Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants

BackgroundFormula-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...

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Main Authors: Przemko Kwinta, Svilena Lazarova, Klaudia Demová, Yipu Chen, Mickaël Hartweg, Laura-Florina Krattinger, Cecilia Fumero, Aleksandra Buczyńska, Wojciech Durlak, Zuzana Uhrikova, Marek Kozar, Tinu Mary Samuel, Mirko Zibolen
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Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Pediatrics
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Online Access:https://www.frontiersin.org/articles/10.3389/fped.2024.1427050/full
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author Przemko Kwinta
Svilena Lazarova
Klaudia Demová
Yipu Chen
Mickaël Hartweg
Laura-Florina Krattinger
Cecilia Fumero
Aleksandra Buczyńska
Wojciech Durlak
Zuzana Uhrikova
Marek Kozar
Tinu Mary Samuel
Mirko Zibolen
author_facet Przemko Kwinta
Svilena Lazarova
Klaudia Demová
Yipu Chen
Mickaël Hartweg
Laura-Florina Krattinger
Cecilia Fumero
Aleksandra Buczyńska
Wojciech Durlak
Zuzana Uhrikova
Marek Kozar
Tinu Mary Samuel
Mirko Zibolen
author_sort Przemko Kwinta
collection DOAJ
description BackgroundFormula-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.MethodsMale and female very-low-birth-weight preterm infants (birth weight ≤1,500 g; gestational age ≤32 weeks) were recruited from three neonatal units in Poland and Slovakia in a prospective, open-label, interventional study. Stage 1 formula providing 3.6 g intact protein/100 kcal was consumed from enrollment until reaching 1,800 g, followed by a post-discharge (PD) Stage 2 formula with 2.8 g/100 kcal protein, which was consumed for 30 days. Weight gain velocity (WGV in g/kg/day) between the first day of achieving full enteral feeding (FEF D1 rate of 150 ml/kg/day and cessation of parenteral feeding) and day reaching 1,800 g 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 (17.3 g/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).ResultsAdjusted weight gain velocity (95% CI) between the first day of full enteral feeding and day reaching 1,800 g in per protocol (PP, N = 18) was 23.0 (20.1–25.9) g/kg/day; lower limit of the 95% CIs exceeded the non-inferiority margin (15 g/kg/day, p < 0.001) and the superiority margin (17.3 g/kg/day, p < 0.001). Mean stool frequency ranged from 2.5 to 3.3 stools per day. The two-stage formula supported adequate growth patterns throughout 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.ConclusionThe two-stage preterm formulas supported postnatal weight gain, adequate growth, cognitive development within normal ranges, and a safe profile of protein and bone biomarkers. Clinical Trial RegistrationClinicaltrials.gov registration, NCT03728764, NCT04962035.
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spelling doaj-art-8abfa54e94ad42ba98f3b0ba663e1f962024-11-22T04:35:57ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602024-11-011210.3389/fped.2024.14270501427050Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infantsPrzemko Kwinta0Svilena Lazarova1Klaudia Demová2Yipu Chen3Mickaël Hartweg4Laura-Florina Krattinger5Cecilia Fumero6Aleksandra Buczyńska7Wojciech Durlak8Zuzana Uhrikova9Marek Kozar10Tinu Mary Samuel11Mirko Zibolen12Department of Pediatrics, Jagiellonian University, Krakow, PolandNestlé Product Technology Center—Nutrition, Vevey, SwitzerlandDepartment of Neonatology, Faculty Hospital Nové Zámky, Nové Zámky, SlovakiaNestlé Product Technology Center—Nutrition, Vevey, SwitzerlandClinical Research Unit, Nestlé Research, Lausanne, SwitzerlandClinical Research Unit, Nestlé Research, Lausanne, SwitzerlandClinical Research Unit, Nestlé Research, Lausanne, SwitzerlandDepartment of Pediatrics, Jagiellonian University, Krakow, PolandDepartment of Pediatrics, Jagiellonian University, Krakow, PolandJessenius Faculty of Medicine, Martin/Comenius University, Bratislava, SlovakiaJessenius Faculty of Medicine, Martin/Comenius University, Bratislava, SlovakiaNestlé Product Technology Center—Nutrition, Vevey, SwitzerlandJessenius Faculty of Medicine, Martin/Comenius University, Bratislava, SlovakiaBackgroundFormula-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.MethodsMale and female very-low-birth-weight preterm infants (birth weight ≤1,500 g; gestational age ≤32 weeks) were recruited from three neonatal units in Poland and Slovakia in a prospective, open-label, interventional study. Stage 1 formula providing 3.6 g intact protein/100 kcal was consumed from enrollment until reaching 1,800 g, followed by a post-discharge (PD) Stage 2 formula with 2.8 g/100 kcal protein, which was consumed for 30 days. Weight gain velocity (WGV in g/kg/day) between the first day of achieving full enteral feeding (FEF D1 rate of 150 ml/kg/day and cessation of parenteral feeding) and day reaching 1,800 g 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 (17.3 g/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).ResultsAdjusted weight gain velocity (95% CI) between the first day of full enteral feeding and day reaching 1,800 g in per protocol (PP, N = 18) was 23.0 (20.1–25.9) g/kg/day; lower limit of the 95% CIs exceeded the non-inferiority margin (15 g/kg/day, p < 0.001) and the superiority margin (17.3 g/kg/day, p < 0.001). Mean stool frequency ranged from 2.5 to 3.3 stools per day. The two-stage formula supported adequate growth patterns throughout 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.ConclusionThe two-stage preterm formulas supported postnatal weight gain, adequate growth, cognitive development within normal ranges, and a safe profile of protein and bone biomarkers. Clinical Trial RegistrationClinicaltrials.gov registration, NCT03728764, NCT04962035.https://www.frontiersin.org/articles/10.3389/fped.2024.1427050/fullgrowthnutritional biomarkersfeeding toleranceneurodevelopmentinfant developmentpreterm infants
spellingShingle Przemko Kwinta
Svilena Lazarova
Klaudia Demová
Yipu Chen
Mickaël Hartweg
Laura-Florina Krattinger
Cecilia Fumero
Aleksandra Buczyńska
Wojciech Durlak
Zuzana Uhrikova
Marek Kozar
Tinu Mary Samuel
Mirko Zibolen
Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
Frontiers in Pediatrics
growth
nutritional biomarkers
feeding tolerance
neurodevelopment
infant development
preterm infants
title Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
title_full Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
title_fullStr Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
title_full_unstemmed Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
title_short Effects of two-stage preterm formulas on growth, nutritional biomarkers, and neurodevelopment in preterm infants
title_sort effects of two stage preterm formulas on growth nutritional biomarkers and neurodevelopment in preterm infants
topic growth
nutritional biomarkers
feeding tolerance
neurodevelopment
infant development
preterm infants
url https://www.frontiersin.org/articles/10.3389/fped.2024.1427050/full
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