Study Design In this prospective randomized controlled clinical trial, live born preterm
neonates should have a stable clinical status at the time of study enrollment and
therefore it is likely that some neonates will be enrolled after 5-7 days of admission.
The allocation of neonates will be randomized in order to equalize the prognostic factors
(confounding factors) between the groups. By using sequentially numbered envelopes,
participants will be assigned to either intervention or control group by simple random
allocation. In this way, researchers will avoid resulting in an unequal number of
participants between the two groups. Researchers after obtaining parental informed
consent, will request a sealed envelope from a staff member not involved in the study.
The envelope will be opened and the allocation will be documented on a list, and signed
by a member of the research team and a staff member as witness.
Participants The study will recruit preterm neonates. It has been estimated that with a
sample of 35 neonates per group, the study will have more than 85% power to find
differences in biomarkers between the intervention and control group, with an effect size
equal to or greater than 0.72 and a significance level of 0.05.
Music Intervention Neonates will be placed in a closed incubator whose acoustic
properties have been previously studied. Under the close surveillance of a team member,
monitor alarms will be also silenced so as to decrease exposure to sudden and unpleasant
auditory stimuli during music intervention. A mini portable speaker will be settled
inside the incubator in appropriate conditions (volume level, distance e.t.c) for safety
reasons.
Neonates allocated to the intervention group will be exposed to a specific piece of
music, 30 minutes after feeding (if oral feeding exists), for a duration no more than 30
minutes that will be indicated from the certified music - therapist, experienced in
working with preterm infants.
A questionnaire created by the research team will be administered to parents in order to
investigate the neonate's prenatal exposure of music (as a fetus).
Data collection Biomarkers Salivary samples will be obtained from preterm neonates via
salivette swabs. The polyester filter of the device will be partitioned into equal
sections under sterile conditions to account for the small oral size of the neonates. One
sample will be obtained before the music intervention and one sample 60 minutes after the
music intervention, considering diurnal flow patterns. Saliva sampling is unlikely to
cause stress or pain to the neonate. In the control group only one sample per day will be
obtained within the same time period with the intervention group. Sample collection will
be repeated in the same way everyday for 5 consecutive days. Each sample will be obtained
before any stressful intervention (e.g. blood sampling, weighing, bathing, etc.).
Furthermore, it is important to note that no other procedure that may reduce stress will
take place simultaneously with music intervention (i.e. kangaroo care, gentle touching
e.t.c) in order to interpret the effect of music more precisely. Saliva samples will be
centrifuged very soon after collection and stored at -80oC until the laboratory analyses
are performed. Measurements will be performed with cobas e411 automated analyzer or
through ELISA.