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.

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.

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.

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.

Educational disparities in perinatal health in Denmark in the first decade of the 21st century: a register-based cohort study.

OBJECTIVE: To investigate socioeconomic differences in six perinatal health outcomes in Denmark in the first decade of the 21st century. DESIGN: A population-based cohort study. SETTING: Danish national registries. PARTICIPANTS: A total of 646 829 live born children and 3076 stillborn children (≥22+0 weeks of gestation) born in Denmark from 2000 to 2009. We excluded children with implausible relations between birth weight and gestational age (n=644), children without information on maternal country of origin (n=138) and implausible values of maternal year of birth (n=36). MAIN OUTCOME MEASURES: We investigated the following perinatal health outcomes: stillbirth, neonatal and postneonatal mortality, small-for-gestational age, preterm birth grated into moderate preterm, very preterm and extremely preterm, and congenital anomalies registered in the first year of life. RESULTS: Maternal educational level was inversely associated with all adverse perinatal outcomes. For all examined outcomes, the risk association displayed a clear gradient across the educational levels. The associations remained after adjustment for maternal age, maternal country of origin and maternal year of birth. Compared with mothers with vocational education, mothers with more than 15 years of education had an adjusted risk ratio for stillbirth of 0.64(95% CI 0.56 to 0.72). The corresponding adjusted risk ratios for neonatal mortality, postneonatal mortality, congenital anomalies, moderate preterm birth and small-for-gestational age were, respectively, 0.79(95% CI 0.67 to 0.93), 0.57(95% CI 0.42 to 0.78), 0.87(95% CI 0.83 to 0.91), 0.80(95% CI 0.77 to 0.83) and 0.83(95% CI 0.81 to 0.85). CONCLUSION: Substantial educational inequalities in perinatal health were still present in Denmark in the first decade of the 21st century.

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.

Mode of delivery is not associated with celiac disease.

PURPOSE: The purpose of this study was to investigate the association between mode of delivery and the risk of celiac disease in two large population-based birth cohorts with different prevalence of diagnosed celiac disease. PATIENTS AND METHODS: This is an observational register-based cohort study using two independent population cohorts. We used data from administrative registers and health administrative registers from Denmark and Norway and linked the data at the individual level. We included all children who were born in Denmark from January 1, 1995 to December 31, 2010 and all children who were born in Norway from January 1, 2004 to December 31, 2012. RESULTS: We included 1,051,028 children from Denmark. Cesarean sections were registered for 196,512 children (18.9%). Diagnosed celiac disease was registered for 1,395 children (0.13%). We included 537,457 children from Norway. Cesarean sections were registered for 90,128 children (16.8%). Diagnosed celiac disease was registered for 1,919 children (0.35%). We found no association between the mode of delivery and the risk of diagnosed celiac disease. The adjusted odds ratio for celiac disease for children delivered by any type of cesarean section compared to vaginal delivery was 1.11 (95% CI: 0.96-1.29) in the Danish cohort and 0.96 (95% CI: 0.84-1.09) in the Norwegian cohort. The adjusted odds ratio for celiac disease for children delivered by elective cesarean section compared to vaginal delivery was 1.20 (95% CI: 1.00-1.43) in the Danish cohort and 0.96 (95% CI: 0.79-1.17) in the Norwegian cohort. CONCLUSION: In this large registry-based study, mode of delivery was not associated with an increased risk of diagnosed celiac disease.

Birth asphyxia in a Danish hospital uptake area was reduced after centralisation of deliveries
.

INTRODUCTION: Severe birth asphyxia is a major cause of neonatal morbidity and long-term disability and may be prevented. However, the consequences of organisational changes are rarely evaluated. 
Methods: A cohort study comparing morbidity and mortality for term-born infants born with severe birth asphyxia, defined as an Apgar score ≤ 5 at 5 min., before and after major changes in the organisation of births in a Danish district.
 Results: The study included 77 infants born in 1997-2004 and 40 infants born in 2009-2013 who were admitted to a neonatal intensive care unit with an Apgar score ≤ 5 at 5 min. The rate of severe birth asphyxia was 1.9 per 1,000 births in the early years and 2.5 per 1,000 births for the 2009-2013 period (p = 0.16). Mortality in the first three years of life with severe birth asphyxia was 0.24 per 1,000 births in 1997-2004 (ten deaths) and 0.06 per 1,000 births in 2009-2013 (one death) (p = 0.20). We observed a highly significant difference between the two periods in the proportion of infants with neonatal seizures and age at discharge after birth. The outcome of death or cerebral palsy was present in 17/77 (22%) in the early period and 3/40 (7.5%) in the more recent period (p < 0.05).
 Conclusions: Over a relative short time period, death and disability due to severe birth asphyxia at term decreased significantly. This improvement is most likely explained by changes in the organisation of births in the hospital uptake area. as well as in treatment 
Funding: none.
Trial registration: not relevant.

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.

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.

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.

Pregnancy outcomes after fetal exposure to antithyroid medications or levothyroxine.

AIM: To investigate whether fetal exposure to antithyroid drugs (ATD) and levothyroxine affects gestational age (GA), birth weight, birth length, head circumference and prevalence of congenital anomalies. METHODS: Cohort of all pregnancies from GA 12 weeks recorded in Danish registries from 1995-2010. Exposure was having a prescription for ATD or levothyroxine from 91 days before to 91 days after pregnancy start (n=8318). The reference group was pregnant women without exposure of ATD or levothyroxine (n=969303). A subpopulation was linked to the Danish EUROCAT congenital anomaly register. RESULTS: Overall 0.66% of the pregnant women had a prescription for levothyroxine and 0.19% had a prescription for ATD during the exposure period. There was no difference in proportion of live births compared to non-exposed pregnancies, but infants exposed to ATD were more often born very preterm (1.99% versus 0.94% Odds Ratio 2.04, 95% CI 1.46 - 2.86) and had higher infant mortality (Odds ratio 2.37, 95% CI 1.42 - 3.94). Infants exposed to ATD were more likely to have low birth weight and length for GA (Odds ratios 1.29 (1.12 - 1.50) and 1.40 (1.17 - 1.66). There was no difference in head circumference for the 3 exposure groups. Prevalence of congenital anomalies was the same for exposed and non-exposed pregnancies. CONCLUSION: Fetal exposure to ATD resulted in lower GA, birth weight, length and higher infant mortality. Treatment for hypothyroidism had no significant impact on these variables. There was no difference in prevalence of congenital anomalies.

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.

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.

Epidemiology of cerebral palsy in Southern Denmark.

INTRODUCTION: The aim of this study was to describe the prevalence, subtypes, severity and neuroimaging findings of cerebral palsy (CP) in a cohort of children born in Southern Denmark. Risk factors were analysed and aetiology considered. METHODS: A population-based cohort study covering 17,580 live births from 2003 to 2008. RESULTS: The study included 43 children diagnosed with CP. The overall prevalence of CP was 2.4 per 1,000 live births (95% confidence interval (CI): 1.8-3.2). The gestational age (GA)-specific prevalence ranged from 63.5 per 1,000 live births for GA < 32 weeks to 1.3 for GA ≥ 37 weeks. Almost half of the children were born preterm and 28% were from multiple pregnancies. The prevalence of CP was 1.8 per 1,000 in singletons and 15.4 per 1,000 in multiples. Low GA and birth weight were risk factors for CP, also after stratification for multiple births. Spastic CP was the predominating subtype of CP, and 24 children (56%) were able to walk independently. White-matter lesions were the most common magnetic resonance imaging finding, and the aetiology of CP was known in 37% of cases. CONCLUSION: The overall prevalence of CP was slightly higher than that found in other Scandinavian studies due to its higher prevalence in the preterm group. Possible explanations include the high rate of multiple births in the background population. Neuroimaging findings were abnormal in the majority of children with CP, but aetiology could only be established in one third of the children. Primary prevention of CP is possible if the numbers of preterm births and multiple pregnancies can be reduced. FUNDING: The Danish Cerebral Palsy Follow-up Programme is supported by the foundation "Ludvig og Sara Elsass Fond". TRIAL REGISTRATION: 2008-58-0034.

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.

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.