Growth and Safety of Two Partially-hydrolyzed Feeding Systems for Preterm Infants (Capetown)

Growth and Safety of Two Partially-hydrolyzed Feeding Systems for Preterm Infants: a Multi-centered, Open-label Clinical Trial

This is an open-label trial consisting of two sub-studies to be conducted sequentially with the purpose of evaluating the safety and suitability of a two feeding systems in pre-term infants (one containing HMOs and one without HMOs).

Study Overview

• Status: Completed
• Conditions: Pre-term Infant
• Intervention / Treatment: Other: Preterm formulas with HMO; Other: Preterm formulas without HMO

Detailed Description

This is a multi-center, open-label trial to be conducted in up to 70 pre-term infants in order to evaluate the safety and suitability of two feeding systems as they would typically be used in the neonatal care unit. Growth (in comparison to recommended growth goals), feeding tolerance, biochemical parameters, and adverse event reporting will be evaluated.

The two feeding systems will be tested in two sub-studies to be conducted sequentially: sub-study 1 will evaluate a two-staged feeding system with HMOs in up to 35 pre-term infants; sub-study 2 will evaluate a two-staged feeding system without HMOs in up to 35 pre-term infants.

A follow up period from 12 to 24 months have been added to the study protocol, to assess the neurocognitive development of the subjects during this period.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Nuremberg, Germany
    • Klinikum Nuernberg
• Poland
  • Bydgoszcz, Poland, 85-067
    • Klinika Neonatologii, Szpital Uniwersyteck
• Slovakia
  • Martin, Slovakia, 3659
    • Univerzitna Nemocnica Martin
  • Nové Zámky, Slovakia, 940 34
    • Fakultna nemocnica s poliklinikou Nove Zamky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 week (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Written informed consent has been obtained from one or both parent(s) /legally acceptable representative (LAR) in accordance with local regulation.
2. Infants' birth weight ≤1500 g and AGA.
3. Infant's gestational age < 37 weeks.
4. Infant is clinically stable and does not have deteriorating respiratory function after birth.
5. Infant is eligible to start experimental formula after 24 hours of trophic feeding, but still within the first 10 days (≤240 hours) of life.

Exclusion Criteria:

1. Parent(s) not willing / not able to comply with the requirements of study protocol.
2. Infant is experiencing early onset sepsis.
3. Major congenital or chromosomal abnormality known to affect growth.
4. Liver failure.
5. Peri-/intra-ventricular haemorrhage (grade 3-4 in Papille classification).
6. Infant who has siblings with diagnosed allergies or intolerances to lactose or cow's milk.
7. Infant's participation in another interventional clinical trial.
8. Infant has already achieved FEF prior to enrolment, using the definition accepted by Neonatal Unit as per standard practice (150 mL/kg/day).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sub-study 1; Pre-term formulas with HMO	Other: Preterm formulas with HMO; Preterm infants will receive Stage 1 formula as soon as possible after birth until when 1.8 kg of body weight is achieved. Preterm infants will receive Stage 2 preterm formula from when 1.8 kg of body weight is achieved until 2 months after hospital discharge.
Experimental: Sub-study 2; Pre-term formulas without HMO	Other: Preterm formulas without HMO; Preterm infants will receive Stage 1 formula as soon as possible after birth until when 1.8 kg of body weight is achieved. Preterm infants will receive Stage 2 preterm formula from when 1.8 kg of body weight is achieved until 2 months after hospital discharge.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Growth	Weight-adjusted weight gain (g/kg/day)	From FEF Day 1 to when infant reaches 1800 g (on average between 4 to 6 weeks after birth) or hospital discharge (on average 7 weeks after birth), whichever comes earlier

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight at other time points	Changes in weight gain (g/day and g/kg/day)	From Pre-FEF Day 1 to FEF Day 1, and then weekly from FEF Day 1 until hospital discharge (on average 7 weeks after birth), at 30- and 60-days PD, and at 12, 18, and 24 months
Other growth parameter (length)	Change in length (cm/week)	From Pre-FEF Day 1 to hospital discharge (on average 7 weeks after birth), at 30- and 60-days PD, and at 12, 18, and 24 months
Other growth parameter (head circumference)	Change in head circumference (cm/week)	From Pre-FEF Day 1 to hospital discharge (on average 7 weeks after birth), at 30- and 60-days PD, and at 12, 18, and 24 months
Anthropometric z-scores for weight, length and head circumference	Corresponding z-scores and changes in z-scores expressed using Fenton growth chart will be analyzed	From Pre-FEF Day 1 to hospital discharge (on average 7 weeks after birth), at 30- and 60-days PD, and at 12, 18, and 24 months
Feeding intake at neonatal unit	Neonatal unit feeding questionnaire capturing timing, type, rate and amount of feeding (parenteral & enteral), gastric residual volumes, number of missed feedings	Baseline + weekly over 3 consecutive days starting on pre-FEF Day1 + weekly over 3 consecutive days starting on FEF Day1 until Neonatal Unit Discharge (on average 7 weeks after birth)
Stool frequency at neonatal unit	Stool frequency (range from 0-20 times a day) collected via neonatal unit questionnaire	Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth)
Stool consistency at neonatal unit	Stool consistency (watery, mushy soft, runny, formed, hard) collected via neonatal unit questionnaire	Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth)
Bloody stools at neonatal unit	Bloody stools (yes or no) collected via neonatal unit questionnaire	Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth)
GI symptoms at neonatal unit	GI symptoms (incidence of abdominal distention, regurgitation, spitting and vomiting) collected via neonatal unit questionnaire	Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth)
Feeding intake after discharge	Parent-reported 3-Day Intake Diary capturing the total number of bottles of formula and approximate volumes consumed per day	3 consecutive days just prior to the 30-day PD and 60-day PD visits
Stool frequency after discharge	Stool frequency captured via parent-reported 3-Day Intake Diary	3 consecutive days just prior to the 30-day PD and 60-day PD visits
Stool consistency after discharge	Stool frequency captured via parent-reported 3-Day Intake Diary	3 consecutive days just prior to the 30-day PD and 60-day PD visits
GI symptoms after discharge	GI symptoms (such as presence of stomach ballooning, bloody stools, regurgitation, spitting-up and vomiting) captured via parent-reported 3-Day Intake Diary	3 consecutive days just prior to the 30-day PD and 60-day PD visits
GI-related behaviors after discharge	GI-related behaviors (such as crying and sleep quality) captured via parent-reported 3-Day Intake Diary	3 consecutive days just prior to the 30-day PD and 60-day PD visits
Serum biomarkers for protein status	Serum albumin and blood urea nitrogen (BUN)	At Baseline (if possible), pre-FEF Day 1, then weekly pre-FEF Days 7, 14, etc. and FEF Day 1, then weekly on FEF Days 7, 14, 21, until Neonatal Unit Discharge, and at 60 days PD
Serum biomarkers for bone health	Serum P, alkaline phosphatase, calcium and creatinine	At Baseline (if possible), pre-FEF Day 1, then weekly pre-FEF Days 7, 14, etc. and FEF Day 1, then weekly on FEF Days 7, 14, 21, until Neonatal Unit Discharge, and at 60 days PD
Urine biomarkers for bone health	Urinary Ca, P and creatinine	At Baseline (if possible), pre-FEF Day 1, then weekly pre-FEF Days 7, 14, etc. and FEF Day 1, then weekly on FEF Days 7, 14, 21, until Neonatal Unit Discharge, and at 60 days PD
Vitamin D	Vitamin D	FEF Day 1, Neonatal Unit Discharge and at 60 days PD
Fecal microbiota	Fecal microbiota composition, diversity and metabolism markers (SCFAs)	Baseline, FEF Day 1, then weekly on FEF Days 7, 14, 21, until Neonatal Unit Discharge, at 30 day-PD and 60 days PD
Fecal markers for gut health / maturation and immune status	Fecal levels of calprotectin, alpha 1 antitrypsin, pancreatic elastase (i.e. chymotrypsin-like elastase family, member 3B (CELA3B)), Human beta-defensin 2 (HBD2) and secretory IgA	Baseline (if feasible), FEF Day 1, Day 21, Neonatal Unit Discharge, 30 day-PD and 60 day-PD
Urine markers for gut health / maturation and immune status	Urinary level (spot urine sample) of intestinal fatty acid binding protein (iFABP)	Baseline (if feasible), FEF Day 1, Day 21, Neonatal Unit Discharge, 30 day-PD and 60 day-PD
AE reporting	Number of AEs through investigator-confirmed AE reporting	From the time the mother has consented to the infant's participation in the study until the 60 days PD visit
Bayley-III scores	Bayley scales of Infants and Toddler development - 3rd edition	At 12, 18, and 24 months
Developmental Milestone scores	Parent-reported achievements of specific-age appropriate milestones (yes/no reponses to child performing specific milestones or not)	At 12, 18, and 24 months
Child temperament scores	Parent-reported child temperament questionnaire	At 12, 18, and 24 months
Number of healthcare usage	Retrospective paret-reported recall of the number of healthcare usage and hospitalizations	At 12, 18, and 24 months
Feeding patterns	Feeding practice outcomes collected retrospectively at each visit via a parent-reported questionnaire related to breastfeeding duration, prevalence of formula feeding, and age at initiation of complementary feeding	At 12, 18, and 24 months

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2020
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): April 28, 2025

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 20, 2020

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Premature Birth; Professional Practice; Organization and Administration; Health Services Administration; Delivery of Health Care; Health Care Economics and Organizations; Patient Care Management; Financing, Organized; Economics; Insurance, Health; Insurance; Managed Care Programs; Prepaid Health Plans; Group Practice; Health Maintenance Organizations
• Other Study ID Numbers: 18.09.INF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No