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Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To determine whether differences in efficacy and safety exist between hydrocortisone and dexamethasone in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants through a network meta-analysis, generating pairwise comparisons between all treatments and rankings of the treatments.

Key Points Question Does sildenafil reduce the risk of perinatal mortality or morbidity in children of pregnant women with severe early onset fetal growth restriction? Findings In this randomized clinical trial including 216 pregnant women, perinatal mortality or major morbidity was not statistically different and occurred in the offspring of 60.2% of participants allocated to sildenafil vs 54.2% of those allocated to placebo. Pulmonary hypertension occurred in 18.8% of neonates in the sildenafil group compared with 5.1% of neonates in the placebo group, which was statistically significantly different. Meaning These findings suggest that treatment of severe early onset fetal growth restriction by maternal sildenafil did not reduce the risk of perinatal mortality or major neonatal morbidity, but increased neonatal pulmonary hypertension was observed., This randomized clinical trial examines whether sildenafil reduces the risk of perinatal mortality or morbidity vs placebo in children of pregnant women with severe early onset fetal growth restriction., Importance Severe early onset fetal growth restriction caused by placental dysfunction leads to high rates of perinatal mortality and neonatal morbidity. The phosphodiesterase 5 inhibitor, sildenafil, inhibits cyclic guanosine monophosphate hydrolysis, thereby activating the effects of nitric oxide, and might improve uteroplacental function and subsequent perinatal outcomes. Objective To determine whether sildenafil reduces perinatal mortality or major morbidity. Design, Setting, and Participants This placebo-controlled randomized clinical trial was conducted at 10 tertiary referral centers and 1 general hospital in the Netherlands from January 20, 2015, to July 16, 2018. Participants included pregnant women between 20 and 30 weeks of gestation with severe fetal growth restriction, defined as fetal abdominal circumference below the third percentile or estimated fetal weight below the fifth percentile combined with Dopplers measurements outside reference ranges or a maternal hypertensive disorder. The trial was stopped early owing to safety concerns on July 19, 2018, whereas benefit on the primary outcome was unlikely. Data were analyzed from January 20, 2015, to January 18, 2019. The prespecified primary analysis was an intention-to-treat analysis including all randomized participants. Interventions Participants were randomized to sildenafil, 25 mg, 3 times a day vs placebo. Main Outcomes and Measures The primary outcome was a composite of perinatal mortality or major neonatal morbidity until hospital discharge. Results Out of 360 planned participants, a total of 216 pregnant women were included, with 108 women randomized to sildenafil (median gestational age at randomization, 24 weeks 5 days [interquartile range, 23 weeks 3 days to 25 weeks 5 days]; mean [SD] estimated fetal weight, 458 [160] g) and 108 women randomized to placebo (median gestational age, 25 weeks 0 days [interquartile range, 22 weeks 5 days to 26 weeks 3 days]; mean [SD] estimated fetal weight, 464 [186] g). In July 2018, the trial was halted owing to concerns that sildenafil may cause neonatal pulmonary hypertension, whereas benefit on the primary outcome was unlikely. The primary outcome, perinatal mortality or major neonatal morbidity, occurred in the offspring of 65 participants (60.2%) allocated to sildenafil vs 58 participants (54.2%) allocated to placebo (relative risk, 1.11; 95% CI, 0.88-1.40; P = .38). Pulmonary hypertension, a predefined outcome important for monitoring safety, occurred in 16 neonates (18.8%) in the sildenafil group vs 4 neonates (5.1%) in the placebo group (relative risk, 3.67; 95% CI, 1.28-10.51; P = .008). Conclusions and Relevance These findings suggest that antenatal maternal sildenafil administration for severe early onset fetal growth restriction did not reduce the risk of perinatal mortality or major neonatal morbidity. The results suggest that sildenafil may increase the risk of neonatal pulmonary hypertension. Trial Registration ClinicalTrials.gov Identifier: NCT02277132

Importance Most preterm infants require respiratory support to establish lung aeration after birth. Intermittent positive pressure ventilation and continuous positive airway pressure are standard therapies. An initial sustained inflation (inflation time >5 seconds) is a widely practiced alternative strategy. Objective To conduct a systematic review and meta-analysis of sustained inflation vs intermittent positive pressure ventilation and continuous positive airway pressure for the prevention of hospital mortality and morbidity for preterm infants. Data Sources MEDLINE (through PubMed), Embase, the Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials were searched through June 24, 2019. Study Selection Randomized clinical trials of preterm infants born at less than 37 weeks’ gestation that compared sustained inflation (inflation time >5 seconds) vs standard resuscitation with either intermittent positive pressure ventilation or continuous positive airway pressure were included. Studies including other cointerventions were excluded. Data Extraction and Synthesis Two reviewers assessed the risk of bias of included studies. Meta-analysis of pooled outcome data used a fixed-effects model specific to rarer events. Subgroups were based on gestational age and study design (rescue vs prophylactic sustained inflation). Main Outcomes and Measures Death before hospital discharge. Results Nine studies recruiting 1406 infants met inclusion criteria. Death before hospital discharge occurred in 85 of 736 infants (11.5%) treated with sustained inflation and 62 of 670 infants (9.3%) who received standard therapy for a risk difference of 3.6% (95% CI, −0.7% to 7.9%). Although analysis of the primary outcome identified important heterogeneity based on gestational age subgroups, the 95% CI for the risk difference included 0 for each individual gestational age subgroup. There was no difference in the primary outcome between subgroups based on study design. Sustained inflation was associated with increased risk of death in the first 2 days after birth (risk difference, 3.1%; 95% CI, 0.9%-5.3%). No differences in the risk of other secondary outcomes were identified. The quality-of-evidence assessment was low owing to risk of bias and imprecision. Conclusions and Relevance There was no difference in the risk of the primary outcome of death before hospital discharge, and there was no evidence of efficacy for sustained inflation to prevent secondary outcomes. These findings do not support the routine use of sustained inflation for preterm infants after birth.

Background: Our double-blind, placebo-controlled, randomised trial investigating systemic hydrocortisone in mechanically ventilated preterm infants (gestational age

Over 75% of severely thrombocytopenic neonates receive platelet transfusions, though little evidence supports this practice, and only 10% develop major bleeding. In a recent randomized trial, giving platelet transfusions at a threshold platelet count of 50x109/L compared to a threshold of 25x109/L was associated with an increased risk of major bleeding or mortality. This finding highlights the need for improved and individualized guidelines on neonatal platelet transfusion, which require accurate prediction of bleeding risk. Therefore, the objective of this study was to develop a dynamic prediction model for major bleeding in thrombocytopenic preterm neonates. This model allows for calculation of bleeding risk at any time-point during the first week after the onset of severe thrombocytopenia. In this multicenter cohort study, we included neonates with a gestational age

BackgroundPlacebo-controlled trials have shown that caffeine is highly effective in treating apnoea of prematurity and reduces the risk of bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI).ObjectiveTo identify, appraise and summarise studies investigating the modulating effect of different caffeine dosages.MethodsA systematic review identified all randomised controlled trials (RCTs) comparing a high versus a standard caffeine treatment regimen in infants with a gestational age ResultsSix RCTs including 620 infants were identified. Meta-analysis showed a significant decrease in BPD, the combined outcome BPD or mortality, and failure to extubate in infants allocated to a higher caffeine dose. No differences were found in mortality alone and NDI. The quality of the outcome measures were deemed low to very low according to the Grading of Recommendations Assessment, Development and Evaluation guidelines.ConclusionsAlthough this review suggests that administering a higher dose of caffeine might enhance its beneficial effect on death or BPD, firm recommendations on the optimal caffeine dose cannot be given due to the low level of evidence. A large RCT is urgently needed to confirm or refute these findings and determine the optimal dose of caffeine.

Introduction: Necrotizing enterocolitis (NEC) is a severe inflammatory disease, mostly occurring in preterm infants. The Dutch guidelines for active treatment of extremely preterm infants changed in 2006 from 26 + 0 to 25+ 0 weeks of gestation, and in 2010 to 24+0 of gestation. We aimed to gain insight into the incidence, clinical outcomes and treatment strategies, in three academic referral centers in the Netherlands over the last nine years.Methods: We performed a multicenter retrospective cohort study of all patients with NEC (Bell stage >= 2a) in three academic referral centers diagnosed between 2005 and 2013. Outcome measures consisted of incidence, changes in clinical presentation, treatment strategies and mortality.Results: Between 2005 and 2013 14,161 children were admitted to the neonatal intensive care unit in the three centers. The overall percentage of children born at a gestational age of 24 weeks and 25 weeks increased with 1.7% after the introduction of the guidelines in 2006 and 2010. The incidence of NEC increased significantly (period 2005-2007: 2.1%; period 2008-2010 3.9%; period 2011-2013: 3.4%; P = 0.001). We observed a significant decrease of peritoneal drainages (down arrow 16%; P= 0.001) and a decrease of laparotomies (down arrow 24%; P= 0.002). The mortality rate (33% in 2011-2013) remained unchanged.Conclusion: The incidence of NEC significantly increased in the last nine years. The increase in incidence of NEC seemed to be related to an increase in infants born at a gestational age of 24 and 25 weeks. The percentage of patients needing surgery decreased, while 30-day mortality did not change. (C) 2017 Published by Elsevier Inc.

Background: Although most preterm infants breathe at birth, their respiratory drive is weak and supplemental oxygen is often needed to overcome hypoxia. This could in turn lead to hyperoxia. To reduce the risk of hyperoxia, currently an initial low oxygen concentration (21–30%) is recommended during stabilization at birth, accepting the risk of a hypoxic period. However, hypoxia inhibits respiratory drive in preterm infants. Starting with a higher level of oxygen could lead to a shorter duration of hypoxia by stimulating breathing effort of preterm infants, and combined with subsequent titration based on oxygen saturation, prolonged hyperoxia might be prevented. Study design: This multi-center randomized controlled trial will include 50 infants with a gestational age between 24 and 30 weeks. Eligible infants will be randomized to stabilization with an initial FiO2 of either 1.0 or 0.3 at birth. Hereafter, FiO2 will be titrated based on the oxygen saturation target range. In both groups, all other interventions during stabilization and thereafter will be similar. The primary outcome is respiratory effort in the first 5 min after birth expressed as average minute volume/kg. Secondary outcomes include inspired tidal volumes/kg, rate of rise to maximum tidal volume/kg, percentage of recruitment breaths with tidal volumes above 8 mL/kg, duration of hypoxia and hyperoxia and plasma levels of markers of oxidative stress (8-iso-prostaglandin F2α). Discussion: Current resuscitation guidelines recommend oxygen titration if infants fail to achieve the 25th percentile of the SpO2 reference ranges. It has become clear that, using this approach, most preterm infants are at risk for hypoxia in the first 5 min after birth, which could suppress the breathing effort. In addition, for compromised preterm infants who need respiratory support at birth, higher SpO2 reference ranges in the first minutes after birth might be needed to prevent prolonged hypoxia. Enhancing breathing effort by achieving an adequate level of oxygenation could potentially lead to a lower incidence of intubation and mechanical ventilation in the delivery room, contributing to a lower risk on lung injury in high-risk preterm infants. Measuring 8-iso-prostaglandin F2α could lead to a reflection of the true amount of oxygen exposure in both study groups.

BACKGROUND: Platelet transfusions are commonly used to prevent bleeding in preterm infants with thrombocytopenia. Data are lacking to provide guidance regarding thresholds for prophylactic platelet transfusions in preterm neonates with severe thrombocytopenia. METHODS: In this multicenter trial, we randomly assigned infants born at less than 34 weeks of gestation in whom severe thrombocytopenia developed to receive a platelet transfusion at platelet-count thresholds of 50,000 per cubic millimeter (high-threshold group) or 25,000 per cubic millimeter (low-threshold group). Bleeding was documented prospectively with the use of a validated bleeding-assessment tool. The primary outcome was death or new major bleeding within 28 days after randomization. RESULTS: A total of 660 infants (median birth weight, 740 g; and median gestational age, 26.6 weeks) underwent randomization. In the high-threshold group, 90% of the infants (296 of 328 infants) received at least one platelet transfusion, as compared with 53% (177 of 331 infants) in the low-threshold group. A new major bleeding episode or death occurred in 26% of the infants (85 of 324) in the high-threshold group and in 19% (61 of 329) in the low-threshold group (odds ratio, 1.57; 95% confidence interval [CI], 1.06 to 2.32; P=0.02). There was no significant difference between the groups with respect to rates of serious adverse events (25% in the high-threshold group and 22% in the low-threshold group; odds ratio, 1.14; 95% CI, 0.78 to 1.67). CONCLUSIONS: Among preterm infants with severe thrombocytopenia, those randomly assigned to receive platelet transfusions at a platelet-count threshold of 50,000 per cubic millimeter had a significantly higher rate of death or major bleeding within 28 days after randomization than those who received platelet transfusions at a platelet-count threshold of 25,000 per cubic millimeter. (Funded by the National Health Service Blood and Transplant Research and Development Committee and others; Current Controlled Trials number, ISRCTN87736839 .).

Objective: The objective of the Dutch Sildenafil therapy in dismal prognosis early onset fetal growth restriction (STRIDER) randomised clinical trial is to assess the beneficial and harmful effects of sildenafil versus placebo on fetal and neonatal mortality in pregnant women with severe early-onset fetal growth restriction. The objective of this detailed statistical analysis plan is to minimize the risks of selective reporting and data-driven analysis. Setting: The setting is 10 tertiary care hospitals and one secondary care hospital in The Netherlands. Participants: The participants will be 360 pregnant women with severe early-onset fetal growth restriction. Interventions: The intervention is sildenafil 25 mg or placebo orally three times a day. Primary and secondary outcome measures: The primary outcome is a composite of death or major neonatal morbidity assessed at hospital discharge. The secondary outcomes are neurodevelopmental impairment; mean scores of the Bayley III cognitive and motor assessment; the proportion of patients experiencing either preeclampsia or haemolysis, elevated liver enzymes, and low platelets syndrome; pulsatility index of uterine arteries, umbilical artery, and middle cerebral artery; birthweight; and gestational age at either delivery or intra-uterine death. Results: A detailed statistical analysis is presented, including pre-defined exploratory outcomes and planned subgroup analyses. One interim analysis after 180 patients had completed the study was planned and a strategy to minimise the risks of type I errors due to repetitive testing is presented. During review of this manuscript the interim analysis was performed by the Data Safety Monitoring Board and early stopping of the trial was recommended. Final analyses will be conducted independently by two statistically qualified persons following the present plan. Conclusion: This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data and updated after stopping of the trial at interim analysis. Trial registration: ClinicalTrials.gov, NCT02277132. Registered on 29 September 2014. Original protocol for the study: doi: https://doi.org/10.5281/zenodo.56148

This is a protocol for a Cochrane Review (Overview). The objectives are as follows: The primary objective of this overview is to summarize and appraise the evidence from systematic reviews regarding the effects of postnatal corticosteroids for both efficacy and harms in preterm infants at risk of developing bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common morbidity of preterm infants, and its incidence has not responded to research and intervention efforts to the same degree as other major morbidities associated with prematurity. The complexity of neonatal respiratory care as well as persistent inter-institutional variability in BPD rates suggest that BPD may be amenable to quality improvement (QI) efforts. We present a systematic review of QI for BPD in preterm infants. We identified 22 reports from single centers and seven from collaborative efforts published over the past two decades. In almost all of the reports, respiratory QI interventions successfully reduced BPD or other key respiratory measures, particularly for infants with birth weight over 1000 g. Several themes and lessons from existing reports may help inform future efforts in both research and QI to impact the burden of BPD.

BACKGROUND: The Thompson encephalopathy score is a clinical score to assess newborns suffering from perinatal asphyxia. Previous studies revealed a high sensitivity and specificity of the Thompson encephalopathy score for adverse outcomes (death or severe disability). Because the Thompson encephalopathy score was developed before the use of therapeutic hypothermia, its value was reassessed. OBJECTIVE: The purpose of this study was to assess the association of the Thompson encephalopathy score with adverse short-term outcomes, defined as death before discharge, development of severe epilepsy, or the presence of multiple organ failure in asphyxiated newborns undergoing therapeutic hypothermia. METHODS: The study period ranged from November 2010 to October 2014. A total of 12 tertiary neonatal intensive care units participated. Demographic and clinical data were collected from the "PharmaCool" multicenter study, an observational cohort study analyzing pharmacokinetics of medication during therapeutic hypothermia. With multiple logistic regression analyses the association of the Thompson encephalopathy scores with outcomes was studied. RESULTS: Data of 142 newborns were analyzed (male: 86; female: 56). Median Thompson score was 9 (interquartile range: 8 to 12). Median gestational age was 40 weeks (inter quartile range 38 to 41), mean birth weight was 3362 grams (standard deviation: 605). All newborns manifested perinatal asphyxia and underwent therapeutic hypothermia. Death before discharge occurred in 23.9% and severe epilepsy in 21.1% of the cases. In total, 59.2% of the patients had multiple organ failure. The Thompson encephalopathy score was not associated with multiple organ failure, but a Thompson encephalopathy score >= 12 was associated with death before discharge (odds ratio: 3.9; confidence interval: 1.3 to 11.2) and with development of severe epilepsy (odds ratio: 8.4; confidence interval: 2.5 to 27.8). CONCLUSION: The Thompson encephalopathy score is a useful clinical tool, even in cooled asphyxiated newborns. A score >= 12 is associated with adverse outcomes (death before discharge and development of severe epilepsy). The Thompson encephalopathy score is not associated with the development of multiple organ failure.

Introduction: Survivors of necrotizing enterocolitis (NEC) often develop a post-NEC intestinal stricture, causing severe and prolonged morbidity. Objectives: We first aimed to determine the incidence of post-NEC strictures. Second, we aimed to determine risk factors associated with intestinal post-NEC strictures.Materials and Methods: A total of 441 patients diagnosed with NEC Bell's stage >= 2 were retrospectively included in three academic pediatric surgical centers between January 2005 and January 2013. Clinical data were related to the occurrence of intestinal post-NEC strictures. Post-NEC strictures were defined as clinically relevant strictures with a radiological and/or surgical confirmation of this post-NEC stricture.Results: The median gestational age of the 337 survivors of the acute phase of NEC was 29 weeks (range 24-41) and median birth weight was 1130 g (range 410-4130). Of the survivors, 37 (17%) medically treated NEC patients developed a post-NEC strictures versus 27 surgically treated NEC patients (24%; p = 0.001). Highest Creactive protein (CRP) level measured during the NEC episode was associated with the development of post-NEC strictures (OR 1.20, 95% confidence interval 1.11-1.32; p = 0.03). No post-NEC strictures were detected in patients with CRP levelsConclusion: This multicenter retrospective cohort study demonstrates an overall incidence of clinical relevant post-NEC strictures of 19%, with a higher rate (24%) in NEC cases treated surgically. Increased CRP levels during the NEC episode were associated with the development of post-NEC strictures. (C) 2016 Elsevier Inc. All rights reserved.

ObjectiveTo investigate the association between invasive mechanical ventilation (IMV) duration and long-term neurodevelopmental outcomes in preterm infants in an era of restricted IMV.DesignRetrospective cohort study.SettingSingle neonatal intensive care unit in Amsterdam.PatientsAll ventilated patients with a gestational age between 24 and 30 weeks born between 2010 and 2015.Main outcome measuresNeurodevelopmental impairment (NDI) at 24 months corrected age (CA). Data on patient characteristics, respiratory management, neonatal morbidities, mortality and bronchopulmonary dysplasia were collected. The relationship between IMV duration and NDI was determined by multivariate logistic regression analysis.ResultsDuring the study period, 368 admitted infants received IMV for a median duration of 2 days. Moderate and severe bronchopulmonary dysplasia was diagnosed in 33% of the infant. Multivariate regression analysis with adjustment for gestational age, small for gestational age and socioeconomic status showed a significant association between every day of IMV and NDI at 24 months CA (adjusted OR [aOR] 1.08, 95% CI 1.004 to 1.16, p=0.04). This association only reached borderline significance when also adjusting for severe neonatal morbidity (aOR 1.08, 95% CI 1.00 to 1.17, p=0.05).ConclusionEven in an era of restricted IMV, every additional day of IMV in preterm infants is strongly associated with an increased risk of NDI at 24 months CA. Limiting IMV should be an important focus in the treatment of preterm infants.

Background: Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age (GA) less than 28weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a PDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. Methods: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA1.5mm. Early treatment (between 24 and 72h postnatal age) with the cyclooxygenase inhibitor(COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage ≥ IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. Discussion: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36weeks., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Treatment of apnea is highly dependent on the type of apnea. Chest impedance (CI) has inaccuracies in monitoring respiration, which compromises accurate apnea classification. Electrical activity of the diaphragm measured by transcutaneous electromyography (EMG) is feasible in preterm infants and might improve the accuracy of apnea classification. Objectives: To compare the accuracy of apnea classification based on diaphragmatic EMG (dEMG) and CI tracings in preterm infants. Methods: Fifteen cases of central apnea, 5 of obstructive apnea, and 10 of mixed apnea were selected from recordings containing synchronized continuous tracings of respiratory inductive plethysmography (RIP), airway flow, heart rate (HR), oxygen saturation (SpO2), and breathing activity measured by dEMG and CI. Twenty-two assessors (neonatologists, pediatricians-in-training, and nurses) classified each apnea twice; once based on dEMG, HR, and SpO2 tracings, and once based on CI, HR, and SpO2. The assessors were blinded to the type of respiratory tracing (dEMG or CI) and to the RIP and flow tracings. Results: In total 1,320 assessments were performed, and in 71.1% the apnea was classified correctly. Subgroup analysis based on respiratory tracing showed that 74.8% of the dEMG tracings were classified correctly compared to 67.3% of the CI tracings (p < 0.001). This improved apnea classification based on dEMG was present for central (86.7 vs. 80.3%, p < 0.02) and obstructive (56.4 vs. 32.7%, p < 0.001) apnea. The improved apnea classification based on dEMG tracing was independent of the type of assessor. Conclusion: Transcutaneous dEMG improves the accuracy of apnea classification when compared to CI in preterm infants, making this technique a promising candidate for future monitoring systems.

Background: Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP). Objective: To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established. Methods: From a retrospective cohort of preterm infants with a gestational age (GA) Results: Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI Conclusions: This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial.

Background and Objective: Restrictive use of invasive mechanical ventilation (IMV) in preterm infants reduces the risk of bronchopulmonary dysplasia (BPD). Our objective was to determine its effect on neurodevelopmental impairment (NDI) at 24 months' corrected age (CA). Methods: This retrospective single-center cohort study included all patients with a gestational age Results: Four hundred and four preterm infants were included. Compared to those in epoch 1, infants in epoch 2 were less likely to be intubated and the duration of IMV was shorter. Other noninvasive adjuvant therapies such as caffeine, doxapram, and nasal ventilation were more often used during epoch 2. There was a trend to less BPD in epoch 2 compared to epoch 1 (17 vs. 23%, adjusted OR = 0.75, 95% CI: 0.48, 1.16). Mortality did not change over time. The combined outcome death or NDI at 24 months' CA was significantly lower in epoch 2 compared to epoch 1 (24.7 vs. 33.9%, adjusted OR = 0.71, 95% CI: 0.53, 0.97). Conclusions: Restricted use of IMV is feasible in preterm infants and might be associated with a reduced risk of the combined outcome death or NDI at 24 months' CA. Larger studies are needed to confirm these findings.

A case of severe scalp laceration due to a scalp electrode in our hospital prompted us to review the available literature on this matter. Roughly three categories of adverse effects due to scalp electrodes can be distinguished: common minor skin lesions (41% of cases of electrode application), scalp abscesses (0.1–4.5%) and rarer, sometimes major, complications only described in case reports. We present a complete overview of published case reports. A recently published Cochrane review on the effectiveness of continuous fetal heart rate monitoring sheds doubt on the benefits of continuous monitoring over intermittent auscultation. Reported complications, considering this controversy regarding the benefits, should prompt clinicians to reconsider at what threshold the benefits of scalp electrode placement outweigh its risks.

Introduction Limited evidence supports the widely used practice of administering platelet transfusions to prevent major bleeding in preterm thrombocytopenic neonates. Only 1 randomized controlled trial addressed this issue, but used thresholds higher than those currently used in clinical practice. In order to assess the impact of platelet transfusions on bleeding risk, the primary objective of this study was to develop a prediction model for bleeding. Platelet transfusion was included as variable in this model. In these secondary analyses, we further explored the impact of platelet transfusions on bleeding risk. Materials and methods In this multicenter cohort study, neonates with a gestational age (GA) 20x109/L only allowed in case of GA Results A total of 640 neonates were included with a median gestational age of 28 weeks. 70 neonates developed a major bleed. IUGR, postnatal age, platelet count and mechanical ventilation were independent predictors of bleeding. The model allowed calculation of two bleeding risks for individual neonates: one in case of platelet transfusion and one in case of no platelet transfusion. 1361 platelet transfusions were administered to 449 of 640 (70%) neonates, of which 87 were hyperconcentrates. The hazard ratio for transfusion in the original model was 1.0, indicating no predictive power. Sensitivity analysis 1: 704 (52%) transfusions were given according to protocol. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.5, but the p-value remained > 0.05.Sensitivity analysis 2: 764 (56%) of transfusions resulted in a count >50x109/L within 24 hours. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.25, but the p-value remained >0.05. 115 (8%) transfusions did not have a follow up platelet count within 24 hours. Sensitivity analysis 3: of the non-hyperconcentrated platelet transfusions, 517 of 1274 (41%) transfusions were ≥ 11 ml/kg. When selecting these transfusions, the hazard ratio for transfusion changed from 1.0 to 0.1, with a p-value of 0.05. Conclusion With this tool, absolute risk of bleeding in individual preterm thrombocytopenic neonates can be calculated. Additionally, risk of bleeding can be assessed for 2 scenarios: with and without platelet transfusion. This can help clinicians in deciding whether or not to transfuse a patient. In the primary model, platelet transfusion was not a predictor for bleeding risk. However, the findings of the sensitivity analyses suggest that transfusions with a dose > 11ml/kg may have a more profound effect on bleeding risk. Disclosures No relevant conflicts of interest to declare.

CONTEXT. Postnatal dexamethasone therapy reduces the incidence of bronchopulmonary dysplasia in preterm infants but may be associated with an increased risk for adverse neurodevelopmental outcome.OBJECTIVE. Our goal was to determine if the effects of dexamethasone on mortality and pulmonary and neurodevelopmental sequelae in preterm infants are modified by the cumulative dose given.METHODS. Randomized, controlled trials comparing dexamethasone with placebo in ventilated preterm infants >7 days old were identified by searching the electronic databases and the abstracts from the Pediatric Academic societies and by performing manual reference searches. Two reviewers independently assessed eligibility and quality of trials and extracted data on study design, patient characteristics, and relevant outcomes. Original trialists were asked to provide additional data.RESULTS. Sixteen trials including 1136 patients were analyzed by using meta-analysis and metaregression. Additional data were provided by 12 original trialists. Trials with a moderately early (7- to 14-day) or delayed (>3-week) postnatal treatment onset were analyzed separately. Higher dexamethasone doses reduced the relative risk for the combined outcome, mortality or bronchopulmonary dysplasia, with the largest effect in trials that used a cumulative dose of >4 mg/kg. No effect was found of doses on the risk of neurodevelopmental sequelae in the delayed treatment studies, but in the moderately-early-treatment studies the risk of mortality or cerebral palsy decreased by 6.2%, and the risk of a Mental Developmental Index below −2 SDs decreased by 6.6% for each incremental mg/kg cumulative dexamethasone dose.CONCLUSIONS. Higher cumulative dexamethasone doses administered after the first week of life may decrease the risk for bronchopulmonary dysplasia without increasing the risk for neurodevelopmental sequelae in ventilated preterm infants. A large randomized trial is needed to confirm or refute these findings.

To determine the efficacy and safety of automated adjustment of the fraction of inspired oxygen (FiO2) in maintaining arterial oxygen saturation (SpO2) within a higher (91%-95%) and a lower (89%-93%) target range in preterm infants. Eighty preterm infants (gestational age [median]: 26 weeks, age [median] 18 days) on noninvasive (n = 50) and invasive (n = 30) respiratory support with supplemental oxygen, were first randomized to one of the SpO2 target ranges and then treated with automated FiO2 (A-FiO2) and manual FiO2 (M-FiO2) oxygen control for 24 hours each, in random sequence. The percent time within the target range was higher during A-FiO2 compared with M-FiO2 control. This effect was more pronounced in the lower SpO2 target range (62 ± 17% vs 54 ± 16%, P < .001) than in the higher SpO2 target range (62 ± 17% vs 58 ± 15%, P < .001). The percent time spent below the target or in hypoxemia (SpO2 98%) was only reduced during A-FiO2 when targeting the lower SpO2 range (89%-93%). These outcomes did not differ between infants on noninvasive and invasive respiratory support. Manual adjustments were significantly reduced during A-FiO2 control. A-FiO2 control improved SpO2 targeting across different SpO2 ranges and reduced hypoxemia in preterm infants on noninvasive and invasive respiratory support. ISRCTN 56626482

To evaluate the accuracy of the diagnosis of bronchopulmonary dysplasia (BPD) in a national database of a referral-based health care system, where preterm infants are often transferred back to regional hospitals before 36 weeks postmenstrual age (PMA). We evaluated preterm infants

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.

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.

Commentary on: Baud O, Maury L, Ramful D, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016;387:1827–36[OpenUrl][1][CrossRef][2][PubMed][3]. Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth, with a reported incidence of 40% in extremely preterm infants (

Background Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative. Objectives To determine if administration of inhalation corticosteroids after the first week of life to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes. Search methods We identified randomised, controlled trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), PubMed (from 1966), EMBASE (from 1974), CINAHL (from 1982), references from retrieved trials and handsearches of journals, all assessed to February 2012. Selection criteria Randomised controlled trials comparing inhalation corticosteroids, started >= 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD were included. Trials investigating systemic corticosteroids versus inhalation corticosteroids were excluded. Data collection and analysis Data on patient characteristics, trial methodology, and inhalation regimens were collected. The primary outcomes were death or BPD, or both, at 28 days PNA or 36 weeks PMA. Secondary outcomes were short-term respiratory outcomes, such as failure to extubate, total days of mechanical ventilation and oxygen use, and the need for systemic corticosteroids. The original trialists were contacted to verify the validity of extracted data and to provide missing data. All data were analysed using RevMan 5.0.24. When possible, meta-analysis was performed using typical risk ratio (TRR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). Ventilated and non-ventilated participants were analysed separately. Main results Eight trials randomising 232 preterm infants were included in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. Furthermore, inhalation steroids did not impact short-term respiratory outcomes such as failure to extubate and total duration of mechanical ventilation or oxygen dependency. There was a trend to a reduced use of systemic corticosteroids in favour of inhalation corticosteroids (TRR 0.51; 95% CI 0.26 to 1.00). There was a paucity of data on short-term and long-term adverse effects. These results should be interpreted with caution because the total number of randomised patients is relatively small and most trials differed considerably in patient characteristics, inhalation therapy and outcome definitions. Authors' conclusions Based on the results of the currently available evidence, inhalation corticosteroids initiated at >= 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis. Discussion This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants. Trial registration number Netherlands Trial Register (NTR): NTR2768

CONTEXT: Open-label glucocorticoids (OLGs) were often used in trials that investigated postnatal dexamethasone treatment in ventilated preterm infants. OBJECTIVE: To determine if OLG use modulates the dexamethasone treatment effect on mortality, bronchopulmonary dysplasia (BPD), and neurodevelopmental outcome. METHODS: Electronic databases, abstracts from the Pediatric Academic Societies, and results of manual reference searches were used as data sources. Fifteen randomized controlled trials comparing dexamethasone with placebo in 721 ventilated preterm infants older than 7 days were identified. The interaction between dexamethasone treatment effect and OLG use was assessed by meta-regression analysis and subgroup meta-analysis according to the percentage of OLG use in the placebo group. Trials with a moderately early (7- to 14-day) or delayed (>3-week) treatment onset were analyzed separately. RESULTS: Moderately early, but not delayed, dexamethasone treatment significantly reduced mortality rates in trials with OLG use at CONCLUSIONS: When OLG use is taken into account moderately early dexamethasone treatment reduced mortality rates and the combined outcome mortality and BPD without increasing the risk of adverse neurodevelopmental outcome in ventilated preterm infants. A large randomized controlled trial is needed to confirm or refute these findings.

Although it is generally accepted that antenatal corticosteroids reduce neonatal complications after preterm labor, it is unclear at what gestational age this effect starts to occur. We conducted a systematic review of the literature to determine the effects of antenatal corticosteroids given to women at risk of preterm birth

OBJECTIVES. Systemic postnatal dexamethasone treatment reduces the risk of chronic lung disease in preterm infants but also may be associated with increased risk of neurodevelopmental impairment. Because it is not known whether these effects are modulated by the cumulative dexamethasone dose, we systematically reviewed the available randomized evidence on the effects of lower versus higher cumulative dexamethasone doses, in terms of death, pulmonary morbidity, and neurodevelopmental outcomes, in preterm infants.METHODS. Randomized, controlled trials comparing higher- versus lower-dosage dexamethasone regimens in ventilated preterm infants were identified by searching the main electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research (from 1990 onward). Eligibility and quality of trials were assessed, and data on study design, patient characteristics, and relevant outcomes were extracted.RESULTS. Six studies that enrolled a total of 209 participants were included; 2 studies contrasted cumulative dexamethasone doses in the higher ranges (>2.7 mg/kg in the higher-dosage regimen) and 4 in the lower ranges (≤2.7 mg/kg in the higher-dosage regimen). Meta-analysis revealed no effect of dexamethasone dose on rates of death and neurodevelopmental sequelae in these 2 subgroups. Subgroup analysis of the studies contrasting dexamethasone doses in the higher ranges showed that the higher dose of dexamethasone was more effective in reducing the occurrence of chronic lung disease than was the lower dose. Interpretation of these data was hampered by the small samples of randomly assigned children, heterogeneity of study populations and designs, use of late rescue glucocorticoids, and lack of long-term neurodevelopmental data in some studies.CONCLUSIONS. Recommendations for optimal dexamethasone doses for preterm infants at risk for chronic lung disease cannot be based on current evidence. A well-designed, large, randomized, controlled trial is urgently needed to establish the optimal dexamethasone dosage regimen.

Objectives To use the ethanol-lock technique (in conjunction with systemic antibiotics) to salvage central lines from removal and to prevent persistence of catheter-related infections among pediatric patients with long-term intravascular devices. Design Medical records of patients treated with ethanol locks were retrospectively reviewed from June 1, 2004, through June 22, 2005. Setting Childrens Hospital Los Angeles, Los Angeles, Calif, a tertiary care pediatric hospital. Patients Forty children with diverse underlying disorders were treated for 51 catheter-related infections using the Childrens Hospital Los Angeles ethanol-lock technique. Interventions Eligible infected central lines were instilled with a dose volume of 0.8 to 1.4 mL of 70% ethanol into the catheter lumen during 12 to 24 hours and then withdrawn. The volume of ethanol used was based on the type of intravascular device. Main Outcome Measures Clearance of infection and incidence of recurrence. Results Of the 51 ethanol-lock treatments in 40 children, no catheters were removed because of persistent infection. Eighty-eight percent (45/51) of the treated episodes cleared without recurrence (defined as a relapse within 30 days with the same pathogen). Twelve (75%) of 16 polymicrobial isolates and 33 (94%) of 35 monomicrobial isolates were successfully treated. There were no adverse reactions or adverse effects reported. Conclusion This retrospective study supports the use of the ethanol-lock technique in conjunction with systemic antibiotics as an effective and safe method to retain the use of a previously infected central venous catheter, decrease the need for line removal, and eradicate persistent pathogens in catheter-related infections.

Background Preterm infants spend only 50% of time within the target oxygen saturation (SpO 2 ) during manual FiO 2 control (M-FiO 2 ). Automated FiO 2 control (A-FiO 2 ) improves SpO 2 targeting but it is uncertain if this applies to different SpO 2 target ranges and during non-invasive support (NIVS) and mechanical ventilation (MV). Objective To compare the efficacy of A-FiO 2 vs M-FiO 2 in keeping two different SpO 2 targets during NIVS or MV. Design/methods Preterm infants on FiO 2 >0.21 receiving NIVS or MV were randomised to SpO 2 targets 89–93% or 91–95% and underwent M-FiO 2 and A-FiO 2 for 24 h each, in random sequence. Results 80 infants (GA:26 w, age:18 d) were included (NIVS = 48, MV = 32). Time within target increased and below target decreased during A-FiO 2 compared with M-FiO 2 , especially in the lower target range. There was a reduction in time and hypoxemia episodes with SpO 2 2 . Outcomes did not differ between NIVS or MV. Conclusions Automated FiO 2 control improved SpO 2 targeting across different SpO 2 ranges and reduced hypoxemia with less workload during both NIVS and MV.

Item does not contain fulltext The diarrhea-associated form of the hemolytic uremic syndrome (D+ HUS) is characterized by a triad of symptoms, namely thrombocytopenia, hemolytic anemia, and acute renal failure. Histopathological studies of patients with D+ HUS show microthrombi in arterioles and glomeruli of the kidney. Recently, it was suggested that antiphospholipid antibodies might play a pathogenic role in D+ HUS. However, an epiphenomenon could not be excluded. In this study we investigated the relationship between antiphospholipid antibodies and clinical symptoms in 22 patients with the classical form of HUS (D+ HUS). The first sample was obtained on the day of admission. The next samples were taken on day 7 and 14. We measured anticardiolipin (aCL) antibodies (IgM, IgA, and IgG) in the samples using an ELISA. A significant increase in IgM (60%) and IgG (41%) aCL antibodies was seen in patients versus controls. No relationship between aCL antibody levels and severity of renal failure could be demonstrated. These data suggest that antiphospholipid antibodies are increased, but have not been shown to have a role in the pathogenesis of the microangiopathy seen in D+HUS.

Background Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants. Methods/Design The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age

Background Bronchopulmonary dysplasia (BPD), defined as oxygen dependence at 36 weeks postmenstrual age (PMA), remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD. Attenuating pulmonary inflammation with postnatal systemic corticosteroids reduces the incidence of BPD in preterm infants but may be associated with an increased risk of adverse neurodevelopmental outcomes. Local administration of corticosteroids via inhalation might be an effective and safe alternative. Objectives To determine if administration of inhalation corticosteroids after the first week of life until 36 weeks PMA to preterm infants at high risk of developing BPD is effective and safe in reducing the incidence of death and BPD as separate or combined outcomes. Search methods We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 4), MEDLINE via PubMed (1966 to 19 May 2017), Embase (1980 to 19 May 2017), and CINAHL (1982 to 19 May 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Selection criteria We included randomised controlled trials comparing inhalation corticosteroids, started ≥ 7 days postnatal age (PNA) but before 36 weeks PMA, to placebo in ventilated and non-ventilated infants at risk of BPD. We excluded trials investigating systemic corticosteroids versus inhalation corticosteroids. Data collection and analysis We collected data on participant characteristics, trial methodology, and inhalation regimens. The primary outcome was death or BPD at 36 weeks PMA. Secondary outcomes were the combined outcome death or BPD at 28 days PNA, the seperate outcomes of death and BPD at both 28 days PNA, and at 36 weeks PMA, and short-term respiratory outcomes, such as failure to extubate; total days of mechanical ventilation and oxygen use; and the need for systemic corticosteroids. We contacted the original trialists to verify the validity of extracted data and to provide missing data. We analysed all data using Review Manager 5. When possible, we performed meta-analysis using typical risk ratio (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes along with their 95% confidence intervals (CI). We analysed ventilated and non-ventilated participants separately. We used the GRADE approach to assess the quality of the evidence. Main results We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I2 statistic 73% and 86%, respectively). Furthermore, inhalation steroids did not impact total duration of mechanical ventilation or oxygen dependency. There was a trend toward a reduction in the use of systemic corticosteroids in infants receiving inhalation corticosteroids (TRR 0.51, 95% CI 0.26 to 1.00; 4 studies, 74 infants; very low-quality evidence). There was a paucity of data on short- and long-term adverse effects. Our results should be interpreted with caution because the total number of randomised participants is relatively small, and most trials differed considerably in participant characteristics, inhalation therapy, and outcome definitions. Authors' conclusions Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.