Oxygen toxicity continues to be one of the inevitable injuries to the immature lung. Reactive oxygen species (ROS) production is the initial step leading to lung injury and, subsequently, the development of bronchopulmonary dysplasia (BPD). Today, BPD remains the most important disease burden following preterm delivery and results in life-long restrictions in lung function and further important health sequelae. Despite the tremendous progress in the pathomechanistic understanding derived from preclinical models, the clinical needs for preventive or curative therapies remain unmet. This review summarizes the clinical progress on guiding oxygen delivery to the preterm infant and elaborates future directions of research that need to take into account both hyperoxia and hypoxia as ROS sources and BPD drivers. Many strategies have been tested within clinical trials based on the mechanistic understanding of ROS actions, but most have failed to prove efficacy. The majority of these studies were tested in an era before the latest modes of non-invasive respiratory support and surfactant application were introduced or were not appropriately powered. A comprehensive re-evaluation of enzymatic, antioxidant, and anti-inflammatory therapies to prevent ROS injury is therefore indispensable. Strategies will only succeed if they are applied in a timely and vigorous manner and with the appropriate outcome measures.

Background: Microbiome dysbiosis can have long-lasting effects on our health and induce the development of various diseases. Bronchopulmonary dysplasia (BPD) is a multifactorial disease with pre- and postnatal origins including intra-amniotic infection as main risk factor. Recently, postnatal pathologic lung microbiota colonization was associated with BPD. The objectives of this prospective observational cohort study were to describe differences in bacterial signatures in the amniotic fluid (AF) of intact pregnancies without clinical signs or risk of preterm delivery and AF samples obtained during preterm deliveries and their variations between different BPD disease severity stages. Methods: AF samples were collected under sterile conditions during fetal intervention from intact pregnancies (n = 17) or immediately before preterm delivery < 32 weeks (n = 126). Metabarcoding based approaches were used for the molecular assessment of bacterial 16S rRNA genes to describe bacterial community structure. Results: The absolute amount of 16S rRNA genes was significantly increased in AF of preterm deliveries and detailed profiling revealed a reduced alpha diversity and a significant change in beta diversity with a reduced relative abundance of 16S rRNA genes indicative for Lactobacillus and Acetobacter while Fusobacterium, Pseudomonas, Ureaplasma and Staphylococcus 16S rRNA gene prevailed. Although classification of BPD by disease severity revealed equivalent absolute 16S rRNA gene abundance and alpha and beta diversity in no, mild and moderate/severe BPD groups, for some 16S rRNA genes differences were observed in AF samples. Bacterial signatures of infants with moderate/severe BPD showed predominance of 16S rRNA genes belonging to the Escherichia-Shigella cluster while Ureaplasma and Enterococcus species were enriched in AF samples of infants with mild BPD. Conclusions: Our study identified distinct and diverse intrauterine 16S rRNA gene patterns in preterm infants immediately before birth, differing from the 16S rRNA gene signature of intact pregnancies. The distinct 16S rRNA gene signatures at birth derive from bacteria with varying pathogenicity to the immature lung and are suited to identify preterm infants at risk. Our results emphasize the prenatal impact to the origins of BPD.

Bronchopulmonary dysplasia (BPD) is a multifactorial disease mainly provoked by pre- and postnatal infections, mechanical ventilation, and oxygen toxicity. In severely affected premature infants requiring mechanical ventilation, association of bacterial colonization of the lung and BPD was recently disclosed. To analyze the impact of bacterial colonization of the upper airway and gastrointestinal tract on moderate/severe BPD, we retrospectively analyzed nasopharyngeal and anal swabs taken weekly during the first 6 weeks of life at a single center in n = 102 preterm infants <1000 g. Colonization mostly occurred between weeks 2 and 6 and displayed a high diversity requiring categorization. Analyses of deviance considering all relevant confounders revealed statistical significance solely for upper airway colonization with bacteria with pathogenic potential and moderate/severe BPD (p = 0.0043) while no link could be established to the Gram response or the gastrointestinal tract. Our data highlight that specific colonization of the upper airway poses a risk to the immature lung. These data are not surprising taking into account the tremendous impact of microbial axes on health and disease across ages. We suggest that studies on upper airway colonization using predefined categories represent a feasible approach to investigate the impact on the pulmonary outcome in ventilated and non-ventilated preterm infants.

Background/Objectives: Breastmilk offers numerous benefits for the health and development of preterm infants, while prolonged hospitalization may impair neurodevelopment. At our institution, the implementation of enhanced family-centered care (FCC) has enabled earlier discharge of preterm infants. This study aimed to assess the impact of early discharge on breastfeeding and breastmilk provision. Methods: This analysis is based on data from a prospective single-center longitudinal cohort study conducted from October 2020 to November 2023, involving six consecutive cohorts (one baseline and five intervention cohorts; n = 184). FCC was progressively enhanced across cohorts. The primary outcome of the main study was postmenstrual age (PMA) at discharge. In this secondary analysis, breastfeeding and breastmilk provision were assessed at four time points: 4 weeks postnatal age, at discharge, 4 weeks post-discharge, and at 3 months PMA. Results: From baseline to intervention cohort 5, the PMA at discharge declined significantly from 37.8 ± 2.1 to 35.7 ± 0.91 weeks (p = 0.03), while the percentage of infants necessitating home nasogastric tube feeding increased from 6.3% to 66.7% (p < 0.01). The proportion of breastmilk of daily feeding volume remained unchanged at 4 weeks postnatal age (0.66 ± 0.42 vs. 0.9 ± 0.28) and at discharge (0.6 ± 0.45 vs. 0.79 ± 0.36). At 4 weeks post-discharge, 65.8% vs. 62.5% of the infants were on partial or exclusive breastmilk (p = 0.91) feeding. Similarly, the percentage of exclusively breastfed infants at 4 weeks post-discharge (23.7% vs. 19.8%) and at 3 months PMA (20% vs. 28.6%) did not differ significantly between baseline and intervention cohort 5. Conclusions: Early discharge did not reduce breastmilk supply or exclusive breastfeeding. However, the persistently low rate of exclusive breastfeeding post-discharge highlights the need for additional support strategies during and after hospitalization.

Background/Objectives: Postnatal growth restriction and duration of hospital stay have been identified as risk factors for adverse neurodevelopment in preterm infants. Implementation of a family-centered care (FCC) program in our institution reduced length of stay in preterm infants. This study evaluates the effect of more early discharge on growth up to three months postmenstrual age (PMA). Methods: We conducted a prospective, single-center cohort study in a German level III neonatal unit (October 2020–November 2023) including six consecutive cohorts (n = 184) with progressive FCC implementation. This secondary analysis examined growth at discharge, term-equivalent age (TEA), and three months PMA. Results: PMA at discharge significantly decreased from the baseline to intervention cohort 5 (37.8 ± 2.1 vs. 35.7 ± 0.91 weeks PMA; p = 0.03). Compared to the baseline cohort, infants in intervention cohort 5 had significantly lower weight, length, and head circumference at discharge. However corresponding Z-Scores did not differ significantly between the cohorts. No significant differences in growth outcomes were observed at TEA or at three months PMA. Furthermore, there were no significant differences in the change in Z-Score for weight, length, and HC from birth to three months PMA. Conclusions: Early discharge under FCC did not impair growth to three months PMA, suggesting that early discharge is a safe practice with respect to growth outcomes in preterm infants. Further randomized multicenter studies are needed to confirm these results.