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The effect of music on the development of the preterm
infant: A feasibility study on intervention and recruitment.
Author: Dion Rietveld , Student number: 11308958, Mentors: Agnes van den Hoogen, Jeroen Dudink
& Maria Luisa Tataranno, Date: 29-05-2020
Keywords: Feasibility, Electroencephalography, Neonates, Music, Randomized control trial
Abstract
Background and purpose: Infants born preterm have a high risk factor for poor neurological outcome. To
protect and optimize the preterm infants’ brain development laying on the neonatal intensive care unit (NICU), exposure to music is a promising intervention, but there is a lack of complete randomized control trials with heterogeneous data. Therefore, the University Medical Centre of Utrecht made a protocol to execute a randomized control trial with heterogeneous data, where the effect of music intervention on the brain maturation of preterm infants will be studied. The aim of this study was to test the intervention and recruitment protocol of the future randomized control trial on feasibility.
Materials and method: The feasibility of the musical intervention was determined by comparing the sound
level measurements on the NICU with the sound levels of the musical intervention. The recruitment and time frame feasibility was tested based on a datasheet of previous eligible patients in the year 2018. At last, a pilot intervention and EEG measurement was done to determine the feasibilities of the intervention protocol and the neonatal EEG caps.
Results: The mean sound levels per hour measured on the Neonatal intensive care units did not exceed the
criteria of 50 decibel (dB(A)), but the sound levels measured on the NICU did exceed 50 dB every hour. The percentage of the sound measurements equal or above 50 dB was higher in an open bed than in an incubator. Only Volume 4 (Max: 52.3 dB) did not exceed the recommended maximum sound level. Based on the datasheet of 2018, 38 participants were estimated to be concluded in 2 years. The intervention and EEG protocols were executed successfully.
Conclusions: The future randomized control trial protocol of a music intervention study for preterm infants
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Introduction
Over the last few years more and more preterm infants have survived their period in the Neonatal intensive care units (NICU) (WBC-LNR, 1998; Perined., 2019). Nevertheless these infants still have a high risk for poor neurological outcome (Adams, Feldman, Huffman, & Loe, 2015; Pierrat et al., 2017). Prematurity is frequently related to destructive and developmental brain disturbances, which causes neurodevelopmental disabilities in infants born preterm such as: motor deficits, impairments in attention, visual and perceptual skills, memory and learning, language and executive functioning, but also socio-emotional and psychiatric disorders (Volpe, 2009;Anderson, 2014; Montagna & Nosarti, 2016).
In the end of the second trimester and beginning of the third trimester, the fetal brain goes through major developmental changes: thalamocortical fibres grow into the cortical plate and there is an overall explosive synaptogenesis in all the layers of the brain (Kostović & Jovanov-Milošević, 2006). From 26 weeks GA (gestational age) a fetus can hear and react to auditory information and between 26 and 30 weeks GA hair cells in the cochlea can send electric signals to the brainstem (Mcmahon,
Wintermark, & Lahav, 2012). Therefor most infants born preterm can already hear and process auditory stimuli. It is thought that the auditory system of preterm infants needs stimulation of low decibel sounds with variable frequencies (positive auditory stimulation) to tune the hair cells and to develop, but when preterm infants are exposed to loud noise (70> dB), the development of the cochlear hair cells will be blocked (Graven & Browne, 2008). To protect and facilitate the normal development of the auditory system of preterm infants, it is thought that there is a need to prevent preterm infants from loud noise and promote their auditory development with positive auditory stimulation (Wachman & Lahav,
2011;Mcmahon et al., 2012).
The NICU environment is different from the protective environment of the mother’s uterus. In the womb a fetus is surrounded by amniotic fluid and experiences low-frequency noises mostly through bone conduction (Sohmer, Perez, Sichel, Priner, & Freeman, 2001). On the other hand, preterm infants outside
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the mother are surrounded by air instead of fluid and therefor experience sounds only through air conduction. The differences in the mode of hearing (air instead of bone conduction) and the medium of the sounds (air instead of fluid) enhances an “acoustic gap” between the NICU and the womb (table 1) (Lahav & Skoe, 2014). Because of this acoustic gap, infants on the NICU are not only exposed to unnatural high frequency noises, but are also thought to be deprived of sensory experiences that are needed for the brain development. A fetus in the womb experiences auditory stimulation like the voice and the heartbeat of the mother and these experiences are needed for the development of the sensory systems in pre- and postnatal infants (Lickliter, 2011). Studies suggest that these deprived sensory experiences of an infant born preterm cause alterations in the development and growth of the infant’s brain (Lahav & Skoe, 2014; Lickliter, 2011). Beside deprived sensory experiences, the environment of the NICU also induces stress in preterm infants, caused by the bright lights, loud noises and painful
procedures (Wachman & Lahav, 2011; Brummelte et al., 2012). An important aim on the NICU is to protect and optimize the preterm infants’ brain development. To reach that goal, there is a need to protect and facilitate the development of the auditory system of preterm infants by preventing preterm infants from loud noise in the NICU and promote their auditory development with positive auditory stimulation.
A promising positive auditory stimulation method is exposure to music. Music is a cross-cultural art form, which creates a positive feeling among people. Human beings have a specialty in organizing and combining sounds together to create and identify pleasant melodies. Infants can already recognise musical patterns and pitch differences, which indicates that humans have a predisposition of musical skills
(Trehub, 2012). It seems that music can have a positive soothing, learning and developmental effect, especially on neurological parameters (J. M. Standley, 2001). The music can mask the loud noises in the NICU, which reduces the stress of the preterm infant and provide more energy for growth and
development (J. Standley, 2012). Other researchers think that music might help preterm infants to improve their self-regulation and increase their energy, because the preterm infants are entertained to the music (Cevasco, 2008). This also leads to better growth and maturation.
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Earlier research found positive findings of musical interventions on preterm infants. Musical interventions of Mum’s and Brahm’s lullaby increased oxygen saturation in infants born preterm
(Jabraeili, Sabet, Mustafa Gharebaghi, Asghari Jafarabadi, & Arshadi, 2016). Furthermore a randomized control trial of Sa de Almeida et al. (2020) showed an increased white matter maturation involved in social emotional processes of preterm infants exposed to musical interventions in comparison with preterm infants with no intervention. Anderson & Patel (2018) highlighted positive behavioural and physiological outcomes of musical interventions in their review. Additionally, changes in the functional connectivity of the brain areas associated with music in preterm infants were found after musical interventions (Lordier, Loukas, et al., 2019).
These are promising outcomes, but on the other hand there is a lack of complete randomized controlled trials with heterogeneous data. In the review of Van der Heijden et al. (2016) was concluded that a meta-analyses was not feasible, because there was a great variation between duration and type of intervention, criteria of included subjects and outcome measures between music intervention studies with premature infants. To draw stronger conclusions about the effects of music on infants born preterm, there is a need for more randomized controlled trials with music interventions of methodological soundness (van der Heijden et al., 2016).
Therefore the University Medical Center of Utrecht (UMCU) set out to perform a randomized controlled trial named: ‘Music As Medicine’(MAM), where the effect of music intervention (with
methodological soundness) on the brain maturation of preterm infants staying at the NICU will be studied using EEG and ultrasound assessment. The protocol of the MAM study was already written and approved by the Medical Ethical Review Committee (METC) of Utrecht.
Earlier research showed that it is difficult to execute randomized controlled trials on preterm infants having enough scientific power (van der Heijden et al., 2016). Also, different researchers questioned if musical interventions were significantly heard by infants on the NICU, because the high sound level of environmental noise on these units (Olischar, Shoemark, Holton, Weninger, & Hunt, 2011). Additionally, other research concluded that the noise levels on NICU’s in Portugal exceeded the
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sound levels recommended by the American Academy of Pediatrics (1997) (Santos, Carvalhais, Xavier, & Silva, 2018).
In this feasibility and pilot study, the MAM study protocol was tested and discussed in order to execute the main study properly and to gain knowledge about how to successfully perform a randomized control trial with music as intervention on the NICU. The protocol of the MAM study was already written and approved by the Medical Ethical Review Committee (METC) of Utrecht. Therefore, The execution of the MAM study protocol was expected to be feasible. The feasibility of the MAM study was tested based on the model of Thabane et al., (2010). The focus of this feasibility study laid on the sound levels of the musical intervention compared to the sound level of the environment of the NICU. Also the methodology of the recruitment, intervention and measurements was tested on feasibility.
Table 1: Acoustic differences NICU and the Womb. (retrieved from: Lahav & Skoe, 2014)
Method
Participants and setting
* Study PopulationParticipants that will be included in the future randomized control trial will be drawn from the population of preterm infants who are admitted to the neonatal intensive, high and medium care of the Wilhelmina
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Children’s Hospital (WCH). Inclusion criteria for the future study are: a postmenstrual age (PMA) of 29-33 weeks at birth, a PMA of 30-29-33 weeks at the start of the intervention, not enrolled in any other study and written informed parental consent. Infants are excluded from the study if they have invasive mechanical ventilation at the start of the study or if they have severe neurological injuries or severe congenital brain malformation.
In this pilot study the participants were included by the same criteria as the future randomized control trial.
Randomization, blinding
The future randomized control trial will be single-blind, because physicians who will execute the study could not be blinded to the kind of treatment each subject will get. The data of the study will be analysed blind for treatment allocation.
The randomization was performed within this feasibility study with the use of a true random number generator retrieved from: https://www.random.org (Haahr, 2020). Participants were randomly divided into the intervention or control group. The upper and lower limits were set on 1 and 2 and 80 times a random number was generated. Each result was written down and put in a sealed envelope in the same order the numbers were generated. Number 1 represented the music intervention group and number 2 the control group.
For each new subject that will be included in the future randomized control trial, the envelop corresponding with the subject’s number will be opened and allocated to group 1 (music intervention group) or group 2 (control group).
Recruitment participants
To recruit participants in the future randomized control trial, treating physicians will identify potential subjects who meet the inclusion and exclusion criteria. After the identification of the potential subject, the medical specialist of the subject will determine if the patient could participate in the study. The member
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of the research team will inform the parents of the subjects orally about the MAM-study and hand them the Parent Information Form (PIF). After time for consideration (one week), the member of the research team will ask the parents if they want to participate in the study by signing the informed consent. When both of the parents have signed the informed consent, the subject will be included in the study.
In this feasibility study the subjects participated in the intervention pilot were recruited in the same way, only the consideration time was shorter (1 day).
Sample size
At first the goal of this feasibility study was to include 20 participants per group (control and intervention group), so in total 40 participants to determine the feasibility of the future randomized trial. The sample size was determined based on the sample size calculation of Viechtbauer et al. (2015).
Study setting
This feasibility study was executed in the Wilhelmina Children’s hospital. Feasibility measurements were done on the intensive-, high- and medium care units.
Interventions*
Musical intervention
The music intervention will be started after informed consent was obtained. The participants in the intervention group will exposed to music for 8 minutes.
Choice of music for intervention
The music, that is used in this feasibility study, is the same music that will be used in the future randomized control trial. The song Brahm’s Lullaby retrieved from the CD: Music for Dreaming by Music for Dreaming Australia (http://www.musicfordreaming.com/) was used as music.
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Decibels of intervention
The sound level of the musical intervention of the future randomized control trial will be slightly above ambient sound levels of the NICU, but will never exceed the sound level of 55 dB, taking the
recommended noise level for premature infants into consideration (American Academy of Pediatrics, 1997; Graven, 2000).
Musical Device used
A CE-marked mp3 player and sound box were used to present the musical intervention. The sound box connected to the mp3 player was placed in the bed or incubator at midline of the head of the infant as recommended (Cassidy & Ditty, 1998)
Brain maturation measurements
In the future MAM study brain maturation will be measured with EEG and ultrasound. In this feasibility study only the EEG measurements were performed using the ANT Neuro EEG monitor in combination with the Waveguardtm neonatal caps (CE-approved, developed by ANT Neuro®).
*For more information about the protocol of the future randomized control trial see: Supplementary information.
Procedure
Sound measurements NICU
As described in the protocol of the MAM study the musical intervention will not exceed the
recommended noise criteria for NICU’s of 55 decibels. To be sure the music is heard by the infants, the environmental noise on the NICU must not exceed 50 decibels. Unfortunately, other studies showed that
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the sound level of the NICU of multiple hospitals often exceeded this criterion (Smith, Ortmann, & Clark, 2018; Santos, Carvalhais, Xavier, & Silva, 2018).
In this study the decibel levels on the NICU were measured to control for the feasibility of the musical intervention. The sound levels of the intensive and medium care units were measured with the Benetech GM1356 sound level meter (CE-approved, developed by Shenzhen Jumaoyuan Science and Technology Co.). To imitate the same sound environment as an infant has, the decibel meter was put in an empty bed or incubator on the medium or intensive care to measure the sound level on the units (slow response, scale A). From Monday to Friday sound measurements were done in the range of 8 a.m. till 5 p.m. Each 10th sound measurement was saved on the sound level meter.
Measurements sound levels Brahm’s lullaby
To determine the appropriate settings of the mp3 player and sound box to play Brahm’s Lullaby in the music intervention, sound measurements of different environments and volumes were done. The music box was tested on an empty silent NICU. To measure the sound levels of different volumes of the music box the Benetech GM1356 sound level meter was used. To simulate the real environment of an infant laying on the NICU, the music box was placed in a closed incubator or open bed, additionally the decibel meter was placed in the same incubator or bed approximately 30 cm from the music box, which is the same distance to the head of the infant as the music box will be placed in the MAM study. The mean and highest sound level (dBA) of each volume per different environment (bed and incubator) were measured. This data was analyzed and the optimal volume of the sound box and mp3 player was detected.
Time frame feasibility
To determine whether the future randomized control trial was feasible within 2 years, the number of participants who met the inclusion criteria of the future randomized control trial from 2018 till 2019 was calculated from the database of the Wilhelmina Children’s Hospital. Based on this calculation an estimation was made of the number of infants born preterm that could be included in two years. The
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inclusion criteria used for the estimation were: 1. Born at a PMA of 29-33 weeks, 2. A minimum stay of 2 weeks laying on the medium- , high- or intensive care of the Wilhelmina Children’s Hospital in Utrecht, 3. No severe brain damage or congenital brain malformation and 4. Not having invasive mechanical ventilation. The sample size aim of the future randomized control trial was to include 29 participants per control and intervention group in 2 years, so 58 participants in total (supplementary information 1.).
Music intervention pilot
A pilot case of the Music intervention was performed on the intensive care. An infant on the neonatal intensive care unit was exposed to the musical intervention in an open bed by putting the music box, linked to the mp3 player, in the bed of the infant and playing Brahm’s Lullaby for 8 minutes long. During the intervention the sound level was measured (slow response, scale A) and saved every 10 seconds. The observations and sound measurements before, during and after the intervention were detected and discussed.
Neonatal EEG caps feasibility
The Waveguardtm neonatal EEG caps were rarely used by NICU staff, therefor these caps in combination with the ANT EEG monitor were tested on infants admitted to the intensive-, high- or medium care units. A short EEG measurement of 30 minutes was performed. The conduction of the electrodes was compared between the use of EEG electrode paste and gel (Spectra® 360 electrode gel, Parker Laboratories, Inc.). The observations of the measurements were described and discussed.
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Figure 1. An example of the neonatal EEG cap (Retrieved from: ANT Neuro, Photo courtesy of Dr.
Vanhatalo, November 2016)
Objectives
The primary outcomes of this study were the outcomes of the sound level measurements of the NICU and the Brahm’s Lullaby intervention. The outcomes of the NICU sound level measurements were the mean sound level per hour and the amount of times the sound level exceeded 50 dBA per hour. The outcomes of the Brahm’s Lullaby measurement were the means and highest sound levels per volume and
environment measured in dBA, calculated with the use of Excel. The feasibility of the sound levels of the musical intervention were determined on the basis of the previous described outcomes.
The secondary outcomes were the results of the music intervention pilot, the time frame feasibility and the neonatal EEG caps feasibility. The Musical intervention pilot outcomes were (1) the observations of the behaviour of the infant and parents and (2) the mean sound level every 10 seconds measured in dB(A). The time frame feasibility calculation outcomes were the amount of patients who met the inclusion criteria of the future randomized control trial in the year 2018. At last was the feasibility of the neonatal EEG caps determined by observational outcomes of the EEG protocol made by a
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Statistical analysis
Sound level measurement NICU
To analyze the sound level data measured on the medium and intensive care units, the mean sound level in dBA per hour and the amount of times the sound level was higher or equal to 50 dB(A) per hour was calculated for each day. The mean sound levels and the amount of times the sound level was 50 dB(A) ≥ were compared between every time frame of an hour and between open bed and incubator.
Results
Results are written in a narrative way and grouped in 5 categories: Sound level measurements NICU, Sound levels music intervention, Music intervention pilot, Datasheet inclusions 2018 and Observations neonatal EEG caps.
Sound level measurements NICU
The values of the mean sound levels per hour are shown in Table 2. In Figure 1. the mean sound levels of the incubator, bed and NICU environment per hour are plotted. Each sound level measurement was included for the matching hour of the day (a measuring from 10:00 a.m. – 10:15 a.m. was included in the category 10:00 a.m. – 11:00 a.m.). The mean sound level of the NICU environment was calculated on the basis of the sound levels measured closed incubators and open beds together. The mean sound level on the NICU’s was higher in an open bed (47.0 dB(A)) than in an closed incubator (45.5 dB(A)). The highest mean sound level measured in an incubator was between 8 a.m. and 9 a.m. (46.5 dB(A)). In an open bed the highest mean sound level was measured between 4 p.m. and 5 p.m. (48.5 dB(A)) and the highest mean sound level on the NICU overall was measured between 10 a.m. and 11 a.m. (46.4 dB(A)). Additionally the lowest mean sound level of the environment of the NICU measured, taking the closed incubator and open bed in consideration, was between 2 p.m. and 3 p.m. (45.1 dB(A)).
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The mean percentages of all the sound measurements per hour above or equal to 50 dB(A) were calculated and listed in Table 3. The percentage was higher for the sound levels measured in an open bed (22.4 %) compared to the percentage of the sound levels measured in a closed incubator (2.8%). Between 12 p.m. and 1 p.m. the percentage above or equal to 50 dB(A) measured in a closed incubator was the highest (4.0%). In an open bed the highest percentage was calculated between 1 p.m. and 2 p.m. (27.2%). The highest percentage of sound level measurements above or equal to 50 dB in one hour overall was between 4 p.m. and 5 p.m. (12,2 %). At last the lowest percentage of the sound level above or equal to 50 dB measured on the NICU (Bed and incubator) was between 2 p.m. and 3 p.m.
Table 2. Mean values of sound levels NICU environment. (N = the amount of sound level measurements
used to calculate the corresponding percentage, Na = not available).
Time of the day Incubator
(dBA) N (incubator) Bed (dBA) N (Bed) NICU environment (dBA) N (NICU environment) 8 a.m. - 9 a.m. 46,5 1 Na Na Na Na 9 a.m. - 10 a.m. 45,8 6 Na Na Na Na 10 a.m. - 11 a.m. 45,9 11 47,8 4 46,4 15 11 a.m. - 12 p.m. 45,6 13 47,3 5 46,1 18 12 p.m. - 1 p.m. 45,5 11 46,9 5 45,9 16 1 p.m. - 2 p.m. 45,2 11 47,0 5 45,8 16 2 p.m. - 3 p.m. 45,2 11 44,1 2 45,1 13 3 p.m. - 4 p.m. 45,3 8 46,3 3 45,6 11 4 p.m. - 5 p.m. 44,0 3 48,5 2 46,0 5 8 a.m. - 5 p.m. 45,5 75 47,0 26 45,8 101
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Figure 2. Mean sound levels NICU environment
Table 3. Mean percentage of the sound measurements on the NICU ≥ 50 dBA. (N = the amount of sound
level measurements used to calculate the corresponding percentage, Na = not available).
Time of the day Incubator
(%) N (incubator) Bed (%) N (Bed) NICU environment (%) N (NICU environment) 8 a.m. - 9 a.m. 0,6 1 Na Na Na Na 9 a.m. - 10 a.m. 3,2 6 Na Na Na Na 10 a.m. - 11 a.m. 3,8 11 20,4 4 8,3 15 11 a.m. - 12 p.m. 2,9 13 24,0 5 8,8 18 12 p.m. - 1 p.m. 4,0 11 24,4 5 10,4 16 1 p.m. - 2 p.m. 2,0 11 27,2 5 9,9 16 2 p.m. - 3 p.m. 1,8 11 9,2 2 3,0 13 3 p.m. - 4 p.m. 1,5 8 17,5 3 6,3 11 4 p.m. - 5 p.m. 3,5 3 25,3 2 12,2 5 8 a.m. - 5 p.m. 2,8 75 22,4 26 7,8 101 41 42 43 44 45 46 47 48 49 8-9 hour 9-10 hour 10-11 hour 11-12 hour 12-13 hour 13-14 hour 14-15 hour 15-16 hour 16-17 hour So un d lev el (dB A)
Time of the day (hours)
Mean sound level incubator Mean sound level Bed
Mean sound level NICU environment
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Sound levels music intervention
The sound level measurements of the musical intervention are listed in table 4. The amount of decibels for each volume was higher in a closed incubator than in an open bed. Only Volume 4 did not exceed the recommended maximum sound level of 55 dB (Max. bed: 48.9 dB; Max. incubator: 52.3 dB). The sound level outside an open (36.9 dB) or closed incubator (35.7 dB) during the song was played on volume 4 did not exceed the minimum sound level of the Lullaby on volume 4 (bed: 40 dB; incubator: 43 dB).
Table 4. Sound level measurements musical intervention: Brahm’s Lullaby (db(A)). (Na = not available).
Datasheet inclusions 2018
Between 2018 and 2019, 38 infants born preterm met the inclusion criteria of the future randomized control trial. To estimate the amount of subjects that would be included in the MAM study in 2018 a inclusion rate of 50% was applied, because 50% was the mean inclusion rate of comparable studies done by researchers in the WCH (unpublished data). After the inclusion rate was applied a total of 38 infants in 2 years could be included in the future randomized control trial based on the data of 2018.
Music intervention pilot
The song of the musical intervention pilot was played on volume 5, which has a mean sound level between 45 and 50 dB and a maximum of 56.2 dB (Table 4.). Volume 5 was chosen, because the infant layed in an open bed and Volume 4 (mean sound level: 40-45 dB(A)) should not exceed the noise level of the environment of the NICU. The intervention pilot took place from 14:17 p.m. until 14:25 p.m. (Figure
Volume MP3 player Open bed Closed incubator Outside closed incubator Outside open incubator
No music 34-35 31-33 Na Na Volume 4: Max 48,9 52,3 35,7 36,9 Volume 4: Mean 40-45 43-48 Na Na Volume 5: Max 56,2 59,2 36,2 39,4 Volume 5: mean 45-50 45-50 Na Na Volume 6: Max 59,6 62,6 Na Na Volume 6: mean 50-55 55-60 Na Na
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2.). Most of the time the sound level did not exceeded the sound level of 55 dB, but at 14:19 p.m. the sound level did reach the point of 55 dB. Observations made by the researcher at 14:19 p.m. showed that there was loud talking on the NICU (Table 5.). Other observations showed that the Child became quieter during the intervention.
Figure 3. Sound levels intervention pilot NICU. The black dotted lines represent the timeframe of the
musical intervention.
Table 5. Observations intervention pilot Time of the day Observations
Before intervention The child was recently put down in bed after being pouched, There was
little space to put the decibel meter and the music box in the bed
14:15 Start intervention, Child was restless and moved.
14:19 There is a lot of loud talking on the NICU
14:21 Child is being more quiet and moves less
14:23 Child is very quiet and has closed the eyes, it may be sleeping
14:25 End intervention
After intervention
The nurses, researchers and parents started talking more and louder again. Parents mentioned that they say there infant became more soothing
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Observations Neonatal EEG caps
The The Waveguardtm neonatal EEG caps in combination with the ANT neo monitor were tested on 2 participants laying on the Medium care. An EEG session of 30 minutes was executed to test the setup. In the first EEG session a paste was used to improve the conductance of the electrodes. After the preparation of the first measurement the impedance of the electrodes was very high (>20 kΩ). For the second EEG pilot the Spectra® 360 electrode gel was used for better conductance. Observed was that the impedance of most of the electrodes used was lower than before (< 20 kΩ).
Discussion
Overall the results showed that the recruitment and intervention protocols of the future randomized control trial cannot be executed successfully and will not be feasible without some adaptations. The sound levels of the musical intervention, that met the recommended criteria of sound levels on the NICU, were questionable feasible within the closed incubator and were not feasible when the musical intervention was executed in an open bed. Also the time frame of the MAM protocol was not feasible based on the data of 2018. On the other side the protocols of the music intervention, the intervention pilot, and the EEG pilot with the use of the Neonatal EEG caps were executed successfully and therefore feasible.
The mean sound levels per hour measured on the Neonatal intensive care units did not exceed the future randomized control trial criteria of 50 dB’s (supplementary information 1.). On the other hand did the environmental noise on the NICU in both bed and incubator exceed 50 dB(A) every hour. The environmental noise on the NICU was louder in an open bed than in an incubator. If the environmental noise must not exceed the amount of 50 dB(A) to hear the music, the musical intervention is not applicable for infants laying in an open bed on the NICU, because the percentage of the measurements above or equal to 50 dB(A) was to high (22.4 %). The musical intervention can be applicable for infants laying in incubators, because the environmental noise measured in an incubator did not exceed 50 dB too
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often (2.8% of the measurements). But if the musical intervention is significantly heard by the infants is questionable, because the mean environmental sound level in the incubator (45.5 dB) lays within the reach of the mean sound level of the music used as intervention (Volume 4: 43-48 dB).
The sound level of the musical intervention should never exceed the maximum of 55 dB(A), therefore the recommended volume of the music box is volume 4 for the Brahm’s Lullaby played in an open bed as well as in an incubator. Earlier research already questioned if a musical intervention can be heard by an infant on the NICU (Olischar et al., 2011). In this research the results showed that the sound level of the music was higher in an incubator than an open bed, which resulted in a mean sound level of the song played at volume 4 of only 40-45 dB in an open bed. Taking the results of the sound level measurements on the NICU in mind, the sound level of 40-45 dB will indeed not exceed the
environmental noise an infant will hear on the NICU, which means that the musical intervention protocol is not feasible in an open bed on the NICU in terms of the recommended sound levels (American
Academy of Pediatrics, 1997; Graven, 2000). To resolve this problem, the protocol of the future randomized control trial should be adapted. Possible protocol adaptations are listed in the
‘Recommendations’ section. At last, it seems that the environment of the closed incubator increased the sound level of the music, this also needs to be taken into account in the future randomized control trial.
The mean sound level measured as well as the mean percentage above or equal to 50 dB(A) was the lowest between 2 p.m. and 3 p.m. These results indicate that between 2 p.m. and 3 p.m. the sound level on the NICU is the lowest and this timeframe is therefore the optimal time to perform the music intervention for preterm infants participating in the future randomized control trial.
Interestingly the mean sound level in the NICU measured in an incubator did often exceed the recommended noise criteria of the American Academy of Pediatrics (1997) (45dB(A)), which indicates that the recommended sound levels of the American Academy of Pediatrics on the NICU of the WCH are not feasible. Earlier research also showed that the sound levels on different NICU’s exceeded the
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Santos et al., 2018). To be sure that the recommendations of the American Academy of Pediatrics are feasible on NICU’s in general more sound level studies should be done with statistical analysis.
At first the sample size goal of this feasibility study was to include 20 participants per group (intervention and control). Unfortunately at the beginning of the inclusion phase of the study the COVID-19 epidemic came to the Netherlands, which caused that no researchers were allowed anymore in the Wilhelmina Children Hospital and no inclusions could be made in this feasibility study. Therefore the time frame feasibility was determined on the basis of the amount of possible inclusions in the year 2018. Based on the possible included participants between the year 2018 and 2019 in the future randomized control trial, the time frame of the MAM study will not be feasible. The aim was to recruit 58 participants in the time frame of two years. Based on the inclusion estimation of the datasheet of 2018, only 38 participants would be included in the future randomized control trial. In the protocol of the MAM study was expected that there will be 100 eligible patients a year, but in 2018 only 38 patients a year met the in- and exclusion criteria of the MAM study (supplementary information 1.). To fit the gap of minimum 20 participants in two years, some adaptations in the MAM protocol should be made. Recommended adaptations are listed in the ‘Recommendations’ section further in this paper.
The intervention pilot was executed successfully. The sound measurements showed that the music intervention is feasible and hearable played at volume 5. On the other hand reached the sound level one time the level of 55 dB, which indicates that there was too much noise on the unit to hear the Lullaby by the infant, what was already questioned in the study of Olischar et al., (2011). The observations
indicate that the child became more quiet during the intervention and the parents mentioned that the music was soothing for them.
With the use of the Spectra® 360 electrode gel, the EEG electrodes showed the lowest impedance and the electrode gel is therefore the most feasible conductance fluid to use. The 30 minute EEG
measurement was successfully executed on the infant with useable EEG signals. Both of the infants included in the EEG pilot were quit most of the time and did not move too often. To make sure that the
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entire EEG measurement is feasible in terms of usable EEG signals, a pilot EEG measurement of 60 minute should be done and analysed.
The protocol of the future randomized control trial cannot be feasible without the use of some recommended adaptations. When the adaptations of the protocol are made, a feasible randomized control trial where the effect of music intervention (with methodological soundness) on the brain maturation of preterm infants can be started. The future study of MAM is essential to gain more knowledge of the effect of music on the brain maturation of infants born preterm and to fit the gap of randomized control trials of music with methodological soundness (van der Heijden et al., 2016).
Recommendations
Musical intervention/sound levels NICU
The recommended time to play the music intervention based on the sound level measurements on the NICU is between 2 p.m. and 3 p.m. This time frame applies for the music intervention executed in an incubator.
To successfully perform the music intervention for infants laying in an open bed on the NICU there are some solutions: 1. The music must be played at volume 5 instead of volume 4 on the music box (the music will sometimes exceed the criterium of 55 dB) 2. The sound level on the NICU must be reduced to below 50 dB as mentioned in the article of Olischar et al. (2011). One possibility to reduce the sound level is by a ‘silence moment’ on the NICU: all the personal and parents on the NICU are asked to whisper for 10 minutes to reduce the sound level on the unit. Also some other strategies that can
significantly reduce the sound levels on the NICU can be used (Ahamed, Campbell, Horan, & Rosen, 2018). 3. The musical intervention must be executed with the use of headphones instead of a music box to silence the noise on the NICU, this is already successfully used in earlier studies (Sa de Almeida et al., 2020; Lordier, Meskaldji, et al., 2019; J. Standley, 2012).
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Recruitment (time frame)
To perform the future randomized control trial within the time frame of 2 years and to include 58
participants in the study (29 per control and intervention group), the inclusion criteria of the MAM study should be adapted. The current inclusion criteria are listed in the MAM protocol (supplementary
information 1.). The first inclusion criterium stated that the participants must have a PMA of 29-33 weeks at birth and a PMA of 30-33 weeks at the start of the study. Observed was that most of the children laying on the high- and intensive care had a lower PMA than 29 weeks. Therefore, a possible solution to fit the gap of participants is that the first criterium should be adapted to a PMA of 26-33 weeks at birth and a PMA of 27-33 weeks at the start of the study. The preterm infants cannot be included under the PMA of 26 weeks, because infants can only hear at the beginning of the Gestational Age of 26 weeks old
(Mcmahon et al., 2012). Another possibility is to extend the time frame to 3 or 4 years, but extending the study has also consequences for the costs of the study.
EEG measurement
The EEG protocol with the use of the ANT Neuro EEG monitor in combination with the Waveguardtm neonatal caps are feasible for usable EEG measurements in intervention study with infants born preterm. The Spectra® 360 electrode gel should be used to decrease the impedance of the electrodes and therefore increase the quality of the EEG results.
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Supplementary information:
