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

Not Applicable
Conditions
Infant, Very Low Birth Weight
Interventions
Behavioral: STIMUL +
Dietary Supplement: NUTR +
Registration Number
NCT03374033
Lead Sponsor
Università Politecnica delle Marche
Brief Summary

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

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
200
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
NUTR 0_STIMUL +STIMUL +Standard Nutrition and Physical Stimulation
NUTR +_STIMUL +STIMUL +Enhanced Nutrition and Physical Stimulation
NUTR +_STIMUL 0NUTR +Enhanced Nutrition, and no Physical Stimulation
NUTR +_STIMUL +NUTR +Enhanced Nutrition and Physical Stimulation
Primary Outcome Measures
NameTimeMethod
Weight gain (Birth-36 Weeks PMA)birth up to 36 weeks postmenstrual age

Weight gain from birth up to 36 weeks postmenstrual age (g/kg/d)

Secondary Outcome Measures
NameTimeMethod
Lean body mass estimate using deuterium dilution36 weeks postmenstrual age (+-1d )

Urinary deuterium enrichment after 6 and 12 hours from deuterium oral administration (baseline)

Skinfold thickness32 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)

Biceps and triceps skinfold thickness (both arms) (cm)

Weightbirth, daily up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age)

weight measured by a digital infant scale (g)

Total body lengthbirth, weekly until 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age)

Total body length measured by a neonatal stadiometer (cm)

Head circumferencebirth, weekly up to 36 weeks postmenstrual age; 40weeks postmenstrual age (+-1d ), between 22 and 24 months (2 years correct age)

Head circumference measured by a flexible non-stretchable tape (cm)

Bayley III Motor Score (PDI)between 22 and 24 months (2 years correct age)

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.

Bone ultrasound (1)32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )

metacarpus speed of sound (m/s)

Bone ultrasound (2)32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )

Metacarpus bone transmission time (ms)

Safety (haematology)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 )

Complete blood count

Bone mineralisation6 weeks of age, 32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )

Plasma and urinary calcium and phosphorus, alkaline phosphatase, parathyroid hormone, osteocalcin measurements

Muscle ultrasound32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d )

Ultrasound measurement of mid thigh and mid arm muscle thickness (cm)

Adipose tissue ultrasound32 weeks postmenstrual age(+-1d ), 34 weeks postmenstrual age(+-1d ), 36 weeks postmenstrual age(+-1d ), 40 weeks postmenstrual age(+-1d )

Ultrasound measurement of mid thigh and mid arm adipose tissue thickness (cm)

Tibial lengthbirth, 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)

Knee-heel length measured by knemometry (cm)

Weight gain (BW recovery-36W PMA)birth weight recovery up to 36 weeks postmenstrual age

Weight gain from the birth weight recovery until 36 weeks postmenstrual age (g/kg/d)

Bayley III Language Scorebetween 22 and 24 months (2 years correct age)

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.

MorbidityHospital stay, on average 36 weeks postmenstrual age

incidence of the main complication of prematurity

Brain MRI40 weeks postmenstrual age (+-1d )

Brain injury, growth and maturation according to Kidokoro et al.

Bayley III Cognitive Score (MDI)between 22 and 24 months (2 years correct age)

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.

Measurement of physical activity32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d ), 40 weeks postmenstrual age (+-1d) if still hospitalized

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.

Safety (metabolic tolerance)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 )

Plasma and urinary urea (mg/dl), Plasma triglycerides (mg/dl), blood glucose (mg/dl)

Safety (gas-analysis)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 )

Gas-analisys

Mortalityhospital stay, on average 36 weeks postmenstrual age

incidence of mortality

Trial Locations

Locations (1)

Ospedale G. Salesi

🇮🇹

Ancona, Italy

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