Influence of Physical Treatments of Human Milk on the Kinetics of Gastric Lipolysis in Preterm Newborns

Study Overview
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Brief Summary
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The optimization of newborns nutrition is a challenge especially for preterm newborns for whom nutrition plays a crucial part in cerebral and global development. Human milk is considered as the best food for newborns. Several short and long-term beneficial health effects were attributed to breastfeeding and have induced the increase of human milk in preterm newborns nutrition. Whereas the chemical composition of infant formula has been optimized to mimic human milk, there is still a major difference between the structure of human milk and commercial infant formulas. It is well known in adult nutrition that the structure of emulsions influences their susceptibility to hydrolysis, such results have been obtained either on in vitro or in vivo studies. Human milk is a natural emulsion (oil in water). Lipids droplets are dispersed under the form of entities called milk fat globules (average diameter 4 µm, span 0.1-20 μm). The globules are stabilized by a trilayered membrane composed mainly of polar lipids (phospholipids, sphingolipids and gangliosides), of proteins, neutral lipids and other minor compounds. The physical treatments apply to human milk or more generally to bovine milk to pasteurize or stabilize the milk modify the structure of the natural emulsion. Heat treatment for instance induces whey proteins denaturation and the adsorption of protein aggregates on the surface of the milk fat globules. Heat treatment also leads to the denaturation of bile salt stimulated lipase. These effects limit intragastric lipolysis in preterm newborns. Conversely, reduction of milk globules size, by homogenisation of milk, increases the specific surface available for lipase adsorption and limits the lost of fat during enteral administration of milk. Such treatment could thus enhance gastric lipolysis and improve fat absorption of preterm newborns. The objective of this trial is to evaluate the effects of physical treatments (pasteurization and homogenisation by ultrasonication) applied to human milk on gastric lipolysis and milk destructuration. This trial is conducted, in vivo, on preterm newborns.

Official Title
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Influence of Physical Treatments of Human Milk on the Kinetics of Gastric Lipolysis in Preterm Newborns

Conditions
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Premature Birth

Intervention / Treatment
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* Other: Raw human milk
* Other: Pasteurized human milk
* Other: Pasteurized-homogenized human milk
* Other: Gastric samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Premature neonates born before 32 weeks of gestation Newborn dwelled near Rennes Volume of enteral nutrition > 120 mL/kg/j (Day 0) Written-informed parental consent for the study Exclusion Criteria: Digestive congenital anomalies Antecedent of enterocolitis Patient included in other study Abdominal distension on Day 0 Treatment by morphine or catecholamine on Day 0

Ages Eligible for Study
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Minimum Age: 5 Days
Maximum Age: 21 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Raw human milk / pasteurized human milk<br>Raw human milk compared to pasteurized human milk. Two meals administration (20mL/kg) per day during 6 days in a randomized order, with an intragastric tube : one with raw milk and one with pasteurized milk. In order to characterise gastric effluents at different postprandial times after ingestion and to measure gastric lipolysis and proteolysis, at each administration two gastric samples will be collected with the intragastric tube : one before the meal, and one either 35, 60 or 90 minutes (randomized time frame) after the meal. | Other: Raw human milk<br> <br> Other: Pasteurized human milk<br> <br> Other: Gastric samples<br> <br> |
| Experimental: Pasteurized human milk / pasteurized-homogenized human milk<br>Pasteurized human milk compared to pasteurized-homogenized human milk. Two meals administration (20mL/kg) per day during 6 days in a randomized order, with an intragastric tube : one with pasteurized milk and one with pasteurized-homogenized milk. In order to characterise gastric effluents at different postprandial times after ingestion and to measure gastric lipolysis and proteolysis, at each administration two gastric samples will be collected with the intragastric tube : one before the meal, and one either 35, 60 or 90 minutes (randomized time frame) after the meal. | Other: Pasteurized human milk<br> <br> Other: Pasteurized-homogenized human milk<br> <br> Other: Gastric samples<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of triacylglycerol hydrolysis | Monitoring of the lipolysis kinetics, using chromatography methods | 35 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Size distribution and specific surface of milk fat globule by laser light scattering |  | 35 min, 60 min, 90 min | 
| Fat composition | Fat composition by chromatographic techniques : High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC) | 35 min, 60 min, 90 min | 
| Lipolysis products | Lipolysis products by thin layer chromatography (TLC), gas chromatography (GC) and IATROSCAN | 35 min, 60 min, 90 min | 
| Proteolysis products | Proteolysis products by electrophoresis (SDS-Page) and free amino acids by chromatography (HPLC) | 35 min, 60 min, 90 min | 
| Kinetic of the gastric emptying | Evaluation of the kinetic of the gastric emptying by measuring the volume remaining in the stomach | 35 min, 60 min, 90 min | 
| Lipolysis level | Comparison of lipolysis level obtained either on in vitro or in vivo studies | 35 min, 60 min, 90 min | 
| Percentage of triacylglycerol hydrolysis |  | 60 min, 90 min | 
| Percentage of free fatty acids appearing | Monitoring of the lipolysis kinetics, using chromatography methods | 35 min, 60 min, 90 min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm newborns, Gastric lipolysis, Physical treatments, Human milk