Growth of Preterm Infants Fed a Infant Milk Formula Containing High Versus Low Amounts of Beta-palmitate

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess weight gain of preterm infants (gestational age lower than 32 weeks) fed infant milk formula with about 60% beta-palmitate (EX_IMF) vs infant milk formula with similar macronutrient, mineral and fatty acid composition but lower amounts of beta-palmitate (ST_IMF). Own mother milk (OMM) fed infants will serve as reference group.

Detailed Description
-----------------
A large number of low birth weight infants during their hospital stay experience poor growth and this has been linked to reduced neurodevelopment scores. Several enriched infant milk formulas are available for preterm infants who cannot be fed human milk. The use of infant milk formulas (IMF) enriched with triglycerides similar to human milk lipids have shown to be associated with better fatty acid and mineral intestinal absorption. In this multicenter, randomized, controlled clinical trial, preterm infants (gestational age lower than 32 weeks), who can not be fed human milk, will be randomized to receive IMF with high or low amounts of beta-palmitate (about 60% vs 10%, respectively). A non-randomized own human milk-fed group will be included as a reference. Patients will be on the study diet as soon as possible after birth and till 36 weeks of gestation. Neurodevelopment follow-up will be performed at 24 months corrected age.

Official Title
-----------------
A Randomized, Multicenter, Controlled Clinical Trial to Assess Weight Gain of Preterm Infants Fed a New Infant Milk Formula Containing High Amounts of Beta-palmitate Versus a Standard Infant Milk Formula Containing Low Amounts of Beta-palmitate

Conditions
-----------------
Weight Gain

Intervention / Treatment
-----------------
* Other: EX_IMF
* Other: ST_IMF


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: gestational age between 24 and 32 weeks of gestation at enrollment, birth weight greater than 750 grams, singleton or twin birth (no triplet or higher), fraction of inspired oxygen lower than 0.60 at enrollment, feasible enteral feeding, cardiovascular stable condition, informed consent form signed by at least one parent or legal guardian. Exclusion Criteria: congenital malformations, genetic, metabolic and endocrine disorders, suspicious infection at enrollment, intrauterine growth restriction (<10th centile) at enrollment, maternal diabetes requiring insulin therapy, neonatal asphyxia.

Ages Eligible for Study
-----------------
Minimum Age: 24 Weeks
Maximum Age: 32 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EX_IMF group<br>Infants will receive infants formula with large amounts of beta-palmitate (EX_IMF). | Other: EX_IMF<br>* Infant formula with large amounts of beta-palmitate (about 60%).<br>|
| Active Comparator: ST_IMF group<br>Infants will receive infants formula with low amounts of beta-palmitate (ST_IMF). | Other: ST_IMF<br>* Infant formula with low amounts beta-palmitate (about 10%).<br>|
| No Intervention: HM group<br>Infants will receive human milk (HM). | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight gain | Body weight will be daily measured by using an electronic balance (g/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Crying | Crying duration will be electronically recorded by a unidirectional microphone (hours/day). | For 1 consecutive day at 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Physical activity | The number of spontaneous movements per hour will be electronically measured by Kinect system. | For 1 consecutive day at 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before.. | 
| Stooling pattern | Stooling pattern will be reported by the parents according to on the Bristol stool form scale (consistency). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool biochemical composition - Total fatty acids | Total fatty acids in the stool samples will be measured by gas chromatography (mg/g of dry feces). | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool biochemical composition - Palmitic acid | Palmitic acid in the stool samples will be measured by gas chromatography (mg/g of dry feces). | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool biochemical composition - Calcium | Fecal calcium will be measured by inductively coupled plasma emission spectrometry. | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool biochemical composition - Phosphorus | Fecal phosphorus will be measured by inductively coupled plasma emission spectrometry | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool biochemical composition - Magnesium | Fecal magnesium will be measured by inductively coupled plasma emission spectrometry. | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool biochemical composition - Hydroxylic acids | Fecal hydroxylic acids will be measured by high-resolution capillary chromatography | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Infant formula intakes | Cumulative infants formulas intakes (mL/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Human milk intakes | Cumulative human milk intakes (mL/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Parenteral nutrition intakes - cumulative volume | Cumulative parenteral nutrition intakes (mL/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Parenteral nutrition intakes - amino acids | Cumulative intravenous amino acid intakes (g/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Parenteral nutrition intakes - glucose | Cumulative intravenous glucose intakes (g/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Parenteral nutrition intakes - lipids | Cumulative intravenous lipid intakes (g/kg). | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Parenteral nutrition duration | Duration of parenteral nutrition (days) | From birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Urinary dicarboxylic acid excretion | Urinary dicarboxylic acids will be measured by gas chromatography-mass spectrometry (mmol/mol of creatinine). | At 32 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Body weight | Body weight will be measured by using an electronic balance (grams). | At 32, 34 and 36 weeks of gestational age or until discharge if this occurred before and then at 24 months of corrected age.. | 
| Total body length | Total body length will be measured by using a stadiometer (cm). | At 32, 34 and 36 weeks of gestational age or until discharge if this occurred before and then at 24 months of corrected age. | 
| Head circumference | Head circumference will be measured by using a unstretchable tape (cm). | At 32, 34 and 36 weeks of gestational age or until discharge if this occurred before and then at 24 months of corrected age. | 
| Blood biochemistry - Glycaemia | Glucose concentrations in blood (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Triglycerides | Triglyceride concentrations in blood (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Cholesterol | Plasma cholesterol by gas chromatography-mass spectrometry (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Phospholipids | Plasma phospholipids by gas chromatography (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Fatty acids | Plasma total fatty acids by gas chromatography (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Urea | Urea concentrations in plasma (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Bilirubin | Total and conjugated bilirubin concentrations (mg/dL). | At 7 and 42 days of postnatal age. | 
| Blood biochemistry - Electrolytes | Na+, K+, Ca2+, Cl- and standard base excess (mmol/L). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Calcium | Calcium concentrations in blood (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Blood biochemistry - Phosphorus | phosphorus concentrations in blood (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Total body water | Total body water (% of body weight) will be measured by the deuterium dilution method. | At 36 weeks of gestational age or until discharge if this occurred before. | 
| Stool bifidobacteria | Number of bifidobacteria per gram of feces will be measured by using fluorescent in situ hybridization. | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Gastrointestinal problems | The incidence of gastrointestinal problems such as abdominal distension, gastric residuals, reflux and vomiting. | Daily from birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| In-hospital death | The incidence of death during the hospital stay. | Daily from birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Complications of prematurity | The incidence of complications of prematurity such as respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), Periventricular Leukomalacia (PVL), sepsis, and cholestasis. | Daily from birth to 36 weeks of gestational age or until discharge if this occurred before. | 
| Neurodevelopmental assessment | Neurodevelopment will be assessed by the Bayley test III. | At 24 months of corrected age. | 
| Urinary urea | Urea concentrations in urine (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Urinary calcium | Calcium concentrations in urine (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Urinary phosphorus | Phosphorus concentrations in urine (mg/dL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Liver function tests | Plasma alkaline phosphatase (ALP, IU/L), aspartate transaminase (AST, IU/L), alanine aminotransferase (ALT, IU/L) and gamma glutamyltranspeptidase concentrations (γ-GT, IU/L). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Parathyroid hormone | Parathyroid hormone concentrations in blood (pg/mL). | At 32, 34 and then at 36 weeks of gestational age or until discharge if this occurred before. | 
| Metabolic complications | hypo/hypernatremia, hypo/hyperkalemia, hypo/hyperchloremia, hypo/hypercalcemia, hypo/hyperparathyroidism, metabolic acidosis, hypo/hyperglycaemia, hypertriglyceridemia and elevated urea. | Daily from birth to 36 weeks of gestational age or until discharge if this occurred before. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Growth, Preterm Infants, Beta-palmitate, Infant formula, Human milk