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.

Variation in term birthweight across European countries affects the prevalence of small for gestational age among very preterm infants.

AIM: This study assessed the prevalence of small for gestational age (SGA) among very preterm (VPT) infants using national and European intrauterine references. METHODS: We generated country-specific and common European intrauterine growth references for 11 European countries, according to Gardosi's approach and Hadlock's foetal growth model, using national data on birthweights by sex. These references were applied to the Effective Perinatal Intensive Care in Europe (EPICE) cohort, which comprised 7766 live VPT births without severe congenital anomalies under 32 weeks of gestation in 2011-2012, to estimate the prevalence of infants with SGA birthweights, namely those below the 10th percentile. RESULTS: The SGA prevalence was 31.8% with country-specific references and 34.0% with common European references. The European references yielded a 10-point difference in the SGA prevalence between countries with lower term birthweights (39.9%) - Portugal, Italy and France - and higher term birthweights, namely Denmark, the Netherlands, Sweden (28.9%; p < 0.001). This was not observed with country-specific references, where the respective figures were 32.4% and 33.9% (p = 0.34), respectively. CONCLUSION: One-third of VPT infants were SGA according to intrauterine references. Common European references showed significant differences in SGA prevalence between countries with high and low-term birthweights.

Clinical prediction models for bronchopulmonary dysplasia: a systematic review and external validation study.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD. METHODS: We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities. RESULTS: We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration. CONCLUSIONS: External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation.

Postnatal growth restriction and neurodevelopment at 5 years of age: a European extremely preterm birth cohort study.

OBJECTIVE: To 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 DESIGN: Population-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. SETTING: 11 European countries. PATIENTS: 957 EPT infants born in 2011-2012. MAIN OUTCOMES: EUGR 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. RESULTS: 40.1% 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. CONCLUSIONS: Severe EUGR among EPT infants was associated with decreased IQ at 5 years of age.

Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Nestlé Belgium, Belgian Red Cross, and Dräger International.

Association between postnatal growth and neurodevelopmental impairment by sex at 2 years of corrected age in a multi-national cohort of very preterm children.

BACKGROUND & AIMS: Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) infants and has been associated with impaired neurodevelopment. Some research suggests that adverse effects of EUGR may be more severe in boys. We investigated EUGR and neurodevelopment at 2 years of corrected age (CA) by sex in a VPT birth cohort. METHODS: Data come from a population-based cohort of children born <32 weeks' gestation from 11 European countries and followed up at 2 years CA. Postnatal growth during the neonatal hospitalization was measured with: (1) birthweight and discharge-weight Z-score differences using Fenton charts (2) weight-gain velocity using Patel's model. Published cut-offs were used to define EUGR as none, moderate or severe. Neurodevelopmental impairment was assessed using a parent-report questionnaire, with standardized questions/instruments on motor function, vision, hearing and non-verbal cognition. We estimated relative risks (RR) adjusting for maternal and neonatal characteristics overall and by sex. RESULTS: Among 4197 infants, the prevalence of moderate to severe impairment at 2 years CA was 17.7%. Severe EUGR was associated with neurodevelopmental impairment in the overall sample and the interaction with sex was significant. For boys, adjusted RR were 1.57 (95% Confidence Intervals (CI): 1.18-2.09) for Fenton's delta Z-score and 1.50 (95% CI: 1.12-2.01) for Patel's weight-gain velocity, while for girls they were 0.97 (0.76-1.22) and 1.12 (0.90-1.40) respectively. CONCLUSION: EUGR was associated with poor neurodevelopment at 2 years among VPT boys but not girls. Understanding why boys are more susceptible to the effects of poor growth is needed to develop appropriate healthcare strategies.

Impact of fetal growth restriction on mortality and morbidity in a very preterm birth cohort.

OBJECTIVE: To assess the impact of being small for gestational age (SGA) on very preterm mortality and morbidity rates by using different birthweight percentile thresholds and whether these effects differ by the cause of the preterm birth. STUDY DESIGN: The study included singletons and twins alive at onset of labor between 24 and 31 weeks of gestation without congenital anomalies from the Models of Organising Access to Intensive Care for very preterm births very preterm cohort in 10 European regions in 2003 (n = 4525). Outcomes were mortality, intraventricular hemorrhage grade III and IV, cystic periventricular leukomalacia, and bronchopulmonary dysplasia (BPD). Birthweight percentiles in 6 classes were analyzed by pregnancy complication. RESULTS: The mortality rate was higher for infants with birthweights <25th percentile when compared with the 50th to 74th percentile (adjusted odds ratio, 3.98 [95% CI, 2.79-5.67] for <10th; adjusted odds ratio, 2.15 [95% CI, 1.54-3.00] for 10th-24th). BPD declined continuously with increasing birthweight. There was no association for periventricular leukomalacia or intraventricular hemorrhage. Seventy-five percent of infants with birthweights <10th percentile were from pregnancies complicated by hypertension or indicated deliveries associated with growth restriction. However, stratifying for pregnancy complications yielded similar risk patterns. CONCLUSIONS: A 25th percentile cutoff point was a means of identifying infants at higher risk of death and a continuous measure better described risks of BPD. Lower birthweights were associated with poor outcomes regardless of pregnancy complications.

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 (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 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%-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 children.

Screening for inter-hospital differences in cesarean section rates in low-risk deliveries using administrative data: an initiative to improve the quality of care.

BACKGROUND: Rising national cesarean section rates (CSRs) and unexplained inter-hospital differences in CSRs, led national and international bodies to select CSR as a quality indicator. Using hospital discharge abstracts, we aimed to document in Belgium (1) inter-hospital differences in CSRs among low risk deliveries, (2) a national upward CSR trend, (3) lack of better neonatal outcomes in hospitals with high CSRs, and (4) possible under-use of CS. METHODS: We defined a population of low risk deliveries (singleton, vertex, full-term, live born, <4500 g, >2499 g). Using multivariable logistic regression techniques, we provided degrees of evidence regarding the observed departure ([relative risk-1]*100) of each hospital (N = 107) from the national CSR and its trend. To determine a benchmark, we defined three CSR groups (high, average and low) and compared them regarding 1 minute Apgar scores and other neonatal endpoints. An anonymous feedback is provided to the hospitals, the College of Physicians (with voluntary disclosure of the outlying hospitals for quality improvement purposes) and to the policy makers. RESULTS: Compared with available information, the completeness and accuracy of the data, regarding the variables selected to determine our study population, showed adequate. Important inter-hospital differences were found. Departures ranged from -65% up to +75%, and 9 "high CSR" and 13 "low CSR" outlying hospitals were identified. We observed a national increasing trend of 1.019 (95%CI [1.015; 1.022]) per semester, adjusted for age groups. In the "high CSR" group 1 minute Apgar scores <4 were over-represented in the subgroup of vaginal deliveries, suggesting CSs not carried out for medical reasons. Under-use of CS was also observed. Given their questionable completeness, except Apgar scores, our neonatal results, showing a significant association of CS with adverse neonatal endpoints, are to be cautiously interpreted. Taking the available evidence into account, the "Average CSR" group seemed to be the best benchmark candidate. CONCLUSION: Rather than firm statements about quality of care, our results are to be considered a useful screening. The inter-hospital differences in CSR, the national CS upward trend, the indications of over-use and under-use, the geographically different obstetric patterns and the admission day-related concentration of deliveries, whether or not by CS, may trigger initiatives aiming at improving quality of care.

Variability in the management and outcomes of extremely preterm births across five European countries: a population-based cohort study.

OBJECTIVE: To explore international variations in the management and survival of extremely low gestational age and birthweight births. DESIGN: Area-based prospective cohort of births SETTING: 12 regions across Belgium, France, Italy, Portugal and the UK PARTICIPANTS: 1449 live births and fetal deaths between 22+0 and 25+6 weeks gestation born in 2011-2012. MAIN OUTCOME MEASURES: Percentage of births; recorded live born; provided antenatal steroids or respiratory support; surviving to discharge (with/without severe morbidities). RESULTS: The 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. CONCLUSIONS: Wide 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.

Variability in Very Preterm Stillbirth and In-Hospital Mortality Across Europe.

BACKGROUND AND OBJECTIVE: Stillbirth and in-hospital mortality rates associated with very preterm births (VPT) vary widely across Europe. International comparisons are complicated by a lack of standardized data collection and differences in definitions, registration, and reporting. This study aims to determine what proportion of the variation in stillbirth and in-hospital VPT mortality rates persists after adjusting for population demographics, case-mix, and timing of death. METHODS: Standardized data collection for a geographically defined prospective cohort of VPTs (22+0-31+6 weeks gestation) across 16 regions in Europe. Crude and adjusted stillbirth and in-hospital mortality rates for VPT infants were calculated by time of death by using multinomial logistic regression models. RESULTS: The stillbirth and in-hospital mortality rate for VPTs was 27.7% (range, 19.9%-35.9% by region). Adjusting for maternal and pregnancy characteristics had little impact on the variation. The addition of infant characteristics reduced the variation of mortality rates by approximately one-fifth (4.8% to 3.9%). The SD for deaths <12 hours after birth was reduced by one-quarter, but did not change after risk adjustment for deaths ≥12 hours after birth. CONCLUSIONS: In terms of the regional variation in overall VPT mortality, over four-fifths of the variation could not be accounted for by maternal, pregnancy, and infant characteristics. Investigation of the timing of death showed that these characteristics only accounted for a small proportion of the variation in VPT deaths. These findings suggest that there may be an inequity in the quality of care provision and treatment of VPT infants across Europe.

Patent Ductus Arteriosus Treatment in Very Preterm Infants: A European Population-Based Cohort Study (EPICE) on Variation and Outcomes.

BACKGROUND: Spontaneous closure of patent ductus arteriosus (PDA) occurs frequently in very preterm infants and despite the lack of evidence for treatment benefits, treatment for PDA is common in neonatal medicine. OBJECTIVES: The aim of this work was to study regional variations in PDA treatment in very preterm infants (≤31 weeks of gestation), its relation to differences in perinatal characteristics, and associations with bronchopulmonary dysplasia (BPD) and survival without major neonatal morbidity. METHODS: This was a population-based cohort study in 19 regions in 11 European countries conducted during 2011 and 2012. A total of 6,896 infants with data on PDA treatment were included. The differences in infant characteristics were studied across regions using a propensity score derived from perinatal risk factors for PDA treatment. The primary outcomes were a composite of BPD or death before 36 weeks postmenstrual age, or survival without major neonatal morbidity. RESULTS: The proportion of PDA treatment varied from 10 to 39% between regions (p < 0.001), and this difference could not be explained by differences in perinatal characteristics. The regions were categorized according to a low (<15%, n = 6), medium (15-25%, n = 9), or high (>25%, n = 4) proportion of PDA treatment. Infants treated for PDA, compared to those not treated, were at higher risk of BPD or death in all regions, with an overall propensity score adjusted risk ratio of 1.33 (95% confidence interval 1.18-1.51). Survival without major neonatal morbidity was not related to PDA treatment. CONCLUSIONS: PDA treatment varies largely across Europe without associated variations in perinatal characteristics or neonatal outcomes. This finding calls for more uniform guidance for PDA diagnosis and treatment in very preterm infants.

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

Importance: 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.

Does the antenatal detection of fetal growth restriction (FGR) have a prognostic value for mortality and short-term morbidity for very preterm infants? Results from the MOSAIC cohort.

OBJECTIVE: We investigated the impact of antenatal diagnosis of fetal growth restriction (FGR) on the risks of mortality and morbidity for very preterm infants given actual birthweight percentiles. METHODS: Data on 4608 live born infants 24-31 weeks of gestational age (GA) in 10 European regions in 2003 were used to compare in-hospital mortality, bronchopulmonary dysplasia (BPD) and severe neurological morbidity by birthweight percentiles and antenatal diagnosis of FGR. Other covariates were GA, sex, multiplicity, maternal complications, antenatal corticosteroids, birth in a level III center and region. RESULTS: Sixteen percent (n = 728) of all infants and 72%, 30% and 6%, respectively, of those with birthweight percentiles <10th, 10th-24th and ≥25th had an antenatal diagnosis of FGR. After adjustment for clinical factors, antenatal diagnosis of FGR was not associated with mortality for infants with a birthweight ≥10th percentile (OR [95% CI]: 0.9 [0.5-1.9] and 1.0 [0.6-1.8] for birthweights between the 10th-24th percentile and ≥25th percentile, respectively), but infants with a birthweight <10th percentile had higher mortality (OR [95% CI]: 2.4 [1.0-5.8]). No association was observed at any birthweight percentile with BPD or severe neurological morbidity. CONCLUSION: Antenatal diagnosis of FGR did not influence risks of mortality or morbidity when birthweight was ≥10th percentile; however, mortality risk was higher in antenatally detected infants with birthweight below the <10th percentile.

Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort.

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.

Rates of bronchopulmonary dysplasia in very preterm neonates in Europe: results from the MOSAIC cohort.

BACKGROUND: A considerable local variability in the rate of bronchopulmonary dysplasia (BPD) has been recorded previously. OBJECTIVES: The objectives of the present study were to describe regional differences in the rate of BPD in very preterm neonates from a European population-based cohort and to further delineate risk factors. METHODS: 4,185 survivors to 36 weeks' postmenstrual age of 4,984 live-born infants born at 24+0-31+6 weeks' gestation in 2003 (the MOSAIC cohort) in 10 European regions were enrolled using predefined structured questionnaires. RESULTS: Overall median gestational age of preterms without BPD was 30 weeks (range 23-31), median birth weight 1,320 g (range 490-3,150) compared with 27 weeks (23-31) and 900 g (370-2,460) in those with BPD. The region-specific crude rate of BPD ranged from 10.2% (Italian region) to 24.8% (UK Northern region). Maternal hypertension, immaturity, male gender, small for gestational age, Apgar <7 and region of care were associated with an increased incidence of BPD on multivariate analysis. CONCLUSION: A wide variability of BPD between European regions may be explained by different local practices; the strongest association however was with degree of immaturity.

Differences in rates and short-term outcome of live births before 32 weeks of gestation in Europe in 2003: results from the MOSAIC cohort.

OBJECTIVES: Advances in perinatal medicine increased survival after very preterm birth in all countries, but comparative population-based data on these births are not readily available. This analysis contrasts the rates and short-term outcome of live births before 32 weeks of gestation in 10 European regions. METHODS: The Models of Organizing Access to Intensive Care for Very Preterm Births (MOSAIC) study collected prospective data on all very preterm births in 10 European regions covering 494,463 total live births in 2003. The analysis sample was live births between 24 and 31 weeks of gestation without lethal congenital anomalies (N = 4908). Outcomes were rates of preterm birth, in-hospital mortality, intraventricular hemorrhage grades III and IV or cystic periventricular leukomalacia and bronchopulmonary dysplasia. Mortality and morbidity rates were standardized for gestational age and gender. RESULTS: Live births between 24 and 31 weeks of gestation were 9.9 per 1000 total live births with a range from 7.6 to 13.0 in the MOSAIC regions. Standardized mortality was doubled in high versus low mortality regions (18%-20% vs 7%-9%) and differed for infants < or = 28 weeks of gestation as well as 28 to 31 weeks of gestation. Morbidity among survivors also varied (intraventricular hemorrhage/periventricular leukomalacia ranged from 2.6% to < or = 10% and bronchopulmonary dysplasia from 10.5% to 21.5%) but differed from mortality rankings. A total of 85.2 very preterm infants per 10,000 total live births were discharged from the hospital alive with a range from 64.1 to 117.1; the range was 10 to 31 per 10,000 live births for infants discharged with a diagnosis of neurologic or respiratory morbidity. CONCLUSIONS: Very preterm mortality and morbidity differed between European regions, raising questions about variability in treatment provided to these infants. Comparative follow-up studies are necessary to evaluate the impact of these differences on rates of cerebral palsy and other disabilities associated with preterm birth.

Characteristics of neonatal units that care for very preterm infants in Europe: results from the MOSAIC study.

OBJECTIVES: We sought to compare guidelines for level III units in 10 European regions and analyze the characteristics of neonatal units that care for very preterm infants. METHODS: The MOSAIC (Models of Organising Access to Intensive Care for Very Preterm Births) project combined a prospective cohort study on all births between 22 and 31 completed weeks of gestation in 10 European regions and a survey of neonatal unit characteristics. Units that admitted > or = 5 infants at < 32 weeks of gestation were included in the analysis (N = 111). Place of hospitalization of infants who were admitted to neonatal care was analyzed by using the cohort data (N = 4947). National or regional guidelines for level III units were reviewed. RESULTS: Six of 9 guidelines for level III units included minimum size criteria, based on number of intensive care beds (6 guidelines), neonatal admissions (2), ventilated patients (1), obstetric intensive care beds (1), and deliveries (2). The characteristics of level III units varied, and many were small or unspecialized by recommended criteria: 36% had fewer than 50 very preterm annual admissions, 22% ventilated fewer than 50 infants annually, and 28% had fewer than 6 intensive care beds. Level II units were less specialized, but some provided mechanical ventilation (57%) or high-frequency ventilation (20%) or had neonatal surgery facilities (17%). Sixty-nine percent of level III and 36% of level I or II units had continuous medical coverage by a qualified pediatrician. Twenty-two percent of infants who were < 28 weeks of gestation were treated in units that admitted fewer than 50 very preterm infants annually (range: 2%-54% across the study regions). CONCLUSIONS: No consensus exists in Europe about size or other criteria for NICUs. A better understanding of the characteristics associated with high-quality neonatal care is needed, given the high proportion of very preterm infants who are cared for in units that are considered small or less specialized by many recommendations.