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

Infant, Very Low Birth Weight Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03374033
• Other study ID #: DG-297
• Status: Recruiting
• Phase: N/A
• Start date: April 10, 2017
• Est. completion date: July 30, 2022

Study information

• Verified date: May 2019
• Source: Università Politecnica delle Marche
• Contact: Virgilio P. Carnielli, MD, PhD
• Phone: 00390715962045
• Email: v.carnielli[@]univpm.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

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 information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 30, 2022
• Est. primary completion date: April 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Weeks to 32 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Birth Weight
• Body Weight
• Infant, Very Low Birth Weight

Intervention

Dietary Supplement:
• NUTR +
one extra g/kg/d of protein and lipids starting before 48 hours after birth until 36 weeks postmenstrual age

Behavioral:
• STIMUL +
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

Locations

Country	Name	City	State
Italy	Ospedale G. Salesi	Ancona

Sponsors (1)

Lead Sponsor	Collaborator
Università Politecnica delle Marche

Country where clinical trial is conducted

Italy, 

References & Publications (10)

Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, Domellöf M, Embleton ND, Fusch C, Genzel-Boroviczeny O, Goulet O, Kalhan SC, Kolacek S, Koletzko B, Lapillonne A, Mihatsch W, Moreno L, Neu J, Poindexter B, Puntis J, Putet G, Rigo J, Riskin A, Salle B, Sauer P, Shamir R, Szajewska H, Thureen P, Turck D, van Goudoever JB, Ziegler EE; ESPGHAN Committee on Nutrition. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):85-91. doi: 10.1097/MPG.0b013e3181adaee0. — View Citation

Bellagamba MP, Carmenati E, D'Ascenzo R, Malatesta M, Spagnoli C, Biagetti C, Burattini I, Carnielli VP. One Extra Gram of Protein to Preterm Infants From Birth to 1800 g: A Single-Blinded Randomized Clinical Trial. J Pediatr Gastroenterol Nutr. 2016 Jun;62(6):879-84. doi: 10.1097/MPG.0000000000000989. — View Citation

Betto M, Gaio P, Ferrini I, De Terlizzi F, Zambolin M, Scattolin S, Pasinato A, Verlato G. Assessment of bone health in preterm infants through quantitative ultrasound and biochemical markers. J Matern Fetal Neonatal Med. 2014 Sep;27(13):1343-7. doi: 10.3 — View Citation

Biolo G, Ciocchi B, Stulle M, Piccoli A, Lorenzon S, Dal Mas V, Barazzoni R, Zanetti M, Guarnieri G. Metabolic consequences of physical inactivity. J Ren Nutr. 2005 Jan;15(1):49-53. — View Citation

Burattini I, Bellagamba MP, Spagnoli C, D'Ascenzo R, Mazzoni N, Peretti A, Cogo PE, Carnielli VP; Marche Neonatal Network. Targeting 2.5 versus 4 g/kg/day of amino acids for extremely low birth weight infants: a randomized clinical trial. J Pediatr. 2013 Nov;163(5):1278-82.e1. doi: 10.1016/j.jpeds.2013.06.075. Epub 2013 Aug 12. — View Citation

Embleton NE, Pang N, Cooke RJ. Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics. 2001 Feb;107(2):270-3. — View Citation

Koletzko B, Goulet O, Hunt J, Krohn K, Shamir R; Parenteral Nutrition Guidelines Working Group; European Society for Clinical Nutrition and Metabolism; European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN); European Society of Paediatric Research (ESPR). 1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), Supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr. 2005 Nov;41 Suppl 2:S1-87. — View Citation

Prado CM, Heymsfield SB. Lean tissue imaging: a new era for nutritional assessment and intervention. JPEN J Parenter Enteral Nutr. 2014 Nov;38(8):940-53. doi: 10.1177/0148607114550189. Epub 2014 Sep 19. Review. Erratum in: JPEN J Parenter Enteral Nutr. 20 — View Citation

Schulzke SM, Kaempfen S, Trachsel D, Patole SK. Physical activity programs for promoting bone mineralization and growth in preterm infants. Cochrane Database Syst Rev. 2014 Apr 22;(4):CD005387. doi: 10.1002/14651858.CD005387.pub3. Review. — View Citation

Uthaya S, Thomas EL, Hamilton G, Doré CJ, Bell J, Modi N. Altered adiposity after extremely preterm birth. Pediatr Res. 2005 Feb;57(2):211-5. Epub 2004 Dec 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 )
Secondary	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 )
Secondary	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 )
Secondary	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)
Secondary	Brain MRI	Brain injury, growth and maturation according to Kidokoro et al.	40 weeks postmenstrual age (+-1d )
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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 )
Secondary	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 )
Secondary	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 )
Secondary	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 )
Secondary	Bone ultrasound (1)	metacarpus speed of sound (m/s)	32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
Secondary	Bone ultrasound (2)	Metacarpus bone transmission time (ms)	32 weeks postmenstrual age (+-1d ), 34 weeks postmenstrual age (+-1d ), 36 weeks postmenstrual age (+-1d )
Secondary	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
Secondary	Morbidity	incidence of the main complication of prematurity	Hospital stay, on average 36 weeks postmenstrual age
Secondary	Mortality	incidence of mortality	hospital stay, on average 36 weeks postmenstrual age