Despite substantial advances in neonatal care over recent decades, approximately 20% of extremely preterm infants—defined as those born before 28+0 weeks of gestation—do not survive. Mortality in this population is commonly associated with severe complications such as sepsis and necrotizing enterocolitis (NEC), a severe inflammatory disease of the intestine. Even in the absence of these life-threatening conditions, many extremely preterm infants experience significant gastrointestinal dysfunction. Clinically, this often manifests as abdominal distension, abdominal discomfort, and feeding intolerance, which complicates the establishment of adequate enteral nutrition with breast milk.
Research objectives and findings
To investigate the effects of probiotic supplementation on gastrointestinal function, immune development, and intestinal microbiota in extremely preterm infants, the PROPEL study was conducted between 2012 and 2015. The study evaluated the probiotic bacterium Lactobacillus reuteri, which previous meta-analyses have shown to reduce the incidence of NEC in moderately and very preterm infants.
In our cohort of extremely preterm infants, probiotic supplementation did not significantly improve gastrointestinal function compared with placebo. However, infants receiving probiotics demonstrated improved head growth relative to the placebo group. Furthermore, a two-year follow-up revealed enhanced language development in the probiotic group. These findings are particularly noteworthy in light of emerging evidence suggesting that the composition of the intestinal microbiota can influence neurological development through the so-called gut–brain axis.
Mechanistic and microbiome analyses
In several sub-studies, we demonstrated that the supplemented probiotic strain successfully colonized the gastrointestinal tract of treated infants. In addition, infants receiving probiotics exhibited greater microbial diversity in their intestinal microbiota compared with those in the placebo group.The biological samples collected as part of the PROPEL study provide a unique resource for investigating the mechanisms underlying impaired growth, severe immune-mediated complications such as NEC, and neurodevelopmental outcomes. Using comprehensive multi-omics approaches and data-driven analytical methods, including machine learning, we aim to identify biomarkers capable of predicting these complications in extremely preterm infants.
Long-term follow-up
Extremely preterm infants are also at increased risk of impaired pulmonary function during childhood and of developing chronic obstructive pulmonary disease (COPD) later in life. Consequently, the most recent extension of the PROPEL study includes a 14-year follow-up designed to evaluate long-term lung function and characterize the types of pulmonary impairment that may occur in this population.
