Effects (Long Term Analysis) of an Hyperproteinic Nutrition on Neonates With Intra-uterine Growth Delay : a Prospective, Multicentric , Randomized, Double Blind Study (Proneonat)

Study Overview
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Brief Summary
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Neonates with intra-uterine growth delay represent more than 2% of the 800 000 annual births in France. Studies have shown that milks enriched with protein allow to accelerate newborns growth. According to some papers, growth acceleration would have a favourable effect on psycho-motor development at age of 2 or 3. However, for other authors, this would not lead to any benefit and even an early hyperproteinic feeding would have bad long term consequences such as appearance of several diseases in the future adult (overweight, diabetes, arterial hypertension, renal function alteration).The main objective of this clinical trial is to check that an hyperproteinic feeding does not lead to any benefit on psycho-motor development at age of 2, compared with a milk containing same level of protein than milk proposed to newborns of normal weight. The secondary objectives of our clinical trial are to compare the effects of these two types of milk on renal function, arterial blood pressure, body composition, corpulence, food preferences, insulin resistance and intestinal integrity at age of 2. A sub study will also be realized to analyse the proteic turn over . This sub-study will be undertaken only with neonates of Nantes Hospital.

Official Title
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Effects (Long Term Analysis) of an Hyperproteinic Nutrition on Neonates With Intra-uterine Growth Delay : a Prospective, Multicentric , Randomized, Double Blind Study (Proneonat)

Conditions
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Intra-uterine Growth Delay

Intervention / Treatment
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* Other: milk enriched in proteins (2.15 g/100ml)
* Other: milk with normal protein concentration (1.45g/100ml)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates with intra-uterine growth delay (with weight < 10th centile) Aged >34 weeks of amenorrhoea For neonates >38 weeks of amenorrhoea, weight < 2500g Mother's refusal of breast feeding Informed consent signed by the 2 parents Possibility to follow newborns until age of 2 Exclusion Criteria: Subject not fulfilling inclusion criteria Severe disease (syndrome and/or congenital abnormality, deficiency of metabolism at birth)

Ages Eligible for Study
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Minimum Age: 34 Weeks
Maximum Age: 39 Weeks

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>hyperproteinic milk | Other: milk enriched in proteins (2.15 g/100ml)<br>* Neonates will drink the hyperproteinic milk until they reach the 25th of Sempé and Pedron curve (milk to be taken at least until 40 weeks of amenorrhoea or at maximum until 4 months of corrected age)<br>|
| Active Comparator: 2<br>Normoproteinic milk | Other: milk with normal protein concentration (1.45g/100ml)<br>* Neonates will drink the normoproteinic milk until they reach the 25th of Sempé and Pedron curve (milk to be taken at least until 40 weeks of amenorrhoea or at maximum until 4 months of corrected age)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quotient of psycho-motor development evaluated by the Brunet-Lezine test at age of 2 |  | at 2 years old | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leptine, glycemia/insulin and pro-insulin blood level |  | At age of 15 (+/- 2) days and at age of 2 years | 
| Plasmatic and urinary citrulline levels |  | At age of 15 (+/- 2) days and at age of 2 years | 
| Micro-albuminuria, creatinine, urea, sodium and potassium urine levels |  | At age of 15 (+/- 2) days and at age of 2 years | 
| Faecal floa, faecal calprotectine and other markers |  | At age of 15 (+/- 2) days and at age of 2 years | 
| Arterial blood pressure, arterial elasticity, adiponectine, preferential food choices, kidney size |  | at age of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonates with intra-uterine growth delay