High Protein and High Energy Intakes and Physical Activity on Growth of Extremely Low Birth Weight Infants

Study Overview
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Brief Summary
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The aim of this study is to evaluate the effect of increasing amino acid and energy intake during parenteral and enteral nutrition with and without the stimulation of the infant's physical activity, on growth of extremely low birth weight infants .

Detailed Description
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Increasing protein and energy intake above the anabolic capacity of a given individual may result in increased lipogenesis and excessive fat deposition. Adults with reduced mobility or with neuromuscular conditions will develop excessive fat deposition if they receive normal to high protein and energy intakes. Excessive fat deposition have been demonstrated in preterm infants receiving high energy intakes. Given that physical activity in preterms is often reduced for the prematurity itself, the associated sickness and the numerous medications, the investigators speculate that physical stimulation may have a beneficial effect on protein accretion and on lean mass accretion. The investigators further hypothesize that today's recommended daily intakes of proteins and energy cannot be fully incorporated into lean body mass without a concomitant physical activity. In spite of the fact that this notion is well accepted in adult physiology and in the elderly, it has never been tested in preterm infants. This factorial randomised controlled trial will evaluate the effect of increasing amino acid intake (by 1 g/kg/d) and energy intake (by 20 kcal/kg/d) during parenteral nutrition and also of increasing protein intake and energy intake by an extra 1 g/kg/d during enteral nutrition, with and without the stimulation of the infant's physical activity, on growth of extremely low birth weight infants. The investigators aim at demonstrating that increasing energy and protein intake above the standard of care intakes will result in better growth only in association with adequate physical activity, in particular in relation to body composition and lean mass accretion.

Official Title
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Effect of High Protein and High Energy Intakes and Physical Activity on Growth and Body Composition of Extremely Low Birth Weight Infants: a Randomised Controlled Trial.

Conditions
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Infant, Very Low Birth Weight

Intervention / Treatment
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* Dietary Supplement: NUTR +
* Behavioral: STIMUL +


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 24 weeks < gestational age < 32 weeks inborn or outborn admitted before 24 hours of age parenteral or enteral nutrition start before 48 hours of age parental consent Exclusion Criteria: difficulty in starting physical activity stimulation before 10 days of life death before 36 W PMA diagnosis of necrotising enterocolitis (before 36 W PMA) any major surgery (before 36 W PMA) congenital syndrome, severe malformations inborn errors of metabolism parental consent withdrawn

Ages Eligible for Study
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Minimum Age: 24 Weeks
Maximum Age: 32 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: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: NUTR (Nutrition) 0_STIMUL(Stimulation) 0<br>Standard Nutrition and no Physical Stimulation | |
| Experimental: NUTR 0_STIMUL +<br>Standard Nutrition and Physical Stimulation | Behavioral: STIMUL +<br>* Physical activity stimulation consists in flexion/extension of the 4 limbs and other motion exercises of the shoulder girdle and of the hips. This stimulation will take place before the feed for a mean of 30 times a week (minimum 24- maximum 36 times a week, 10 minutes each time) and will start within the 10th day of life until 36 weeks postmenstrual age<br>|
| Experimental: NUTR +_STIMUL 0<br>Enhanced Nutrition, and no Physical Stimulation | Dietary Supplement: NUTR +<br>* one extra g/kg/d of protein and lipids starting before 48 hours after birth until 36 weeks postmenstrual age<br>|
| Experimental: NUTR +_STIMUL +<br>Enhanced Nutrition and Physical Stimulation | Dietary Supplement: NUTR +<br>* one extra g/kg/d of protein and lipids starting before 48 hours after birth until 36 weeks postmenstrual age<br>Behavioral: STIMUL +<br>* Physical activity stimulation consists in flexion/extension of the 4 limbs and other motion exercises of the shoulder girdle and of the hips. This stimulation will take place before the feed for a mean of 30 times a week (minimum 24- maximum 36 times a week, 10 minutes each time) and will start within the 10th day of life until 36 weeks postmenstrual age<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight gain (Birth-36 Weeks PMA) | Weight gain from birth up to 36 weeks postmenstrual age (g/kg/d) | birth up to 36 weeks postmenstrual age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle ultrasound | Ultrasound measurement of mid thigh and mid arm muscle thickness (cm) | 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ) | 
| Adipose tissue ultrasound | Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm) | 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ) | 
| Lean body mass estimate using deuterium dilution | Urinary deuterium enrichment after 6 and 12 hours from deuterium oral administration (baseline) | 36 weeks postmenstrual age (+-1d ) | 
| Skinfold thickness | Biceps and triceps skinfold thickness (both arms) (cm) | 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ), between 22 and 24 months (2 years correct age) | 
| Brain MRI | Brain injury, growth and maturation according to Kidokoro et al. | 40 weeks postmenstrual age (+-1d ) | 
| Weight | weight measured by a digital infant scale (g) | birth, daily up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age) | 
| Total body length | Total body length measured by a neonatal stadiometer (cm) | birth, weekly until 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age) | 
| Head circumference | Head circumference measured by a flexible non-stretchable tape (cm) | birth, weekly up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age) | 
| Tibial length | Knee-heel length measured by knemometry (cm) | birth, 32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d ), between 22 and 24 months (2 years correct age) | 
| Weight gain (BW recovery-36W PMA) | Weight gain from the birth weight recovery until 36 weeks postmenstrual age (g/kg/d) | birth weight recovery up to 36 weeks postmenstrual age | 
| Bayley III Cognitive Score (MDI) | Cognitive scale (range 55-145). The Scale has index mean scores of 100 (SD ± 15). An index composite score of < 70 (>2 SD below the mean) is defined to indicate severe impairment, while an index composite score of 70-84 (>1 SD below the mean) is defined to indicate mild impairment. Index composite scores ≥ 85 indicate normal development. | between 22 and 24 months (2 years correct age) | 
| Bayley III Language Score | Language scale (range 45-155). The Scale has index mean scores of 100 (SD ± 15). An index composite score of < 70 (>2 SD below the mean) is defined to indicate severe impairment, while an index composite score of 70-84 (>1 SD below the mean) is defined to indicate mild impairment. Index composite scores ≥ 85 indicate normal development. | between 22 and 24 months (2 years correct age) | 
| Bayley III Motor Score (PDI) | Motor scale (range 45-155). The Scale has index mean scores of 100 (SD ± 15). An index composite score of < 70 (>2 SD below the mean) is defined to indicate severe impairment, while an index composite score of 70-84 (>1 SD below the mean) is defined to indicate mild impairment. Index composite scores ≥ 85 indicate normal development. | between 22 and 24 months (2 years correct age) | 
| Safety (metabolic tolerance) | Plasma and urinary urea (mg/dl), Plasma triglycerides (mg/dl), blood glucose (mg/dl) | At least daily during the first week of life, weekly up to 30 weeks postmenstrual age (when applicable), 30 weeks postmenstrual age (+-1d ), 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) | 
| Safety (haematology) | Complete blood count | At least daily during the first week of life, weekly up to 30 weeks postmenstrual age (when applicable), 30 weeks postmenstrual age (+-1d ), 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) | 
| Safety (gas-analysis) | Gas-analisys | At least daily during the first week of life, weekly up to 30 weeks postmenstrual age (when applicable), 30 weeks postmenstrual age (+-1d ), 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) | 
| Bone mineralisation | Plasma and urinary calcium and phosphorus, alkaline phosphatase, parathyroid hormone, osteocalcin measurements | 6 weeks of age, 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) | 
| Bone ultrasound (1) | metacarpus speed of sound (m/s) | 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) | 
| Bone ultrasound (2) | Metacarpus bone transmission time (ms) | 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ) | 
| Measurement of physical activity | Different levels of activity are assigned according to the Bruck's activity scale as described by Freymond et al. (24 hour continuous recording using a video camera). Levels of activity are defined as follows: 0, no body, arm, or leg movement, facial movement present or not with eyes closed or open; 1, arm or leg movement with eyes closed or open; 2, total body movement with eyes closed or open; 3, crying. Levels of activity in each group are expressed as percentage of time spent during the day in each level. | 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ), 40 weeks postmenstrual age (+-1d) if still hospitalized | 
| Morbidity | incidence of the main complication of prematurity | Hospital stay, on average 36 weeks postmenstrual age | 
| Mortality | incidence of mortality | hospital stay, on average 36 weeks postmenstrual age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm infants, growth, nutrition, physical activity