PROJECT SUMMARY/ABSTRACT
Bronchopulmonary dysplasia (BPD), or infant chronic lung disease, is among the most devastating
complications of preterm birth. BPD affects half of surviving extremely preterm infants, is associated with life-
long deficits in health and cognition, and carries enormous societal burden and cost. Strikingly, there are no
therapies shown to improve outcomes for infants with BPD. Our research seeks to resolve this care gap.
Gastroesophageal reflux disease (GERD) is diagnosed in >40% of infants with BPD. Through aspiration and
neurogenic mechanisms, GERD exacerbates lung disease in BPD by induction of bronchospasm, hypoxemia,
airway injury, infection, and chronic lung inflammation. Unfortunately, there are no proven safe and effective
ways to treat GERD in infants. Acid suppression and GI promotility drugs are ineffective and carry significant
risks. Surgical fundoplication is invasive and often inappropriate for infants with unstable lung disease.
Conversely, transpyloric tube feeding is easily initiated and has been shown to reduce aerodigestive
sequelae of GER in older children and adults. Unfortunately, the safety and efficacy of transpyloric feeding in
BPD is uncertain and the limited infant data are conflicting. Our preliminary data show variable contribution of
GERD to lung disease in BPD and significant heterogeneity in response to transpyloric feeding. In a recent
randomized trial of alternating 4d periods of transpyloric and gastric feeding in 15 infants with BPD, we showed
that transpyloric feeding reduced hypoxemia and FiO2 need in some infants but worsened these in others.
These findings demand identification of evidence-based means to individualize feeding route selection and
GERD management in preterm infants with BPD.
A key first step towards achieving this goal is to determine whether transpyloric feeding safely and effectively
reduces GER in infants. To do so, we propose a randomized trial that will compare moderate duration (2wk)
transpyloric vs. gastric tube feeding in very preterm infants (n=60) with grade 2-3 BPD. Serial gold-standard
esophageal pH-impedance testing will be used to objectively define pre-trial GER and in-study treatment
response. Motivated by our prior data suggesting heterogeneity of treatment effects, we will determine whether
the tolerability and physiologic efficacy of transpyloric feeding varies by pre-trial GER severity. Common GER
and lung aspiration biomarkers will be measured and compared to objective pH/MII and clinical outcome data.
The results of this study will immediately inform evidence-based GER diagnosis and feeding practices in BPD
and establish the foundation required to conduct a definitive, multicenter trial of prolonged transpyloric feeding
in chronically tube fed preterm infants with grade 2-3 BPD who are at high risk for GER-induced lung injury.
