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Objective: We aimed to study neurodevelopmental outcomes and healthcare utilisation at age 5-6 years in very preterm children with bronchopulmonary dysplasia (BPD)., Design: Prospective and national population-based study., Setting: All the neonatal units in 25 French regions (21 of the 22 metropolitan regions and 4 overseas regions)., Patients: Children born before 32 weeks' gestation in 2011., Interventions: Blind, comprehensive and standardised assessment by trained neuropsychologists and paediatricians at age 5-6 years., Main Outcome Measures: Overall neurodevelopmental disabilities, behavioural difficulties, developmental coordination disorders, full-scale IQ, cerebral palsy, social interaction disorders, rehospitalisation in the previous 12 months and detailed developmental support., Results: Of the 3186 children included, 413 (11.7%) had BPD. The median gestational age of children with BPD was 27 weeks (IQR 26.0-28.0) and without BPD was 30 weeks (28.0-31.0). At age 5-6 years, 3150 children were alive; 1914 (60.8%) had a complete assessment. BPD was strongly associated with mild, moderate and severe overall neurodevelopmental disabilities (OR 1.49, 95% CI 1.05 to 2.20; 2.20, 1.41 to 3.42 and 2.71, 1.67 to 4.40). BPD was associated with developmental coordination disorders, behavioural difficulties, lower IQ score as well as rehospitalisation in the last 12 months and developmental support. The association between BPD and cerebral palsy was statistically significant before adjustment but not in adjusted analyses., Conclusions: BPD was strongly and independently associated with many neurodevelopmental disabilities. Improving medical and neurodevelopmental management of BPD in very preterm children should be a priority to reduce its long-term consequences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To review systematically and assess the accuracy of prediction models for bronchopulmonary dysplasia (BPD) at 36 weeks of postmenstrual age., Study Design: Searches were conducted in MEDLINE and EMBASE. Studies published between 1990 and 2022 were included if they developed or validated a prediction model for BPD or the combined outcome death/BPD at 36 weeks in the first 14 days of life in infants born preterm. Data were extracted independently by 2 authors following the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies (ie, CHARMS) and PRISMA guidelines. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (ie, PROBAST)., Results: Sixty-five studies were reviewed, including 158 development and 108 externally validated models. Median c-statistic of 0.84 (range 0.43-1.00) was reported at model development, and 0.77 (range 0.41-0.97) at external validation. All models were rated at high risk of bias, due to limitations in the analysis part. Meta-analysis of the validated models revealed increased c-statistics after the first week of life for both the BPD and death/BPD outcome., Conclusions: Although BPD prediction models perform satisfactorily, they were all at high risk of bias. Methodologic improvement and complete reporting are needed before they can be considered for use in clinical practice. Future research should aim to validate and update existing models., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Postnatal steroids (PNS) have been used to prevent bronchopulmonary dysplasia (BPD) in preterm infants but have potential adverse effects on neurodevelopment. These effects might be modulated by their risk of BPD. We aimed to compare patients' neurodevelopment with PNS treatment according to their risk of BPD in a European cohort., Methods: We developed a prediction model for BPD to classify infants born between 24 + 0 and 29 + 6 weeks of gestation in three groups and compared patients' neurological outcome at two years of corrected age using the propensity score (PS) method., Results: Of 3662 neonates included in the analysis, 901 (24.6%) were diagnosed with BPD. Our prediction model for BPD had an area under the ROC curve of 0.82. In the group with the highest risk of developing BPD, PNS were associated with an increased risk of gross motor impairment: OR of 1.95 after IPTW adjustment (95% CI 1.18 to 3.24, p = 0.010). This difference existed regardless of the type of steroid used. However, there was an increased risk of cognitive anomalies for patients treated with dexa/betamethasone that was no longer observed with hydrocortisone., Conclusions: This study suggests that PNS might be associated with an increased risk of gross motor impairment regardless of the group risk for BPD. Further randomised controlled trials exploring the use of PNS to prevent BPD should include a risk-based evaluation of neurodevelopmental outcomes. This observation still needs to be confirmed in a randomised controlled trial.

Introduction: Bronchopulmonary dysplasia (BPD) represents a tremendous disease burden following preterm birth. The strong association between compromised gas exchange after birth and BPD demands particular focus on the perinatal period. The mode of delivery can impact on lung fluid clearance and microbial colonization, but its impact on BPD and potential trade-off effects between death and BPD are not established., Methods: A total of 7,435 live births (24+0 to 31+6 weeks postmenstrual age) in 19 regions of 11 European countries were included. Principal outcomes were death and BPD at 36 weeks. We estimated unadjusted and adjusted associations with mode of delivery using multilevel logistic regression to account for clustering within units and regions. Sensitivity analyses examined effects, taking into consideration regional variations in C-section rates., Results: Compared to vaginal delivery, delivery by C-section was not associated with the incidence of BPD (OR 0.92, 95% CI: 0.68-1.25) or the composite outcome of death or BPD (OR 0.94, 95% CI: 0.74-1.19) after adjustment for perinatal and neonatal risk factors in the total cohort and in pregnancies for whom a vaginal delivery could be considered. Sensitivity analyses among singletons, infants in cephalic presentation, and infants of ≥26+0 weeks of gestation did not alter the results for BPD, severe BPD, and death or BPD, even in regions with a high C-section rate., Conclusions: In our population-based cohort study, the mode of delivery was not associated with the incidence of BPD. The intention to reduce BPD does not justify a C-section in pregnancies where a vaginal delivery can be considered., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

This study aims to describe the incidence of acute respiratory infections (ARI) during the first year in infants born before 32 weeks' gestation, and to analyze and study the risk factors as well as factors associated with oxygen requirement among infants with an ARI, in the palivizumab era. This study included 2571 infants from a nationwide French population-based cohort (Epipage 2). ARI at 1-year corrected age was identified by parental questionnaires. Risk and severity factors included those already known, and detailed information about neonatal morbidities. ARI occurred in 52.2% (n = 1349) of infants. Oxygen therapy was used in 33.2% (n = 391) of infants with an ARI. Risk factors for AII were male sex, bronchopulmonary dysplasia, presence of siblings at home, and childcare in the community together with incomplete treatment palivizumab. Mechanical ventilation in the neonatal period, bronchopulmonary dysplasia, and discharge between October and March were associated with more frequent oxygen requirement. No other factors describing neonatal morbidities were associated with risk of ARI or oxygen requirement.Conclusion: ARIs are still very common during the first year of life of very preterm children, and oxygen therapy is frequently needed. Educational strategies are needed in all families with a very preterm infant. What is Known: • Acute respiratory infections (ARIs) are the first cause of rehospitalizations in preterm children, with bronchopulmonary dysplasia being the main risk factor. • Palivizumab prophylaxis has proven its effect against severe RSV infections, but it is not universal. What is New: • No factor describing neonatal morbidity, except BPD, was associated with ARI occurrence or severity. • BPD and discharge during RSV season were the only factors associated with O 2 requirement during ARI.

Introduction: Postnatal corticosteroids (PNC) are effective for reducing bronchopulmonary dysplasia (BPD) in very preterm neonates but are associated with adverse effects including an increased risk of cerebral palsy. PNC use in Europe is heterogeneous across regions. This study aimed to assess whether European neonatal intensive care units (NICUs) with a low use of PNC or an explicit policy to reduce PNC use had higher risks of mortality or BPD., Methods: We included 3,126 infants in 105 NICUs born between 24 + 0 and 29 + 6 weeks' gestational age in 19 regions in 11 countries in the EPICE cohort. First, we identified clusters of NICUs using hierarchical clustering based on PNC use and BPD prevalence and compared case mix and mortality between the clusters. Second, a multilevel analysis was performed to evaluate the association between a restrictive PNC policy and BPD occurrence., Results: There were 3 clusters of NICUs: 52 with low PNC use and a low BPD rate, 37 with low PNC use and a high BPD rate, and 16 with high PNC use and a medium BPD rate. Neonatal mortality did not differ between clusters (p = 0.88). A unit policy of restricted PNC use was not associated with a higher risk of BPD (odds ratio 0.68; 95% confidence interval: 0.45-1.03) after adjustment., Conclusion: Up to 49% of NICUs had low PNC use and low BPD rates, without a difference in mortality. Infants hospitalized in NICUs with a stated policy of low PNC use did not have an increased risk of BPD., (© 2020 S. Karger AG, Basel.)

Objectives: Angiogenic factors may be involved in lung development. To evaluate the relations between maternal and cord blood angiogenic factors (sFlt-1, placental growth factor [PlGF], soluble endogline [sEng], transforming growth factor β [TGF-beta]) and their association with moderate and severe bronchopulmonary dysplasia (BPD) in very preterm growth-restricted infants., Study Design: Prospective monocentric cohort study. Twenty-four mother-child dyads featuring antepartum preeclampsia, intra-uterine growth restriction (IUGR) and birth before 30 weeks' gestation were included. This ensured a 80% power to test whether sFlt-1 maternal levels would be twice as high in cases of BPD as in the absence of BPD., Main Outcome Measures: Four pro/anti-angiogenic factors from two pathways (sFlt-1, PlGF and sEng, TGF-beta) were measured in maternal serum before delivery (at the time of hospitalization or the day of birth) and in neonates' cord blood. Neonatal outcome was moderate to severe BPD, defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks' postmenstrual age., Results: sFlt-1 levels were positively correlated in maternal serum and cord blood (r s  = 0.83, p < .001) but levels of PlGF and TGF-beta and its receptor sEng were not. Among all the factors studied in cord and maternal blood, none was associated with BPD., Conclusions: In IUGR preterm babies born before 30 weeks' gestation from preeclamptic mothers, serum sFlt-1, PlGF and sEng, TGF-β levels were not correlated with BPD. The increased BPD risk in preterm neonates born from preeclamptic mothers cannot be related to high sFlt-1 levels., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Introduction: To evaluate the consequences of bronchopulmonary dysplasia (BPD) on academic outcomes and healthcare use in adolescents born very preterm., Methods: This cohort study included 15-year-old adolescents born very preterm (< 32 weeks) between 2011 and 2013, with and without BPD, and controls born full term. Data regarding academic performance, current medical follow-up, and family characteristics were collected. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD., Results: From the 1341 children included in the initial cohort, 985 adolescents were eligible and 351 included (55 preterms with a history of BPD, 249 without, and 47 controls). Among adolescents born very preterm, a history of BPD was associated with a higher risk to attend a school for children with special needs (p < 0.05) and to have repeated a grade (p = 0.01). It was also associated with an increased number of medical and paramedical consultations. A history of BPD was not associated with the parents' employment status, family structure, or the presence of younger siblings., Conclusion: This study highlights that a history of BPD is associated with poorer academic outcomes and high healthcare use in adolescence., Competing Interests: The authors have declared that no competing interests exist.

Background and Objectives: Small for gestational age and preeclampsia have both been described as risk factors for bronchopulmonary dysplasia in preterm neonates, but their respective role in the occurrence of bronchopulmonary dysplasia is debated. We evaluated the relation between small for gestational age and bronchopulmonary dysplasia in neonates born to mothers with preeclampsia. We hypothesized that low birth weight is still associated with bronchopulmonary dysplasia in this homogeneous population., Methods: Retrospective single-center cohort study including 141 neonates born between 24 and 30 weeks' gestation to mothers with preeclampsia. The main outcome measure was moderate to severe bronchopulmonary dysplasia at 36 weeks' postmenstrual age. Neonates born small for gestational age (birthweight < 10th percentile on the AUDIPOG curves) were compared to those with appropriate birthweight for gestational age by bivariable analyses and logistic regression models, estimating odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Bronchopulmonary dysplasia rates were 61.5% (32/52) and 27.4% (20/73) for small for gestational age and appropriate birthweight for gestational age neonates (p < .001). On adjustment for gestational age and other confounding factors, the risk of moderate to severe bronchopulmonary dysplasia was greater for small for gestational age than appropriate birthweight for gestational age neonates (adjusted OR = 5.9, 95% CI [2.2-15.4]), as was the composite outcome death or moderate to severe bronchopulmonary dysplasia (adjusted OR = 4.7, 95% CI [1.9-11.3])., Conclusions: Small for gestational age was associated with bronchopulmonary dysplasia in very preterm neonates born to mothers with preeclampsia., Registration Number: CNIL no. 1747084., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the association between histologic chorioamnionitis (HCA) and bronchopulmonary dysplasia (BPD) in very preterm infants, both in a general population and for those born after spontaneous preterm labor and after preterm premature rupture of membranes (pPROM)., Study Design: This study included 2513 live born singletons delivered at 24-31 weeks of gestation from a national prospective population-based cohort of preterm births; 1731 placenta reports were available. HCA was defined as neutrophil infiltrates in the amnion, chorion of the membranes, or chorionic plate, associated or not with funisitis. The main outcome measure was moderate or severe BPD. Analyses involved logistic regressions and multiple imputation for missing data., Results: The incidence of HCA was 28.4% overall: 38% in cases of preterm labor, 64% in cases of pPROM, and less than 5% in cases of vascular disorders. Overall, the risk of BPD after adjustment for gestational age, sex, and antenatal steroids was reduced for infants with HCA (HCA alone: aOR 0.6 [95% CI 0.4-0.9]; associated with funisitis: aOR 0.5 [95% CI 0.3-0.8]). This finding was explained by the high rate of BPD and low rate of chorioamnionitis among children with fetal growth restriction. HCA was not associated with BPD in the preterm labor (13.4% vs 8.5%; aOR 0.9; 95% CI 0.5-1.8) or in the pPROM group (12.9% vs 12.1%; aOR 0.6; 95% CI 0.3-1.3)., Conclusion: In homogeneous groups of infants born after preterm labor or pPROM, HCA is not associated with BPD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between placenta-mediated pregnancy complications and bronchopulmonary dysplasia (BPD) in very preterm infants., Methods: National prospective population-based cohort study including 2697 singletons born before 32 weeks' gestation. The main outcome measure was moderate to severe BPD. Three groups of placenta-mediated pregnancy complications were compared with no placenta-mediated complications: maternal disorders only (gestational hypertension or preeclampsia), fetal disorders only (antenatal growth restriction), and both maternal and fetal disorders., Results: Moderate to severe BPD rates were 8% in infants from pregnancies with maternal disorders, 15% from both maternal and fetal disorders, 23% from fetal disorders only, and 9% in the control group (P < .001). When we adjusted for gestational age, the risk of moderate to severe BPD was greater in the groups with fetal disorders only (odds ratio [OR] = 6.6; 95% confidence interval [CI], 4.1-10.7), with maternal and fetal disorders (OR = 3.7; 95% CI, 2.5-5.5), and with maternal disorders only (OR = 1.7; 95% CI, 1.0-2.7) than in the control group. When we also controlled for birth weight, the relationship remained in groups with fetal disorders only (OR = 4.2; 95% CI, 2.1-8.6) and with maternal and fetal disorders (OR = 2.1; 95% CI, 1.1-3.9)., Conclusions: Placenta-mediated pregnancy complications with fetal consequences are associated with moderate to severe BPD in very preterm infants independently of gestational age and birth weight, but isolated maternal hypertensive disorders are not. Fetal growth restriction, more than birth weight, could predispose to impaired lung development., (Copyright © 2016 by the American Academy of Pediatrics.)

Background Several countries, including France, have restricted the indications for monoclonal antibodies directed against respiratory syncytial virus (RSV) compared to the marketing authorization (MA). No new data concerning use of palivizumab on a national scale have been published since the 2007 update of the national guidelines. Objectives To describe palivizumab administration for RSV prophylaxis during the first RSV season in infants born prematurely in France in 2011. Methods Infants from the national population-based cohort EPIPAGE-2 born at ≤ 34 weeks’ gestation, discharged home before 31 March 2012 and followed-up at 1 year were included. The RSV season ran from 1 October 2011 to 31 March 2012. Prophylaxis was deemed “initiated” if the infant had received at least one dose of palivizumab during this period and “complete” if it had received at least five doses or as many doses as the number of exposed months. The reference documents were the MA and French Transparency Committee guidelines (TC). Results Prophylaxis was indicated in 3586 of 3608 infants (99.7%) according to the MA and 1315 of 3608 (16.7%) according to the TC. A total of 1906 infants (26.6%) received at least one dose of palivizumab. The overall rate of conformity with TC indications was 85%, but was lower for infants born at 27–32 weeks’ gestation. The rate of complete prophylaxis was 77.2%. The factors associated with prophylaxis initiation were low gestational age, low birthweight, high maternal educational level, type of neonatal unit, and date at discharge. Factors associated with complete prophylaxis were respiratory impairment, high educational level, and characteristics related to living conditions (absence of siblings at home, type of childcare). Conclusions Palivizumab administration in France generally conformed with TC guidelines, but could be further improved for infants born at 27–32 weeks’ gestation without bronchopulmonary dysplasia. [ABSTRACT FROM AUTHOR]