Infant, Small for Gestational Age
Conditions
Brief summary
The purpose of this study is to determine whether term SGA infants who are fed a nutrient-enriched pre-term formula will have a higher cognitive score, a more appropriate length-for-age Z-score (leading to a lower prevalence of Stunting) but higher blood pressure at 2 years of age compared to term SGA infants who are fed on a regular starter formula.
Detailed description
This is multi-sites, interventional, double-blinded, randomized, 2-arm parallel-group clinical trial. Two HM fed groups will be included as comparator group. The primary objectives are: 1. To evaluate neurodevelopment at 2 years of age in term small-for-gestational age (SGA) infants fed standard formula or nutrient-enriched formula from 1 to 6 months of age and compare to each human milk (HM)-fed group. 2. To evaluate length-for-age Z-score at 2 years of age in term SGA infants fed standard formula or nutrient-enriched formula from 1 to 6 months of age and compare to each HM-fed group. 3. To evaluate systolic blood pressure at 2 years of age in term SGA infants fed standard formula or nutrient-enriched formula from 1 to 6 months of age and compare to each HM-fed group.
Interventions
OTHERStandard Formula
Standard Formula
OTHERNutrient-enriched Formula
Nutrient-enriched Formula
Sponsors
Société des Produits Nestlé (SPN)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Days to 44 Days
Healthy volunteers
Yes
Inclusion criteria
1. Having obtained his/her parents' (or his/her legally accepted representative's LAR's\]) written informed consent and having evidence of a personally signed and dated informed consent document indicating that the infant's parents/LAR have been informed of pertinent aspects of the study. 2. For infants in formula fed groups only: infants who require formula feeding due to lactation failure after minimum 2 rounds of breastfeeding counselling. 3. Birth Weight \< 10th percentile at term using the 2013 INTERGROWTH-21st Growth Charts for girls and boys. 4. Full term birth (gestational age ≥ 37 weeks and ≤ 41 weeks + 6 days), with gestational age estimated using fetal anthropometry by ultrasonography in early 1st trimester of pregnancy or calculated using the first day of the last menstrual period + 40 weeks if fetal anthropometry data for term calculation is not available or was collected after the 1st trimester. 5. Age \<45 days at time of enrollment 6. For infants in the HM-fed AGA comparator group only: born to mothers with pre-pregnancy body mass index (BMI) ≥ 18.5 and \<25kg/m2
Exclusion criteria
1. mothers with Type-1 Diabetes 2. mothers who smoked \>10 cigarettes per day during pregnancy. 3. mothers who used Illicit drugs (e.g. marijuana, cocaine, amphetamines, or heroin) or alcohol (\>3 alcoholic beverages per week) during pregnancy 4. Suspected or documented systemic or congenital infections (e.g Human Immunodeficiency virus, cytomegalovirus) 5. Genetic or any other type of congenital malformations, metabolic, cardiovascular, gastrointestinal, pancreatic or hepatic diseases or medical conditions that could compromise growth and/or food intake. 6. Fit to be discharged from neonatal intensive care unit (NICU) in \> 5 consecutive days with the exception of infants in the NICU due to jaundice only. 7. Known or suspected intolerance/ allergy to milk protein or any ingredient in the study formulas 8. For infants in the HM-fed groups only: infants who are consuming fortified human milk or formula. 9. Participation in any other interventional clinical trial during the 14 days prior to enrollment. 10. Infants or infant's family who in the investigator's judgement cannot be expected to comply with the protocol or study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of neurodevelopment | at the baseline (2 years of age) | Assessed using Bayley Scales of Infant and Toddler Development® - Third Edition - (To compare with the standard Bayley scores). |
| Evaluation of length-for-age Z-score | Evaluated once at 2 years of age | Using the WHO growth chart |
| Systolic Blood pressure | at baseline (2 years of age) | Systolic and diastolic blood pressure measurement from 1 to 6 months of age |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Growth (Length) | At 2 years of age | Evaluation of length-for-age in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(\<2.5th percentile indicating prevalence of stunting). |
| Growth (Weight) | At 2 years of age | Evaluation of weight-for-age in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(\<2.5th percentile indicating prevalence of stunting). |
| Growth (Head circumference) | At 2 years of age | Evaluation of head circumference-for-age in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(\<2.5th percentile indicating prevalence of stunting). |
| Evaluation of insulin sensitivity | at Baseline ( 2 years of age). | HOMA-IR (Homeostatic Model Assessment - Insulin Resistance) calculated from Basal (Fasting) plasma glucose and insulin concentrations. |
| Growth (Z-Scores) | At 2 years of age | Evaluation of weight-for-length Z-scores in each formula-fed group by Percentages of study population with length-for-age Z-score less than 2.5th, 5th and 10th Percentile on the WHO reference curve(\<2.5th percentile indicating prevalence of stunting). |
| Evaluation of serum markers of bone metabolism | At visit 1 (<44 days) | Assessed by Incidence of abnormal serum (Calcium, phosphorus, Alkaline phosphatase). |
| Body fat mass (%) | evaluated until 5 years of age. | Assessed by Deterium dilution |
| Evaluation of urinary markers of bone metabolism | At visit 1 (<44 days) | Assessed by Incidence of urine biochemistries (calcium, phosphorous). |
| Neurodevelopment | At last visit ( 5 years of age) | Assessed using Wechsler Preschool and Primary Scale of Intelligence™ - Fourth Edition (WPPSI-IV) - (to compare the scores against the standard scores). |
| Safety (Adverse Event reporting) | From 1 to 6 months of age & 6 months to 5 years of age. | Assessed by Type, incidence, severity, seriousness and relationship to study formulas of AEs (including Infection) among the study subjects. |
Outcome results
None listed