Neonatologist-performed Lung Ultrasound During Immediate Transition After Birth to Predict the Need for Respiratory Support Persisting More Than 1 Hour - a Pilot Study
Conditions: Neonatal Disease
Sponsor: Medical University of Graz

 
 
 
Study protocol  
 
 
Neonatologist-performed lung ultrasound during immediate 
transition after birth to predict the need for respiratory support 
persisting more than 1 hour – a pilot study 
 
 
 
Melina Winkler, MD 
Department of Pediatrics, Division of Neonatology, Medical University of Graz, 
Auenbruggerplatz 30, 8036 Graz, Austria 
 
Bernhard Schwaberger, MD, PhD 
Department of Pediatrics, Division of Neonatology, Medical University of Graz, 
Auenbruggerplatz 30, 8036 Graz, Austria 
 
Nariae Baik-Schneditz, MD, PhD 
Department of Pediatrics, Division of Neonatology, Medical University of Graz, 
Auenbruggerplatz 30, 8036 Graz, Austria 
 
 
 
 
Version 8.1 
08.02.2024 
 
 

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1. Introduction 
Lung ultrasound is an emerging clinical tool to assess the lung in a dynamic way. Recently, the focus 
has been on establishing lung ultrasound in the neonatal intensive care unit (NICU) as a point-of care 
application. As a result, the corresponding guidelines have been issued by the European Society of 
Paediatric and Neonatal Intensive Care (ESPNIC) in 2020. (Kurepa et al., 2018; Singh et al., 2020) 
Neonatologist-performed lung ultrasound (NPLUS) has proven to be a safe, accessible, and reliable 
diagnostic tool in neonatal intensive care. Compared to X-ray examination, NPLUS is a highly specific 
and sensitive approach which is not relying on ionizing radiation (Aichhorn et al., 2021; Singh et al., 
2021; Renz et al., 2022). 
Diagnostic applications for NPLUS include the evaluation and serial monitoring of respiratory 
conditions such as respiratory distress syndrome (RDS), transient tachypnoea of the newborn (TTN), 
pneumonia, pleural effusion, atelectasis, lung oedema, meconium aspiration syndrome (MAS) and 
pneumothorax. By applying the lung ultrasound score, a semi-quantitative method to assess the 
neonatal lung, neonatologists are able to identify infants in need for surfactant or infants at risk of 
bronchopulmonary dysplasia. (Rodriguez-Fanjul et al., 2020; Aichhorn et al., 2021; Küng et al., 2022; 
Schmidt and Ramamoorthy, 2022) 
2. Background 
Lung ultrasound is based on the interpretation of ultrasound artefacts (A- and B- lines), analysis of the 
pleura, and the visualization of consolidations and pleural effusions enhancing the differential 
diagnosis of acute respiratory distress in newborns. The impairment of lung aeration can be quantified 
based on the number and type of visualized artefacts. (Raimondi et al., 2021; Ollier et al., 2022) 
There is emerging evidence that NPLUS is a reliable tool to differentiate between the different causes 
leading to RDS in neonates. By today, different scoring systems have been developed in different 
clinical contexts. (Brat et al., 2015; Mongodi et al., 2021; Rodriguez-Gonzalez et al., 2022) These scores 
aim at giving a comprehensive look on the lung9s condition by screening the lung fields.  
Despite the growing body of evidence, studies on NPLUS during stabilization and resuscitation 
immediately after birth are still scarce. In the study performed by Blank et al., they found that in 
healthy term and late preterm infants within the first 20 min after birth, the lung ultrasound score for 
neonates requiring respiratory support at the NICU was highly predictive. (Blank et al., 2017) In the 
ULTRASURF study, a randomized controlled trial from Rodriguez-Fanjul et al. in 2020, NPLUS was 
performed within 1 hour after birth in preterm neonates (f 32 weeks of gestation) with RDS. In the 
study protocol, three scans of the anterior, lateral, and posterior chest walls were performed on each 
side. A 0- to 3-point score was given for each scanned area with a total score ranging from 0 to 18. One 
randomized group received surfactant based on this lung ultrasound score g 8 and FiO2 thresholds, in 
the other group surfactant was administered solely based on FiO2 thresholds. In the group, in which 
the diagnosis was based on the lung ultrasound score, neonates received earlier surfactant without 
increasing the number of patients requiring surfactant treatment. (Rodriguez-Fanjul et al., 2020)  
Neonates born by a Caesarean section are particularly prone to have an altered adaption to 
extrauterine life. Especially in the first hours after birth, TTN may occur due to delayed lung fluid 
clearance after birth. (Riskin et al., 2005; Poerio et al., 2021) While acute RDS in the first hours after 

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respiratory support persisting more than 1 hour – a pilot study 
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birth may be a self-limiting disorder and therefore a benign condition, it remains difficult to identify 
infants in need for further respiratory support at the NICU. Admission to the NICU not only causes 
parental stress but also contributes to additional healthcare costs. (Pierro et al., 2023). Using the lung 
ultrasound score for the early identification of neonates in need of respiratory support persisting more 
than 1 hour would be highly advantageous. Neonates requiring further treatment could benefit from 
early admission at the NICU, whilst the others could be prevented from an 8unnecessary9 transfer to 
the NICU which would in turn reduce the burden of transport, workload, and healthcare costs.  
3. Objectives 
The objective of this study is to evaluate the role of NPLUS during the immediate transition after birth 
of late preterm and full-term neonates using the lung ultrasound score to predict the need for 
respiratory support persisting more than 1 hour. NPLUS will be conducted at specific time points after 
birth (at 5, 15, 30 and 60 minutes) by a trained medical doctor who will complement as an additional 
member of the medical team.  
 
• 
Hypothesis I: 
We hypothesize that there is a cut-off value of the lung ultrasound score performed 5, 15, 30 
and 60 minutes after birth that is reliable to predict the need for respiratory support persisting 
> 1 hour in late preterm and full-term neonates.  
 
• 
Hypothesis II: 
We hypothesize that there is a cut-off value of the lung ultrasound score performed 5, 15, 30 
and 60 minutes after birth that is reliable to predict the need for admission to the NICU in late 
preterm and full-term neonates.  
 
• 
Hypothesis III: 
We hypothesize that neonates in need of respiratory support persisting > 1 hour have 
significantly higher lung ultrasound scores even when assessed already in 5, 15, 30 and 60 
minutes after birth, compared to neonates requiring respiratory support < 1 hour after birth. 
 
• 
Hypothesis IV: 
We hypothesize that there is a correlation between the lung ultrasound score performed at 5, 
15, 30, and 60 minutes after birth, the length of respiratory support and the required mode of 
ventilation. 
 
• 
Hypothesis V: 
We hypothesize that the lung ultrasound score assessed by NPLUS decreases between 5 and 
60 minutes after birth.  
 
 

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4. Design, setting and participants 
The present study design is conceived as an observational prospective pilot study.  
Study procedures: In this study NPLUS is performed to quantify the lung ultrasound score 5, 15, 30 
and 60 minutes after birth in late preterm and full-term neonates. The lung ultrasound examination of 
the anterior and lateral chest walls is conducted in supine position of the neonate, the examination of 
the posterior chest walls requires turning the neonate into lateral position for a couple of seconds. 
After 60 minutes after birth, the study patients do not require any additional examination. 
Furthermore, we ensure that the clinical routine care is not affected by NPLUS.  
Routine care: Immediately after cord clamping, the neonate is placed under an overhead heater on 
the resuscitation cot (8CosyCot9, Fisher&Paykel Healthcare; New Zealand) in supine position by the 
midwife. If obstructions of the upper airways are obvious, immediate suction of the oropharynx is 
performed. If necessary, respiratory support is applied by using a 8Neopuff Infant T- Piece Resuscitator9 
(Perivent, Fisher& Paykel Healthcare; New Zealand) and a face mask of appropriate size (PVC face mask 
no. 0 or 1, VBM; Germany). For infants with RDS, NPLUS is an optional diagnostic approach to evaluate 
lung aeration during neonatal transition and to rule out morbidities such as a pneumothorax.  
NPLUS is frequently performed in daily routine within the first 30 minutes after birth for an early 
examination of the lungs and/ or following the initial treatment after one to two hours after birth when 
the neonate is admitted to the NICU.  
Lung ultrasound score: Although the score of Brat et. al. is currently the most used one, we intend to 
use the score introduced by Rodriguez-Fanjul et al. in the ULTRASURF study. (Brat et al., 2015; 
Rodriguez-Fanjul et al., 2020) This score was developed to assess the neonate9s lung within the first 
hour after birth, focusing not only on the anterior and lateral parts of the hemithorax but it also 
considers the posterior chest walls. Since our study is particularly aimed at neonates born by a 
Caesarean section, for which TTN is likely to occur, it is advantageous to include the posterior chest 
walls in the lung ultrasound score. (Riskin et al., 2005; Blank et al., 2017) Moreover, a congenital 
pneumonia is detected the best in a comprehensive examination of the lung.  
NPLUS is conducted with a 12-15 MHz linear transducer preferably using the presets <lung= or <small 
parts=. Sequences of 3-5 seconds are saved and scored. To minimize interference with the routine care, 
NPLUS will be performed by an independent trained medical doctor and clinical findings will not be 
passed on to the medical team in charge. The only exception to communicate the obtained NPLUS 
findings would be a pneumothorax. In this situation the diagnosis will be communicated to the medical 
team, and the neonate will be excluded from the study. 
To ensure inter-observer reliability the anonymous video sequences are then blinded and rated by 
two independent neonatologists. 
Inclusion criteria:  
• 
Late preterm neonates (born between 34 0/7 and 36 6/7 weeks of gestation) and full-term 
neonates (born later than 36 6/7 weeks of gestation) delivered by Caesarean section at the 
Department of Obstetrics and Gynaecology, Medical University of Graz 
• 
Presence of any sign of respiratory distress (defined as tachypnoea/ dyspnoea, grunting, flaring 
of the nostrils or chest retractions) 
• 
Written informed consent obtained from the parents prior to birth. 

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Exclusion criteria:  
• 
Presence of cardiopulmonary malformations 
• 
Patients with pneumothorax diagnosed by NPLUS 
 
Sample size: Statistical analysis for cut-off determination will be performed with a sample-size of 40 
individuals, excluding patients with pneumothorax diagnosed by NPLUS. Hence, we aim at comparing 
20 neonates who are transferred to the NICU with 20 neonates who initially need respiratory support 
but then do not require any 60 minutes after birth.  
Sample size calculations cannot be performed beforehand, since no data from previous studies are 
available. Hence, this pilot study is conducted to generate data for the sample size calculation of the 
consecutive main study (Thabane et al., 2010).  
5. Statistical analysis 
Demographic information, clinical characteristics, and lung ultrasound features will be summarized. 
First, the Kolmogorov–Smirnov test will be applied to test the data significance, which will then be 
represented as the mean (standard deviation, SD) or median (interquartile range, IQR). The predictive 
performance of the lung ultrasound score for the need for respiratory support persisting more than 1 
hour after birth and for admission to the NICU will be analysed by plotting the receiver operating 
characteristic (ROC) curve, and areas under the ROC curves (AUCs) determining cut-off values. Group 
differences in primary and secondary outcome parameters between patients who are transferred to 
the NICU in need for respiratory support for more than 60 minutes and patients who do not need any 
respiratory support after 60 minutes after birth are calculated using χ² and Fisher's exact tests for 
discrete variables, and t-test or Mann-Whitney U test for continuous variables. Additionally, the 
correlations between the lung ultrasound score, length of respiratory support and the mode of 
ventilation will be analysed using either the Spearman9s rank correlation coefficient or the Pearson9s 
correlation depending on which one is more appropriate. The correlation analyses are considered in 
an explorative sense; therefore, no multiple testing corrections will be performed. SPSS23.0 (IBM 
Corporation, New York, NY, USA) is used for statistical analysis. 
 
 

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6. Outcome measures 
Primary 
• 
Determination of the lung ultrasound score according to Rodriguez-Fanjul et al. 2020 at 5, 15, 
30 and 60 minutes after birth 
• 
Need for respiratory support persisting more than 1 hour 
• 
Admission to the NICU 
Secondary 
• 
Length of respiratory support (in minutes) 
• 
Mode of respiratory support (non-invasive versus invasive ventilation) 
• 
Routinely obtained capillary blood gas analysis of the newborn 
• 
Routinely obtained monitoring parameters including arterial oxygen saturation (SpO2), heart 
rate (either by pulse oximetry or electrocardiography), and cerebral oxygen saturation (near-
infrared spectroscopy) 
• 
SpO2/FiO2 ratio (S/F ratio) 
• 
pH of the umbilical artery 
• 
Apgar score 
• 
Pregnancy risk factors including intra-amniotic infection, and premature rupture of the 
membranes 
• 
Prenatal corticosteroids 
7. Research plan and time table 
The study will start in spring 2024. 
The study is designed for an approximate running time of three years.  
 
 

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preterm infants immediately after birth, a prospective, observational study9, Resuscitation, 114, pp. 
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Brat, R. et al. (2015) 8Lung ultrasonography score to evaluate oxygenation and surfactant need in 
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