Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study

Abstract

IntroductionFeeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk.Patients and MethodsLAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries.ResultsIn total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment.ConclusionsAlthough this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants.Trial RegistrationClinicalTrials.gov NCT01413581

Human Milk: An Ideal Food for Nutrition of Preterm Newborn

“…Bile salt stimulated lipase, present in human milk, which would improve the digestibility of long-chain fatty acids. In a multi-center randomized trial, recombinant BSSL has been tested vs. placebo with a follow-up for 12 months; there was no improvement in weight growth in preterm infants except in the sub-group of Small for Gestational Age infants but with some imbalance in the adverse effects ( 79 ).…”

Benefits of Lactoferrin, Osteopontin and Milk Fat Globule Membranes for Infants

“…In fact, results of a randomized clinical trial in preterm infants using a crossover design indicate that the addition of recombinant human BSSL vs. placebo to the infant feed (pasteurized human milk or infant formula) improves growth velocity and long chain polyunsaturated fatty acid absorption [ 42 ]. A subsequent multi-center study using a parallel study design enrolling 415 preterm infants confirmed a beneficial effect on growth for small-for-gestational-age infants, but not for the full study population including appropriate-for gestational age infants [ 48 ]. For mothers who produce 2-fucosylated glycans (secretor mothers), it could be shown in vitro that BSSL acts as a decoy receptor for human calicivirus strains and may provide some protection from gastroenteritis due to norovirus infection in breast-fed infants [ 43 ].…”

Enteral Bioactive Factor Supplementation in Preterm Infants: A Systematic Review

“…The effect of recombinant human bile salt-stimulated lipase (rhBSSL) was investigated by Casper et al [ 37 ]. BSSL is a lipolytic enzyme facilitating digestion and absorption of fat in human milk and formula.…”

“…The addition of rhBSSL to formula or donor human milk did not result in a higher growth velocity in a phase 3 study [ 37 ]. This result is in contrast with the phase 2 study, which had a cross-over design with a washout period of 2 days ( n = 65 in total) [ 62 ].…”