Digestive enzyme replacement in very preterm infants: a prospective observational study

Objectives Very preterm infants may display poor postnatal growth despite receiving recommended enteral intakes. This has been linked to transient exocrine pancreatic insufficiency, indicated by low fecal pancreatic elastase-1 (FPE-1) concentrations. We aimed to determine whether growth velocity may be improved by exogenous digestive enzyme replacement. Methods In this bicentric prospective observational study, changes in growth velocity were assessed in very preterm infants (<32 weeks gestational age, <1500 g birth weight) with low FPE-1 concentrations (<200 µg/g). Infants received 350 U lipase from Rhizopus oryzae and 5.4 U protease from Aspergillus oryzae with every meal via gavage; the dosage was doubled once infants reached 1000 g. Average daily weight gain relative to body weight was compared during the 14 days preceding initiation of digestive enzyme replacement and during the first 14 days thereafter. Results In 71 infants (median [interquartile range] birth weight 700 [570–980] g, gestational age 25.4 [24.4–28.4] weeks) born between March 1, 2022, and December 31, 2023, daily weight gain increased from 14.7 [7.3–19.7] to 19.5 [15.7–24.0] g/kg/d ( p < 0.001), relative daily weight gain per kg protein fed from 4.0 [2.0–5.9] to 5.4 [4.4–6.5] g/kg ( p < 0.001), and relative daily weight gain per kcal fed from 0.11 [0.06–0.16] to 0.15 [0.13–0.19] g/kcal/d ( p < 0.001). Effects were non-significant in infants fed raw milk but marked in those who received pasteurized mother’s own milk or donor milk. Conclusion Administration of exogenous digestive enzymes was associated with increased weight gain in very preterm infants with transient exocrine pancreatic insufficiency.