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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Weight Gain
• Intervention / Treatment: Other: EX_IMF; Other: ST_IMF

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Virgilio Carnielli, MD, PHD; Phone Number: 0715962045; Email: v.carnielli@staff.univpm.it
• Study Contact Backup: Name: Alessio Correani, MSc, PHD; Phone Number: 0715962888; Email: a.correani@pm.univpm.it

Study Locations

• Italy
  • Ancona, Italy, 60123
    • Recruiting
    • Ospedali Riuniti di Ancona
    • Contact: Virgilio Carnielli, MD, PHD; Email: v.carnielli@staff.univpm.it
  • Padua, Italy, 35127
    • Not yet recruiting
    • Istituto di Ricerca Città della Speranza
    • Contact: Paola Cogo, MD, PHD; Email: paola.cogo@uniud.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

Collaborators and Investigators

• Sponsor: Ospedali Riuniti Ancona
• Collaborators: Bunge Loders Croklaan; Istituto di Ricerca Pediatrica Città della Speranza

Publications and helpful links

General Publications

• Ehrenkranz RA, Younes N, Lemons JA, Fanaroff AA, Donovan EF, Wright LL, Katsikiotis V, Tyson JE, Oh W, Shankaran S, Bauer CR, Korones SB, Stoll BJ, Stevenson DK, Papile LA. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999 Aug;104(2 Pt 1):280-9. doi: 10.1542/peds.104.2.280.
• Hack M, Breslau N, Weissman B, Aram D, Klein N, Borawski E. Effect of very low birth weight and subnormal head size on cognitive abilities at school age. N Engl J Med. 1991 Jul 25;325(4):231-7. doi: 10.1056/NEJM199107253250403.
• Innis SM, Dyer R, Nelson CM. Evidence that palmitic acid is absorbed as sn-2 monoacylglycerol from human milk by breast-fed infants. Lipids. 1994 Aug;29(8):541-5. doi: 10.1007/BF02536625.
• Straarup EM, Lauritzen L, Faerk J, Hoy Deceased CE, Michaelsen KF. The stereospecific triacylglycerol structures and Fatty Acid profiles of human milk and infant formulas. J Pediatr Gastroenterol Nutr. 2006 Mar;42(3):293-9. doi: 10.1097/01.mpg.0000214155.51036.4f.
• Carnielli VP, Luijendijk IH, Van Goudoever JB, Sulkers EJ, Boerlage AA, Degenhart HJ, Sauer PJ. Structural position and amount of palmitic acid in infant formulas: effects on fat, fatty acid, and mineral balance. J Pediatr Gastroenterol Nutr. 1996 Dec;23(5):553-60. doi: 10.1097/00005176-199612000-00007.
• Carnielli VP, Luijendijk IH, van Goudoever JB, Sulkers EJ, Boerlage AA, Degenhart HJ, Sauer PJ. Feeding premature newborn infants palmitic acid in amounts and stereoisomeric position similar to that of human milk: effects on fat and mineral balance. Am J Clin Nutr. 1995 May;61(5):1037-42. doi: 10.1093/ajcn/61.4.1037.
• Lucas A, Quinlan P, Abrams S, Ryan S, Meah S, Lucas PJ. Randomised controlled trial of a synthetic triglyceride milk formula for preterm infants. Arch Dis Child Fetal Neonatal Ed. 1997 Nov;77(3):F178-84. doi: 10.1136/fn.77.3.f178.

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2027

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): January 25, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Infant formula; Growth; Preterm Infants; Human milk; Beta-palmitate
• Additional Relevant MeSH Terms: Body Weight; Body Weight Changes; Weight Gain
• Other Study ID Numbers: PG-1

Drug and device information, study documents

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