The Role of the Interleukin-1 Family in Complications of Prematurity.

Preterm birth is a major contributor to neonatal morbidity and mortality. Complications of prematurity such as bronchopulmonary dysplasia (BPD, affecting the lung), pulmonary hypertension associated with BPD (BPD-PH, heart), white matter injury (WMI, brain), retinopathy of prematurity (ROP, eyes), necrotizing enterocolitis (NEC, gut) and sepsis are among the major causes of long-term morbidity in infants born prematurely. Though the origins are multifactorial, inflammation and in particular the imbalance of pro- and anti-inflammatory mediators is now recognized as a key driver of the pathophysiology underlying these illnesses. Here, we review the involvement of the interleukin (IL)-1 family in perinatal inflammation and its clinical implications, with a focus on the potential of these cytokines as therapeutic targets for the development of safe and effective treatments for early life inflammatory diseases.

Anakinra Pilot - a clinical trial to demonstrate safety, feasibility and pharmacokinetics of interleukin 1 receptor antagonist in preterm infants.

Background: Bronchopulmonary dysplasia (BPD), its complication pulmonary hypertension (BPD-PH) and preterm brain and gut injury lead to significant morbidity and mortality in infants born extremely prematurely. There is extensive evidence that the pro-inflammatory cytokine interleukin 1 (IL-1) plays a key role in the pathophysiology of these illnesses. Two decades of clinical use in paediatric and adult medicine have established an excellent safety and efficacy record for IL-1 blockade with IL-1 receptor antagonist (IL-1Ra, medication name anakinra). Building on robust pre-clinical evidence, the Anakinra Pilot trial aims to demonstrate safety and feasibility of administering anakinra to preterm infants, and to establish pharmacokinetics in this population. Its ultimate goal is to facilitate large studies that will test whether anakinra can ameliorate early-life inflammation, thus alleviating multiple complications of prematurity. Methods and analysis: Anakinra Pilot is an investigator-initiated, single arm, safety and feasibility dose-escalation trial in extremely preterm infants born between 24 weeks 0 days (240) and 276 weeks of gestational age (GA). Enrolled infants will receive anakinra intravenously over the first 21 days after birth, starting in the first 24 h after birth. In the first phase, dosing is 1 mg/kg every 48 h, and dosage will increase to 1.5 mg/kg every 24 h in the second phase. Initial anakinra dosing was determined through population pharmacokinetic model simulations. During the study, there will be a interim analysis to confirm predictions before undertaking dose assessment. Anakinra therapy will be considered safe if the frequency of adverse outcomes/events does not exceed that expected in infants born at 240-276 weeks GA. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05280340.

Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units.

OBJECTIVE: To assess the procedural and clinical outcomes associated with the introduction of minimally invasive surfactant therapy (MIST) into standard care at 2 tertiary Australian neonatal intensive care units. STUDY DESIGN: A prospective audit was designed before the introduction of MIST in 2018, with data collected over a period of 18 months. Procedural data were completed by the clinical team performing MIST, including clinical observations, medication use, and adverse events. The audit team collected demographic data and subsequent clinical outcomes from medical records. RESULTS: There were 135 MIST procedures recorded in 122 infants. For the included infants, the median gestation was 302/7 weeks (IQR, 276/7 to 322/7 weeks) and birth weight was 1439 g (IQR, 982-1958 g). During the MIST procedure, desaturation to a peripheral oxygen saturation of <80% was common, occurring in 75.2% of procedures. Other adverse events included need for positive pressure ventilation (10.6%) and bradycardia <100 beats per minute (13.3%). The use of atropine premedication was associated with a significantly lower incidence of bradycardia: 8.6% vs 52.9% (P < .01). Senior clinicians demonstrated higher rates of procedural success. The majority of infants (63.9%) treated with MIST did not require subsequent intubation and mechanical ventilation. CONCLUSIONS: MIST can be successfully introduced in neonatal units with limited experience of this technique. The use of atropine premedication decreases the incidence of bradycardia during the procedure. Success rates can be optimized by limiting MIST to clinicians with greater competence in endotracheal intubation.