Pre-term Infant
Conditions
Brief summary
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).
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.
Interventions
OTHERPreterm 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.
OTHERPreterm 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.
Sponsors
Société des Produits Nestlé (SPN)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Two sequential sub-studies
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Days
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Growth | 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 | Weight-adjusted weight gain (g/kg/day) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight at other time points | 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 | Changes in weight gain (g/day and g/kg/day) |
| Other growth parameter (length) | 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 | Change in length (cm/week) |
| Other growth parameter (head circumference) | 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 | Change in head circumference (cm/week) |
| Anthropometric z-scores for weight, length and head circumference | 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 | Corresponding z-scores and changes in z-scores expressed using Fenton growth chart will be analyzed |
| Feeding intake at neonatal unit | 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) | Neonatal unit feeding questionnaire capturing timing, type, rate and amount of feeding (parenteral \& enteral), gastric residual volumes, number of missed feedings |
| Stool frequency at neonatal unit | Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth) | Stool frequency (range from 0-20 times a day) collected via neonatal unit questionnaire |
| Stool consistency at neonatal unit | Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth) | Stool consistency (watery, mushy soft, runny, formed, hard) collected via neonatal unit questionnaire |
| Bloody stools at neonatal unit | Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth) | Bloody stools (yes or no) collected via neonatal unit questionnaire |
| GI symptoms at neonatal unit | Weekly between FEF Day 1 and hospital discharge (on average 7 weeks after birth) | GI symptoms (incidence of abdominal distention, regurgitation, spitting and vomiting) collected via neonatal unit questionnaire |
| Feeding intake after discharge | 3 consecutive days just prior to the 30-day PD and 60-day PD visits | Parent-reported 3-Day Intake Diary capturing the total number of bottles of formula and approximate volumes consumed per day |
| Stool frequency after discharge | 3 consecutive days just prior to the 30-day PD and 60-day PD visits | Stool frequency captured via parent-reported 3-Day Intake Diary |
| Stool consistency after discharge | 3 consecutive days just prior to the 30-day PD and 60-day PD visits | Stool frequency captured via parent-reported 3-Day Intake Diary |
| GI symptoms after discharge | 3 consecutive days just prior to the 30-day PD and 60-day PD visits | GI symptoms (such as presence of stomach ballooning, bloody stools, regurgitation, spitting-up and vomiting) captured via parent-reported 3-Day Intake Diary |
| GI-related behaviors after discharge | 3 consecutive days just prior to the 30-day PD and 60-day PD visits | GI-related behaviors (such as crying and sleep quality) captured via parent-reported 3-Day Intake Diary |
| Serum biomarkers for protein status | 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 albumin and blood urea nitrogen (BUN) |
| Serum biomarkers for bone health | 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 P, alkaline phosphatase, calcium and creatinine |
| Urine biomarkers for bone health | 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 | Urinary Ca, P and creatinine |
| Vitamin D | FEF Day 1, Neonatal Unit Discharge and at 60 days PD | Vitamin D |
| Fecal microbiota | 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 microbiota composition, diversity and metabolism markers (SCFAs) |
| Urine markers for gut health / maturation and immune status | Baseline (if feasible), FEF Day 1, Day 21, Neonatal Unit Discharge, 30 day-PD and 60 day-PD | Urinary level (spot urine sample) of intestinal fatty acid binding protein (iFABP) |
| AE reporting | From the time the mother has consented to the infant's participation in the study until the 60 days PD visit | Number of AEs through investigator-confirmed AE reporting |
| Bayley-III scores | At 12, 18, and 24 months | Bayley scales of Infants and Toddler development - 3rd edition |
| Developmental Milestone scores | At 12, 18, and 24 months | Parent-reported achievements of specific-age appropriate milestones (yes/no reponses to child performing specific milestones or not) |
| Child temperament scores | At 12, 18, and 24 months | Parent-reported child temperament questionnaire |
| Number of healthcare usage | At 12, 18, and 24 months | Retrospective paret-reported recall of the number of healthcare usage and hospitalizations |
| Fecal markers for gut health / maturation and immune status | Baseline (if feasible), FEF Day 1, Day 21, Neonatal Unit Discharge, 30 day-PD and 60 day-PD | 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 |
| Feeding patterns | At 12, 18, and 24 months | 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 |
Countries
Germany, Poland, Slovakia
Outcome results
None listed