Duration of Feeding intolerance in preterm infants reduced by use of Enteral insulin

Delhi: In a new study conducted by Elise Mank and team, it was found that enteral treatment of two distinct recombinant human (rh) insulin doses was safe and significantly decreased time to full enteral feeding (FEF) in preterm babies with a gestational age (GA) of 26 to 32 weeks when compared to placebo. The findings of this study were published in the Journal of American Medical Association - Pediatrics.

Due to the immaturity of the gastrointestinal system, feeding intolerance is a prevalent problem in premature newborns. It indicates that enteral insulin promotes intestinal development. Because insulin concentrations in human milk decrease fast postpartum and insulin is lacking in formula, enteral injection of rh insulin as a supplement to human milk and formula may alleviate feeding intolerance in preterm babies. Therefore, the objective of this study was To evaluate the effectiveness and safety of two distinct rh insulin doses as a supplement to both preterm formula and human milk.

This FIT-04 double-blind, multicenter, placebo-controlled randomized clinical study was carried out in 46 neonatal intensive care units in Europe, Israel, and the United States. Between October 9, 2016, and April 25, 2018, preterm babies with a gestational age of 26 to 32 weeks and a birth weight of 500 g or more were recruited. In January 2020, the data was evaluated. For 28 days, preterm babies were randomly randomized to receive either low-dose rh insulin (400 IU/mL milk), high-dose rh insulin (2000 IU/mL milk), or placebo. The primary outcome was the time to reach full enteral feeding (FEF), which was defined as an enteral intake of 150 mL/kg per day or greater for three days in a row.

The key findings are as follow:

1. In the final intention-to-treat analysis, 303 premature babies were included.

2. Based on an intermediate futility analysis, the data safety monitoring board recommended that the trial be terminated early since the conditional power did not meet the predetermined threshold of 35% for both rh-insulin doses.

3. While the data safety monitoring board evaluated and debated the data, the study continued. The median time to attain FEF was significantly shortened in 94 babies receiving low-dose rh insulin and 82 infants getting high-dose rh insulin compared to 85 infants receiving placebo in the final intention-to-treat analysis.

4. The difference in median time to FEF between the low-dose and high-dose groups was 4.0 days for the low-dose group and 4.0 days for the high-dose group.

5. The rates of weight growth did not differ substantially across groups. Necrotizing enterocolitis (Bell stage 2 or 3) occurred in 7 of 108 (6%) babies in the low-dose group, 4 of 88 (5%) in the high-dose group, and 10 of 97 (10%) in the placebo group.

6. Serum insulin antibodies were not produced in any of the babies.

In conclusion, the findings of this randomized clinical research demonstrated that enteral administration of two distinct rh-insulin doses was safe and significantly decreased the time to attain FEF in preterm infants with a GA of 26 to 32 weeks when compared to placebo. These findings back up the use of rh insulin as an addition to human milk and preterm formula.

Reference:

Mank E, Sáenz de Pipaón M, Lapillonne A, et al. Efficacy and Safety of Enteral Recombinant Human Insulin in Preterm Infants: A Randomized Clinical Trial. JAMA Pediatr. Published online February 28, 2022. doi:10.1001/jamapediatrics.2022.0020