The Effect of Physical Activity on Bone Mineralization and Immune System in Very Low Birth Weight Infants

Study Overview
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Brief Summary
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Studies have demonstrated that brief (5-10 min a day) passive range-of-motion exercise is beneficial for bone development in very low birth weight (VLBW) preterm infants. However, the optimal duration and frequency of exercise for bone development in preterm infants is yet unknown. The effect of exercise on the immune system was widely studied in adult and children. Exercise induces increase in IL-6, IL-10, and IL1ra. In adult even 10 minutes of flexion and extension of the wrist cause systemic increase in IL-6. The effect of physical activity on pro and anti inflammatory cytokines in preterm infant was not studied. Objectives: To assess weather twice daily exercise intervention will enhance bone strength compared to once a day intervention To evaluate the effect of a single exercise intervention on inflammatory mediators. Methods: Single center (Meir Medical Center), double blind, randomized control study.

Detailed Description
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Infants will be randomly assigned to one of 3 study groups. Group 1 - physical activity once a day. Group 2 - physical activity twice a day and group 3 - control. The physical activity program is based on the Moyer-Mileur et al protocol (1). Briefly, this protocol involves extension and flexion range-of-motion exercise against passive resistance of both the upper and lower extremities. Both extension and flexion were performed five times at the wrist, elbow, shoulder, ankle, knee, and hip joints (about 10 minutes for each session). Infant in group 1 have the physical activity intervention once a day, 5 days a week. Infant in group 2 will have the same physical activity intervention twice a day, five times a week. Infant in group 3, the control group will have a similar time (10 minutes) of daily interactive periods of holding and stroking without range-of-motion activity. The physical activity will be done by the same person (the NICU physiotherapist) Growth parameters, and bone strength, will be measured at enrollment and every 2 weeks till discharge. Bone strength assessment will be determined by quantitative ultrasound measurement of bone speed of sound (SOS) at the middle left tibial shaft (Sunlight Omnisense Premier). All measurements will be performed by the same person, who will be blinded to the group assignment. Cytokines study In a sub-group of patients who will have arterial line at enrollment blood sample ( 0.6 CC) will be drawn before and immediately following activity for assessment of proinflammatory (IL-6) and anti-inflammatory ( IL1-ra) cytokines. Samples will be kept at -20º C and will be analyzed after completion of the study.

Official Title
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The Effect of Physical Activity on Bone Strength and Immune System in Very Low Birth Weight Infants: is More Really Better??

Conditions
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Osteopenia of Prematurity

Intervention / Treatment
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* Behavioral: passive physical activity


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Birth weight<1500gr, appropriate for gestational age. After initial cardio-respiratory stabilization < 14 days postnatal age Written parental informed consent Exclusion Criteria: Intrauterine growth retardation Severe central nervous system disorder (including IVH grade 3-4). Congenital anomalies/chromosomal abnormalities. Congenital bone disease.

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 14 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: physical activity once a day<br> | Behavioral: passive physical activity<br>* extension and flexion range-of-motion exercise against passive resistance of both the upper and lower extremities. Both extension and flexion were performed five times at the wrist, elbow, shoulder, ankle, knee, and hip joints<br>* Other names: passive range-of-motion exercise against passive resistance.;|
| Experimental: physical activity twice a day<br> | Behavioral: passive physical activity<br>* extension and flexion range-of-motion exercise against passive resistance of both the upper and lower extremities. Both extension and flexion were performed five times at the wrist, elbow, shoulder, ankle, knee, and hip joints<br>* Other names: passive range-of-motion exercise against passive resistance.;|
| No Intervention: control<br> | Behavioral: passive physical activity<br>* extension and flexion range-of-motion exercise against passive resistance of both the upper and lower extremities. Both extension and flexion were performed five times at the wrist, elbow, shoulder, ankle, knee, and hip joints<br>* Other names: passive range-of-motion exercise against passive resistance.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Speed of sound |  | during hospitalization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anthropometric measurements |  | During hospitalization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteopenia, very low birthweight infants, bone speed of sound, quantitative ultrasound