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ORIGINAL RESEARCH article
Front. Pediatr.
Sec. Neonatology
Volume 12 - 2024 |
doi: 10.3389/fped.2024.1427050
Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
Provisionally accepted- 1 Nestle (Switzerland), Vevey, Switzerland
- 2 Jagiellonian University Medical College, Kraków, Lesser Poland, Poland
- 3 Faculty Hospital and Polyclinic Nové Zámky, Nové Zámky, Slovakia
- 4 Nestlé Research, Lausanne, Switzerland
- 5 Jessenius Faculty of Medicine, Comenius University, Martin, Slovakia
Background: Formula-fed preterm infants require nutrient-enriched formulas with optimized protein levels to support growth and neurodevelopment. The purpose of this study was to evaluate the safety, tolerability, and effectiveness of a new liquid two-staged formula system designed to provide tailored nutrition during hospital stay and after discharge.Methods: Male and female very-low-birth-weight preterm infants (birth weight≤1500g; gestational age≤32 weeks) were recruited from 3 neonatal units in Poland and Slovakia in a prospective, openlabel, interventional study. Stage 1 formula providing 3.6g intact protein/100kcal was consumed from enrolment until reaching 1800g, followed by a post-discharge (PD) Stage 2 formula with 2.8g/100kcal protein which was consumed for 30 days PD. Weight gain velocity (WGV; g/kg/day) from FEF D1 (first day of achieving Full Enteral Feeding rate of 150mL/kg/day and cessation of parenteral feeding) and day reaching 1800g was compared to the minimally required WGV (15 g/kg/day) for non-inferiority (primary endpoint), and to the Fenton median growth rate for superiority (17.3g/kg/day), adjusting for sex, gestational age, site, visit, and WGV. Changes in z-scores, feeding tolerance, nutritional biomarker status, and safety were also assessed from FEF D1 to 30 days PD. In an observational follow-up at 2 years of age, neurodevelopment was evaluated using the Bayley Scales of Infant and Toddler Development (BSID-III).Results: Adjusted weight gain velocity (95% CI) between the first day of full enteral feeding and 1800g in PP (N=18, per-protocol) was 23.0 (20.1, 25.9) g/kg/day; lower limit of the 95% CIs exceeded the non-inferiority margin (15g/kg/day, p<0.001) and the superiority margin (17.3g/kg/day, p<0.001). Mean stool frequency ranged from 2.5-3.3 stools per day. The two-stage formula supported adequate growth patterns through the study and nutritional biomarkers of protein and mineral status were within normal ranges. At 24 months corrected age, the mean±SD of the BSID cognitive scale was 97.3±13.9 in PP, with all infants achieving a score >70. None of the adverse events reported were related to the study formulas.The two-stage preterm formulas supported postnatal weight gain, adequate growth, cognitive development within normal ranges, and a safe profile of protein and bone biomarkers.
Keywords: Growth, Nutritional biomarkers, Feeding tolerance, neurodevelopment, Infant Development, preterm infants, preterm formula Clinicaltrials.gov registration: NCT03728764, NCT04962035
Received: 02 May 2024; Accepted: 21 Oct 2024.
Copyright: © 2024 Lazarova, Kwinta, Demová, Chen, Hartweg, Krattinger, Fumero, Buczyńska, Durlak, Uhrikova, Kozár, Samuel and Zibolen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Svilena Lazarova, Nestle (Switzerland), Vevey, Switzerland
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