Original Paper Received: January 4, 2010 Accepted after revision: April 8, 2010 Published online: August 23, 2010
Neonatology 2011;99:112–117 DOI: 10.1159/000313024
Rates of Bronchopulmonary Dysplasia in Very Preterm Neonates in Europe: Results from the MOSAIC Cohort Ludwig Gortner a Björn Misselwitz b David Milligan c Jennifer Zeitlin d Louis Kollée e Klaus Boerch f Rocco Agostino g Patrick Van Reempts h Jean-Louis Chabernaud i Gérard Bréart d Emile Papiernik j, † Pierre-Henri Jarreau k Manuel Carrapato l Janusz Gadzinowski m Elizabeth Draper n for the members of the MOSAIC Research Group
a Pediatric University Hospital, University of Saarland, Homburg, and b Geschäftsstelle Qualitätssicherung Hessen, Eschborn, Germany; c Department of Neonatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK; d INSERM, UMR S149, Epidemiological Research Unit on Perinatal and Women’s Health, Université Pierre et Marie Curie – Paris 6, Paris, France; e Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; f Department of Paediatrics, Hvidovre University Hospital, Hvidovre, Denmark; g Department for Mother’s and Infant’s Health, Hospital San Giovanni Calibita - Fatebenefratelli, Rome, Italy; h Department of Neonatology, Antwerp University Hospital, University of Antwerp and Study Centre for Perinatal Epidemiology Flanders, Antwerp, Belgium; i Service de Réanimation Néonatale, Hôpital Antoine Béclere, Clamart, j Université Paris V Réné Descartes et Service de Gynécologie-Obstétrique de Port-Royal, and k Université Paris V Réné Descartes et Service de Médecine Néonatale de Port-Royal, Paris, France; l Department of Pediatrics, Hospital Sao Sebastiao, Sta Maria de Feira, Portugal; m Department of Neonatology, University of Medical Sciences, Poznan, Poland; n Neonatal Unit, Department of Health Sciences, Leicester Royal Infirmary, University of Leicester, Leicester, UK
Key Words Bronchopulmonary dysplasia ⴢ Very preterm neonate ⴢ Immaturity ⴢ Neonatal intensive care ⴢ Regional factors
Abstract 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
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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.
Ludwig Gortner, MD University Children’s Hospital, UDS DE–66421 Homburg/Saar (Germany) Tel. +49 6841 16 28300, Fax +49 6841 16 28310 E-Mail kilgor @ uks.eu
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. Copyright © 2010 S. Karger AG, Basel
Introduction
The radiological and pathological changes of persistent lung damage following respiratory distress syndrome were first described as bronchopulmonary dysplasia (BPD) more than 40 years ago [1]. The pattern of lung damage has changed over the same time interval and the principal markers observed by clinicians now are longterm dependency on oxygen and/or respiratory support [2]. Considerable local variations in the occurrence of BPD were described already during the 1980s [3]. Recent reports indicate that up to 25% of survivors born before 32 weeks’ gestation develop BPD [4]. Risk factors have been described including clinical characteristics and respiratory management [5, 6] as well as genetic factors [7, 8]. Variability in the incidence of BPD has been well illustrated by data from the Vermont Oxford Network but published reports are based on data from individual institutions [9]. An analysis of the rate of BPD obtained from representative population-based European cohorts has not yet been described. The aims of the present study therefore were to describe the region-specific rate of BPD within the MOSAIC cohort (Models for OrganiSing Access to Intensive Care for Very Preterm Babies in Europe) of very preterm neonates !32 weeks’ gestation from 10 EU regions [10] and to further identify clinical risk factors for BPD.
Patients and Methods
regions of the UK. The MOSAIC regions covered between 30,000 and 65,000 live births in 2003, with the exception of the larger French region (135,000 births). Regions represented different organizational models of perinatal care, based on the results of a previous European collaboration. The study’s further objectives were to describe the organization of maternity and neonatal units [11] and to assess regional perinatal health outcome, using predefined variables [12]. Definition of Maternal Variables Maternal complications were defined as the occurrence of premature rupture of membranes (PROM) and pregnancy-induced hypertension (PIH), preeclampsia and HELLP syndrome summarized as maternal hypertension. Infection was coded if assumed by the attending obstetrician as an indication or cause for delivery. Antenatal corticosteroid prophylaxis (ANC) was defined as any administration of betamethasone or alternative steroids before birth. Definition of Neonatal Characteristics Gestational age (GA) was based on best obstetrical estimate in the medical records. Small for gestational age (SGA) was defined as birth weight less than the 10th centile for GA using local references. Apgar scores were recorded 5 min postnatally. The following variables on respiratory support and therapy were recorded: oxygen therapy, continuous positive airway pressure (CPAP) and mechanical ventilation with their duration. The administration of postnatal corticosteroids was registered. BPD was defined as oxygen supplementation or mechanical ventilation at 36 weeks’ postmenstrual age. The need for supplemental oxygen was determined by the infants’ neonatologists. In general, a threshold of arterial oxygen saturation of 90–92% was accepted. Infants being discharged home at 36 weeks’ postmenstrual age or less without oxygen supplementation were considered as survivors without BPD. Ethic approval was obtained for the collection of these data as required in each of the regions. Statistical Analyses Data were collected using a standardized questionnaire and further computerized and analyzed by SPSS 12 (Chicago, Ill., USA). Multivariate regression analysis included all variables that were significantly associated with BPD in bivariate analyses.
Results
The study population was a subset of the total cohort in the MOSAIC study on models of perinatal care and health outcomes of very preterm babies in Europe which prospectively collected data using a common predefined protocol on population-based cohorts of all infants born at !32 weeks’ gestation regardless of birth weight from 10 regions covering about half a million total births in 2003 [10]. Participating regions were: Flanders in Belgium, the Eastern region of Denmark, 6 of 8 districts in the Ile-de-France region of France, Hesse in Germany, Lazio in Italy, the Central and Eastern region of The Netherlands, Wielkopolska and Lubuskie in Poland, the Northern region of Portugal and the Northern and Trent
A total of 4,185 preterm neonates surviving up to 36 weeks with a GA between 24+0 and to 31+6 weeks were enrolled; 677 (16.7%) of these were still receiving oxygen or mechanical ventilation at 36 weeks’ postmenstrual age. In 119 preterm neonates, data with respect to BPD were incomplete, ranging from 1 to 5% (median 3%) between the Trent and Danish regions. These preterm neonates were not included in the computation of prevalence estimates or multivariate models. Median GA of the entire cohort was 30 weeks (region-specific range 29–30),
Bronchopulmonary Dysplasia in European Neonates
Neonatology 2011;99:112–117
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Table 1. Rates of BPD by clinical characteristics, region of care and survival by region All cases BPD (n = 4,185) (n = 677) n/%
GA, weeks
