title: Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study.
abstract: Feeding 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.
  
  
  
  LAIF (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.
  
  
  
  In 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.
  
  
  
  Although 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.
  
  
  
  ClinicalTrials.gov NCT01413581.
authors.affiliation: Unit of Neonatology, Paul Sabatier University, Toulouse, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Casper
authors.affiliation: Department of Neonatology, Université de Lorraine, Nancy, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Hascoet
authors.affiliation: Department of Neonatology, Medical School, University of Pécs, Pécs, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Ertl
authors.affiliation: Chair and Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Janusz S
authors.initials: JS
authors.lastname: Gadzinowski
authors.affiliation: Polytechnic University of Marche and Salesi's Children Hospital, Ancona, Italy.
authors.forename: Virgilio
authors.initials: V
authors.lastname: Carnielli
authors.affiliation: Department of Neonatology, University of Liège, Liège, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Rigo
authors.affiliation: Necker Enfants Malades Hospital, Paris Descartes University, EA 7328, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lapillonne
authors.affiliation: Neonatology Department, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: Couce
authors.affiliation: Swedish Orphan Biovitrum (Sobi), Stockholm, Sweden.
authors.forename: Mårten
authors.initials: M
authors.lastname: Vågerö
authors.affiliation: Swedish Orphan Biovitrum (Sobi), Stockholm, Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Palmgren
authors.affiliation: Swedish Orphan Biovitrum (Sobi), Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Timdahl
authors.affiliation: Pediatrics, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Hernell
mesh_terms: D001903:Bottle Feeding / Q000379:methods; D019587:Dietary Supplements / Q000009:adverse effects*; D004311:Double-Blind Method; D004750:Enteral Nutrition / Q000379:methods*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development*; D008297:Male; D008895:Milk, Human / Q000737:chemistry; D061352:Pasteurization; D010919:Placebos; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology*; D002787:Sterol Esterase / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; C054784:bile salt-stimulated lipase; D002787:Sterol Esterase