Continuous Versus Intermittent Bolus Feeding in Very Preterm Infants - Effects on Respiratory Morbidity: A Multicentre Randomised Controlled Clinical Trial

The pathogenesis of bronchopulmonary dysplasia (BPD) is complex and multifactorial. As a result of premature birth, developmental arrest during a critical period of fetal lung development compounded by mechanical, oxidative and other injuries sustained during neonatal respiratory care forms the basis of pathogenesis. BPD affects up to 50% of infants with birth weight less than 1000 g. Between 2000 and 2009, despite advancement of neonatal care, annual BPD rates reported by Vermont Oxford Network among very low birth weight infants varied from 26.2% to 30.4% without any decline. Severely affected infants often require prolonged ventilation, high oxygen use, alternative airway and several potent medications over the first few months to years of their lives. High mortality rates, neurodevelopmental delay, respiratory morbidity and growth failure are associated with BPD.

Treatment of severe BPD with or without pulmonary hypertension is challenging. Prolonging the pregnancy in the face of premature labour, treating perinatal infections, augmenting pulmonary maturity with corticosteroids, judicious oxygen use, lung protective ventilation and optimizing nutrition to promote growth are important and well established measures to prevent or modify the progress of the chronic lung disease.

It is common to find infants with BPD also having significant symptoms of reflux. Gastroesophageal reflux (GER) is a well-known co-morbidity among preterms and ex-preterms on chronic ventilation, many of whom go on to require surgical fundoplication to stop the reflux thus preventing further lung damage. Some have reported dramatic respiratory improvement after resolution of GER. In the early days of a preterm baby with respiratory distress, GER is common and silent. Among infants, diagnosis of pathologic GER from a benign one is difficult. Many neonatal intensive care units (NICUs) would investigate for GER only when faced with moderate to severe BPD to achieve better respiratory symptom control. However GER has not been studied well as a factor precipitating the development of BPD among VLBW neonates. This is the focus of the study.

Aspiration of gastric contents into the lung is a widespread phenomenon in mechanically ventilated preterm infants. In animal models of gastric aspiration, gastric particulates altered the pulmonary mechanics, increased pulmonary inflammatory cells, released pro-inflammatory mediators, and inactivated surfactant. Development of bacterial pneumonia is a well-recognized complication following aspiration of gastric contents. The investigators hypothesize that repeated aspirations would aggravate and accelerate an inflammatory response in the lung finally leading on to BPD. In addition oxygen mediated damage and mechanical ventilation potentiate lung injury due to aspiration. Logically, if GER and aspiration could be minimized, it could decrease the incidence and severity of BPD.

Certain positioning of the baby, small volume of feed increment, keeping a close watch on feed tolerance are practical ways of improving feeding tolerance and reducing GER. The intermittent bolus intra-gastric feeding method is commonly used to feed premature babies. Other alternatives are continuous intra-gastric (feed volume is slowly infused in the stomach over couple of hours through the nasogastric tube) and continuous transpyloric feeding (feeding tube passes beyond the stomach to the duodenum and feed volume is slowly infused over hours). Transpyloric continuous feeding as compared to intermittent gastric bolus feeding, has been found to significantly reduce ventilatory support requirements in extremely low birth weight (ELBW) infants, possibly via its effect of minimising GER. In this study, none of the babies who received transpyloric feeding developed significant BPD and in addition babies with significant BPD improved after switching to transpyloric method. Transpyloric feeding tubes however are challenging to insert, and intestinal perforation is an uncommon but significant adverse effect. This feeding method is also not physiological as it bypasses the stomach. It remains to be seen if continuous gastric feeds, which is easily administered and safer, would yield some of the advantages of continuous transpyloric feeds over intermittent gastric feeding.