Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (the SToP-BPD study): Statistical analysis plan

Background: Bronchopulmonary dysplasia (BPD) is the most common complication of preterm birth with short-term and long-term adverse consequences. Although the glucocorticoid dexamethasone has been proven to be beneficial for the prevention of BPD, there are concerns about an increased risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. The aim of the Systemic Hydrocortisone To Prevent Bronchopulmonary Dysplasia in preterm infants (SToP-BPD) trial is to assess the efficacy and safety of postnatal hydrocortisone administration for the reduction of death or BPD in ventilator-dependent preterm infants. Methods/design: The SToP-BPD study is a multicentre, double-blind, placebo-controlled hydrocortisone trial in preterm infants at risk for BPD. After parental informed consent is obtained, ventilator-dependent infants are randomly allocated to hydrocortisone or placebo treatment during a 22-day period. The primary outcome measure is the composite outcome of death or BPD at 36 weeks postmenstrual age. Secondary outcomes are short-term effects on pulmonary condition and long-term neurodevelopmental sequelae assessed at 2 years corrected age. Complications of treatment, other serious adverse events and suspected unexpected serious adverse reactions are reported as safety outcomes. This pre-specified statistical analysis plan was written and submitted without knowledge of the unblinded data

Doxapram versus placebo in preterm newborns: a study protocol for an international double blinded multicentre randomized controlled trial (DOXA-trial)

Abstract Background Apnoea of prematurity (AOP) is one of the most common diagnoses among preterm infants. AOP often leads to hypoxemia and bradycardia which are associated with an increased risk of death or disability. In addition to caffeine therapy and non-invasive respiratory support, doxapram might be used to reduce hypoxemic episodes and the need for invasive mechanical ventilation in preterm infants, thereby possibly improving their long-term outcome. However, high-quality trials on doxapram are lacking. The DOXA-trial therefore aims to investigate the safety and efficacy of doxapram compared to placebo in reducing the composite outcome of death or severe disability at 18 to 24 months corrected age. Methods The DOXA-trial is a double blinded, multicentre, randomized, placebo-controlled trial conducted in the Netherlands, Belgium and Canada. A total of 396 preterm infants with a gestational age below 29 weeks, suffering from AOP unresponsive to non-invasive respiratory support and caffeine will be randomized to receive doxapram therapy or placebo. The primary outcome is death or severe disability, defined as cognitive delay, cerebral palsy, severe hearing loss, or bilateral blindness, at 18–24 months corrected age. Secondary outcomes are short-term neonatal morbidity, including duration of mechanical ventilation, bronchopulmonary dysplasia and necrotising enterocolitis, hospital mortality, adverse effects, pharmacokinetics and cost-effectiveness. Analysis will be on an intention-to-treat principle. Discussion Doxapram has the potential to improve neonatal outcomes by improving respiration, but the safety concerns need to be weighed against the potential risks of invasive mechanical ventilation. It is unknown if the use of doxapram improves the long-term outcome. This forms the clinical equipoise of the current trial. This international, multicentre trial will provide the needed high-quality evidence on the efficacy and safety of doxapram in the treatment of AOP in preterm infants. Trial registration ClinicalTrials.gov NCT04430790 and EUDRACT 2019-003666-41. Prospectively registered on respectively June and January 2020

Unsuccessful resuscitation of a preterm infant due to a pneumothorax and a masked tension pneumopericardium

Pneumopericardium is the least common form of air leak in infants. A tension pneumopericardium is even more infrequent but associated with a very high mortality rate. We describe the case of an unsuccessful resuscitation in a preterm infant due to a pneumothorax and tension pneumopericardium. Despite relatively mild pressure ventilation the patient developed massive pulmonary interstitial emphysema. The extra-alveolar air spread from the interstitium towards the mediastinal space (Macklin effect) and caused a pneumothorax and pneumopericardium, which evolved towards a tension pneumopericardium after a traumatic mechanical procedure. The infant deteriorated acutely. Despite prompt pleural drainage there were no signs of recovery at any time. Postmortal examination revealed a tension pneumopericardium and massive interstitial pulmonary emphysema, which was not obvious on radiographical investigation. In cases of acute deterioration of a ventilated neonate, one should always rule out pneumothorax. If the patient does not recover after pleural drainage and cardiac resuscitation a (tension) pneumopericardium should be considered.status: publishe

Neurodevelopmental outcomes of very preterm and very-low-birthweight infants in a population-based clinical cohort with a definite perinatal treatment policy

BACKGROUND: With constant changes in neonatal care practices, recent information is valuable for healthcare providers and for parental counselling. The aim of the study was to describe the neurodevelopmental outcome in a cohort of very preterm (VPT)/very-low-birthweight (VLBW) infants at 2 years corrected age (CA). MATERIAL AND METHODS: This is a population-based cohort study of all infants born with a GA <31 weeks and/or BW < 1500 g between 2014 and 2016 admitted to the Flemish (Belgium) neonatal intensive care units. Infants had routine clinical follow-up around 2 years CA. The diagnosis of cerebral palsy (CP), visual and hearing impairments were recorded. Motor, cognitive and language outcomes were assessed using the Bayley-III. Neurodevelopmental impairment (NDI) was classified as mild (<1 standard deviation [SD]) or moderate-severe (<2SD) based on the defined categories of motor, cognitive, hearing, and vision impairments. RESULTS: Of the 1941 admissions, 92% survived to discharge and follow-up data were available for 1089 infants (61.1%). Overall, 19.3%, 18.9% and 41.8% of infants had a motor, cognitive and language delay, respectively. CP was diagnosed in 4.3% of the infants. Mild and moderate-to-severe NDI was observed in 25.2% and 10.9% of the infants, respectively. The number of infants with a normal outcome increased from nearly 40% in the category of GA<26 weeks to 70% for infants in the category of 30─31 weeks GA. CONCLUSION: At 2 years CA, 64% were free from NDI and 90% were free from moderate-to-severe NDI. However, a lower GA and BW are associated with higher rates of adverse neurodevelopmental outcomes at 2 years CA.status: publishe