Duration and Time Trends in Hospital Stay for Very Preterm Infants Differ Across European Regions

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New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study

Objectives: Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA), a fatal progressive neurodegenerative disorder associated with autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the clinical spectrum of OH in a large European cohort of patients with MSA and (2) to investigate whether a prolonged postural challenge increases the sensitivity to detect OH in MSA. Methods: Assessment of OH during a 10 min orthostatic test in 349 patients with MSA from seven centres of the European MSA-Study Group (age: 63.6±8.8 years; disease duration: 4.2±2.6 years). Assessment of a possible relationship between OH and MSA subtype (P with predominant parkinsonism or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS) scores and drug intake. Results: 187 patients (54%) had moderate (>20 mm Hg (systolic blood pressure (SBP)) and/or >10 mm Hg (diastolic blood pressure (DBP)) or severe OH (>30 mm Hg (SBP) and/or >15 mm Hg (DBP)) within 3 min and 250 patients (72%) within 10 min. OH magnitude was significantly associated with disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and supine hypertension. OH severity was not associated with MSA subtype. Drug intake did not differ according to OH magnitude except for antihypertensive drugs being less frequently, and antihypotensive drugs more frequently, prescribed in severe OH. Conclusions: This is the largest study of OH in patients with MSA. Our data suggest that the sensitivity to pick up OH increases substantially by a prolonged 10 min orthostatic challenge. These results will help to improve OH management and the design of future clinical trials.Fil: Pavy Le Traon, Anne. University Hospital of Toulouse; Francia. Inserm; FranciaFil: Piedvache, A.. Université Paul Sabatier; FranciaFil: Pérez Lloret, Santiago. University Hospital of Toulouse; Francia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Calandra Buonara, G.. Università di Bologna; Italia. Istituto delle Scienze Neurologiche di Bologna; ItaliaFil: Cochen De Cock, V.. University Hospital of Toulouse; Francia. University of Montpellier; FranciaFil: Colosimo, C.. Sapienza Università di Roma; ItaliaFil: Cortelli, P.. Università di Bologna; Italia. Istituto delle Scienze Neurologiche di Bologna; ItaliaFil: Debs, R.. University Hospital of Toulouse; FranciaFil: Duerr, S.. Universidad de Innsbruck; AustriaFil: Fanciulli, A.. Universidad de Innsbruck; AustriaFil: Foubert Samier, A.. Centre Hospitalier Universitaire de Bordeaux; Francia. Universite de Bordeaux; FranciaFil: Gerdelat, Angela. University Hospital of Toulouse; FranciaFil: Gurevich, T.. Tel-Aviv University; IsraelFil: Krismer, F.. Universidad de Innsbruck; AustriaFil: Poewe, W.. Universidad de Innsbruck; AustriaFil: Tison, Francois. Universite de Bordeaux; Francia. Centre Hospitalier Universitaire de Bordeaux; FranciaFil: Tranchant, C.. University Hospital Hautepierre; FranciaFil: Wenning, G.. Universidad de Innsbruck; AustriaFil: Meissner, Wassilios G.. Universite de Bordeaux; Francia. Centre Hospitalier Universitaire de Bordeaux; FranciaFil: Rascol, Olivier. University Hospital of Toulouse; Franci

Association of Short Antenatal Corticosteroid Administration-to-Birth Intervals With Survival and Morbidity Among Very Preterm Infants: Results From the EPICE Cohort

Administration-to-birth intervals of antenatal corticosteroids (ANS) vary. The significance of this variation is unclear. Specifically, to our knowledge, the shortest effective administration-to-birth interval is unknown. Objective:To explore the associations between ANS administration-to-birth interval and survival and morbidity among very preterm infants. Design, Setting, and Participants: The Effective Perinatal Intensive Care in Europe (EPICE) study, a population-based prospective cohort study, gathered data from 19 regions in 11 European countries in 2011 and 2012 on 4594 singleton infants with gestational ages between 24 and 31 weeks, without severe anomalies and unexposed to repeated courses of ANS. Data were analyzed November 2016. Exposure: Time from first injection of ANS to delivery in hours and days. Main Outcomes and Measures: Three outcomes were studied: in-hospital mortality; a composite of mortality or severe neonatal morbidity, defined as an intraventricular hemorrhage grade of 3 or greater, cystic periventricular leukomalacia, surgical necrotizing enterocolitis, or stage 3 or greater retinopathy of prematurity; and severe neonatal brain injury, defined as an intraventricular hemorrhage grade of 3 or greater or cystic periventricular leukomalacia. Results: Of the 4594 infants included in the cohort, 2496 infants (54.3%) were boys, and the mean (SD) gestational age was 28.5 (2.2) weeks and mean (SD) birth weight was 1213 (400) g. Mortality for the 662 infants (14.4%) unexposed to ANS was 20.6% (136 of 661). Administration of ANS was associated with an immediate and rapid decline in mortality, reaching a plateau with more than 50% risk reduction after an administration-to-birth interval of 18 to 36 hours. A similar pattern for timing was seen for the composite mortality or morbidity outcome, whereas a significant risk reduction of severe neonatal brain injury was associated with longer administration-to-birth intervals (greater than 48 hours). For all outcomes, the risk reduction associated with ANS was transient, with increasing mortality and risk for severe neonatal brain injury associated with administration-to-birth intervals exceeding 1 week. Under the assumption of a causal relationship between timing of ANS and mortality, a simulation of ANS administered 3 hours before delivery to infants who did not receive ANS showed that their estimated decline in mortality would be 26%. Conclusions and Relevance:Antenatal corticosteroids may be effective even if given only hours before delivery. Therefore, the infants of pregnant women at risk of imminent preterm delivery may benefit from its use.The research received funding from grant agreement 259882 from the European Union Seventh Framework Program (2007-2013). Additional funding in France was provided by the French Institute of Public Health Research/Institute of Public Health and its partners, including the French Health Ministry, the National Institute of Health and Medical Research, the National Institute of Cancer, and the National Solidarity Fund for Autonomy, by grant ANR-11-EQPX-0038 from the National Research Agency through the French Equipex Program of Investments in the Future, and by the PremUp Foundation; in Poland, by 2012-2015 allocation of funds for international projects from the Polish Ministry of Science and HigherEducation; and in Sweden, by regional agreementon medical training and clinical research betweenStockholm County Council and Karolinska Institutetand by the Department of Neonat al Medicine at theKarolinska University Hospital

Low breastfeeding continuation to 6 months for very preterm infants: A European multiregional cohort study

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Duration and time trends in hospital stay for very preterm infants differ across European regions*

Objectives: To compare duration and changes over time in length of hospital stay for very preterm and extremely preterm infants in 10 European regions.Design: Two area-based cohort studies from the same regions in 2003 and 2011/2012.Setting: Ten regions from nine European countries.Patients: Infants born between 22 + 0 and 31 + 6 weeks of gestational age and surviving to discharge (Models of Organising Access to Intensive Care for Very Preterm Births cohort in 2003, n = 4,011 and Effective Perinatal Intensive Care in Europe cohort in 2011/2012, n = 4,336).Interventions: Observational study, no intervention.Measurements and Main Results: Maternal and infant characteristics were abstracted from medical records using a common protocol and length of stay until discharge was adjusted for case-mix using negative binomial regression. Mean length of stay was 63.6 days in 2003 and varied from 52.4 to 76.5 days across regions. In 2011/2012, mean length of stay was 63.1 days, with a narrower regional range (54.0-70.1). Low gestational age, small for gestational age, low 5-minute Apgar score, surfactant administration, any surgery, and severe neonatal morbidities increased length of stay. Infant characteristics explained some of the differences between regions and over time, but large variations remained after adjustment. In 2011/2012, mean adjusted length of stay ranged from less than 54 days in the Northern region of the United Kingdom and Wielkopolska, Poland to over 67 days in the Ile-de-France region of France and the Eastern region of the Netherlands. No systematic decrease in very preterm length of stay was observed over time after adjustment for patient case-mix.Conclusions: A better understanding of the discharge criteria and care practices that contribute to the wide differences in very preterm length of stay across European regions could inform policies to optimize discharge decisions in terms of infant outcomes and health system costs.</br

Wide variation in severe neonatal morbidity among very preterm infants in European regions

Objective To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates. Design Area-based cohort study of all births before 32 weeks of gestational age. Setting 16 regions in 11 European countries in 2011/2012. Patients Survivors to discharge from neonatal care (n=6422). Main outcome measures Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics. Results 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%–23.5%) and 13.8% including severe BPD (regional range 10.0%–23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%–18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50). Conclusion Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.The research leading to these results received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n°259882. Additional funding is acknowledge from the following regions: France (French Institute of Public Health Research/Institute of Public Health and its partners the French Health Ministry, the National Institute of Health and Medical Research, the National Institute of Cancer, and the National Solidarity Fund for Autonomy; grant ANR-11-EQPX-0038 from the National Research Agency through the French Equipex Program of Investments in the Future; and the Prem Up Foundation); Poland (2012- 2015 allocation of funds for international projects from the Polish Ministry of Science and Higher Education); Sweden (Stockholm County Council (ALF-project and Clinical Research Appointment) and by the Department of Neonatal Medicine, Karolinska University Hospital), UK (funding for The Neonatal Survey from Neonatal Networks for East Midlands and Yorkshire and Humber regions)

Wide variation in severe neonatal morbidity among very preterm infants in European regions

Objective: To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates.Design: Area-based cohort study of all births before 32 weeks of gestational age.Setting: 16 regions in 11 European countries in 2011/2012.Patients: Survivors to discharge from neonatal care (n=6422).Main outcome measures: Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades &gt;= 3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics.Results: 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%23.5%) and 13.8% including severe BPD (regional range 10.0%-23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P&lt; 0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P= 0.50).Conclusion: Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.</br

EPICE cohort: Two year neurodevelopmental outcomes after very preterm birth.

Objective: to determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm birth (VPT) cohort using a standardised approach to neurodevelopmental assessment at two years of age. Design: Prospective standardised cohort study. Setting: 15 regions in 10 European countries. Patients: VPT births: 22+0-31+6 weeks of gestation. Data collection: standardised data collection tools relating to pregnancy, birth and neonatal care and developmental outcomes at 2 years corrected age using a validated parent completed questionnaire. Main outcome measures: Crude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models. Results: Parent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2% to 26.1% between regions grouped by country) with crude standardised prevalence ratios ranging from 0.60 to 1.53. Adjustment for population, maternal and infant factors resulted in a small reduction in the overall variation (ranging from 0.65 to 1.30). Conclusion: There is wide variation in the rates of moderate to severe neurodevelopmental impairment for VPT cohorts across Europe, much of which persists following adjustment for known population, maternal and infant factors. Further work is needed to investigate whether other factors including quality of care and evidence based practice have an effect on neurodevelopmental outcomes for these chil