Amino Acid-Based Formula vs. Extensively Hydrolyzed Formula in the Treatment of Feeding Intolerance in Preterm Infants: Study Protocol for a Randomized Controlled Trial.

Background: Feeding intolerance is a common problem in preterm infants, which is associated with an increased risk of infections, prolonged hospitalization, and increased economic costs. When human milk is not available, formula feeding is required. Amino acid-based formula and extensively hydrolyzed formula could be considered for use for severe feeding intolerance. A recent Cochrane meta-analysis found that preterm infants fed extensively hydrolyzed formula compared with standard formula could not reduce the risk of feeding intolerance and necrotizing enterocolitis, and weight gain was slower. Some studies reported that preterm infants fed amino acid-based formula could reduce the gastric residual volume. We hypothesize that amino acid-based formula can improve feeding intolerance and establish full enteral feeding more rapidly in preterm infants compared with extensively hydrolyzed formula. Method: The randomized, prospective, controlled trial was conducted at the Children's Hospital of Chongqing Medical University (Chongqing, China). A total of 190 preterm infants with gestational age <32 weeks or birth weight <1,500 g and with a diagnosis of feeding intolerance were included. Patients were randomized to an amino acid-based formula-fed group and an extensively hydrolyzed formula-fed group. The primary outcome is the time (days) to reach full enteral feedings. Secondary outcomes include duration of vomiting and abdominal distension, gastric residual volume, body weight, length and head circumference during hospitalization, length of hospital stay (days), cost of hospitalization, time (days) of parenteral nutrition, change of abdomen circumference, main serum parameters, and incidence of adverse events. Discussion: The successful implementation of our study will provide robust evidence for formula alternatives in preterm infants with feeding intolerance. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT05347706.