Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Lung recruitment strategies and surfactant in neonatal intensive care unit.

Several studies in the lamb model have shown that hyperinflation of the lungs early in life may cause a blunted response to surfactant with signs of lung injury and any attempt to recruit lung volume in the surfactant deficient preterm infant by large lung inflations at birth should be potentially dangerous. As regards the situation when surfactant is given later, as rescue treatment for established RDS, the evidence for a clinically beneficial effect of a recruitment maneuver is yet insufficient and, hopefully, future studies will gather more data on this aspect.

Adrenocortical insufficiency is not a problem in preterm infants treated with antifungal prophylaxis with fluconazole.

AIM: Fluconazole prophylaxis of invasive fungal infections is a cornerstone of neonatal care, but in vitro studies have shown that it inhibits corticosteroid production. This study assessed whether preterm infants demonstrated an association between fluconazole administration, and its duration, and symptoms of adrenocortical insufficiency. METHODS: We compared two groups who were treated before and after we introduced the use of fluconazole to our neonatal intensive care unit. Infants with a gestational age of ≤27 weeks or with a birth weight of ≤750 g were considered for the retrospective analysis. In order to assess whether the duration of prophylaxis was related to adrenocortical insufficiency, regression models were performed in all preterm infants in the fluconazole group. RESULTS: The fluconazole group (n = 37) and nonfluconazole group (n = 41) were compared. No differences were found in the percentage of infants with symptoms of adrenocortical insufficiency, such as hypotension or need of vasopressor therapy. The incidence of hypotension and the use of vasopressor therapy were not related to duration of fluconazole prophylaxis. CONCLUSION: Fluconazole and it duration were not associated with the incidence of symptoms related to adrenocortical insufficiency. Further prospective trials are needed to better define the relationship between fluconazole and adrenocortical insufficiency.

Effectiveness of treatment with surfactant in premature infants with respiratory failure and pulmonary infection.

INTRODUCTION: Surfactant inactivation is present in neonatal pneumonia. MATERIALS AND METHODS: One hundred thirty-nine preterm babies with Birth Weight (BW) < or = 1250 grams were studied and subdivided in two groups: RDS Group, with a diagnosis of "simple" RDS (N 80) and RDS with Pneumonia Group, consisting of babies with a diagnosis of RDS and a positive BALF culture in the first 24-48 h of life (N 59). OUTCOMES: Surfactant administration seems less effective in the latter group, because a significantly higher number of infants needed a second dose of surfactant, compared to the patients suffering from RDS alone. (www.actabiomedica.it).

Target fraction of inspired oxygen during open lung strategy in neonatal high frequency oscillatory ventilation: a retrospective study.

BACKGROUND: There is no agreement to define the target FiO2 to adopt in the lung recruitment phase during HFOV in preterm infants. We report our experience of an optimal lung volume strategy (OLVS), defined as FiO2≤0.25 during the recruitment phase, in a cohort of neonates with gestational age (GA) ≤27 weeks treated with elective HFOV for respiratory distress syndrome (RDS) between July 2006 and September 2008. METHODS: FiO2 used during the recruitment phase was different according to physician' evaluation. 51 newborns were then divided into two groups: patients reaching FiO2≤0.25 (OLVS Group, N.=28), and patients reaching FiO2>0.25 (No-OLVS Group, N.=23). RESULTS: Prior to surfactant administration OLVS Group, respect to No-OLVS Group, received a significantly higher continuous distending pressure (CDP): 12.8±1.1 cmH2O vs 11.2±1.3 cmH2O (P<0.0001) and a significantly lower FiO2: 0.25±0.01 vs 0.35±0.06 (P<0.0001). A multivariate modeling approach confirmed that OLVS was significantly associated to the need for less surfactant doses (OR 0.19[95% CI 0.05-0.84]), a decreased risk of ductus arteriosus surgically ligated (OR 0.13[95% CI 0.02-0.86]) and to a lower number of ventilation hours before extubation: -152 (95% CI -284- -20). CONCLUSION: OLVS to fully recruit the lungs achieving FiO2≤0.25 during elective HFOV is associated with better short-term pulmonary outcomes respect to a strategy where the patients received a FiO2>0.25 during the recruitment phase. Utilizing HFOV in this way provides a more effective means to recruit and protect acutely injured lungs.

Proteomics and neonatal infection.

Antimicrobial peptides plays an important role in the host innate defence network, even in humans. Recent studies demonstrated the capacity of human airways epithelial cells to synthesize antimicrobial peptides, and their multifunctional role in the primary immunity. The presence of ct-defensins in bronchoalveolar lavage fluid (BALF) was investigated in a cohort of preterm newborns with gestational age (GA) < or =30 weeks. BALF samples were analysed by High Performance Liquid Chromatography Electrospray Ionization Mass Spectrometer. Our data show that preterm newborns, also at the lower GA, are able to produce defenses, underlining that their innate defence system is already active before the at-term delivery date.

Lutein absorption in premature infants.

The objective of this study was to measure lutein and zeaxanthin plasma levels after oral lutein administration in preterm infants. Lutein was given orally in a single dose of 0.5 mg/kg to 10 preterm infants at a mean age of 52 h of life. Plasma lutein and zeaxanthin were measured before and 6, 24, 48, and 120 h after lutein administration. All infants had detectable plasma levels of lutein and zeaxanthin before treatment. Lutein concentration increased by 13.5% at 6 h and by 16.7% at 24 h, and returned to the basal level at 120 h after treatment. Zeaxanthin remained unchanged during the study period. Lutein is well absorbed in preterm infants when given orally. The clinical impact of increasing plasma lutein concentrations on macular development and visual function needs further investigation.

Epithelial lining fluid neutrophil-gelatinase-associated lipocalin levels in premature newborns with bronchopulmonary dysplasia and patency of ductus arteriosus.

Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD) development represent severe affections for premature newborns, therefore the research of early markers for these two conditions is really important. The aim of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase-associated lipocalin (NGAL) levels for prediction of lung injury or possible involvement of this molecule in PDA. Only scarce and contrasting results have previously been published in this field. In contrast, this molecule, included in a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9), is considered an acceptable marker of infectious/inflammatory processes, cancer monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term newborns by means of a commercially available kit in bronchoalveolar lavage fluid (BALF). The results have been corrected to ELF levels, by the urea method, to eliminate bias due to BALF collection. ELF NGAL levels were found significantly increased both in infants developing BPD or in those affected by PDA. By means of multivariate logistic regression analysis the significances were confirmed after adjusting for possible interfering variables such as gestational age and concomitant presence of both PDA and BPD. Our results stress the involvement of NGAL in the mechanisms leading to BPD and also suggest a possible association with PDA, which is often linked to prematurity and BPD development, probably due to the involvement of inflammatory and angiogenetic processes in both pathologies.

[Use of Meropenem in preterm newborns. Survey of the literature and case series]. / L'uso del Meropenem nel neonato prematuro. Revisione della letteratura e casistica clinica.

AIM: The aim of this paper was to evaluate usefulness and safety of Meropenem in severe infections in neonatal intensive care unit (NICU) patients. New broad spectrum carbapenem class of -lactam antibiotics has been investigated for the treatment of a wide range of infections, including nosocomial infections with cephalosporin-resistant pathogens, an emergent problem in NICU, and meningitis. Meropenem represents the first cabapenem-class that has received Food and Drug Administration (FDA) approval for use in children 3 months of age and older. The pharmacokinetics of Meropenem has been well studied in preterm neonates. METHODS: We report the use of Meropenem in 26 neonates with median gestational age (GA) of 27 weeks (25-32) and median birth weight of 940 g (510-1900), with severe infections due to Gram-negative or Gram-positive organisms, from 2001 to 2004. The median postnatal age was 21 days (4-75). Meropenem was administrated intravenously in 30 min at dosage of 20 mg/kg every 12 h (every 8 h in Pseudomonas Aeruginosa infections). RESULTS: In all cases Meropenem has been used as second choice. No adverse effects (eosinophilia, trombocytosis or thrombocytopenia, increase in liver enzyme, increase in creatinine, diarrhea, vomiting and seizures) were observed. Clinical and bacterial response was ontaine in all cases but one. CONCLUSIONS: This report suggests that Meropenem may be a useful and safe antimicrobial agent in neonatal infections caused by resistant organisms and in meningitis. Further studies are needed to confirm these results.

[Pulmonary infections in preterm newborns]. / Infezioni polmonari nel neonato prematuro.

AIM: The aim of this study was to evaluate retrospectively the incidence and etiology of connatal pneumonia and ventilator-associated pneumonia (VAP) in preterm newborns who had birth weight = or < 1250 g and required intubation for at least 12 h. METHODS: We have reported data about preterm newborns who had birth weight = or < 1250 g and required intubation for at least 12 h with diagnosis of connatal pneumonia and VAP, admitted to the neonatal intensive care unit from 1994 to 2004. We divided these 11 years into 4 periods. For each period we determined etiology associated with connatal pneumonia or VAP. RESULTS: A total of 417 patients were studied; 311 (74.6%) required mechanical ventilation (MV) for more than 48 h (the least for the diagnosis of VAP). Connatal pneumonia occurred in 35/417 patients (8.4%). VAP incidence did not change over time showing a slight increase in the last 2 years (from 27% to 33%). Mycoplasma and Chlamydia as causative organisms of connatal pneumonia dissapear during years. Gram-negative micro-organisms were isolated more frequently in last years in VAP episodes. CONCLUSIONS: The incidence of VAP does not decrease over time although length of MV was reduced. Additional studies are needed to improve criteria for the diagnosis and prevention of VAP in NICU patients.