Growth, Safety, Subjects in Need of a Human Milk Fortifier (HMF), Tolerance
Conditions
Brief summary
Preterm birth (birth before start of the 37th week of gestation) is a major determinant of neonatal morbidity and mortality and has long-term adverse consequences for health and neurodevelopment. Preterm infants have much higher nutrient requirements than term infants. The preferred nutrition for all infants including preterm infants is human milk from the infant's own mother, or alternatively donor human milk, provided it is fortified with several nutrients as human milk alone does not sufficiently meet the nutritional needs of preterm infants. Human milk fortifiers (HMFs) are multicomponent enrichments that can be added to human milk (own mother´s milk or donor milk) to meet the increased nutritional needs of preterm infants. The current Nutricia HMF (control product) has been available in its current composition since 2010. It is a multicomponent HMF providing protein, energy, minerals, and vitamins in accordance with the ESPGHAN recommendations. Recent investigation suggests positive effects on growth and development of preterm infants when lipids are added to their nutrition. Therefore, Nutricia has added lipids to their HMF (test product) for a nutritionally more complete fortification of human milk aiming for optimal growth and optimal cognitive and brain development. The Renoir study will investigate the difference between both HMFs with regards to the growth velocity as well as the safety and tolerance of the new HMF.
Interventions
OTHERTest product
HMF with added lipids - Intervention group
OTHERControl product
Commercially available HMF (without lipids) - control group
Sponsors
Nutricia Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Weeks to 32 Weeks
Healthy volunteers
No
Inclusion criteria
1. Preterm infants fed own mother's milk (or donor human milk) in need of a HMF (as decided by the investigator) 2. Gestational age \<32 weeks and birth weight \<1500 g 3. Receiving enteral feeding 4. Expected to need a HMF for minimally 21 days 5. Written informed consent from custodial parent(s)
Exclusion criteria
1. Any relevant proven or suspected chromosomal anomaly, metabolic disorder, genetic syndrome or congenital central nervous system malformation; 2. Presence or history of any gastrointestinal malformation, including Necrotising enterocolitis (NEC) (defined as Bell's stage two or higher); 3. No realistic prospect of survival at the discretion of the attending physician; 4. Participation in any other studies involving investigational or marketed products concomitantly or within two weeks prior to entry into the study; 5. Expected or foreseen inability of the subject and/or their families to adhere to protocol instructions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight growth velocity | 21 days | Weight growth velocity (in g/kg/day) from baseline to study day 21 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Enteral feed | up to 16 weeks, depending on gestational age at birth. | Number of days that an infant is not fed enterally |
| Length | up to 16 weeks, depending on gestational age at birth | Length gain (cm/week) |
| Head circumference | up to 16 weeks, depending on gestational age at birth | Head circumference gain (cm/week) |
| Weight for Length | up to 16 weeks, depending on gestational age at birth | Weight for Length |
| Regurgitation | up to 16 weeks, depending on gestational age at birth | Incidence of regurgitation (number/day) |
| Stool consistency | up to 16 weeks, depending on gestational age at birth | Stool consistency (4-point scale Amsterdam stool scale: watery, soft, formed, hard) |
| Stool frequency | up to 16 weeks, depending on gestational age at birth | Stool frequency (number of stools per day) |
| Enteral intake | up to 16 weeks, depending on gestational age at birth | Total enteral intake (mL/kg/day) |
| vomiting | up to 16 weeks, depending on gestational age at birth | Incidence of vomiting (number/day) |
| Z-scores | up to 16 weeks, depending on gestational age at birth | Z-scores (no unit) of anthropometric measures (weight for age, length for age, head circumference for age) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory - Neurodevelopmental outcome | at 24 months CA | Neurodevelopmental outcome assessed by Bayley Scales of Infant and Toddler Development, Third Edition, on three subscales (cognitive, fine and gross motor) |
| Safety - Incidence (S)AE's | up to 24 months CA | Incidence of (Serious) Adverse Events that are assessed by the Investigator to be possibly, probably or definitely related to the study product |
| Safety - Frequency (S)AE's | up to 24 months CA | Frequency of (Serious) Adverse Events that are assessed by the Investigator to be possibly, probably or definitely related to the study product |
| Safety - Severity (S)AE's | up to 24 months CA | Severity of (Serious) Adverse Events (mild/moderate/severe) that are assessed by the Investigator to be possibly, probably or definitely related to the study product |
| Safety - Relatedness (S)AE's | up to 24 months CA | Relatedness of Serious Adverse Events |
| Exploratory - Age | 2-16 weeks, depending on gestational age at birth | Age at discharge from the neonatal intensive care unit (NICU, level III) |
| Safety - NEC | up to 16 weeks, depending on gestational age at birth) | NEC (defined as Bell's stage two or higher) (as part of the assessment of neonatal morbidity) |
| Safety - Bronchopulmonary dysplasia | up to 16 weeks, depending on gestational age at birth) | Bronchopulmonary dysplasia (as part of the assessment of neonatal morbidity), categorized into mild/moderate/severe based on Sahni et al |
| Safety - Serious neonatal infections | up to 16 weeks, depending on gestational age at birth | Serious neonatal infections (as part of the assessment of neonatal morbidity), i.e. confirmed sepsis, pneumonia, or meningitis |
| Safety - Retinopathy of Prematurity | up to 16 weeks, depending on gestational age at birth | Retinopathy of Prematurity, based on International Committee for the Classification of Retinopathy of Prematurity (as part of the assessment of neonatal morbidity) |
| Safety - Metabolic acidosis | up to 16 weeks, depending on gestational age at birth | Metabolic acidosis (as part of the assessment of neonatal morbidity) leading to correction and/or change in clinical management of the subject (according to the investigator's assessment) |
| Safety - Severity Blood in stool | up to 16 weeks, depending on gestational age at birth) | Severity of blood in stool (mild, moderate, severe) |
| Exploratory - Mortality | up to 16 weeks depending on gestational age at birth | Mortality (yes/no) during stay in NICU/hospital |
| Exploratory - Enteral feeding volume | around 1-4 weeks, depending on gestational age at birth | Time in days to achieve an enteral feeding volume of at least 150 mL/kg/day +/- 10 mL for 3 consecutive days |
| Exploratory - Gastric residuals | up to 16 weeks, depending on gestational age at birth | Frequency of clinically significant gastric residuals, defined as gastric residuals leading to a change in feeding according to the investigator's assessment (if assessed per local standard practice) |
| Exploratory - Diarrhoea | up to 16 weeks, depending on gestational age at birth) | Occurrence of diarrhoea |
| Exploratory - Constipation | up to 16 weeks, depending on gestational age at birth) | Occurrence of constipation |
| Exploratory - Weight | at 6, 12 and 24 months corrected age (CA) | Weight (g) |
| Exploratory - Length | at 6, 12 and 24 months corrected age (CA) | Length (cm) |
| Safety - Incidence Blood in stool | up to 16 weeks, depending on gestational age at birth) | Incidence blood in stool |
| Safety - Frequency Blood in stool | up to 16 weeks, depending on gestational age at birth) | Frequency of blood in stool |
| Exploratory - Head circumference | at 6, 12 and 24 months corrected age (CA) | Head circumference (cm) |
Countries
France, Germany, Netherlands, United Kingdom
Outcome results
None listed