The discovery BPD (D-BPD) program: study protocol of a prospective translational multicenter collaborative study to investigate determinants of chronic lung disease in very low birth weight infants

Abstract

Background: Premature birth is a growing and serious public health problem affecting more than one of every ten infants worldwide. Bronchopulmonary dysplasia (BPD) is the most common neonatal morbidity associated with prematurity and infants with BPD suffer from increased incidence of respiratory infections, asthma, other forms of chronic lung illness, and death (Day and Ryan, Pediatr Res 81: 210-213, 2017; Isayama et la., JAMA Pediatr 171:271-279, 2017). BPD is now understood as a longitudinal disease process influenced by the intrauterine environment during gestation and modulated by gene-environment interactions throughout the neonatal and early childhood periods. Despite of this concept, there remains a paucity of multidisciplinary team-based approaches dedicated to the comprehensive study of this complex disease.

Methods: The Discovery BPD (D-BPD) Program involves a cohort of infants < 1,250 g at birth prospectively followed until 6 years of age. The program integrates analysis of detailed clinical data by machine learning, genetic susceptibility and molecular translation studies.

Discussion: The current gap in understanding BPD as a complex multi-trait spectrum of different disease endotypes will be addressed by a bedside-to-bench and bench-to-bedside approach in the D-BPD program. The D-BPD will provide enhanced understanding of mechanisms, evolution and consequences of lung diseases in preterm infants. The D-BPD program represents a unique opportunity to combine the expertise of biologists, neonatologists, pulmonologists, geneticists and biostatisticians to examine the disease process from multiple perspectives with a singular goal of improving outcomes of premature infants.

Trial registration: Does not apply for this study.

Fig. 1

The D-BPD research areas integration. The clinical data core, using machine learning strategies will leverage the detailed longitudinal clinical data the gene susceptibility program using genome-wide association mapping and positional cloning in murine strains to identify candidate susceptibility genes, and a basic science molecular program exploring mechanistic correlates of clinical and genetic findings associated with BPD endotypes. Image credits: Wikimedia Commons

Fig. 2

Discovery BPD (D-BPD) structure

Fig. 3

D-BPD Program Protocol Time Line spans from birth to 6 years of corrected age collecting health data and biospecimens. The babies will be monitored daily during their NICU stay by the participating neonatologist (without direct clinical responsibilities) using structured data collection log sheets. Information of the clinical course will be collected daily during the first 28 days and every 2 days thereafter. Afterwards phone calls will be made every 6 months until 6 years of age are completed

Fig. 4

D-BPD cohort diagram