Early Predictors of Bronchopulmonary Dysplasia in Extremely Preterm Infants

NCT07771387 | Not Yet Recruiting

• 1 other identifier: 2182/2023
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

Bronchopulmonary dysplasia (BPD) remains one of the most common complications in extremely preterm infants despite advances in neonatal intensive care. Early identification of infants at high risk for BPD could facilitate individualized treatment strategies and improve long-term respiratory outcomes. However, current prediction models rely primarily on conventional clinical variables and have limited predictive accuracy. This prospective observational study aims to evaluate the predictive value of novel physiological, imaging, and biomarker-based indicators for the development of BPD in infants born before 26 weeks of gestation. Participants admitted to the neonatal intensive care units of the Medical University of Vienna will undergo non-invasive assessments during routine clinical care. These include respiratory function monitoring during neonatal transition, lung ultrasound, diaphragmatic ultrasound, targeted neonatal echocardiography, forced oscillation technique, neurally adjusted ventilatory assist-derived diaphragmatic electrical activity, electrical impedance tomography, and proteomic analyses of plasma and tracheal aspirate samples. The association between these novel indicators and respiratory disease severity will be assessed using the Respiratory Severity Score (RSS). Their ability to predict BPD will be evaluated using receiver operating characteristic (ROC) analysis and uni- and multivariable logistic regression models. Predictive performance will be assessed using the C-statistics. The primary objectives are to determine the correlation between the novel indicators and the RSS and to evaluate their diagnostic accuracy for predicting BPD. Secondary objectives include identifying the combination of indicators that provides the best prediction of BPD, evaluating longitudinal changes in respiratory and cardiovascular parameters during the neonatal period, assessing the effects of respiratory interventions and treatments on these indicators, and investigating associations with survival and major neonatal morbidities. A total of 140 extremely preterm infants is planned for inclusion in the study. The results are expected to improve early risk stratification and contribute to the development of individualized strategies for preventing and managing BPD.

Conditions

Bronchopulmonary Dysplasia

Keywords

Bronchopulmonary Dysplasia; Infant, Extremely Premature; Lung; Ultrasonography; Echocardiography; Electric Impedance Tomography; Diaphragm; Proteomics; Respiration

Outcome Measures

Primary Outcomes (31)

• Bronchopulmonary Dysplasia (BPD)

  No BPD: no support. BPD grade 1: nasal cannula ≤ 2 L/min. BPD grade 2: nasal cannula \> 2 L/min or noninvasive positive airway pressure. BPD grade 3: invasive mechanical ventilation.

  At 36 weeks' postmenstrual age

• Respiratory Severity Score (RSS)

  Daily median Respiratory Severity Score (RSS), calculated as the product of the mean airway pressure (MAP, cmH₂O) and the fraction of inspired oxygen (FiO₂), using all recorded ventilator settings during a 24-hour period.

  Day of Life 1, Day 3, Day 7, Day 14, Day 21and Day 28.

• Peak inspiratory pressure (RFM-PIP)

  Peak inspiratory pressure during neonatal transition and resuscitation assessed by the Respiratory Function Monitor (RFM)

  First hour of life.

• Expiratory tidal volume (RFM-VTe)

  Expiratory tidal volume during neonatal transition and resuscitation assessed by the Respiratory Function Monitor (RFM)

  Frist hour of life

• Lung Ultrasound Score (LUS)

  Lung ultrasound is performed in six lung regions, comprising the upper anterior, lower anterior, and lateral regions of each hemithorax. Each region is assigned a score from 0 to 3 according to the most severe ultrasound pattern observed: 0, normal aeration with A-lines; 1, at least three separated B-lines; 2, coalescent B-lines or a white-lung pattern; and 3, extended consolidation. The regional scores were summed to obtain a total LUS score ranging from 0 (minimum) to 18 (maximum), with higher scores indicating more severe loss of lung aeration.

  Day of life 1, Day 3, Day 7, Day 14, and Day 28.

• Diaphragm shortening fraction (DSF)

  In M-Mode, the minimal (TET) and the maximal thickness (TIT) during a breathing cycle are measured three times and mean values are considered for the diaphragmatic shortening fraction (DSF) which is determined by the following formula: DSF(%) = 100x(TIT-TET)/TET.

  Day of life 1, Day 3, Day 7, Day 14, and Day 28.

• Patent Ductus Arteriosus (PDA) status

  PDA status (TnEcho): open/closed (binary variable)

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• PDA - shunt pattern

  PDA - shunt direction (TnECHO): non restrictive left-to-right, restrictive left-to-right, bi-directional, right-to-left, no shunt

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• Patent Ductus Arteriosus Score

  Patent Ductus Arteriosus Score (PDA Score): Each item is assigned 0, 1, or 2 points. The total score is calculated as the sum of all item scores, ranging from 0 (minimum) to 12 points (maximum). A higher score indicates greater hemodynamic compromise due to the PDA. Items: Mitral E-wave velocity (cm/s), IVRT (ms), pulmonary vein D-wave velocity (cm/s), LA:Ao ratio, LVO (mL/min/kg), and descending aortic flow and/or celiac/middle cerebral artery flow.

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of pulmonary hypertension

  tricuspid regurgitation jet-derived right ventricular systolic pressure

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of pulmonary hypertension

  interventricular septal curvature represented as eccentricity index

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of pulmonary hypertension

  pulmonary vascular resistance indices derived from right ventricular ejection time and pulmonary artery acceleration time

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• Respiratory Oscillometry

  Respiratory reactance (Xrs) \[cmH2 O⋅sec/Lt\]

  Day of life 1, Day 3, Day 7 and Day 14 (when intubated) and 3 and 5 years of age

• Respiratory Oscillometry

  Respiratory resistance (Rrs) \[cmH2 O⋅s/L\].

  Day of life 1, Day 3, Day 7 and Day 14 (when intubated) and 3 and 5 years of age

• Neurally-Adjusted Ventilatory Assist (NAVA)

  NAVA Level \[cmH2 O/μV\] Values will be averaged over a representative period during which the patient is in a restful state.

  Day of life 3, Day 7 and Day 14

• Neurally-Adjusted Ventilatory Assist (NAVA)

  Edimax (maximum electrical activity of the diaphragm during inspiration) \[μV\] Edimin (minmal electrical activity of the diaphragm during inspiration) \[μV\] All values will be averaged over a representative period during which the patient is in a restful state.

  Day of life 3, Day 7 and Day 14

• Neurally-Adjusted Ventilatory Assist (NAVA)

  Inspiration time \[sec\]

  Day of life 3, Day 7 and Day 14

• Electrical Impedance Tomography (EIT)

  Center of ventilation: CoV

  Day of life 7 and Day 14

• Electrical Impedance Tomography (EIT)

  Regional ventilation delay: RVD

  Time Frame: Day of life 7 and Day 14

• Electrical Impedance Tomography (EIT)

  Global inhomogeneity index: GI

  Day of life 7 and Day 14

• Electrical Impedance Tomography (EIT)

  Regional respiratory system compliance

  Day of life 7 and Day 14

• Electrical Impedance Tomography (EIT)

  Regional time constant

  Day of life 7 and Day 14

• Electrical Impedance Tomography (EIT)

  VQ matching

  Day of life 7 and Day 14

• Proteomics

  Plasma and tracheal protein profiles from 50 µL blood (approximately one drop of blood on a dried blood spot card) and 1 mL of tracheal aspirate.

  Day of life 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 14, and Day 28.

• ECHO-Indices of volume loading

  pulmonary vein velocity \[m/s\]

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of volume loading

  mitral inflow E/A

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of volume loading

  isovolumetric relaxation time

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of qualitative ventricular function

  TAPSE (Tricuspid Annular Plane Systolic Excursion) \[sec\]

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of qualitative ventricular function

  Fractional shortening (FS) \[%\]

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of qualitative ventricular function

  Left and right cardiac output \[mL/min/kg\]

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

• ECHO-Indices of qualitative ventricular function

  Global strain

  Day of life 1, Day 3, Day 7, Day 14, Day 28, 32 weeks gestational age (GA) and 36 weeks GA

Secondary Outcomes (4)

• Composite outcome: Death or Grade 3 BPD

  At 36 weeks' postmenstrual age

• Ventilation parameters

  Time to 36 weeks' postmenstrual age

• Major morbidities

  Time to 36 weeks' postmenstrual age

• Neurological outcome

  at two and five years of corrected age

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Preterm infants admitted to the neonatal intensive care units of the Medical University of Vienna.

You may qualify if:

• Preterm infants born at \<26 weeks' gestational age, as determined by the best obstetric estimate based on the first day of the last menstrual period and/or first-trimester ultrasonography.
• Admitted to the neonatal intensive care unit (NICU) of the Medical University of Vienna immediately after birth.
• Written informed consent obtained prospectively from a parent or other legally authorized representative prior to study participation.

You may not qualify if:

• Major congenital anomaly or anticipated alternative cause for respiratory failure.

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, State of Vienna, 1090, Austria

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood and tracheal aspirate samples

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Respiratory Aspiration

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Tobias Werther, MD, PhD

CONTACT

+43140400 67400; tobias.werther@meduniwien.ac.at

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof. Priv. Doz. DDr.

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 18, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): June 30, 2030
• Last Updated: August 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: De-identified individual participant data and supporting information will be available from 3 months until 5 years after publication of the study results.
• Access Criteria: Qualified researchers whose proposed use of the data has been approved by the study investigators and, where required, by the relevant ethics committee and the Medical University of Vienna will be granted access. Researchers may access de-identified individual participant data underlying the published results, the data dictionary, and the relevant statistical analysis code. Access will be provided following submission of a methodologically sound research proposal, completion of applicable institutional and legal review, and signature of a data-sharing agreement. Approved data will be transferred through a secure, access-controlled institutional platform. The data may only be used for the approved research purpose and may not be redistributed or used to attempt participant re-identification.

Locations

AU (1)