The Baby Lung Study

Inflammatory Markers and Surfactant Proteins in Preterm Infants at Risk of Developing Chronic Lung Disease: an Observational Study

The introduction of exogenous surfactant therapy has significantly improved the mortality in preterm infants born between 23- and 28-weeks of gestation. However, the therapy has not affected the prevalence of sequelae such as bronchopulmonary dysplasia [BPD] and it may be argued that it has actually increased. BPD is a lung condition that affects up to 40% of premature babies born between 23 and 28 weeks gestational age. The prevalence of BPD decreases with increasing gestational age but can affect infants born at term who have required mechanical ventilation. It is most commonly defined based on the need for oxygen past 36 weeks post-menstrual age [PMA]. The pathogenesis of BPD is multifactorial and involves a complex balance between the underdeveloped lungs, infection, inflammation, oxygen toxicity and ventilator induced injury.

In this study the investigators aim to develop a greater understanding of the interactions between the inflammatory markers present in endotracheal aspirates [ETA] and serum of preterm infants and surfactant components (including surfactant protein D-SP-D levels) in the lungs and in the serum of preterm ventilated infants.

The investigators aim to recruit infants born between 23+0 and 29+6 weeks of gestation at University College London Hospital admitted to the neonatal unit, who are at risk of developing respiratory distress syndrome [RDS] and progression to BPD. The investigators plan to study the correlation between the concentrations of surfactant components (in particular SP-D) and inflammatory markers in infants across the range of gestations specified. In order to do this, the investigators will obtain gastric aspirates, endotracheal aspirates [ETA] and blood samples at birth, 24hrs and days 2 through to day 7 from participants. ETA will only be obtained if the infants are intubated and ventilated, collected by a standard technique routinely used in nursing care of ventilated babies using 1-2mls of saline.ETA and blood samples will then be analysed for levels of surfactant proteins in particular SP-D and inflammatory and immunological markers [cell counts of neutrophils, macrophages, MMPs, neutrophil elastase, IL-8, IL-6, IL 11 and IL-1]. This will allow us to map the influence of SP-D on pro and anti-inflammatory markers that have a role in the inflammatory component of BPD in these infants.

Clinical data will also be collected at specified time points correlating with the plasma, gastric aspirates and endotracheal aspirates. The investigators aim to correlate clinical ventilatory parameters, infection factors and maternal factors with the inflammatory and surfactant protein profiles. In addition, the investigators will apply the international neonatal consortium Neonatal Adverse severity scores to gain a better understanding of the baseline incidence of adverse events in premature infants that are admitted to a neonatal unit.

Study Overview

• Status: Completed
• Conditions: Bronchopulmonary Dysplasia; Neonatal Disease
• Intervention / Treatment: Other: Observational study

• Study Type: Observational
• Enrollment (Actual): 61

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College London Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 6 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Preterm infants born between 23 + 0 weeks post menstrual age and 30 weeks post menstrual age.

Description

Inclusion Criteria:

. Preterm infants born between 23 weeks and 0 days and 30 weeks and 0 days gestation.

Exclusion Criteria:

• Congenital anomalies i.e any major antenatal diagnosed congenital abnormalities such as congenital heart disease, suspected or known chromosomal abnormalities.
• Infants not born at UCLH where baseline data and samples cannot be collected

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To analyses the profile of surfactant protein D in preterm infants at risk of bronchopulmonary dysplasia.	To measure the surfactant protein D levels in gastric and tracheal aspirates and plasma samples taken at birth, 24hrs, 48hrs, 72hrs, 96hrs, D7 of life and 36weeks post menstrual age if still intubated.	24 months
Characterise the inflammatory cell profile in preterm infant at high risk of developing bronchopulmonary dysplasia.	To analyse the gastric and tracheal aspirates and plasma samples taken at birth, 24hrs, 48hrs, 72hrs, 96hrs, D7 of life and 36weeks post menstrual age if still intubated for cell counts (macrophages and neutrophils) to better understand the correlation with SP-D over a period of time.	24 months
Characterise the cytokine profile in preterm infants at high risk of developing bronchopulmonary dysplasia.	To analyse the gastric and tracheal aspirates and plasma samples taken at birth, 24hrs, 48hrs, 72hrs, 96hrs, D7 of life and 36weeks post menstrual age if still intubated for pro- and anti-inflammatory cytokines to better understand the correlation with SP-D over a period of time.	24 months
To understand the incidence of adverse events in preterm infants at risk of developing bronchopulmonary dysplasia.	To apply the Neonatal Adverse Events Severity Score developed by the International Neonatal Consortium to better evaluate the incidence of adverse events in this vulnerable population.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association of inflammatory profile and surfactant components with clinical parameters.	To study the association of the inflammatory profile and concentration of surfactant components with clinical factors comprising of baseline factors, such as infant sex, ethnicity, administration of antenatal steroids, evidence of maternal sepsis/chorioamnionitis, and treatment factors, such as ventilator settings and tracheal colonisation.	24 months

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Study Chair: Howard Clark, Professor, University College, London; Principal Investigator: Reena Bhatt, Dr, University College, London

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2021
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: November 5, 2021
• First Submitted That Met QC Criteria: November 26, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Injury; Infant, Premature, Diseases; Ventilator-Induced Lung Injury; Bronchopulmonary Dysplasia; Infant, Newborn, Diseases
• Other Study ID Numbers: 138731

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data gathered will be the property of University College London and will not be shared with other research groups.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No