Early Prediction of Lung Injury in Preterm Infants Score

104 preterm infants born between 26 and 32 weeks of gestational age and/or with a birth weight < 1500g (very low birth weight infants - VLBW) with respiratory distress syndrome (RDS). are enrolled in the study In non-invasive ventilation (nasal continuous positive airway pressure -nCPAP- or high flow nasal -HFNC-) at 72h of life.

The study will be conducted at the Neonatal Intensive Care Unit of the Fondazione Policlinico San Matteo IRCSS,Pavia, Italy; PI Dr. S. Ghirardello; Chief of NICU.. Participation at the study will not modify the standard clinical care. In particular, the data obtained from this study will not be used to change the clinical practice in use at the time of the study and the investigators will supervise the proper conduct of the research.Recruitment of patients will be consecutive and continuous through the project investigator in daily clinical practice, if the criteria for inclusion in the study will be met and after obtaining informed consent from the parents.

The study procedures follow the standard clinical practice at our Unit, inclusive of lung ultrasound (LUS). In addition, Electrical Impedance Tomography (EIT) will be performed.

Briefly, after stabilization in delivery room, the clinicians start nCPAP or HFNC and administer surfactant therapy, according to "European guidelines 2022" and standardized internal protocols. The surfactant therapy should be given early in the course of the disease. The suggested protocol would be to treat worsening babies with RDS when FiO2 > 0.30 on CPAP pressure ≥6 cm H2O or if lung ultrasound suggests surfactant need. Less invasive surfactant administration (LISA) is the current preferred method of surfactant administration for spontaneously breathing babies on CPAP. The decision to intubate and start endotracheal mechanical ventilation (MV) is based on the development of respiratory acidosis (pH < 7.20, pCO2 > 60-65mmHg) or severe apnea. While on MV, the SatO2 target was 90%-94%; pH is kept between 7.25 and 7.35, and pCO2 is maintained between 45 and 60mmHg as per local protocols. Infants will be extubated if mean airway pressure (MAP) < 8 cmH20, FiO2 < 0.30, and good respiratory drive is evident.

EIT ENLIGHT 2100 (Timpel®) is a bedside system that uses high-frequency, low-intensity electric signals to provide live images of the breathing lung showing pulmonary performance in real-time. The specific neonatal 16-electrode bands made of hypoallergenic material, soft and thin, will be applied to the chest at the nipple level and will be connected to the tomograph for 60 minutes. During each intervention period, four 10-minute EIT sequences are recorded and for each recording, the first 30 stable consecutive breaths of artefact-free tidal ventilation will be identified. EIT recordings will be made after allowing the infant to stabilize, and in supine position. The raw EIT data will be reconstructed according to standardized guidelines with an anatomically correct and customized human chest algorithm using the manufacturer's software package to exclude impedance variations outside the boundaries of the left and right lungs. Once reconstructed, each of the recordings will be manually examined. Functional EIT images of the current volume distribution will be created, and data extracted from the entire lung, the right and left lungs.

The net signal at end-expiration (end-expiratory lung impedance; EELI) is isolated as the impedance signal at the end of each expiration in arbitrary units to assess overall lung aeration. This is determined in the whole lung (EELI total) and in four regions of interest (ROIs): horizontal quantiles ranging from non-gravity dependent (NGD) to gravity dependent (GD) lung fields (EELINGD, EELImidNGD, EELImidGD, EELIGD) to assess global and regional aeration. Homogeneity of lung aeration during non-invasive ventilation will be measured. To do this, signals in each quantile of regional aeration will be first weighted to the known pixel contribution of each region to normalise for differences in lung size. Then, the NGD half of the EIT signal will be divided by the GD half:

Aeration homogeneity ratio (AHR) = EELINGD +EELI mid NGD/ EELIGD +EELI mid GD A value of 1 represents equal distribution of air and a value <1 or >1 describes an aeration which favours the GD or NGD lung, respectively.

As per study protocol, electrical impedance tomography will be applied following specific timing: the first one (T0) is performed at 72 h of life, the second one (T1) at seven days of life, and the last one at 14 days of life (T2).

At the same time points, lung ultrasound will be performed. Images are obtained with a Hitachi Arietta v70 ultrasound scanner. A linear probe (5-12 MHz) is used. Trained physicians perform the LUS and assign the nLUS score. According to the study by Brat et al., each lung is divided into three areas, and a score from 0 to 3 was given to each scan. 0 indicates A-pattern (defined by the presence of only A-lines); 1 indicates B-pattern (i.e., alveolar-interstitial pattern, described as the presence of at least three well-spaced B lines); 2 indicates severe B-pattern (i.e., severe alveolar-interstitial pattern, defined as the presence of crowded and coalescent B-lines with or without subpleural consolidations with a depth < 1 cm); and 3 indicates consolidation (i.e., subpleural echo-poor or tissue-like echotexture area with depth > 1 cm and irregular borders, which may also have mixed hypoechogenic and hyperechogenic spots representing air bronchograms). Therefore, a total score from 0 to 18 is assigned to the LUS.

The exams will be performed after the patient's standard care to minimize neonatal discomfort. Peripheral capillary oxygen saturation (SpO2) and heart and respiratory rate (RR) are measured continuously.