Bar graph depicting body weights of rat pups at birth and P10.

<p>*p<0.05 compared to Normoxia group; #p<0.05 compared to Normoxia+VPA group; and †p<0.05 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p

Histological examination of lung tissues by Haematoxylin-eosin (A-D, 100X magnification), Masson’s trichrome (E-H, 400X magnification), lamellar body membrane protein (LBMP) (I-L, 1000X magnification), and TUNEL-DAB stainings (M-P, 200X magnification) for Normoxia, Normoxia+VPA, Hyperoxia and Hyperoxia+VPA groups.

<p>Representative images show severe alveolar damage (panel C), cell infiltration and edema (panel G, arrow) in Hyperoxia group. Thickening of the alveolar septi or cell infiltration was not observed in Normoxia, Normoxia+VPA and Hyperoxia+VPA groups and panels A, B, D, E, F and H shows healthier and intact lung parenchymal appearance compared to hyperoxia group. Black arrows indicate positive immunoreactivity for LBMP and TUNEL(+) cells in panels I-P.</p

Bar graphs depicting histone deacetylase (HDAC) activity (A) as well as acetylated histone H3 (B) and acetylated histone H4 (C) protein expressions in lung tissues of rat pups.

<p>*p<0.05 and **p<0.001 compared to Normoxia group; #p<0.05 and ##p<0.001 compared to Normoxia+VPA group; and ††p<0.001 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p

Bar graphs depicting TGFβ1 (A), TGFβ3 (B) and phospho-SMAD2 (C) expressions in lung tissues of rat pups.

<p>Panel D depicts representative bands for each protein, including β-Actin, the protein which was used as a loading control for western blotting. *p<0.05 and **p<0.001 compared to Normoxia group; #p<0.05 and ##p<0.001 compared to Normoxia+VPA group; and †p<0.05 and ††p<0.001 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p

Comparison of lung tissue pro-inflammatory cytokine levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxdase (MPO) activities and malonedialdehyde (MDA) content in all groups.

<p>*p<0,05 and</p><p><b>**</b>p<0,01 compared to Normoxia group; and</p><p>^†p<0,05 and</p><p>^‡p<0,01 compared to Hyperoxia group using One-Way ANOVA followed by post-hoc Tukey test.</p><p>Comparison of lung tissue pro-inflammatory cytokine levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and myeloperoxdase (MPO) activities and malonedialdehyde (MDA) content in all groups.</p

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</p