Intratracheal Instillation of Budesonide-Surfactant for Prevention of Bronchopulmonary Dysplasia in Extremely Premature Infants.

OBJECTIVE: This study aimed to determine the effect of intratracheal instillation of a budesonide-surfactant combination on the incidence of bronchopulmonary dysplasia (BPD) or death compared with surfactant alone in extremely preterm infants. STUDY DESIGN: In this retrospective, single-center study, we included extremely preterm infants (<28 weeks' gestation) who received surfactant for respiratory distress in the first 3 days of life. We compared infants who received budesonide-surfactant combination (intervention group: infants born between February 2016 and October 2021) with surfactant alone (control group: infants born from January 2010 through January 2016). The primary outcome was a composite of BPD grade 2 or 3 (as defined by Jensen et al, 2019) or death before 36 weeks' postmenstrual age (PMA). RESULTS: We included 966 extremely preterm infants (528 in the control group and 438 in the intervention group). While the incidence of death/BPD grade 2 or 3 at 36 weeks of PMA was not different between the two groups (66% in the intervention group vs. 63% in the control group; adjusted relative risk [aRR], 0.99; 95% confidence interval [CI], 0.90-1.07; p-value = 0.69), budesonide was associated with a reduction in the primary outcome only in a subgroup of infants with birth weight ≥ 750 grams (36.8 vs. 43.5%, respectively; aRR 0.75; 95% CI, 0.57-0.98). Primary and secondary outcomes did not differ between the two groups within the subgroup of infants weighing <750 grams. CONCLUSION: In extremely preterm infants, the budesonide-surfactant combination therapy reduced the rates of BPD or death in infants weighing ≥750 grams; however, this beneficial effect was not seen in infants weighing <750 grams. Further investigation of this treatment may be indicated before it is considered a standard approach to management. KEY POINTS: · Intratracheal budesonide-surfactant therapy reduces BPD in preterm infants weighing ≥750 grams.. · Intratracheal budesonide-surfactant therapy does not affect BPD in preterm infants weighing <750 grams.. · Intratracheal budesonide-surfactant therapy does not affect the mortality rate in preterm infants..

The Impact of a Prenatal Education Program for Opioid-Dependent Mothers on Breastfeeding Rates of Infants at Risk for Neonatal Abstinence Syndrome.

INTRODUCTION: This study aimed to determine the effect of a prenatal education program for opioid-dependent women on breastfeeding frequency, newborn hospital length of stay, and cost of care for neonates at risk of developing neonatal abstinence syndrome. METHODS: From January 1, 2015 to January 1, 2020, opioid-dependent obstetric patients were educated on non-pharmacological preventative measures for neonatal abstinence syndrome (NAS), with focused counseling on breastfeeding. Data were collected and compared to a control group of opioid-dependent pregnant women who received standard care before initiation of the education program. RESULTS: Sample size calculation revealed that to detect doubling of the breastfeeding rate from 25% to 50% with 80% power and α error of 0.05, 66 participants were required in each group. CONCLUSION: There were 75 women with opioid use disorder who had prenatal NAS education (study group) and 108 women with opioid use disorder who underwent standard care before NAS education (control group). Prenatal NAS education participants significantly increased breastfeeding initiation rates compared to the control group. Newborn length of stay significantly decreased after initiation of prenatal NAS education compared to the 36 months before NAS education program.

Bevacizumab for Retinopathy of Prematurity: 2-Year Neurodevelopmental Follow-up.

OBJECTIVE: This study aimed to determine whether infants who were treated with intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP) were at higher risk of death or neurodevelopmental impairment (NDI) when compared with infants who were not treated with IVB (Laser only). STUDY DESIGN: This retrospective study included 146 infants born from 2009 through 2016 with a birth weight (BW) <1,000 g, gestational age <27 weeks, and required ROP therapy. Death and NDI rates were assessed at 18 to 24 months' corrected age. RESULTS: Rates of death or severe NDI were 62 and 53% in the IVB (n = 61) and Laser only (n = 85) groups, respectively. This difference was not statistically different despite sample selection bias in treating growth-restricted infants with IVB, BW (median [IQR]) was 481 (420-583) versus 547 (473-640) g in IVB and Laser only groups, respectively, p = 0.003. The adjusted odds ratio and 95% confidence interval of death or severe NDI was 0.86 (0.33-2.20). CONCLUSION: Bevacizumab therapy for ROP did not affect survival and neurodevelopment of extremely preterm infants. KEY POINTS: · Intravitreal bevacizumab therapy for retinopathy of prematurity may be safe in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase mortality rate in periviable preterm infants.. · Intravitreal bevacizumab therapy does not increase adverse neurodevelopmental outcome in periviable infants..

A single-dose indomethacin prophylaxis for reducing perinatal brain injury in extremely low birth weight infants: a non-inferiority analysis.

OBJECTIVE: To evaluate whether rates of perinatal brain injury among extremely low birth weight infants are comparable between two treatments: single-dose indomethacin prophylaxis (SGL-IP) (0.2 mg/kg, given once) vs. standard-dose indomethacin prophylaxis (STD-IP) (0.1 mg/kg/day, 3 days). METHODS: In this retrospective study, the primary outcome was perinatal brain injury (neuro-imaging evidence of intraventricular hemorrhage or periventricular leukomalacia) or death before discharge. A non-inferior efficacy of an SGL-IP regimen compared with a STD-IP regimen was determined by calculating the adjusted difference in the risk of the primary outcome using a multivariable logistic regression model. A 10-percentage point non-inferiority margin was favored. RESULTS: Prevalence rates of primary outcome were 41.7% in the SGL-IP group (n = 403) and 42.5% in the STD-IP group (n = 509) (adjusted risk difference: -1.2, 95% CI: -7.6 to +5.2, p = 0.71). CONCLUSION: Use of a single prophylactic indomethacin dose was as effective as a standard regimen in preventing perinatal brain injury.

Nonsurgical Management of Persistent and Hemodynamically Significant Patent Ductus Arteriosus among Extremely Low Birth Weight Infants: A Propensity Score Matched Analysis.

OBJECTIVE: The objective of this study was to evaluate the impact of a nonsurgical approach (with the incorporation of late postnatal hydrocortisone treatment to facilitate extubation) in comparison to the surgical approach for the management of persistent hemodynamically significant patent ductus arteriosus (hsPDA) among chronically ventilator-dependent extremely low birth weight (ELBW) infants. METHODS: In this retrospective study, ELBW infants with a diagnosis of hsPDA (diagnosed based on the echocardiographic criteria and chronic ventilator dependence) that were persistent beyond 14 days of postnatal age despite adequate medical treatment were included. RESULTS: Out of 127 infants (surgical approach group, n = 67 and nonsurgical approach group, n = 60), 72 infants were matched based on the propensity scores. In the matched cohort, in comparison to infants managed with the surgical approach (control group, n = 36), infants in the nonsurgical approach group (treatment group, n = 36) had a lower rate of surgical ligation (14 vs. 100%, p = < 0.001), but there were no differences in both primary outcome (death or bronchopulmonary dysplasia) and secondary outcome measures. CONCLUSION: For chronically ventilator-dependent ELBW infants with persistent hsPDA, a nonsurgical management approach is associated with a reduced rate of surgical ligation of PDA, but not associated with increased risk of adverse major short-term neonatal outcomes.

Reduction in alveolar macrophages attenuates acute ventilator induced lung injury in rats.

OBJECTIVE: Alveolar macrophages are the sentinel cell for activation of the inflammatory cascade when the lung is exposed to noxious stimuli. We investigated the role of macrophages in mechanical lung injury by comparing the effect of high-volume mechanical ventilation with or without prior depletion of macrophages. DESIGN AND SETTING: Randomized sham-controlled animal study in anesthetized rats. METHODS: Lung injury was induced by 15 min of mechanical ventilation (intermittent positive pressure ventilation) using high peak pressures and zero end-expiratory pressure. The mean tidal volume was 40+/-0.7 ml/kg. One group of animals was killed immediately after this period of volutrauma (HV), while in a second group normoventilation was continued for 2 h at a tidal volume less than 10 ml/kg (HV-LV). One-half of the animals were depleted of alveolar macrophages by pretreatment with intratracheal liposomal clodronate (CL2MDP). MEASUREMENTS: Arterial blood gas, blood pressure. After kill: lung static pressure volume curves, bronchoalveolar fluid concentration for protein, macrophage inflammatory protein 2, tumor necrosis factor alpha, and wet/dry lung weight ratio (W/D). RESULTS: During HV and HV+LV oxygenation, lung compliance, and alveolar stability were better preserved in animals pretreated with CL2MDP. In both groups W/D ratio was significantly greater in ventilated than in nonventilated animals (4.5+/-0.6), but the increase in W/D was significantly less in CL2MDP treated HV and HV-LV groups (6.1+/-0.4, 6.6+/-0.6) than in the similarly ventilated nontreated groups (8.7+/-0.2 and 9.2+/-0.5). CONCLUSIONS: Alveolar macrophages participate in the early phase of ventilator-induced lung injury.

Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice.

Lung vascular permeability is acutely increased by high-pressure and high-volume ventilation. To determine the roles of mechanically activated cytosolic PLA2 (cPLA2)and Clara cell secretory protein (CCSP), a modulator of cPLA2 activity, we compared lung injury with and without a PLA2 inhibitor in wild-type mice and CCSP-null mice (CCSP-/-) ventilated with high and low peak inflation pressures (PIP) for 2- or 4-h periods. After ventilation with high PIP, we observed significant increases in the bronchoalveolar lavage albumin concentrations, lung wet-to-dry weight ratios, and lung myeloperoxidase in both genotypes compared with unventilated controls and low-PIP ventilated mice. All injury variables except myeloperoxidase were significantly greater in the CCSP-/- mice relative to wild-type mice. Inhibition of cPLA2 in wild-type and CCSP-/- mice ventilated at high PIP for 4 h significantly reduced bronchoalveolar lavage albumin and total protein and lung wet-to-dry weight ratios compared with vehicle-treated mice of the same genotype. Membrane phospho-cPLA2 and cPLA2 activities were significantly elevated in lung homogenates of high-PIP ventilated mice of both genotypes but were significantly higher in the CCSP-/- mice relative to the wild-type mice. Inhibition of cPLA2 significantly attenuated both the phospho-cPLA2 increase and increased cPLA2 activity due to high-PIP ventilation. We propose that mechanical activation of the cPLA2 pathway contributes to acute high PIP-induced lung injury and that CCSP may reduce this injury through inhibition of the cPLA2 pathway and reduction of proinflammatory products produced by this pathway.

Ventilator-induced lung injury: in vivo and in vitro mechanisms.

A lung-protective ventilator strategy significantly reduces mortality in patients with acute lung injury. Substantial progress has been made in understanding how mechanical stress can injure the lung, both in terms of alterations in barrier properties of the pulmonary endothelium and epithelium as well as in stimulating proinflammatory responses of macrophages and neutrophils.