European Population-based Study Research Articles

Iron Status, Thyroid Dysfunction, and Iron Deficiency Anemia: A Two-Sample Mendelian Randomization Study.

Given the clinical association between thyroid dysfunction and iron deficiency anemia (IDA), as well as their shared association with iron status, this study aimed to investigate the causal relationship between iron status and thyroid dysfunction, while also examining the risk of IDA in relation to thyroid dysfunction. A two-sample mendelian randomization (MR) study was conducted to identify the causal relationship of iron status on thyroid dysfunction, as well as thyroid dysfunction on IDA. Large-scale European population-based genome-wide association study databases were utilized (Genetics of Iron Status consortium, ThyroidOmics consortium, FinnGen consortium, and UK Biobank). Inverse variance-weighted (IVW) was used as the main analysis. In addition, we used weighted median and MR-Egger to enhance the robustness. Sensitivity analysis was conducted to evaluate the robustness of MR results. The IVW estimates did not reveal any significant causal relationship between serum iron status markers and thyroid dysfunction. However, a significant causal relationship was observed between hypothyroidism and IDA (odds ratio [OR] = 1.101, 95% confidence interval [CI] = 1.048-1.157, p < 0.001). Repeated analyses also demonstrated a similar trend (OR = 1.023, 95% CI = 1.011-1.035, p < 0.001). Sensitivity analysis supported that the MR estimates were robust. In our MR study, an upregulation of the hypothyroidism-associated gene was found to be significantly associated with an elevated risk of IDA in the European population. These findings may offer novel therapeutic insights for clinicians managing patients with hypothyroidism, IDA, or their comorbidities.

Association between physical activity over a 10-year period and current insomnia symptoms, sleep duration and daytime sleepiness: a European population-based study

ObjectivesTo explore the relationship between physical activity over a 10-year period and current symptoms of insomnia, daytime sleepiness and estimated sleep duration in adults aged 39–67.DesignPopulation-based, multicentre cohort study.Setting21 centres...

Risk factors for mortality in infancy and childhood in children with major congenital anomalies: A European population-based cohort study.

Preterm birth and young maternal age are known risk factors for infant and childhood mortality. There is limited knowledge of the impact of these risk factors in children born with major congenital anomalies (CAs), who have inherently higher risks of death compared with other children. To investigate the risk factors for mortality up to age 10 years in children born with specific major CAs. This population-based cohort study involved 150,198 livebirths from 1995 to 2014 in 13 European CA registries linked to mortality data. Cox proportional hazards models estimated the association of gestational age, maternal age and child's sex with death <1 year and 1-9 years for the whole cohort and by CA subgroup. Hazard ratios (HR) from each registry were pooled using multivariate meta-analysis. Preterm birth had a dose-response association with mortality; compared with infants born at 37+ weeks gestation, those born at <28, 28-31 and 32-36 weeks had 14.88 (95% CI 12.57, 17.62), 8.39 (95% CI 7.16, 9.85) and 3.88 (95% CI 3.40, 4.43) times higher risk of death <1 year, respectively. The corresponding risks at 1-9 years were 4.99 (95% CI 2.94, 8.48), 3.09 (95% CI 2.28, 4.18) and 2.04 (95% CI 1.69, 2.46) times higher, respectively. Maternal age <20 years (versus 20-34 years) was a risk factor for death <1 year (HR 1.30, 95% CI 1.09, 1.54) and 1-9 years (HR 1.58, 95% CI 1.19, 2.10). Females had 1.22 (95% CI 1.07, 1.39) times higher risk of death between 1 and 9 years than males. Preterm birth was associated with considerably higher infant and childhood mortality in children with CAs, comparable to estimates reported elsewhere for the background population. Additional risk factors included young maternal age and female sex. Information on risk factors could benefit clinical care and guide counselling of parents following CA diagnoses.

Risk factors for admission and length of stay in hospital for children with and without congenital anomalies: A EUROlinkCAT study

ObjectiveTo explore risk factors for hospital admission, and length of stay (LOS) in hospital, among children with congenital anomalies (CAs) and reference children without CAs in Europe.&#x0D; MethodA European population-based data-linkage cohort study was conducted including children with CAs (born 1995-2014) registered in seven EUROCAT CA registries and children without CAs (reference children) living in the same geographical areas. Data on hospitalisation and LOS (1995-2015) for all children aged &lt;1 year and 1-4 years were obtained by linkage to hospital discharge databases.&#x0D; The effects of birth cohort, sex, gestational age, maternal age, multiple birth and socioeconomic status on risk of admission and LOS were estimated using Cox’s Proportional Hazards and negative binomial regression models. Random effects meta-analysis and quantile estimation methods were used to pool the estimates.&#x0D; ResultsA total of 79,036 children with CAs and 2,016,042 reference children were linked to hospital records. Children with CAs born pre-term (&lt;32 weeks) were more than twice as likely to be admitted (adj. HR 2.35, 95% CI 1.45-3.80) and had almost 8 times longer stays (adj. IRR 7.95, 95% CI 6.12-10.33) compared to children with CAs born at term. Reference children were almost six times as likely to be admitted (adj. HR 5.87, 95% CI 3.10-11.09), and had almost 50 times longer stays (adj. IRR 49.49, 30.92-79.21) compared to reference children born at term. Children with CAs and reference children born preterm were also at increased risk of admission at 1-4 years of age, although the effect was less than for children aged &lt;1 year.&#x0D; ConclusionThe impact of risk factors for admission to hospital and LOS were similar between children with CAs and reference children but the impact was often greater in reference children. This study highlights the value of linking to hospital discharge records to obtain population-based information on morbidity for counselling parents.

P14-004-23 Derived Dietary Patterns Using Reduced Rank Regression in Postmenopausal Women and Risk of Mortality: A European Population-Based Study

P14-004-23 Derived Dietary Patterns Using Reduced Rank Regression in Postmenopausal Women and Risk of Mortality: A European Population-Based Study

Survival, hospitalisation and surgery in children born with Pierre Robin sequence: a European population-based cohort study

ObjectiveTo evaluate survival, hospitalisations and surgical procedures for children born with Pierre Robin sequence (PRS) across Europe.DesignMulticentre population-based cohort study.SettingData on 463 live births with PRS from a population of...

Patterns of care and survival forlung cancer: Results of the European population-based high-resolution study.

To investigate differences in lung cancer (LC) management and survival using data from European population cancer registries. We analysed 4,602 lung cancer cases diagnosed in 2010-2013, followed-up to 2019 in five countries. Multivariable logistic regression was used to calculate the Odds Ratio (OR) of surgery for stages I-II LC or chemo- or radiotherapy for stages III-IV LC. Relative survival (RS) was estimated by the actuarial method; Relative Excess Risk of death (RER), with 95% CI, was calculated by generalized linear models. Diagnostic work-up was extensive for 65.9% patients (range 57%, Estonia, Portugal - 85% (Belgium). Sixty-six percent of stages I-II patients underwent surgery; compared to non-operated, their adjusted OR decreased with age and was associated with main bronchus cancer (OR vs. lobes 0.25, CI, 0.08-0.82), stage II (OR vs. stage I: 0.42, CI, 0.29-0.60), comorbidity (OR vs. absent: 0.55, CI, 0.33-0.93), country (ORs: Estonia 1.82, CI, 1.28-2.60; Belgium 0.62, CI, 0.42-0.91; Portugal 0.69, CI, 0.52-0.93).Almost half of stages III-IV patients received chemo- or radiotherapy only; the adjusted OR vs. non receiving decreased with age and was associated with unspecified cancer topography or morphology. The adjusted five-year RER increased with age and stage and was lower for women (0.78, CI, 0.72-0.86), above the reference for main bronchus cancer (1.37, CI, 1.21-1.54) and unspecified morphology (1.17, CI, 1.05-1.30). Surgery carried the lowest mortality (RS 56.9; RER 0.13, CI, 0.11-0.15) with RER above the mean in Estonia (1.20, CI, 1.10-1.30), below it in Portugal (0.88, CI, 0.82-0.93) and Switzerland (0.91, CI, 0.84-0.99). Comorbidity (1.21, CI, 1.09-1.35) and not smoking (0.68, CI, 0.57-0.81) were associated with RER. The survival benefit of early diagnosis, allowing curative surgery, was evident at the population level. Screening for subjects at risk and adhesion to standard care should be incremented across the EU by funding better equipment and training health personnel.

Obesity and functional gastrointestinal disorders: What is the link?

Obesity and functional gastrointestinal disorders: What is the link?

Hospital length of stay among children with and without congenital anomalies across 11 European regions-A population-based data linkage study.

BackgroundCongenital anomalies are a leading cause of childhood morbidity, but little is known about the long-term outcomes.ObjectiveTo quantify the burden of disease in childhood for children with congenital anomalies by assessing the risk of hospitalisation, the number of days spent in hospital and proportion of children with extended stays (≥10 days).MethodsEuropean population-based record-linkage study in 11 regions in eight countries including children with congenital anomalies (EUROCAT children) and without congenital anomalies (reference children) living in the same regions. The children were born between 1995 and 2014 and were followed to their tenth birthday or 31/12/2015. European meta-analyses of the outcome measures were performed by two age groups, <1 year and 1–4 years.Results99,416 EUROCAT children and 2,021,772 reference children were linked to hospital databases. Among EUROCAT children, 85% (95%-CI: 79–90%) were hospitalised in the first year and 56% (95%-CI: 51–61%) at ages 1–4 years, compared to 31% (95%-CI: 26–37%) and 25% (95%-CI: 19–31%) of the reference children. Median length of stay was 2–3 times longer for EUROCAT children in both age groups. The percentages of children with extended stays (≥10 days) in the first year were 24% (95%-CI: 20–29%) for EUROCAT children and 1% (95%-CI: 1–2%) for reference children. The median length of stay varied greatly between congenital anomaly subgroups, with children with gastrointestinal anomalies and congenital heart defects having the longest stays.ConclusionsChildren with congenital anomalies were more frequently hospitalised and median length of stay was longer. The outlook improves after the first year. Parents of children with congenital anomalies should be informed about the increased hospitalisations required for their child’s care and the impact on family life and siblings, and they should be adequately supported.

Gastrostomy and congenital anomalies: a European population-based study

ObjectiveTo report and compare the proportion of children with and without congenital anomalies undergoing gastrostomy for tube feeding in their first 5 years.MethodsA European, population-based data-linkage cohort study (EUROlinkCAT). Children...

Mode of delivery and adverse short- and long-term outcomes in vertex-presenting very preterm born infants: a European population-based prospective cohort study.

To compare mortality, morbidity and neurodevelopment by mode of delivery (MOD) for very preterm births with low prelabour risk of caesarean section (CS). The study was a population-based prospective cohort study in 19 regions in 11 European countries. Multivariable mixed effects models and weighted propensity score models were used to estimate adjusted odds ratios (aOR) by observed MOD and the unit's policy regarding MOD. Population: Singleton vertex-presenting live births at 24+0 to 31+6 weeks of gestation without serious congenital anomalies, preeclampsia, HELLP or eclampsia, antenatal detection of growth restriction and prelabour CS for fetal or maternal indications. Main outcome measures: A composite of in-hospital mortality and intraventricular haemorrhage (grade III/IV) or periventricular leukomalacia. Secondary outcomes were components of the primary outcome, 5min Apgar score <7 and moderate to severe neurodevelopmental impairment at two years of corrected age. The rate of CS was 29.6% but varied greatly between countries (8.0-52.6%). MOD was not associated with the primary outcome (aOR for CS 0.99; 95% confidence interval [CI] 0.65-1.50) when comparing units with a systematic policy of CS or no policy of MOD to units with a policy of vaginal delivery (aOR 0.88; 95% CI 0.59-1.32). No association was observed for two-year neurodevelopment impairment for CS (aOR 1.15; 95% CI 0.66-2.01) or unit policies (aOR 1.04; 95% CI 0.63-1.70). Among singleton vertex-presenting live births without medical complications requiring a CS at 24+0 to 31+6 weeks of gestation, CS was not associated with improved neonatal or long-term outcomes.

Treatment patterns and overall survival for recurrent esophageal or gastroesophageal junctional cancer: A nationwide European population-based study.

186 Background: Esophageal cancer has a high risk for recurrence after treatment with curative intent. This study describes the characteristics of patients with esophageal or gastroesophageal junctional cancer at the time of recurrence, treatment patterns and overall survival (OS) after recurrence. Methods: Patients selected from the nationwide Netherlands cancer registry had received a primary diagnosis of non-metastatic squamous cell carcinoma or adenocarcinoma of esophagus or gastroesophageal junction in 2015 or 2016 and experienced recurrence after primary treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. Recurrence within or after six months was calculated from resection date or end of dCRT. OS was calculated from recurrence and analysed using Kaplan-Meier curves with Log-Rank test. Results: We identified 856 patients who presented with disease recurrence after potentially curative treatment with resection (75%) or dCRT (25%). At recurrence, the majority of patients were male (78%),the median age was 68 years and 77% of patients had adenocarcinoma. Twenty-six percent of patients had disease recurrence within six months after curative treatment. Eighteen percent of patients had locoregional recurrence only, 48% distant recurrence only and 33% both locoregional and distant recurrence. Among patients with a distant recurrence, 37% had metastases in non-regional lymph nodes, 31% in the liver and 30% in the lung. After disease recurrence, 29% of patients received systemic therapy (chemo- or targeted therapy), 5% chemoradiotherapy, 1% surgery and 66% best supportive care only. The most common systemic treatment regimen was CapOx/FOLFOX (54%) and13% of patients received a targeted agent: trastuzumab containing regimen (n = 26) or paclitaxel and ramucirumab (n = 5). Among all patients, the median OS from date of recurrence was 4.4 months. Patients with recurrence within six months had a poorer median survival (2.1 months) compared to patients with recurrence after six months (5.7 months; p &lt; 0.001). Median OS in patients with locoregional recurrence only was 7.4 months, distant recurrence only was 4.0 months, and both locoregional and distant recurrence was 3.4 months (p &lt; 0.001). Patients with prior primary treatment with resection had median OS of 4.2 months and patients with prior dCRT of 5.1 months (p = 0.605). Conclusions: The majority of patients had distant metastases at disease recurrence and a small proportion received systemic therapy after recurrence. Overall prognosis was poor, and survival outcomes were poorest among patients with recurrence within six months of initial curative treatment suggesting a worse biological tumor behaviour.

Novel non-invasive particles in exhaled air method to explore the lining fluid of small airways—a European population-based cohort study

IntroductionRespiratory tract lining fluid of small airways mainly consists of surfactant that can be investigated by collection of the particles of exhaled aerosol (PExA) method. This offers an exciting prospect...

Are normoglycaemic individuals at risk of depression? The depression-dysglycaemic phenotype from a European population-based cross-sectional study

BackgroundDepression is a chronic non communicable disease. It is a growing public health concern with established links with a number of co-morbidities, including diabetes mellitus. The study aimed to estimate the prevalence of depression at a population level, establish the depression sub-population phenotypic characteristics while exploring for links between depression and a spectrum of glycemic abnormalities.MethodsA nationally representative cross-sectional study was conducted in Malta between 2014 and 2016. Participants were categorized into different sub-populations according to their glycaemic status. Depression prevalence rates and phenotypic characteristics for each sub-population were established. Multiple regression analysis was performed to identify links with depression.ResultsDepression was prevalent in 17.15% (CI 95%: 16.01–18.36) with a female predominance. Those with known (as opposed to newly diagnosed) diabetes had the highest depression prevalence when compared to other glycemic sub-groups. These also exhibited a significant link with self-reported depression. However, at a population level, depression was mostly prevalent within the normoglycaemic sub-population.ConclusionsThe study confirms the strong link between diabetes and depression, especially, in a high risk dysglycaemic population. Of public health concern is the high depression occurrence within the normoglycaemic sub-population, which attributed for the majority of the Maltese population. In order to reduce the impact of mental health on the population, physicians may consider implementing depression screening clinical tools as part of their routine health check-ups at primary care level, irrespective of the glycaemic status of their patients.

Comorbidities, timing of treatments, and chemotherapy use influence outcomes in stage III colon cancer: A population-based European study

IntroductionFor stage III colon cancer (CC), surgery followed by chemotherapy is the main curative approach, although optimum times between diagnosis and surgery, and surgery and chemotherapy, have not been established. Materials and methodsWe analysed a population-based sample of 1912 stage III CC cases diagnosed in eight European countries in 2009–2013 aiming to estimate: (i) odds of receiving postoperative chemotherapy, overall and within eight weeks of surgery; (ii) risks of death/relapse, according to treatment, Charlson Comorbidity Index, time from diagnosis to surgery for emergency and elective cases, and time from surgery to chemotherapy; and (iii) time-trends in chemotherapy use. ResultsOverall, 97% of cases received surgery and 65% postoperative chemotherapy, with 71% of these receiving chemotherapy within eight weeks of surgery. Risks of death and relapse were higher for cases starting chemotherapy with delay, but better than for cases not given chemotherapy. Fewer patients with high comorbidities received chemotherapy than those with low (P < 0.001). Chemotherapy timing did not vary (P = 0.250) between high and low comorbidity cases. Electively-operated cases with low comorbidities received surgery more promptly than high comorbidity cases. Risks of death and relapse were lower for elective cases given surgery after four weeks than cases given surgery within a week. High comorbidities were always independently associated with poorer outcomes. Chemotherapy use increased over time. ConclusionsOur data indicate that promptly-administered postoperative chemotherapy maximizes its benefit, and that careful assessment of comorbidities is important before treatment. The survival benefit associated with slightly delayed elective surgery deserves further investigation.

Maternal education and language development at 2 years corrected age in children born very preterm: results from a European population-based cohort study

BackgroundSocioeconomic factors influence language development in the general population, but the association remains poorly documented in children born very preterm (VPT). We assessed the impact of maternal education on language...

The depression phenotype in a European population-based study

Abstract Introduction Depression is a growing public health concern and associated with a number of co-morbidities including diabetes mellitus. The aim was to estimate the prevalence of depression at a population level across different glycaemic statuses while establishing phenotypic characteristics of this sub-population. Methods A national representative cross-sectional study was conducted in Malta (2014-6). Participants were categorized into different sub-populations according to their glycaemic status. Depression prevalence rates and bio-socio-economic characteristics for each sub-population were established. Multiple regression analyses performed to identify links between glycaemic status and depression. Results Depression was prevalent in 17.15% of our study population (CI 95%: 16.01 - 18.36) with a female predominance. The normoglycaemic sub-population had the highest depression rates. Persons with known diabetes had a higher probability of having a history of depression (OR:2.36 CI 95%:1.12 - 4.96), as well as with being of female gender, having lower educational status, smoking tobacco and having established cardiovascular disease. Conclusions Depression was highly prevalent among the normoglycaemic population. Primary care physicians should implement a depression screening tool as part of their routine health check-ups, with special attention to those with cardiovascular co-morbidities and low socioeconomic status. Key messages Depression prevalent mostly in the normoglycemic population. Screening for depression should be part of routine health check-ups.

Epidemiology of Dandy-Walker Malformation in Europe: A EUROCAT Population-Based Registry Study

Background: Dandy-Walker (DW) malformation is a rare and severe congenital anomaly of the posterior fossa affecting the development of the cerebellum and the fourth ventricle. Objective: The aim of this study was to investigate the epidemiology of DW malformation, using data from the European population-based registries of congenital anomalies in the European Surveillance of Congenital Anomalies network. Methods: Anonymous individual data on cases of DW malformation diagnosed in 2002–2015 from 28 registries in 17 countries were included. Prevalence, prenatal detection rate, proportions and types of associated anomalies were estimated. Cases of DW variant were considered and analysed separately. Results: Out of 8,028,454 surveyed births we identified a total of 734 cases, including 562 DW malformation cases and 172 DW variant cases. The overall prevalence of DW malformation was 6.79 per 100,000 births (95% CI 5.79–7.96) with 39.2% livebirths, 4.3% foetal deaths from 20 weeks gestational age, and 56.5% terminations of pregnancy after prenatal diagnosis of foetal anomaly at any gestation (TOPFA). The livebirth prevalence was 2.74 per 100,000 births (95% CI 2.08–3.61). The prenatal detection rate was 87.6%. Two-hundred and seventy-three cases (48.6%) had an isolated cerebral anomaly and 24.2, 19.2 and 5.5% cases were associated with other structural non-cerebral anomalies, chromosomal anomalies and genetic syndromes respectively. The prevalence of DW variant was 2.08 per 100,000 (95% CI 1.39–3.13). Conclusions: This European population-based study provides the epidemiological profile of DW malformation. All birth outcomes were analysed and TOPFA represented more than half of the cases. About 50% of the cases of DW malformation were associated with other non-cerebral anomalies. Large populations and all birth outcomes are essential in epidemiological studies of rare and severe congenital anomalies.

Epidemiology of achondroplasia: A population-based study in Europe.

Achondroplasia is a rare genetic disorder resulting in short-limb skeletal dysplasia. We present the largest European population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network. All cases of achondroplasia notified to 28 EUROCAT registries (1991-2015) were included in the study. Prevalence, birth outcomes, prenatal diagnosis, associated anomalies, and the impact of paternal and maternal age on de novo achondroplasia were presented. The study population consisted of 434 achondroplasia cases with a prevalence of 3.72 per 100,000 births (95%CIs: 3.14-4.39). There were 350 live births, 82 terminations of pregnancy after prenatal diagnosis, and two fetal deaths. The prenatal detection rate was significantly higher in recent years (71% in 2011-2015 vs. 36% in 1991-1995). Major associated congenital anomalies were present in 10% of cases. About 20% of cases were familial. After adjusting for maternal age, fathers >34 years had a significantly higher risk of having infants with de novo achondroplasia than younger fathers. Prevalence was stable over time, but regional differences were observed. All pregnancy outcomes were included in the prevalence estimate with 80.6% being live born. The study confirmed the increased risk for older fathers of having infants with de novo achondroplasia.

Topical glucocorticoids and risk of type 2 diabetes mellitus.

A positive association between topical corticosteroid use and risk of type 2 diabetes mellitus has been reported in a large European population-based study. However, the increase in risk is small and should not influence the prescribing of topical corticosteroids when clinically indicated.