Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. / Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. / Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. / Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. / Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. / Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). / Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. / Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943

Supraglottic airway devices during neonatal resuscitation: An historical perspective, systematic review and meta-analysis of available clinical trials

INTRODUCTION: Various supraglottic airway devices are routinely used to maintain airway patency in children and adults. However, oropharyngeal airways or laryngeal masks (LM) are not routinely used during neonatal resuscitation. METHODS: The aim of this article was to review the available literature about the use of supraglottic airway devices during neonatal resuscitation. We reviewed books, resuscitation manuals and articles from 1830 to the present using the search terms "Infant", "Newborn", "Delivery Room", "Resuscitation", "Airway management", "Positive Pressure Respiration", "Oropharyngeal Airway" and "Laryngeal Mask". RESULTS: No study was identified using oropharyngeal airways during neonatal resuscitation. Four trials including 509 infants compared positive pressure ventilation with a LM, bag and mask or an endotracheal tube. Infants in the LM group were intubated less frequently compared to infants in the bag and mask ventilation group 4/275 vs. 28/234 (OR 0.13, 95% CI 0.05-0.34). Infants resuscitated with the LM had significantly less unsuccessful resuscitations 4/275 vs. 31/234 (OR 0.10, 95% CI 0.03-0.28). Two trials including 34 preterm infants compared surfactant administration via LM vs. endotracheal tube. LM surfactant administration was safe and no adverse events were reported. CONCLUSION: The efficacy and safety of oropharyngeal airways during neonatal resuscitation remain unclear and randomized trials are required. The current evidence suggests that resuscitation with a LM is a feasible and safe alternative to mask ventilation in infants >34 weeks gestation and birth weight >2000 g. However, further randomized control trials are needed to evaluate short- and long-term outcomes following use of laryngeal masks. In addition, surfactant administration via LM should be used only within clinical trials

Medical retrieval and needs of infants with bronchiolitis: An analysis by gestational age

AIM: Viral bronchiolitis is the most common lower respiratory tract infection in children less than 12 months of age. Prematurity is an independent risk factor for disease severity. Many infected infants require hospitalisation and those living in regional centres frequently require transfer to metropolitan hospitals capable of providing assisted ventilation. METHOD: We reviewed infants with bronchiolitis transported by the Victorian Newborn Emergency Transport Service between January 2003 and June 2007. We compared the clinical presentation and treatment required by infants born preterm with those of their term counterparts. RESULTS: Of the 192 infants transported, 92 were born preterm. Preterm infants were younger at time of transport (mean post-menstrual age 41 weeks vs. 45 weeks) and were more likely to require invasive ventilation (60% vs. 32%, P < 0.001) and to receive a fluid bolus (47% vs. 34%, P = 0.04) when compared with infants who had been born at term. Apnoea, either as a presenting symptom or in combination with respiratory distress, was more common in the preterm group (70% vs. 36%, P < 0.001). CONCLUSION: Higher illness severity should be anticipated in ex-preterm infants who present with bronchiolitis. Preterm infants with bronchiolitis are more likely to require invasive ventilation and fluid resuscitation than term infants, suggesting the need for a lower threshold for referral and medical retrieval

Lung ultrasound during newborn resuscitation predicts the need for surfactant therapy in very- and extremely preterm infants

INTRODUCTION: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants. METHODS: Infants born at <320/7 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10 min, 11-20 min, and 1-3 h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO2 threshold of 0.3 to predict subsequent surfactant therapy. RESULTS: Fifty-two infants with a median age of 276/7 weeks (IQR 260/7-286/7) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10 min, 11-20 min and 1-3 h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO2 at the 5-10 min timepoint (AUC 0.45, 95% CI 0.29-0.62, p = 0.001). At 11-20 min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-276/7 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment. CONCLUSIONS: LUS in the delivery room and accurately predicts surfactant therapy in infants <320/7 weeks

Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities

Necrotizing enterocolitis (NEC) is a severe, currently untreatable intestinal disease that predominantly affects preterm infants and is driven by poorly characterized inflammatory pathways. Here, human and murine NEC intestines exhibit an unexpected predominance of type 3/TH17 polarization. In murine NEC, pro-inflammatory type 3 NKp46−RORγt+Tbet+ innate lymphoid cells (ILC3) are 5-fold increased, whereas ILC1 and protective NKp46+RORγt+ ILC3 are obliterated. Both species exhibit dysregulation of intestinal TLR repertoires, with TLR4 and TLR8 increased, but TLR5-7 and TLR9-12 reduced. Transgenic IL-37 effectively protects mice from intestinal injury and mortality, whilst exogenous IL-37 is only modestly efficacious. Mechanistically, IL-37 favorably modulates immune homeostasis, TLR repertoires and microbial diversity. Moreover, IL-37 and its receptor IL-1R8 are reduced in human NEC epithelia, and IL-37 is lower in blood monocytes from infants with NEC and/or lower birthweight. Our results on NEC pathomechanisms thus implicate type 3 cytokines, TLRs and IL-37 as potential targets for novel NEC therapies