Clinical trial NCT03354988: Effect of Assisted Exercise on Musculoskeletal System and Growth in Preterm Infants
Official title: Effect of Assisted Exercise on Musculoskeletal System and Growth in Preterm Infants
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Osteopenia Prematurity
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2017-11-28
Enrollment: 36
Sex: ALL
Minimum age (years): 1
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The primary aim of this study is to assess whether physical activity programs in preterm infants improve bone mineralization as well as growth and reduce the risk of fractures.

The secondary aim is to include other potential benefits in terms of length of hospital stay, weaning from mechanical ventilation, feeding tolerance and adverse events

Detailed description: This is a prospective randomized controlled clinical trial that will be conducted on 36 VLBW preterm infants admitted to the neonatal intensive care unit (NICU) - Ain Shams University

METHODS:

All the newborns included in the study will be subjected to the following:

1. Comprehensive history taking including:

   * Antenatal history: Maternal age, maternal diseases, maternal diabetic control, maternal infection (STORCH infection), maternal medication during this pregnancy, and last menstrual period.
   * Natal history: Gestational age, neonatal sex and mode of delivery.
   * Postnatal history: Respiratory distress and cyanosis.
   * Family history: Consanguinity, congenital anomalies, previous abortion, sibling death, and still birth.
2. Thorough clinical examination with particular emphasis on:

   * Assessment of Apgar scores at 1 and 5 minutes
   * Assessment of gestational age based on last menstrual period and confirmed by ultrasonography in early pregnancy if possible and Ballard scores
   * Complete examination including cardiac, chest, abdominal, and neurological examination.
3. Sample size calculation and Randomization:

   The sample size was calculated using power and sample size calculation program and was based on the previously reported intervention changes in Bone mineral density (BMD) following assisted exercise. A mean difference of 5.3 mg cm2 between the groups, with a standard deviation of 5.6 mg cm2 was used, based on the study by Considering a 0.05 significance level and power equal to 80%, an n of 19 patients per group was determined.

   Patients who will meet the inclusion criteria will be randomized into the physical exercise (n=18) and control (n=18) groups. Randomization will be made by birth order; the first born preterm infant will be recruited to the exercise group, the second to the control group, etc.
4. Standard neonatal care:

   * Babies admitted to NICU bathed, placed in incubator, attached to monitor.
   * Cannula inserted, IV fluids is started (Dexstrose10%) and IV antibiotics.
   * If there is respiratory distress: O2 or ventilation is started, usually feeds are delayed to day 2 or day 3 (or even later) according the severity of condition (clinical decision according to the attending neonatologist).
   * If no distress and the baby is well: trophic feeds is started (10ml/kg/day milk), feeds is increased in 10-20ml/kg/day according to baby tolerance, and the condition of the baby (clinical decision according to the attending neonatologist), IV fluids are reduced gradually.
5. Exercise protocol:

   The exercise protocol was designed for Infants in treatment and control groups received well defined interventions applied by the same trained occupational therapist, described as follows:

   For the exercise group, systematic physical activity programs consisting of range-of-motion exercises with gentle compression, extension and flexion of all joints of both bilateral upper extremities; including the shoulder, elbow, and wrist and lower extremities; including the hip, knee and ankle, with a total of 12 joints. Each activity was about 10 min a day and was carried out 5 times per week for 4 weeks. This program was started after 1 week of birth. Physical activity continued until discharge from hospital.

   Because tactile stimulation might have influenced growth and development, control subjects had a daily interactive period of holding and stroking but no range-of-motion activity. The time schedule of each activity was the same as the exercise group. Other routine care activities such as bathing (every day) and kangaroo care (30 minutes/day), will be done for both the control and exercise group subjects according to the neonatal intensive care unit (NICU) recommendations, however, without movement and standardized articular compression.
6. Laboratory investigation:

   * Complete blood count with differential leucocytic count.
   * Serum calcium concentration.
   * Serum phosphorous concentration.
   * Serum magnesium concentration.
   * Serum alkaline phosphates concentration.
   * Serum Alanine Aminotransferase (ALT).
   * Serum carboxy-terminal cross linked telopeptides of type 1 collagen (CTX).
   * Urinary calcium/phosphorous ratio.

   All the previous investigations will be done before at after the end of the exercise protocol for patients and control groups.
7. Bone mineralization will be assessed by measured by dual- energy x- ray absorptiometry (DEXA) :

   DEXA evaluates body composition (total body will be done after the end of the exercise protocol for patients and control groups by measuring:
   * Bone mineral Content (BMC, mg),
   * Bone Mineral Density (BMD, mg/ cm2),
   * Bone area (BA/ cm2),
   * Lean mass (LM, g) and
   * Fat mass (g).
8. Ethical Considerations:

Collected data will be used for study purpose only. The mothers of the newborns under study will be informed about the purpose of the study and the plan of work before agreeing to participate. They will be provided informed consent before the testing began. Study protocol will be presented to and approved by the Ethical Committee of the Scientific Research-Ain Shams University.

Eligibility criteria: Inclusion Criteria:

* Preterm infants (gestational age \<37 completed weeks) who did not receive physical therapy for any indication other than osteopenia of prematurity (e.g. severe contractures);
* Birth weight ≤ 1.500gm;
* Body size appropriate for gestational age;
* Postnatal age of ≥1 week with medically stable condition and favorable evolution that is presenting no associated diseases besides prematurity;
* Tolerating enteral feeds of either fortified breast milk or preterm formula at or above 100 kcal/kg/d.
* Not requiring oxygen or mechanical ventilation at the start of the exercise protocol.

Exclusion Criteria:

* Congenital or acquired anomaly of the Respiratory tract (i.e., diaphragmatic hernia, pulmonary hypoplasia, pulmonary sequestration, bronchogenic cysts);
* Other major congenital anomalies (congenital heart disease, neural tube defect, omphalocele, trisomy, etc.);
* Premature infants diagnosed with serious periventricular hemorrhaging (degrees 3 and 4) or serious sepsis;
* Use of medications (diuretics, methylxanthines and corticosteroids); Infants who had received major surgery within the first two weeks of life

Primary outcomes:
measure: serum calcium
timeFrame: 2 weeks
measure: serum PO4
timeFrame: 2 weeks
measure: serum magnesium
timeFrame: 2 weeks
measure: ALP
timeFrame: 2 weeks
measure: CTX
timeFrame: 2 weeks
measure: Whole body BMD
timeFrame: 2 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain shams university hospital
Study officials:
affiliation: Ain Shams univeristy
name: rania elfarrash, assprofessor
role: PRINCIPAL_INVESTIGATOR
References: