risk of specific congenital anomalies: A European case-malformed control study.

BACKGROUND: Pregnant women with asthma need to take medication during pregnancy. OBJECTIVE: We sought to identify whether there is an increased risk of specific congenital anomalies after exposure to antiasthma medication in the first trimester of pregnancy. METHODS: We performed a population-based case-malformed control study testing signals identified in a literature review. Odds ratios (ORs) of exposure to the main groups of asthma medication were calculated for each of the 10 signal anomalies compared with registrations with nonchromosomal, nonsignal anomalies as control registrations. In addition, exploratory analyses were done for each nonsignal anomaly. The data set included 76,249 registrations of congenital anomalies from 13 EUROmediCAT registries. RESULTS: Cleft palate (OR, 1.63; 95% CI, 1.05-2.52) and gastroschisis (OR, 1.89; 95% CI, 1.12-3.20) had significantly increased odds of exposure to first-trimester use of inhaled ß2-agonists compared with nonchromosomal control registrations. Odds of exposure to salbutamol were similar. Nonsignificant ORs of exposure to inhaled ß2-agonists were found for spina bifida, cleft lip, anal atresia, severe congenital heart defects in general, or tetralogy of Fallot. None of the 4 literature signals of exposure to inhaled steroids were confirmed (cleft palate, cleft lip, anal atresia, and hypospadias). Exploratory analyses found an association between renal dysplasia and exposure to the combination of long-acting ß2-agonists and inhaled corticosteroids (OR, 3.95; 95% CI, 1.99-7.85). CONCLUSIONS: The study confirmed increased odds of first-trimester exposure to inhaled ß2-agonists for cleft palate and gastroschisis and found a potential new signal for renal dysplasia associated with combined long-acting ß2-agonists and inhaled corticosteroids. Use of inhaled corticosteroids during the first trimester of pregnancy seems to be safe in relation to the risk for a range of specific major congenital anomalies.

Maternal use of selective serotonin reuptake inhibitors and risk of miscarriage - assessing potential biases.

BACKGROUND: The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with miscarriage, but the association may be biased by maternal mental illness, lifestyle and exposure misclassification. METHODS: A register study on all pregnancies in Denmark between 1996 and 2009 was conducted using individualised data from the Danish National Patient Register, the Medical Birth Register, the Danish Psychiatric Central Register, the Danish National Prescription database and the Danish National Birth Cohort (DNBC). RESULTS: A total of 1 191164 pregnancies were included in the study, of which 98275 also participated in the DNBC. Pregnancies exposed to SSRIs during or before pregnancy were more likely than unexposed pregnancies to result in first trimester miscarriage, hazard rate (HR)=1.08 [95% confidence interval (CI) 1.04, 1.13] and HR=1.26 [95% CI 1.16, 1.37], respectively. No difference was observed for second trimester miscarriage. SSRI-exposed pregnancies without a maternal depression/anxiety diagnosis from a psychiatric department were less likely to result in first trimester miscarriage than unexposed pregnancies with a diagnosis, HR=0.85 [95% CI 0.76, 0.95]. SSRI-exposed pregnancies were characterised by an unhealthier maternal lifestyle and mental health profile than unexposed pregnancies, whereas no convincing differences were observed between pregnancies exposed to SSRIs during versus before pregnancy. Substantial disagreement was found between prescriptions and self-reported use of SSRIs, but it did not affect the estimated hazard ratios. CONCLUSION: Confounding by indication and lifestyle in pregnancy may explain the association between SSRI use and miscarriage.

A Register-Based Study of Diseases With an Autosomal Recessive Origin in Small Children in Denmark According to Maternal Country of Origin.

BACKGROUND: Compared with children born of Danish mothers, the mortality of children, born and living in Denmark, is significantly increased in those with a mother from Afghanistan, Iraq, Pakistan, Somalia, and Turkey. Consanguinity has been suggested to account for part of this disparity. Since information on consanguinity is lacking, this suggestion is difficult to test. With an indirect approach, we addressed this question by comparing the risk of diseases with autosomal recessive inheritance in children born in Denmark of Danish-born women and of women born in these five countries, respectively. METHODS: All children born in Denmark (1994-2010) were followed until 5 years of age or end-of-study period for the risk of hospitalisation with diseases of autosomal recessive aetiology, and therefore considered consanguinity-related. Diagnoses of autosomal recessive diseases were identified using two different methods: a literature review of consanguinity-associated diseases and a search in the Online Catalogue of Human Genes and Genetic Disorders. Risks were also calculated for diseases with known non-autosomal recessive aetiology (considered non-consanguinity-related). We estimated adjusted hazard ratios for the diseases in children of foreign-born women compared with children of Danish-born women. RESULTS: Compared with offspring of Danish-born women, the risk of a consanguinity-related disease was significantly increased in children of foreign-born women, although the absolute risk was low. The risk of non-consanguinity-related diseases did not differ between the groups compared. CONCLUSIONS: The findings support the hypothesis that consanguinity accounts for some, however a minor part, of the disparity in child mortality among migrants in Denmark.

Use of ADHD medication during pregnancy from 1999 to 2010: a Danish register-based study.

OBJECTIVE: This study aimed to describe the trends in use of Attention Deficit Hyperactivity Disorders (ADHD) medication during pregnancy in Denmark from 1999 to 2010, as well as to explore characteristics of women who use ADHD medication during pregnancy and whether exposure is associated with outcome of pregnancy. METHOD: A linkage between various Danish national health registries was performed to identify all recorded pregnancies from 1999 to 2010. Use of ADHD medication was defined as a redeemed prescription on methylphenidate, modafinil, or atomoxetine from 28 days prior to the first day of the last menstrual period until the end of pregnancy. RESULTS: Of the 1 054 494 registered pregnancies, 480 were exposed to ADHD medication. From 2003 to the first quarter of 2010, use of ADHD medication during pregnancy increased from 5 to 533 per 100 000 person-years. A similar increase was observed among Danish women of childbearing age. Compared with unexposed, women who used ADHD medication during pregnancy were more often younger, single, lower educated, received social security benefits, and used other psychopharmaca. Exposed pregnancies were more likely to result in induced abortions on maternal request (odds ratio = 4.70, 95%CI = 3.77-5.85), induced abortions on special indication (odds ratio = 2.99, 95%CI = 1.34-6.67), and miscarriage (odds ratio = 2.07, 95%CI = 1.51-2.84) compared with unexposed pregnancies. CONCLUSIONS: The number of pregnancies exposed to ADHD medication has increased similarly to the increase in use of ADHD medication among women of childbearing age. Use of ADHD medication in pregnancy was associated with different indicators of maternal disadvantage and with increased risk of induced abortion and miscarriage.

Healthcare databases in Europe for studying medicine use and safety during pregnancy.

PURPOSE: The aim of this study was to describe a number of electronic healthcare databases in Europe in terms of the population covered, the source of the data captured and the availability of data on key variables required for evaluating medicine use and medicine safety during pregnancy. METHODS: A sample of electronic healthcare databases that captured pregnancies and prescription data was selected on the basis of contacts within the EUROCAT network. For each participating database, a database inventory was completed. RESULTS: Eight databases were included, and the total population covered was 25 million. All databases recorded live births, seven captured stillbirths and five had full data available on spontaneous pregnancy losses and induced terminations. In six databases, data were usually available to determine the date of the woman's last menstrual period, whereas in the remainder, algorithms were needed to establish a best estimate for at least some pregnancies. In seven databases, it was possible to use data recorded in the databases to identify pregnancies where the offspring had a congenital anomaly. Information on confounding variables was more commonly available in databases capturing data recorded by primary-care practitioners. All databases captured maternal co-prescribing and a measure of socioeconomic status. CONCLUSION: This study suggests that within Europe, electronic healthcare databases may be valuable sources of data for evaluating medicine use and safety during pregnancy. The suitability of a particular database, however, will depend on the research question, the type of medicine to be evaluated, the prevalence of its use and any adverse outcomes of interest. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Increased risk of severe congenital heart defects in offspring exposed to selective serotonin-reuptake inhibitors in early pregnancy--an epidemiological study using validated EUROCAT data.

BACKGROUND: Previous studies suggest a possible association between maternal use of selective serotonin-reuptake inhibitors (SSRIs) during early pregnancy and congenital heart defects (CHD). The purpose of this study was to verify this association by using validated data from the Danish EUROCAT Register, and secondary, to investigate whether the risk differs between various socioeconomic groups. METHODS: We conducted a cohort study based on Danish administrative register data linked with the Danish EUROCAT Register, which includes all CHD diagnosed in live births, fetal deaths and in pregnancies terminated due to congenital anomalies. The study population consisted of all registered pregnancies (n = 72,280) in Funen, Denmark in the period 1995-2008. SSRI-use was assessed using The Danish National Prescription Registry, information on marital status, maternal educational level, income, and country of origin from Statistics Denmark was used as indicators of socioeconomic situation, and the CHD were studied in subgroups defined by EUROCAT. Logistic Regression was used to investigate the association between redeemed prescriptions for SSRIs and CHD. RESULTS: The risk of severe CHD in the offspring of the 845 pregnant women who used SSRIs during first trimester increased four times (AOR 4.03 (95% CI 1.75-9.26)). We found no increased risk of septal defects. Socioeconomic position did not modify the association between maternal SSRI-use during pregnancy and severe CHD. CONCLUSION: This study, which is based on data with high case ascertainment, suggests that maternal use of SSRIs during first trimester increases the risk of severe CHD, but does not support findings from previous studies, based on administrative register data, regarding an increased risk of septal defects. The study was unable to document an interaction between socioeconomic status and maternal SSRI-use on the risk of severe CHD.

Predicting mortality and visualizing health care spending by predicted mortality in Danes over age 65.

Health care expenditure in the last year of life makes up a high proportion of medical spending across the world. This is often framed as waste, but this framing is only meaningful if it is known at the time of treatment who will go on to die. We analyze the distribution of health care spending by predicted mortality for the Danish population over age 65 over the year 2016, with one-year mortality predicted by a machine learning model based on sociodemographics and use of health care services for the two years before entry into follow-up. While a reasonably good model can be built, extremely few individuals have high ex-ante probability of dying, and those with a predicted mortality of more than 50% account for only 2.8% of total health care expenditure. Decedents outspent survivors by a factor of more than ten, but compared to survivors with similar predicted mortality they spent only 2.5 times as much. Our results suggest that while spending in the last year of life is indeed high, this is nearly all spent in situations where there is a reasonable expectation that the patient can survive.

Stressful life events in childhood and risk of infectious disease hospitalization.

UNLABELLED: Individuals exposed to high levels of stress might have an increased risk of infectious diseases. However, most of the previous studies have been conducted among adults. To examine the effect of childhood stress, we conducted a nationwide cohort study including all Danish children born from 1977 to 2004. Stressful life events (SFLE) included parental death, death of sibling or parental divorce. Outcome was defined as hospitalizations due to less severe (LSID) or severe infectious diseases (SID). Children were followed until the age of 15 years. The association between SFLE and risk of infections was evaluated through rate ratios (RR) comparing infectious disease incidence ratios in children with and without a history of SFLE. Overall, children exposed to SFLE were at 13% increased risk of LSID (RR = 1.13 (1.10-1.15)), but at no increased risk of SID hospitalization (RR = 1.05 (0.97-1.14)). Looking at the specific type of SFLE, parental divorce increased the risk of LSID (RR = 1.11 (1.09-1.14)) and SID hospitalization (1.11 (1.02-1.21)) by 11%, whereas no increased risk of LSID and SID hospitalization was observed following parental death. Finally, a 34% increased risk of LSID hospitalization (RR = 1.34 (1.23-1.45)) was observed following death of sibling, in contrast to no increased risk of SID hospitalization. CONCLUSION: Childhood exposure to SFLE, especially parental divorce seems to increase the risk of infectious disease hospitalization. Although we cannot determine whether our observations are the result of a biological effect of stress, adoption of unhealthy behaviours or increased likelihood of hospitalization, our findings do have public health relevance as a considerable proportion of the children today will be exposed to SFLE, the majority to parental divorce.

Prenatal stress and risk of infectious diseases in offspring.

Animal studies have suggested that prenatal stress could affect the immune system of the offspring. In a nation-wide cohort of all Danish children born from 1977 to 2004, the authors examined the association between prenatal stress, defined as maternal exposure to a stressful life event during pregnancy or in the 3-year period before conception, and the risk of severe or less severe infectious disease hospitalization in childhood. Log-linear Poisson regression models provided estimates of rate ratios. Compared with nonexposed children, children exposed prenatally to stress had a 25% (rate ratio (RR) = 1.25, 95% confidence interval (CI): 1.06, 1.47) and a 31% (RR = 1.31, 95% CI: 1.27, 1.35) increased risk of being hospitalized with a severe or a less severe infectious disease, respectively. Children born to mothers exposed to a stressful life event during pregnancy, during the 11 months before, or during the 12-35 months before conception were at 71% (RR = 1.71, 95% CI: 1.20, 2.45), 42% (RR = 1.42, 95% CI: 1.13, 1.78), and no increased (RR = 0.86, 95% CI: 0.63, 1.18) risk of severe infectious disease hospitalization. No obvious association between risk of less severe infectious disease hospitalization and timing of maternal exposure was observed. Although the authors could not determine whether this is a biologic effect of prenatal stress or an effect of other factors related indirectly to a stressful life event, their results add new information about the consequences of prenatal stress.

Health care expenditure in the last five years of life is driven by morbidity, not age: A national study of spending trajectories in Danish decedents over age 65.

BACKGROUND: The high level of medical spending at the end of life is well-documented, but whether there is any real potential for cost reductions there is still in question, and studies have tended to overlook the costs of care. AIM: To identify the most common health care spending trajectories over the last five years of life among older Danes, as well as the determinants of following a given trajectory. METHODS: We linked Danish health registries to obtain data on all health care expenditure (including hospital treatment, prescription drugs, primary care and costs of communal care) over the last five years of life for all Danish decedents above age 65 in the period 2013 through 2017. A latent class analysis identified the most common cost trajectories, which were then related to socio-economical characteristics and health status at five years before death. RESULTS: Total health care expenditures in the last five years of life were largely independent of age and cause of death. Costs of home care and residential care increased steeply with age at death whereas hospital costs decreased correspondingly. We found four main spending trajectories among decedents: 3 percent followed a late-rise trajectory, 11 percent had accelerating costs, and two groups of 43 percent each followed moderately or consistently high trajectories. The main predictor of total expenditure was the number of chronic diseases. INTERPRETATION: Spending at the end of life is largely determined by chronic disease, and age and cause of death only determine the distribution of expenses into care and cure.

Cerebrovascular disease after placental abruption: A population-based prospective cohort study.

OBJECTIVE: To test whether abruption during pregnancy is associated with long-term cerebrovascular disease by assessing the incidence and mortality from stroke among women with abruption. METHODS: We designed a population-based prospective cohort study of women who delivered in Denmark from 1978 to 2010. We used data from the National Patient Registry, Causes of Death Registry, and Danish Birth Registry to identify women with abruption, cerebrovascular events, and deaths. The outcomes included deaths resulting from stroke and nonfatal ischemic and hemorrhagic strokes. We fit Cox proportional hazards regression models for stroke outcomes, adjusting for the delivery year, parity, education, and smoking. RESULTS: The median (interquartile range) follow-up in the nonabruption and abruption groups was 15.9 (7.8-23.8) and 16.2 (9.6-23.1) years, respectively, among 828,289 women with 13,231,559 person-years of follow-up. Cerebrovascular mortality rates were 0.8 and 0.5 per 10,000 person-years among women with and without abruption, respectively (hazard ratio [HR] 1.6, 95% confidence interval [CI] 0.9-3.0). Abruption was associated with increased rates of nonfatal ischemic stroke (HR 1.4, 95% CI 1.1-1.7) and hemorrhagic stroke (HR 1.4, 95% CI 1.1-1.9). The association of abruption and stroke was increased with delivery at <34 weeks, when accompanied by ischemic placental disease, and among women with ≥2 abruptions. These associations are less likely to have been affected by unmeasured confounding. CONCLUSION: Abruption is associated with increased risk of cerebrovascular morbidity and mortality. Disruption of the hemostatic system manifesting as ischemia and hemorrhage may indicate shared etiologies between abruption and cerebrovascular complications.

Searching for longevity hotspots in Denmark.

While existing research on regions with high prevalence of centenarians has focused on selected candidate geographical regions, we explore the existence of hotspots in the whole of Denmark.We performed a Kulldorff spatial scan, searching for regions of birth, and of residence at age 71, where an increased percentage of the cohort born 1906-1915 became centenarians. We then compared mortality hazards for these regions to the rest of the country.We found a birth hotspot of 222 centenarians, 1.37 times more than expected, centered on a group of rural islands. Lower mortality hazards from age 71 onwards were confined to those born within the hotspot and persisted over a period of at least 30 years. At age 71, we found two residence-based hotspots of 348 respectively 238 centenarians, 1.46 and 1.44 times the expected numbers. One hotspot, located in high-income suburbs of the Danish capital, seems driven by selective in-migration of low-mortality individuals. The other hotspot seems driven by selective migration and lower morality among those born and residing in the hotspot.Thus, Danish centenarian hotspots do exist. The locations and interpretation depend on whether we look at place of birth or of residence late in life.