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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 explore international variations in the management and survival of extremely low gestational age and birthweight births.DesignArea-based prospective cohort of birthsSetting12 regions across Belgium, France, Italy, Portugal and the UKParticipants1449 live births and fetal deaths between 22+0 and 25+6 weeks gestation born in 2011–2012.Main outcome measuresPercentage of births; recorded live born; provided antenatal steroids or respiratory support; surviving to discharge (with/without severe morbidities).ResultsThe percentage of births recorded as live born was consistently low at 22 weeks and consistently high at 25 weeks but varied internationally at 23 weeks for those weighing 500 g and over (range 33%–70%) and at 24 weeks for those under 500 g (range 5%–71%). Antenatal steroids and provision of respiratory support at 22–24 weeks gestation varied between countries, but were consistently high for babies born at 25 weeks. Survival to discharge was universally poor at 22 weeks gestation (0%) and at any gestation with birth weight <500 g, irrespective of treatment provision. In contrast, births at 23 and 24 weeks weighing 500 g and over showed significant international variation in survival (23 weeks: range: 0%–25%; 24 weeks range: 21%–50%), reflecting levels of treatment provision.ConclusionsWide international variation exists in the management and survival of extremely preterm births at 22–24 weeks gestation. Universally poor outcomes for babies at 22 weeks and for those weighing under 500 g suggest little impact of intervention and support the inclusion of birth weight along with gestational age in ethical decision-making guidelines.

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.

ObjectiveTo determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 years of age.DesignProspective standardised cohort study.Setting15 regions in 10 European countries.PatientsVPT births: 22+0–31+6 weeks of gestation.Data collectionStandardised 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 measuresCrude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models.ResultsParent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2%–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).ConclusionThere 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 children.

Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0·95 (95% CI 0·88–1·03), of death or severe adverse neurological event 1·00 (0·88–1·13), or any of these outcomes 0·98 (0·91–1·05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. Nestlé Belgium, Belgian Red Cross, and Dräger International.

Importance The Apgar score is used worldwide as an assessment tool to estimate the vitality of newborns in their first minutes of life. Its applicability to estimate neurodevelopmental outcomes in infants born extremely preterm (EPT; <28 weeks’ gestation) is not well established. Objective To investigate the association between the Apgar score and neurodevelopmental outcomes in infants born EPT. Design, Setting, and Participants This cohort study was conducted using data from the Effective Perinatal Intensive Care in Europe-Screening to Improve Health in Very Preterm Infants in Europe (EPICE-SHIPS) study, a population-based cohort in 19 regions of 11 European countries in 2011 to 2012. Clinical assessments of cognition and motor function at age 5 years were performed in infants born EPT and analyzed in January to July 2023. Exposures Apgar score at 5 minutes of life categorized into 4 groups (0-3, 4-6, 7-8, and 9-10 points). Main Outcomes and Measures Cognitive and motor outcomes were assessed using the Wechsler Preschool and Primary Scale of Intelligence test of IQ derived from locally normed versions by country and the Movement Assessment Battery for Children–Second Edition. Parents additionally provided information on communication and problem-solving skills using the Ages and Stages Questionnaire, third edition (ASQ-3). All outcomes were measured as continuous variables. Results From the total cohort of 4395 infants born EPT, 2522 infants were live born, 1654 infants survived to age 5 years, and 996 infants (478 females [48.0%]) followed up had at least 1 of 3 outcome measures. After adjusting for sociodemographic variables, perinatal factors, and severe neonatal morbidities, there was no association of Apgar score with IQ, even for scores of 3 or less (β = −3.3; 95% CI, −10.5 to 3.8) compared with the score 9 to 10 category. Similarly, no association was found for ASQ-3 (β = −2.1; 95% CI, −24.6 to 20.4). Congruent results for Apgar scores of 3 or less were obtained for motor function scores for all children (β = −4.0; 95% CI, −20.1 to 12.1) and excluding children with a diagnosis of cerebral palsy (β = 0.8, 95% CI −11.7 to 13.3). Conclusions and Relevance This study found that low Apgar scores were not associated with longer-term outcomes in infants born EPT. This finding may be associated with high interobserver variability in Apgar scoring, reduced vitality signs and poorer responses to resuscitation after birth among infants born EPT, and the association of more deleterious exposures in the neonatal intensive care unit or of socioeconomic factors with greater changes in outcomes during the first 5 years of life.

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.

This study evaluated whether the early use of high frequency ventilation (HFV) decreased the incidence of oxygen dependency at 36 weeks postconceptual age [chronic lung disease (CLD)] and improved developmental outcome. Neonates of less than 32 weeks gestational age needing ventilatory support for RDS who were admitted to a tertiary academic neonatal intensive care unit (NICU) within 6 h of birth were included in a prospective controlled clinical trial. With randomisation they were given either HFV (n=147) or conventional ventilation (CV) (n=153). As a primary outcome variable, ventilator and/or oxygen dependence at a postconceptual age of 36 weeks (CLD) was measured. Secondary outcome variables were: mortality at discharge, treatment failure, ventilator and/or oxygen dependence at 28-30 days (bronchopulmonary disease [BPD]), duration of ventilation, use of surfactant, days in oxygen and on continuous positive airway pressure (CPAP), survival without BPD or CLD, air leak, intracranial haemorrhages (ICH) grades 3 and 4, periventricular leukomalacia (PVL) grades 1 and 2, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), necrotising enterocolitis (NEC), developmental outcome at 7 to 12 months and if necessary at 18-24 months corrected age. The results showed that CLD (16.3 vs. 12.4%), BPD (33.3 vs. 36.6%), early cerebral abnormalities, mortality at discharge (17.2 vs. 13.2%), failure rate (11.6 vs. 6.5%) and motor and mental developmental outcome at a corrected age of 18 to 24 months (p>0.05) did not differ between the two groups. Under the present study design HFV compared with CV did not decrease chronic lung disease and no developmental outcome differences could be found at a corrected age of almost 2 years.