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Objectives To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity.Design Prospective multinational population based observational study.Setting 19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project.Participants 7336 infants born between 24+0 and 31+6 weeks’ gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission.Main outcome measures Combined use of four evidence based practices for infants born before 28 weeks’ gestation using an “all or none” approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital.Results Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants.Conclusions More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity.

ObjectiveExtrauterine growth restriction (EUGR) among very preterm infants is related to poor neurodevelopment, but lack of consensus on EUGR measurement constrains international research. Our aim was to compare EUGR prevalence in a European very preterm cohort using commonly used measures.DesignPopulation-based observational study.Setting19 regions in 11 European countries.Patients6792 very preterm infants born before 32 weeks’ gestational age (GA) surviving to discharge.Main outcome measuresWe investigated two measures based on discharge-weight percentiles with (1) Fenton and (2) Intergrowth (IG) charts and two based on growth velocity (1) birth weight and discharge-weight Z-score differences using Fenton charts and (2) weight-gain velocity using Patel’s model. We estimated country-level relative risks of EUGR adjusting for maternal and neonatal characteristics and associations with population differences in healthy newborn size, measured by mean national birth weight at 40 weeks’ GA.ResultsAbout twofold differences in EUGR prevalence were observed between countries for all indicators and these persisted after case-mix adjustment. Discharge weight <10th percentile using Fenton charts varied from 24% (Sweden) to 60% (Portugal) and using IG from 13% (Sweden) to 43% (Portugal), while low weight-gain velocity ranged from 35% (Germany) to 62% (UK). Mean term birth weight strongly correlated with both percentile-based measures (Spearman’s rho=−0.90 Fenton, −0.84 IG, p<0.01), but not Patel’s weight-gain velocity (rho: −0.38, p=0.25).ConclusionsVery preterm infants have a high prevalence of EUGR, with wide variations between countries in Europe. Variability associated with mean term birth weight when using common postnatal growth charts complicates international benchmarking.

ObjectiveTo 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.DesignArea-based cohort study of all births before 32 weeks of gestational age.Setting16 regions in 11 European countries in 2011/2012.PatientsSurvivors to discharge from neonatal care (n=6422).Main outcome measuresSevere 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.Results10.6% 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).ConclusionSevere neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.

ObjectiveTo investigate whether extrauterine growth restriction (EUGR) during the neonatal hospitalisation by sex among extremely preterm (EPT) infants is associated with cerebral palsy (CP) and cognitive and motor abilities at 5 years of age.Study designPopulation-based cohort of births <28 weeks of gestation with data from obstetric and neonatal records and parental questionnaires and clinical assessments at 5 years of age.Setting11 European countries.Patients957 EPT infants born in 2011–2012.Main outcomesEUGR at discharge from the neonatal unit was defined as (1) the difference between Z-scores at birth and discharge with <−2 SD as severe, −2 to −1 SD as moderate using Fenton’s growth charts (Fenton) and (2) average weight-gain velocity using Patel’s formula in grams (g) per kilogram per day (Patel) with <11.2 g (first quartile) as severe, 11.2–12.5 g (median) as moderate. Five-year outcomes were: a CP diagnosis, intelligence quotient (IQ) using the Wechsler Preschool and Primary Scales of Intelligence tests and motor function using the Movement Assessment Battery for Children, second edition.Results40.1% and 33.9% children were classified as having moderate and severe EUGR, respectively, by Fenton and 23.8% and 26.3% by Patel. Among children without CP, those with severe EUGR had lower IQ than children without EUGR (−3.9 points, 95% Confidence Interval (CI)=−7.2 to −0.6 for Fenton and −5.0 points, 95% CI=−8.2 to −1.8 for Patel), with no interaction by sex. No significant associations were observed between motor function and CP.ConclusionsSevere EUGR among EPT infants was associated with decreased IQ at 5 years of age.

Background Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. Methods We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N = 3635). Results Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks’ gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. Conclusions Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age.

ObjectivesTo develop research priorities on the consequences of very preterm (VPT) birth for the RECAP Preterm platform which brings together data from 23 European VPT birth cohorts.Design and settingThis study used a two-round modified Delphi consensus process. Round 1 was based on 28 research themes related to childhood outcomes (<12 years) derived from consultations with cohort researchers. An external panel of multidisciplinary stakeholders then ranked their top 10 themes and provided comments. In round 2, panel members provided feedback on rankings and on new themes suggested in round 1.ResultsOf 71 individuals contacted, 64 (90%) participated as panel members comprising obstetricians, neonatologists, nurses, general and specialist paediatricians, psychologists, physiotherapists, parents, adults born preterm, policy makers and epidemiologists from 17 countries. All 28 initial themes were ranked in the top 10 by at least six panel members. Highest ranking themes were: education (73% of panel members' top 10 choices); care and outcomes of extremely preterm births, including ethical decisions (63%); growth and nutrition (60%); emotional well-being and social inclusion (55%); parental stress (55%) and impact of social circumstances on outcomes (52%). Highest ranking themes were robust across panel members classified by background. 15 new themes had at least 6 top 10 endorsements in round 2.ConclusionsThis study elicited a broad range of research priorities on the consequences of VPT birth, with good consensus on highest ranks between stakeholder groups. Several highly ranked themes focused on the socioemotional needs of children and parents, which have been less studied.

BackgroundInnovation is important to improve patient care, but few studies have explored the factors that initiate change in healthcare organizations.MethodsAs part of the European project EPICE on evidence-based perinatal care, we carried out semi-structured interviews (N = 44) with medical and nursing staff from 11 randomly selected neonatal intensive care units in 6 countries. The interviews focused on the most recent clinical or organizational change in the unit relevant to the care of very preterm infants. Thematic analysis was performed using verbatim transcripts of recorded interviews.ResultsReported changes concerned ventilation, feeding and nutrition, neonatal sepsis, infant care, pain management and care of parents. Six categories of drivers to change were identified: availability of new knowledge or technology; guidelines or regulations from outside the unit; need to standardize practices; participation in research; occurrence of adverse events; and wish to improve care. Innovations originating within the unit, linked to the availability of new technology and seen to provide clear benefit for patients were more likely to achieve consensus and rapid implementation.ConclusionsInnovation can be initiated by several drivers that can impact on the success and sustainability of change.

Correspondence to Anna-Veera Seppänen, Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, Inserm, INRA, F-75004 Paris, France; anna-veera.seppanen@inserm.fr Follow-up programmes aim to detect neurodevelopmental and health problems and enable early interventions for children born very preterm (<32 weeks of gestational age (GA)). The data were collected for the Effective Perinatal Intensive care in Europe and Screening to Improve Health in Very Preterm Infants studies, which constituted and followed up an area-based cohort of children born very preterm in 2011/2012 in 19 regions across 11 European countries.4 Perinatal data were collected from obstetric and neonatal records, and parents completed questionnaires at 2 and 5 years of age. Adjustments for social and perinatal characteristics failed to explain differences between countries.Table 1 Family sociodemographic and perinatal factors associated with routine follow-up for children born very preterm, at 5 years of age Does child have routine check-ups for children born very preterm at 5 years? N No, never Not anymore Yes, still Reference: still in follow-up at 5 years No, never Not anymore % % % aRRR 95% CI aRRR 95% CI Mother’s age at delivery (years)  ≤24 422 17.3 55.2 27.5 2.0 1.2 to 3.5 1.1 0.8 to 1.6  25–34 2057 9.2 63.0 27.8 ref ref  ≥35 1098 6.8 67.2 26.0 0.7 0.5 to 1.2 1.0 0.8 to 1.3 Parity at delivery  Multiparous 2156 8.3 63.6 28.1 ref ref  Nulliparous 1390 11.2 62.7 26.1 1.1 0.7 to 1.6 1.0 0.8 to 1.2 Multiple birth  No (singleton) 2531 10.6 62.0 27.4 ref ref  Yes (twins or more) 1056 7.5 65.4 27.1 0.5 0.3 to 0.9 1.0 0.7 to 1.2 Mother’s educational level  Lower (ISCED levels 0–2: lower secondary or lower) 589 13.7 58.9 27.4 2.0 1.1 to 3.5 0.9 0.7 to 1.3  Intermediate (ISCED levels 3–5: upper or post-secondary, non-tertiary or short cycle tertiary) 1474 9.7 64.0 26.3 1.4 0.9 to 2.2 0.8 0.7 to 1.1  Higher (ISCED levels 6–8: bachelor degree or higher) 1478 6.3 66.3 27.4 Ref Ref Country of birth  Native 2857 8.9 63.5 27.6 Ref Ref  European born 238 7.7 63.9 28.4 0.9 0.4 to 2.0 0.8 0.5 to 1.2  Born outside Europe 476 13.3 61.9 24.9 2.5 1.4 to 4.2 1.4 1.0 to 1.9 GA, completed weeks  <26 305 5.5 53.9 40.6 0.2 0.1 to 0.4 0.3 0.2 to 0.5  26–27 657 6.0 54.2 39.9 0.2 0.1 to 0.4 0.5 0.4 to 0.6  28–29 937 6.3 66.1 27.6 0.3 0.2 to 0.5 0.7 0.6 to 0.9  30–31 1688 13.8 66.2 20.0 Ref Ref Small for GA**  <3 centile 766 7.7 62.0 30.2 0.5 0.3 to 0.7 0.7 0.5 to 0.9  3–9 centile 417 11.0 59.3 29.6 1.0 0.6 to 1.6 0.7 0.5 to 0.9  >10 centile 2404 10.2 63.8 26.0 Ref Ref Severe neonatal morbidity††  No 3141 10.4 63.5 26.1 Ref Ref  Yes 365 5.0 57.7 37.3 0.5 0.2 to 1.1 0.9 0.7 to 1.3 Bronchopulmonary dysplasia  No 3034 10.7 64.4 24.9 Ref Ref  Yes 466 3.8 53.8 42.4 0.4 0.2 to 0.8 0.6 0.5 to 0.9 Congenital anomaly  No 3292 9.9 62.7 27.4 Ref Ref  Yes 295 8.5 65.5 26.0 0.6 0.3 to 1.2 0.9 0.6 to 1.2 Child sex  Male 1914 10.0 59.3 30.7 0.9 0.6 to 1.3 0.7 0.6 to 0.9  Female 1673 9.4 67.1 23.5 Ref Ref Country (region) (ref sample mean) (ref sample mean)  Portugal (Lisbon, Northern Region) 425 4.8 36.8 58.4 0.6 0.3 to 1.2 0.2 0.1 to 0.2  Belgium (Flanders) 259 12.8 40.5 46.7 3.6 2.0 to 6.3 0.3 0.2 to 0.4  Netherlands (Central Eastern) 146 6.3 52.2 41.5 1.7 0.7 to 4.1 0.5 0.3 to 0.7  France (Burgundy, Ile-de-France, Northern Region) 770 10.3 58.6 31.2 3.0 1.9 to 4.6 0.6 0.5 to 0.8  Denmark (Eastern Region) 151 10.8 62.5 26.7 6.3 2.9 to 13.8 0.9 0.6 to 1.4  Sweden (Greater Stockholm) 141 2.8 70.7 26.6 1.1 0.2 to 6.3 1.0 0.7 to 1.5  UK (East Midlands, Northern, Yorkshire and the Humber) 419 13.6 69.4 17.0 10.9 6.1 to 19.4 1.9 1.4 to 2.7  Germany (Hesse, Saarland) 266 21.5 65.4 13.0 21.1 11.3 to 39.4 1.9 1.2 to 3.1  Estonia (entire country) 133 0.0 87.2 12.8 0.0 0.0 to 0.0 2.6 1.6 to 4.2  Italy (Emilia-Romagna, Lazio, Marche) 691 4.5 83.2 12.3 4.5 2.3 to 8.7 2.5 1.9 to 3.3  Poland (Wielkopolska) 186 13.4 75.7 10.9 18.9 9.4 to 38.3 2.9 1.8 to 4.8 Inverse probability weights after multiple imputation were used for all analyses. *Using intrauterine charts modelled for the Effective Perinatal Intensive care in Europe cohort. †Intraventricular haemorrhage grades III and IV, cystic periventricular leucomalacia, retinopathy of prematurity stages III–V or necrotising enterocolitis needing surgery. aRRR, adjusted relative risk ratio; GA, gestational age; ISCED, International Standard Classification of Education. France: French National Institute of Public Health Research (IRESP TGIR 2009–01 programme)/Institute of Public Health and its partners (the French Health Ministry, the National Institute for Health and Medical Research), the National Institute of Cancer and the National Solidarity Fund for Autonomy), the National Research Agency through the French EQUIPEX programme of investments for the future (grant

Background Motor disorders resulting from extremely preterm birth (EPT; <28 weeks’ gestation) can limit daily activities, schooling and social relationships. Cerebral palsy (CP) affects about 10% of children and non-CP movement difficulties (MD) are highly prevalent, although they tend to be under-diagnosed, especially in children without other developmental difficulties. We investigated the association between motor disorders and health-related quality of life (HRQoL) among five-year-old children born EPT. Methods We included children at age five from a population-based EPT birth cohort born in 2011-2012 in 11 European countries (N = 1,021). Children without CP were classified using the Movement Assessment Battery for Children - 2nd edition as having significant MD (≤5th percentile of standardised norms) or being at risk of MD (6th-15th percentile). Parents reported on CP diagnoses and HRQoL using the Pediatric Quality of Life InventoryTM. We used linear regression to compare HRQoL scores by motor status adjusting for social characteristics. Results Children born EPT with CP, significant MD and at risk of MD had lower adjusted HRQoL total scores [95% confidence intervals] than those without MD: -26.1 [-31.0; -21.2], -9.1 [-12.0; -6.1] and -5.0 [-7.7; -2.3]. Decreases were greater for physical scores: -35.3 [-42.7; -27.9], -11.9 [-16.1; -7.8] and -5.4 [-9.1; -1.6] than psychosocial scores: -20.6 [-25.2; -16.0], -7.4 [-10.3; -4.5] and -4.9 [-7.6; -2.1]. These differences persisted after exclusion of children with other developmental difficulties. Conclusions Motor disorders among 5-year-old children born EPT were associated with lower HRQoL, even among children with less severe motor difficulties and without other developmental difficulties. Key messages Among five-year-old children born extremely preterm, severity level of motor disorders was associated with reductions of their health-related quality of life. Differences persisted after exclusion of children with other developmental difficulties and among children not receiving motor-related health care services had lower health-related quality of life.

Abstract Background There is an ongoing debate about the best practices to handle mother's own milk (MOM) for infants born very preterm (VPT, ≤32 weeks of gestation), specifically to prevent the human cytomegalovirus (HCMV) transmission and bacterial contamination of expressed MOM. Thus, we aimed to compare practices for managing MOM for VPT infants in European neonatal intensive care units (NICUs). Methods Data were collected as part of the EPICE (Effective Perinatal Intensive Care in Europe) study which explored the use of evidence-based practices for the care of VPT infants in 11 European countries. Structured questionnaires were sent to the head of all participating NICUs with at least 10 VPT admissions. Of the eligible 135 NICUs, 134 replied. Results A written protocol for breastfeeding/human milk use was available in 91% of the NICUs. Overall, 34% used human bank milk for all VPT infants whose mothers did not express and 56% reported using fresh MOM without restrictions regarding minimum gestational age, birth weight or risk of HCMV transmission (country range: 0-100%). In 22% of units all VPT infants received MOM pasteurized (country range: 0-73%). HCMV serology on all mothers who express their milk was not required in 71% of units (country range: 7-100%). Among NICUs that performed HCMV serology, 3% provided untreated fresh MOM and 23.5% formula in the case of positive mothers. Systematic bacteriological analyses of MOM were not performed in 76% NICUs (country range: 29-100%) while less than 10% did it for the first milk feeding, 7% every week and 8% with another frequency. Conclusions There are large variations in managing MOM across countries, which could reflect differences in regulations or guidelines, and among the same country NICUs, revealing that different options can operate locally. This variability suggests substantial differences in attitudes about what constitutes best practices among European neonatologists. Key messages We found significant differences across and within European countries for managing MOM for VPT infants suggesting lack of strong recommendations at the international and national level. There is wide variation in what European neonatologists consider best practices. To guide practice and not jeopardise VPT infants from MOM we need strong evidence-based data.