This work was funded by the foundation Vontobel-Stiftung Zurich.

The clinical protocol follows the ethical guidelines of the University Hospital at Zurich. All methods and techniques are based on the described approach of CMT in the NICU and are recommended to be provided by music therapists specially trained in CMT (CMT training or the Rhythm Breath and Lullaby training with CMT modules39,40,41). CMT can be delivered when the infant is clinically stable, as defined by nurses and doctors of the neonatal team, 2-3 times per week, for approximately 20 min each session.
1. Preparation
<ol>
	<li>Before initiating music therapy, conduct an in-depth assessment with team members of the unit (e.g., doctors, nurses, psychologists) and as soon as possible with the parents to identify the needs of the infant and parents. Based on these needs create therapeutic objectives oriented towards the principles of neonatal music therapy and family-integrated care approaches42,43,44.</li>
	<li>Introduce music therapy to the parents. Assess their needs, resources, musical heritage, and culture. Assess what song or music they wish for as well as their natural vocal range. Assess if they already provided music to their infant during pregnancy, and if so, integrate this music in the therapy procedures referred to as &#34;song of kin&#34;45.</li>
	<li>Supply the parents with empowering intercultural music material (e.g., the lullaby book &#34;Wiegenlieder f&#252;r die Kleinsten. Ausgew&#228;hlte Lieder von Eltern f&#252;r Eltern fr&#252;hgeborener Kinder&#34; [Lullabies for the most little ones. Songs of parents for parents of preterm infants])46. Parents of preterm infants sang all the international songs in this book and framed each song with their written experiences on why and how they sang to empower and to motivate other parents to sing for their infant as well47. Alternatively, provide further information (e.g., a flyer) to motivate parents to engage in vocal interaction with their infant.</li>
	<li>Continue to assess the infants&#39; and parents&#39; needs during their clinical trajectory over time by attending interdisciplinary neonatal rounds and or meetings regularly and by intensifying the dialogue with the parents. Continue to adapt to these families&#39; needs to facilitate a needs-, and resource-based therapeutic process.</li>
	<li>Identify a reasonable time frame with the neonatal staff and the parents in which to conduct the music therapy session to minimize the chance of interfering with healthcare routines, treatments, emergencies, infant resting periods, and needs of the parents.</li>
	<li>Discuss with neonatal staff and/or parents if the session should take place at the incubator or bedside only with the infant or together with the parents. For example, when the parents spend a lot of time in the NICU and enjoy the shared sessions, conduct as many joint sessions as possible, mostly and preferably during KC. When parents have less time, fewer possibilities to visit, or are not accountable, offer music therapy with other caregivers or just the infant as well.</li>
	<li>Before providing CMT, seek the latest meaningful clinical information on the infant and its family as well as approval of the neonatal team. Tune the monochord in the key of the unit (the most dominant and frequent monitor beeping tone of the unit) if the instrument is needed for the session48.</li>
	<li>Before conducting each music therapy session and entering the patient zone, disinfect hands, arms, and the instrument by following the hygiene guidelines of the neonatal unit and the individual infant. Disinfect and prepare a chair at the bedside of the infant or next to the parents.</li>
</ol>
2. Creative Music Therapy with the Preterm Infant at the Bedside or Incubator
<ol>
	<li>When the infant tolerates touch, start with initial touch by touching the infant at the head and feet and change it into therapeutic touch by lightly laying one hand on the chest or the back49,50. While touching the infant connect with the infant, notice any increased or decreased muscle tension, any voluntary or involuntary movement, and support the breathing movements and patterns by adapting the pressure and weight of the hand on the chest or back to these patterns.</li>
	<li>After a period of observation, start with infant-directed humming entrained to the infant&#39;s breathing pattern, incorporating the infant&#39;s signs of mimicry and movements to attune to the infant&#39;s needs and to support or regulate breathing. Fade in the music: Start with a few long and calm notes proceeding in small steps with a high degree of repetitions and continuity.</li>
	<li>Develop the melody slowly over time. Often this occurs synchronously: for example, when the infant&#39;s eyebrows lift, move the melodic pitch and tempo upwards16. In contrast, when the infant is overly aroused, reduce the melody&#39;s span of pitches and pitch range and shift it downwards, slow the tempo, and repeat the closing notes to soothe the infant.</li>
	<li>Hum to sooth and sing to activate, synchronize and interact with older infants, or infants who open their eyes and mouth and/or start &#34;mouthing&#34; (i.e., shaping their mouth to make &#34;oh&#34; and &#34;ah&#34; sounds and tongue play) and/or move their fingers or arms smoothly50.</li>
	<li>Hum and sing simply in lullaby style in order not to overwhelm the infant: Keep the voice calm, slow, simple, predictable, repetitive, and contingent with the pitch range of children&#39;s songs based on the guidelines of neonatal music therapy24,43,44. Hum with flowing breath and a free natural voice full of overtones and total ease.</li>
	<li>Incorporate the &#34;song of kin&#34;25 in lullaby style in the individualized, attuned improvisation. If necessary, attune to environmental sounds to integrate and thereby mitigate disturbing noises such as a monitor beeping50 oriented towards environmental music therapy approaches4,48.</li>
	<li>After ~15-20 min (adapt the duration to the individual needs of the infant) fade the humming or singing slowly out by reducing the notes, the tempo, the rhythms, and conclude by repeating the last note51.</li>
	<li>Hold the infant some seconds longer before removing hands slowly and cautiously.</li>
</ol>
3. Creative Music Therapy with the Parents During Skin-to-skin Care
<ol>
	<li>Assess the current needs of the parents (e.g., assess if they would like to listen and relax during the music therapy session or if they would like to sing along).</li>
	<li>Invite the parents to sit or lie down comfortably. Position the monochord next to the side chair of the parent with the infant in KC. Place the instrument next to the elbow or arm of the parents so that the relaxing vibrations can transmit to their body.</li>
	<li>If appropriate, invite the parents to breathe in and out deeply. Invite the parents to close their eyes, to focus on their breathing, and afterward to focus on feeling their infant. Alternatively, invite the parents to observe and interact with their infant, as they prefer. This procedure may be appropriate as preparation for the joint music therapy session and/or during the session accompanied by monochord sounds and singing and/or speaking.</li>
	<li>After a short period of observing the parent-infant dyad, start with long, calm sound waves on the monochord, entrained to the infant&#39;s breathing pattern (e.g., three sets of infant inhalations and exhalations = one long continuous strum on the monochord). Fade the sound in smoothly.</li>
	<li>After a while (~90 s) hum along with the monochord sound, as described above, or accompany and support the parental humming/singing for their infant.
	<ol>
		<li>Attune and tailor the humming and singing to the affects, rhythms, and needs of the infant and environmental sounds as described above and additionally to the parents&#39; needs (compare previous publication23,47).</li>
		<li>Hum or sing within the parents&#39; vocal range to facilitate parental humming or singing. To honor the family&#39;s musical and cultural heritage integrate their favorite music in the singing23,25.</li>
	</ol>
	</li>
	<li>After ~15-20 min (adapt the duration to the individual needs of the infant), fade the humming or singing slowly out by reducing the notes, the tempo, the rhythms, and repeating the last note. Continue to play the monochord for 1 or 2 min more and fade the monochord sound smoothly out. Hold the moment of reverberation and silence some seconds longer before removing the instrument slowly and cautiously.</li>
	<li>If appropriate, ask the parents how they experienced the music therapy session for themselves and how they perceived their infant&#39;s reactions. If appropriate, share perceptions of the infant&#39;s behavioral state and reactions (e.g., smiling, finger movements, if occurred). Give feedback about observations and thereby encourage and value observed appropriate parental and infant behavior as well as appropriate parental-infant interactions to promote parental self-efficacy and parent-infant attachment.</li>
	<li>Encourage the parents to use their voice to connect with their infant in their daily NICU routine. Encourage the parents to use infant-directed speech with &#34;motherese&#34;52,53 and humming and singing, as preferred by the parents.</li>
	<li>When therapeutically indicated, invite the parents to engage in song writing, a widely used music therapy method to express and validate experiences, to externalize emotions and thoughts54, and to intensify and personalize the parent-infant interactions in neonatal music therapy in particular30,55,56. Invite the parents to write about their musical experiences in their dairy (or the diary pages of the lullaby book &#34;Wiegenlieder f&#252;r die Kleinsten&#34;) and to quote their song.</li>
</ol>
4. Creative Music Therapy with Additional Family Members
<ol>
	<li>Prepare and adapt to the current needs of the infant and parents as described above, but assess the needs of siblings, grandparents, or other significant caregivers, if and how they wish to participate in the music therapy sessions. Assess well-known family songs and model the song in lullaby style for the preterm infant.</li>
	<li>Assess the context, history, and heritage of the chosen songs and invite the family to share their associations and emotions regarding the chosen music. Sing the song for or with the family based on the infant&#39;s and family&#39;s current needs. Sing and or accompany as described above or let the family members sing for the infant and accompany or listen and coach them. Encourage the family to use infant-directed speech or singing when they visit the infant as well.</li>
</ol>
5. Follow-up
<ol>
	<li>Make a new appointment with the parents, if appropriate. Upon exiting the patient zone, disinfect following the neonatal hygiene guidelines.</li>
	<li>Document the sessions as described elsewhere16. Give feedback to and discuss with neonatal staff and parents (if available). Attend integrative rounds and continuously assess the needs of the team and parents to incorporate these needs in the therapeutic process.</li>
	<li>Write a final patient report before hospital discharge and advise parents on how to use music at home, including written recommendations. If appropriate, give the parents a call 2 weeks after discharge to inquire how they are doing and to recommend further musical support.</li>
</ol>

The authors have nothing to disclose.

The therapeutic, responsive, empowering, and creative use of music in CMT may be of great potential for preterm infants, their parents, and the parent-infant attachment. Individually tailored soft music, shared affects attunement, and joint attention may support relaxation, development, and the bonding process even in the stressful and artificial environment of an intensive care unit.
However, music therapy plays a subordinated and complementary role in the lifesaving priority setting of medical treatment and intensive care. Mostly, CMT should be delivered when the infants are clinically stable and do not suffer severe or life-threatening instability as defined by the neonatal team. Nonetheless, music therapists can provide CMT as palliative care as well when recommended by the neonatal team and or requested by the parents61. CMT with parental integration can only occur when the parents are present and willing to participate. Often, the music therapist has to reschedule planned sessions so as not to interfere with healthcare routines, treatments, emergencies, and infant resting periods. Sometimes, planned joint music therapy sessions in KC have to be changed to sessions at the bedside of the infant because the infant is too medically unstable for KC. The needs of the infant are of highest priority in all decision-making processes because the preterm infant is the most vulnerable component of the parent-infant-environment triad, even when this may evoke parental feelings of disappointment. This priority setting is warranted for the whole music therapy process as well.
When working with the parents, the aim is to enable intuitive parental roles to emerge through interactions with their infants, more than to explicitly teach new skills. While working with the family, the music therapist should act as a facilitator and collaborator, rather than as an educator or expert teaching parents how to use their voice and or sing since many parents experience helplessness, dependence on NICU experts, and a lack of self-control, self-confidence, and autonomy as primary caregivers9,62. Therefore, the role of the therapist is to advice by supporting the parental role as primary caregiver rather than compromising it. The task of the therapist is to integrate the cultural heritage of the family because supporting parents in their cultural identity is argued to be particularly empowering and may build transcultural bridges47,63,64. Because infant-directed humming is characterized by musical parameters across cultures such as slower tempo, higher pitch, and a distinctive style of humming and singing65, these musical parameters can be used to facilitate communication and interaction with the parent-infant dyad even beyond potential cultural and language barriers66. In cases when parents are not accountable (e.g., due to severe mental health issues or drug addiction), CMT should aim to integrate other potential caregivers of the infant. Moreover, the overarching challenge of the music therapist is to assess steadily the interweaving and constantly changing needs of the infant, parents, and neonatal intensive care environment in order to be flexible, creative, and therapeutically responsive. Therefore, only specially trained music therapists are recommended to provide CMT in neonatal care by following the described step-by-step protocol.
Nowadays, CMT is aligned with key principles of family-centered care: e.g., empowering each child and family, honoring choices and cultures, adapting to caregivers&#39; needs, and collaborating with parents in treatment24. CMT draws further on the elements of family-integrated care by integrating parents as partners and primary and most meaningful (vocal) caregiver as soon as possible11.
CMT may enhance the widely used approach of KC by reducing stress, promoting relaxation, and intensifying feelings of safety and connectedness38,67. CMT may be of particular significance not least because of providing meaningful, socio-emotional, joyful, and playful &#34;moments of meeting&#34; which are argued to foster a secure relationship between the parent-infant dyad9,68. CMT aims at relaxing, stimulating, and coregulating premature infants at a time when many other interventions are still at risk to overwhelm the vulnerable patient group. Particularly in the first weeks after preterm birth when very preterm infants are sometimes too unstable for KC, infant-directed humming can facilitate nurturing connectedness. Additionally, the music therapist can provide CMT during sleep without awakening but stimulating the infant50.
Socio-emotional experiences and early auditory experiences make an impact on brain development as suggested by human and animal studies69,70,71. Because preterm infants are in the most rapid and vulnerable period of brain development, auditory and socio-emotional experiences may influence the plasticity of auditory and cortical brain regions72,73.
We may speculate that the enriched musical and socio-emotional experience in CMT may promote brain development, notably functional and structural connectivity, as well as emotional and cognitive development74. Rigorously designed trials are required to evaluate short and longitudinal effects of music therapy on brain development in preterm infants and psychosocial adaption. In Switzerland, such a study is implemented, and a multicenter study is prepared17. In conclusion, CMT may be a promising and feasible family-integrated therapy involving communicative musicality to promote neurodevelopment, parental psychosocial adaption, and mutual socioemotional connectedness from the very beginning.

Preterm infants represent a growing population in health care, and many infants suffer neurodevelopmental impairments that persist into later life (e.g., motor dysfunction, cognitive and behavioral problems)1,2. In addition to other risk factors, sensory deprivation (e.g., the lack of the intrauterine multisensory experience of the regular maternal heartbeat and the maternal voice) and the stressful sensory overload of the NICU, or neonatal intensive care unit (e.g., monitor beeping, mechanical noises), may negatively impact brain maturation3,4.
Preterm birth is a stressful and traumatic event for preterm infants and their parents5. Infants and parents are separated too early, and the parents lack their autonomy as primary caregivers, which can impede the development of healthy bonding between parents and their infants6. Parents may suffer from feelings of disappointment, ambivalence, helplessness, anxiety, and guilt7. Unresolved psychological trauma is linked to parental stress, thereby compromising parental well-being, attitudes, and behaviors, potentially adversely impacting the attachment process between infants and their parents8,9,10.
Family-integrated early interventions are warranted to decrease these adverse consequences of preterm birth and to actively involve parents as primary caregivers as soon as possible11. Music therapy in neonatal care is exactly that: an early and promising intervention to stabilize and nurture the infant as well as to promote connectedness at a time when many other interventions are still at risk to overwhelm the fragile infant. CMT for preterm infants and their parents has emerged as one of these interactive music therapy approaches in the NICU12,13,14. CMT is an individualized and interactive approach, resource and needs-oriented15,16,17. CMT is related to Nordoff-Robbins music therapy18, which assumes that being responsive to music is an intrinsic quality to being human, regardless how handicapped or even premature a human being is19,20. CMT directs the trained music therapist to assess the meaning of the infant&#39;s breathing rhythms, facial expressions, and gesticulations, and to construct a musical response15,21. The therapist hums or sings in an infant-directed improvised lullaby style, continually coregulating the infant&#39;s behavioral states (affects, emotion, arousal22). CMT aims to relax the infant as well as to offer individualized interaction, meaningful stimulation, and entrained rhythms (e.g., to facilitate stable and regular breathing rhythm and suck-swallow-breath rhythm)23,24.
Based on the principles of family-integrated care11, the family is incorporated individually in the therapeutic process, namely by delivering CMT during KC when the infant is placed chest-to-chest or skin-to-skin on the chest of the parents to enhance parental feelings of security and thereby prevent their retraumatization5. The music is tailored continuously to the affects, rhythms, and needs of the infants as well. CMT aims to honor the family&#39;s musical and cultural heritage and to integrate their favorite music or song to empower the family in their cultural identity23 similar to the &#34;song of kin&#34; techniques of Loewy et al.25. CMT further aims to promote parental self-confidence and autonomy and to enhance the parent-infant attachment process. The music therapist generates the parent&#39;s awareness to reconnect with their musical self and their infant via vocal interaction by supporting parental infant-directed speaking and/or singing in a responsive and attuned way. During KC the therapist may accompany the voice with a monochord, a single-stringed wooden instrument (~30 strings tuned to one base tone with octaves and fifth generating vibroacoustic sounds of overtones). It may evoke the deep-frequency sounds and vibroacoustic of the womb. It generates an open, nurturing sound that may be inviting to sing along with in all musical keys and styles, as proposed by the parents. Techniques such as positioning the instrument against the parent&#39;s elbow allows its vibrations to convey relaxation. The monochord has proven itself effective in inducing relaxation and lending a feeling of intensity to parent-infant encounters26. Parents in the NICU reported after CMT that particularly the monochord sound generated the feelings of security, relaxation, and increased physical closeness to their infant27. Additionally, KC itself is a natural technique for enhancing the multisensory bonding experience between mother (or father) and infant and has become standard routine in many NICU units28.
Even among siblings, premature birth is challenging. Siblings may struggle with feelings of neglect, envy, and sometimes grief, which can lead them to refuse to accept their preterm sibling29. Consequently, CMT also aims to include preterm infants&#39; siblings by letting them choose a song for their prematurely born sister or brother and by singing it together, for example. Generally speaking, CMT aims to facilitate communicative musicality to promote parent-infant connectedness. Music is the pathway for each family to engage in a meaningful ongoing relationship &#34;to support the infant coming into being, the parents into parenthood, and the triad into bonding&#34;30.
Several systematic reviews and a meta-analysis31,32,33 suggest favorable effects of music therapy in neonatal care (e.g., physiological parameters, behavior state, respiration). The meta-analysis, including 964 preterm infants and 266 parents, showed a beneficial effect of music therapy on the infants&#39; respiratory rate and maternal anxiety31. The authors highlight the need for neonatal music therapy provided by specially trained music therapists31. Equally, the authors of a multicenter randomized controlled trial (RCT)13, a mixed-method study34, and a qualitative study35, call for the informed use of music in a therapeutic relationship by certified music therapists. Several trials revealed that music therapy, and particularly entrained music therapy13, has a favorable impact on preterm infants&#39; respiratory rate, and quiet alert and sleep states13,31. Integrating parental-preferred lullabies in the live music therapy process was associated with enhanced bonding and decreased parental stress and anxiety13,34.
Researchers have further investigated if live music therapy during KC may affect the well-being and stress levels of parents more than KC alone. Two randomized studies from Israel demonstrated that active harp music therapy during KC may reduce maternal anxiety more than KC alone36 and that a mother&#39;s anxiety may decrease when singing while holding the baby in KC and increase calmness in preterm infants more than KC alone37. Similarly, researchers from Finland38 suggest that live music therapy combined with KC may have more relaxing effects than KC alone. Although these results have to be confirmed with more extensive trials, they already indicate the potentials and possible advantages of music therapy over other nonpharmacological interventions such as KC and call for family-integrated music therapy in neonatal care. In this manuscript, we present a detailed step-by-step protocol on how to use CMT as a family-integrated, needs-oriented, and individualized live music therapy approach in the NICU to empower preterm infants and their parents from the very beginning.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>K&#246;rpermonochord</td>
			<td>Saitenklang</td>
			<td></td>
			<td>http://www.saitenklang.ch/koerpermonochord/</td>
		</tr>
	</tbody>
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clinical practice protocol of creative music therapy for preterm infants and their parents in the neonatal intensive care unit

Creative music therapy for preterm infants and their parents (CMT) has emerged as a promising family-integrated early intervention involving communicative musicality to improve infant development, parental well-being, and bonding. It aims at relaxing and nurturing the infant as well as promoting safety and social interaction for the parent-infant dyad. A music therapist specially trained in CMT hums or sings in an infant-directed, improvised, lullaby style continually adjusting to the individual needs, expressions, and breathing pattern of the preterm infant. Based on the principles of family-integrated care, the family is incorporated individually in the therapeutic process, namely by delivering CMT during kangaroo care (KC) and by motivating and facilitating parental vocal interaction with their infant to strengthen the parent-infant bonding. CMT aims at relaxing, stimulating, and coregulating premature infants at a time when many other interventions are still risky and can overwhelm the vulnerable patient group. CMT may be advantageous not by educating and teaching parents, but rather by uncovering the intuitive capacities of parenting that are often overshadowed by the traumatic experience of preterm birth. However, CMT can only be provided when the infants are clinically stable. CMT with parental integration is feasible when parents are available and receptive to participate. This paper presents a detailed protocol on how to use CMT to empower preterm infants and their families.

A microanalysis of video material (122 videos) collected for a qualitative, grounded-theory-based, multiperspective study of CMT23,50, identified three central interaction categories: 1) responsiveness of the therapist and parents, 2) resulting in communicative musicality with the infant, and 3) infants&#39; and parents&#39; empowerment as a consequence of categories 1 and 2 (Figure 1). The study results suggest that the therapists&#39; prevailing attitude of responsiveness via musical attunement and entrainment may facilitate shared communicative musicality (e.g., interactional synchrony, moment of meeting, interplay). By experiencing this relatedness in music, parents and infants may be supported to relax and to engage in mutual relationship. However, preterm infants still act and re-act with most subtle facial expressions and movements23.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/60412/60412fig1.jpg" /> 
Figure 1: Logic diagram of categories inherent in the CMT process. This figure has been modified from Haslbeck23. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
In this context, responsiveness means the therapist`s ability to observe, interpret, and respond reasonably with musical capacity57. The video microanalysis revealed that when the infant is aroused, the therapist sings as simple and repetitive as possible to calm down the infant. The therapist softly hums only two long holding notes centering around the tonic of the scale to provide a musical holding, stability, and safety (Figure 2, blue circle voice line, 0:21-0:55). The therapist continually entrains the singing to the breathing rhythms of the infant (Figure 2-4: infant`s breathing and therapist`s voice line continuously rhythmically entrained).
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/60412/60412fig2.jpg" /> 
Figure 2: Transcription of responsiveness and therapist-infant synchronization. Detailed transcription of music therapy session with Melissa by using conservative music notation with Finale 2011 notation software50 including three layers on the same timescale: 1) environment, 2) infant behavior (four layers: a) behavioral state b) gestures c) mimicry d) breathing pattern, if visible) and 3) therapist`s voice. This figure has been modified from Haslbeck50. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Further responsiveness involves attuning to the environmental sounds such as the monitor beeping. The therapist sings in the key of the monitor alarms (Figure 3, blue arrows, 1:00-1:07) to integrate sudden stressful digital sounds in the music and thereby to mitigate disturbing noises. Consequently, &#34;Melissa&#34; remains calm (Figure 3, blue rectangles, 1:04-1:10) after the sudden alarm during music therapy (Figure 3, red star, 1:04) in contrast to beeping noise evoked stressed reactions without music therapy50. The therapist continuously tailors the singing to the facial expressions and gestures of the infant (Figure 3, orange arrows, 0:58, 1:09). For instance, when Melissa smiles and rises her fingers the therapist rises the melody, tempo and dynamics synchronously (Figure 4, blue circle: compare voice line with breathing, mimic mouth and gesture line, 1:30-1:45).
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/60412/60412fig3.jpg" /> 
Figure 3: Transcription of responsiveness, entrainment, therapist-infant synchronization, and integrating of monitor alarm. Detailed transcription of music therapy session with Melissa as described in Figure legend 2. This figure has been modified from Haslbeck50. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/60412/60412fig4.jpg" /> 
Figure 4: Transcription of communicative musicality and therapist-infant synchronization. Detailed transcription of music therapy session with Melissa as described in Figure legend 2. This figure has been modified from Haslbeck50. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Communicative musicality acts like the intuitive affect attunement of a healthy caregiver-infant relationship. This sharing of emotional experiences is like a dance, like a musical performance52,58,59,60. Through shared rhythms, tempi, and affects, communicative musicality may support the infants&#39; coregulation and stabilization and may transform the arrhythmic intensive care environment into a relational environment required for healthy socio-emotional development and growth59. The video microanalysis50 implies that CMT may enhance relaxation, participation, self-regulation, and engagement in premature infants through experienced communicative musicality. Communicative musicality can evolve through interactional synchronization of affects. In Figure 2, at first, Melissa synchronizes her stressed movements with the tension in the music. She splays her fingers synchronously with the higher more suspenseful note or in the tense pause (Figure 2, red arrows, 0:24-0:37). After synchronizing with the tension in the music, she may then be able to synchronize with the relaxation of the music. When the first musical phrase ends, she relaxes her body and moves her arms and fingers smoothly down (Figure 2, orange lines, 0:38-0:44). Throughout the session, Melissa remains in this relaxed behavioral state and engages with increasing smooth facial reactions and finger movements (Figure 3, orange arrows, 0:58 -1:09). When the melody rests with the ritardando (rit.), she sighs deeply (Figure 4, blue circle, orange arrow, 2:03) interpreted as a sign of relaxation. When the melody, dynamics, and intensity ascend, she raises her finger and smiles (Figure 4, blue circle, orange arrows, 2:03-2:05) interpreted as engagement in communicative musicality.
By relaxing and engaging the parents in meaningful, sensitive interactions with the infant, the parents may experience self-confidence, self-efficacy, and autonomy. They may thereby be empowered in their role as primary caregivers and participants. In this context, empowerment means to facilitate self-regulation in the infant and to uncover intuitive parental capacities for parental responsiveness that are often overshadowed by anxiety and stress23,47. Parents reported in the qualitative interviews of the study that they could relax and relate more intense to their infant through music therapy: &#34;I notice when I can relax that I am much more connected, much more intense, much more closely connected with my daughter because of the music, because of the singing.&#34;23
The video microanalysis revealed that mothers who were stressed and distanced connected with their infants through meaningful vocal interaction. Figure 5 &#38; Figure 6 show the microanalysis of shared mother-infant rhythms of a previously stressed and detached mother. The mother entrains her singing to the sucking rhythms of her daughter. She sings with &#34;motherese&#34; (infant-directed, with a loving tone and free voice, responsive with facial expression and gestures) rocking the infant in the rhythm of the song. &#34;Emila&#34; begins with her sucking pattern precisely at the beginning of the musical phrase of her mother (Figure 5 &#38; Figure 6, orange arrows) except in bar 9 (Figure 5, red circle, 0:26). The mother immediately recognizes, interprets correctly, reacts appropriately and promptly with sensitivity as referred to as appropriate bonding behavior23. She reduces and ceases her singing to hold and readjust (Figure 5 &#38; Figure 6, blue circle, 0:26-0:28). After this moment of readjustment, she begins the musical phrase again in synchrony with the sucking pattern of Emila (Figure 6, blue circle, 0:28 following). Mother and daughter meet once more within communicative musicality in shared pulse and quality. They connect in a mutual gaze at the end of the musical phrase, and the mother smiles (Figure 5, 0:28 following). Mother and daughter meet in a &#34;neonatal moment of meeting&#34; described as tender moments after birth to generate the attachment bond and the mother&#39;s self-confidence in her role as primary caregiver23. Immediately after this singing episode, the mother expressed her love and empowerment by picturing herself as a lion mother. She phrases her self-confidence and autonomy by the sentences&#39; causal dependence (underlined): &#34;If I would not have so much love, right? Then my daughter would have no chance to survive. I am like a lion.&#34;23
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/60412/60412fig5.jpg" /> 
Figure 5: Mother-infant synchronization. Detailed transcription of mother`s singing for her daughter Emila by using conservative music notation with Finale 2011 notation software50 including three layers on the same timescale: 1) Emila`s nutritive sucking pattern, 2) mother`s behavior and 3) mother`s singing. This figure has been modified from Haslbeck23. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/60412/60412fig6.jpg" /> 
Figure 6: Mother-infant synchronization and moment of meeting. Detailed transcription of mother`s singing for her daughter Emila as described in Figure legend 5. This figure has been modified from Haslbeck23. <a href="https://www.jove.com/files/ftp_upload/60412/60412fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
First results of a mixed-method pilot trial underline these results. The study revealed that parental depressive symptoms decreased and physical closeness increased across hospitalization time in the CMT group compared to the control group27. The parents reported that CMT evoked feelings of relaxation and joy and empowerment to interact more profoundly with their infant27.

Watch this Scientific Journal Video about Clinical Practice Protocol of Creative Music Therapy for Preterm Infants and Their Parents in the Neonatal Intensive Care Unit at JoVE.com

Clinical Practice Protocol of Creative Music Therapy for Preterm Infants and Their Parents in the Neonatal Intensive Care Unit

Creative music therapy for preterm infants and their parents has emerged as a promising family-integrated early intervention. We present a detailed protocol on how to use vocal interaction, humming, or singing to empower preterm infants and their families.

Creative music therapy for preterm infants and their parents (CMT) has emerged as a promising family-integrated early intervention involving communicative ...

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25.9K Views.  University of Zurich. Creative music therapy for preterm infants and their parents has emerged as a promising family-integrated early intervention. We present a detailed protocol on how to use vocal interaction, humming, or singing to empower preterm infants and their families.

Video: Clinical Practice Protocol of Creative Music Therapy for Preterm Infants and Their Parents in the Neonatal Intensive Care Unit

A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world&#8217;s 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials. Variations of the model have been applied in the study of adjunctive neuroprotective methods and piglet studies of xenon and melatonin have led to clinical phase I and II trials1,2. The piglet HIE model is further used for neonatal resuscitation- and hemodynamic studies as well as in investigations of cerebral hypoxia on a cellular level. However, it is a technically challenging model and variations in the protocol may result in either too mild or too severe brain injury. In this article, we demonstrate the technical procedures necessary for establishing a stable piglet model of neonatal HIE. First, the newborn piglet (&#60; 24 hr old, median weight 1500 g) is anesthetized, intubated, and monitored in a setup comparable to that found in a neonatal intensive care unit. Global hypoxia-ischemia is induced by lowering the inspiratory oxygen fraction to achieve global hypoxia, ischemia through hypotension and a flat trace amplitude integrated EEG (aEEG) indicative of cerebral hypoxia. Survival is promoted by adjusting oxygenation according to the aEEG response and blood pressure. Brain injury is quantified by histopathology and magnetic resonance imaging after 72 hr.

Hypoxic-ischemic encephalopathy following perinatal asphyxia can be studied using animal models. We demonstrate the procedures necessary for establishing a piglet model of neonatal hypoxic-ischemic encephalopathy.

Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the ...

Observational Study Protocol for Repeated Clinical Examination and Critical Care Ultrasonography Within the Simple Intensive Care Studies

Longitudinal evaluations of critically ill patients by combinations of clinical examination, biochemical analysis and critical care ultrasonography (CCUS) may detect adverse events of interventions such as fluid overload at an early stage. The Simple Intensive Care Studies (SICS) is a research line that focuses on the prognostic and diagnostic value of combinations of clinical variables.
The SICS-I specifically focused on the use of clinical variables obtained within 24 h of acute admission for prediction of cardiac output (CO) and mortality. Its sequel, SICS-II, focuses on repeated evaluations during ICU admission. The first clinical examination by trained researchers is performed within 3 h after admission consisting of physical examination and educated guessing. The second clinical examination is performed within 24 h after admission and includes physical examination and educated guessing, biochemical analysis and CCUS assessments of heart, lungs, inferior vena cava (IVC) and kidney. This evaluation is repeated at days 3 and 5 after admission. CCUS images are validated by an independent expert, and all data is registered in an online secured database. Follow-up at 90 days includes registration of complications and survival status according to patient&#39;s medical charts and the municipal person registry. The primary focus of SICS-II is the association between venous congestion and organ dysfunction.
The purpose of publishing this protocol is to provide details on the structure and methods of this on-going prospective observational cohort study allowing answering multiple research questions. The design of the data collection of combined clinical examination and CCUS assessments in critically ill patients are explicated. The SICS-II is open for other centers to participate and is open for other research questions that can be answered with our data.

Structured protocols are necessary to provide answers on research questions in critically ill patients. The Simple Intensive Care Studies (SICS) provides an infrastructure for repeated measurements in critically ill patients including clinical examination, biochemical analysis and ultrasonography. SICS projects have specific focus but the structure is flexible to other investigations.

Longitudinal evaluations of critically ill patients by combinations of clinical examination, biochemical analysis and critical care ultrasonography (CCUS) ...

Protocol and Guidelines for Point-of-Care Lung Ultrasound in Diagnosing Neonatal Pulmonary Diseases Based on International Expert Consensus

Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound has received increasing attention from neonatal physicians. Nevertheless, clear reference standards and guideline limits are needed for accurate application of this diagnostic modality. This document aims to summarize expert opinions and to provide precise guidance to help facilitate the use of the lung ultrasound in the diagnosis of neonatal lung diseases.

Lung ultrasound is a noninvasive and valuable tool for bedside evaluation of neonatal lung diseases. However, a relative lack of reference standards, protocols and guidelines may limit its application. Here, we aim to develop a standardized neonatal lung ultrasound diagnostic protocol to be used in clinical decision-making.

Ultrasound is a safe bedside imaging tool that obviates the use of ionizing radiation diagnostic procedures. Due to its convenience, the lung ultrasound ...

A Protocol to Set Up Needle-Free Connector with Positive Displacement on Central Venous Catheter in Intensive Care Unit

Needle-free connectors were initially designed and promoted to avoid blood exposure for healthcare workers. Some recent data suggest that the latest generation of connectors (with positive displacement) may be of interest for reducing central venous line infections. We have been using needle-free connectors for several years in our intensive care unit and here we present a protocol for installing these connectors on central venous catheters. After insertion of the catheter and control of the permeability of the lines, the connectors must be purged with 0.9% NaCl before being connected. The connectors replace all disposable caps used on infusion stopcocks and manifolds. All the connectors are changed every 7 days as recommended by the manufacturer (except when there is macroscopic contamination, which requires an immediate change of the connector). Before each injection, the connector must be disinfected for at least 3 seconds with 70% isopropyl alcohol. The connectors must not be disconnected (unless changed), as the injection is done through the device. Setting up the connectors slightly increases the total time required to place the catheter and there is no formal evidence that these connectors reduce the incidence of infectious or thrombotic complications. However, these devices simplify the management of central venous lines and prevent the catheter circuit from &#34;opening&#34; once it has been sterilely installed.

We present a protocol to show the installation of a needle-free connector with positive displacement on a central venous catheter.

Needle-free connectors were initially designed and promoted to avoid blood exposure for healthcare workers. Some recent data suggest that the latest ...

A Pre-clinical Rat Model for the Study of Ischemia-reperfusion Injury in Reconstructive Microsurgery

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many areas of biomedical research due to its cost-effectiveness and its translation to humans. This protocol describes a method to create a preclinical free skin flap model in rats with ischemia-reperfusion injury. The described 3 cm x 6 cm rat free skin flap model is easily obtained after the placement of several vascular ligatures and the section of the vascular pedicle. Then, 8 h after the ischemic insult and completion of the microsurgical anastomosis, the free skin flap develops the tissue damage. These ischemia-reperfusion injury-related damages can be studied in this model, making it a suitable model for evaluating therapeutic agents to address this pathophysiological process. Furthermore, two main monitoring techniques are described in the protocol for the assessment of this animal model: transit-time ultrasound technology and laser speckle contrast analysis.

Here, we describe a pre-clinical animal model for studying the pathophysiology of ischemia-reperfusion injury in reconstructive microsurgery. This free skin flap model based on the superficial caudal epigastric vessels in the rat may also allow for the evaluation of different therapies and compounds to counteract ischemia-reperfusion injury-related damage.

Ischemia-reperfusion injury is the main cause of flap failure in reconstructive microsurgery. The rat is the preferred preclinical animal model in many ...

International Expert Consensus and Recommendations for Neonatal Pneumothorax Ultrasound Diagnosis and Ultrasound-guided Thoracentesis Procedure

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic compromise, a life-threatening disorder. Traditionally, neonatal pneumothorax diagnosis has been based on clinical images, auscultation, transillumination, and chest X-ray findings. This approach may potentially lead to a delay in both diagnosis and treatment. The use of lung US in diagnosis of PTX together with US-guided thoracentesis results in earlier and more precise management. The recommendations presented in this publication are aimed at improving the application of lung US in guiding neonatal PTX diagnosis and management.

Pneumothorax is a common emergency and critical disease in newborn infants that needs rapid, clear diagnosis and timely treatment. Diagnosis and treatment based on chest X-rays are associated with delayed management and radiation damage. Lung ultrasound (US) provides useful guidance for rapid, accurate diagnosis and the precise thoracentesis of pneumothorax.

Pneumothorax (PTX) represents accumulation of the air in the pleural space. A large or tension pneumothorax can collapse the lung and cause hemodynamic ...

How to Administer Near-Infrared Spectroscopy in Critically ill Neonates, Infants, and Children

Near infrared spectroscopy (NIRS) calculates regional tissue oxygenation (rSO2) using the different absorption spectra of oxygenated and deoxygenated hemoglobin molecules. A probe placed on the skin emits light that is absorbed, scattered, and reflected by the underlying tissue. Detectors in the probe sense the amount of reflected light: this reflects the organ-specific ratio of oxygen supply and consumption - independent of pulsatile flow. Modern devices enable the simultaneous monitoring at different body sites. A rise or dip in the rSO2 curve visualizes changes in oxygen supply or demand before vital signs indicate them. The evolution of rSO2 values in relation to the starting point is more important for interpretation than are absolute values.
A routine clinical application of NIRS is the surveillance of somatic and cerebral oxygenation during and after cardiac surgery. It is also administered in preterm infants at risk for necrotizing enterocolitis, newborns with hypoxic ischemic encephalopathy and a potential risk of impaired tissue oxygenation. In the future, NIRS could be increasingly used in multimodal neuromonitoring, or applied to monitor patients with other conditions (e.g., after resuscitation or traumatic brain injury).

This protocol is designed to assist clinicians to measure regional tissue oxygenation at different body sites in infants and children. It can be used in situations where tissue oxygenation is potentially compromised, particularly during cardiopulmonary bypass, when using non-pulsatile cardiac-assist devices, and in critically ill neonates, infants and children.

Near infrared spectroscopy (NIRS) calculates regional tissue oxygenation (rSO2) using the different absorption spectra of oxygenated and deoxygenated ...

Halogenated Agent Delivery in Porcine Model of Acute Respiratory Distress Syndrome via an Intensive Care Unit Type Device

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent need to find effective therapies. Preclinical studies have shown that inhaled halogenated agents may have beneficial effects in animal models of ARDS. The development of new devices to administer halogenated agents using modern intensive care unit (ICU) ventilators has significantly simplified the dispensing of halogenated agents to ICU patients. Because previous experimental and clinical research suggested potential benefits of halogenated volatiles, such as sevoflurane or isoflurane, for lung alveolar epithelial injury and inflammation, two pathophysiologic landmarks of diffuse alveolar damage during ARDS, we designed an animal model to understand the mechanisms of the effects of halogenated agents on lung injury and repair. After general anesthesia, tracheal intubation, and the initiation of mechanical ventilation, ARDS was induced in piglets via the intratracheal instillation of hydrochloric acid. Then, the piglets were sedated with inhaled sevoflurane or isoflurane using an ICU-type device, and the animals were ventilated with lung-protective mechanical ventilation during a 4 h period. During the study period, blood and alveolar samples were collected to evaluate arterial oxygenation, the permeability of the alveolar-capillary membrane, alveolar fluid clearance, and lung inflammation. Mechanical ventilation parameters were also collected throughout the experiment. Although this model induced a marked decrease in arterial oxygenation with altered alveolar-capillary permeability, it is reproducible and is characterized by a rapid onset, good stability over time, and no fatal complications.
We have developed a piglet model of acid aspiration that reproduces most of the physiological, biological, and pathological features of clinical ARDS, and it will be helpful to further our understanding of the potential lung-protective effects of halogenated agents delivered through devices used for inhaled ICU sedation.

We describe a model of hydrochloric acid-induced acute respiratory distress syndrome (ARDS) in piglets receiving sedation with halogenated agents, isoflurane and sevoflurane, through a device used for inhaled intensive care sedation. This model can be used to investigate the biological mechanisms of halogenated agents on lung injury and repair.

Acute respiratory distress syndrome (ARDS) is a common cause of hypoxemic respiratory failure and death in critically ill patients, and there is an urgent ...

A Reproducible Intensive Care Unit-Oriented Endotoxin Model in Rats

Sepsis and septic shock remain the leading cause of death in intensive care units. Despite significant improvements in sepsis management, mortality still ranges between 20 and 30%. Novel treatment approaches in order to reduce sepsis-related multiorgan failure and death are urgently needed. Robust animal models allow for one or multiple treatment approaches as well as for testing their effect on physiological and molecular parameters. In this article, a simple animal model is presented.
First, general anesthesia is induced in animals either with the use of volatile or by intraperitoneal anesthesia. After placement of an intravenous catheter (tail vein), tracheostomy, and insertion of an intraarterial catheter (tail artery), mechanical ventilation is started. Baseline values of mean arterial blood pressure, arterial blood oxygen saturation, and heart rate are recorded.
The injection of lipopolysaccharides (1 milligram/kilogram body weight) dissolved in phosphate-buffered saline induces a strong and reproducible inflammatory response via the toll-like receptor 4. Fluid corrections as well as the application of norepinephrine are performed based on well-established protocols.
The animal model presented in this article is easy to learn and strongly oriented towards clinical sepsis treatment in an intensive care unit with sedation, mechanical ventilation, continuous blood pressure monitoring, and repetitive blood sampling. Also, the model is reliable, allowing for reproducible data with a limited number of animals in accordance with the 3R (reduce, replace, refine) principles of animal research. While animal experiments in sepsis research cannot easily replaced, repetitive measurements allow for a reduction of animals and keeping septic animals anesthetized diminishes suffering.

Here, we present a reproducible intensive care unit-oriented endotoxin model in rats.

Sepsis and septic shock remain the leading cause of death in intensive care units. Despite significant improvements in sepsis management, mortality still ...

Hemodynamic Precision in the Neonatal Intensive Care Unit using Targeted Neonatal Echocardiography

Targeted neonatal echocardiography (TnECHO) refers to the use of comprehensive echocardiographic evaluation and physiologic data to obtain accurate, reliable, and real-time information on developmental hemodynamics in sick newborns. The comprehensive assessment is based on a multiparametric approach that overcomes the reliability issues of individual measurements, allows for earlier recognition of cardiovascular compromise and promotes enhanced diagnostic precision and timely management. TnECHO-driven research has led to an enhanced understanding of the mechanisms of illness and the development of predictive models to identify at-risk populations. This information may then be used to formulate a diagnostic impression and provide individualized guidance for the selection of cardiovascular therapies. TnECHO is based on the expert consultative model in which a neonatologist, with advanced training in neonatal hemodynamics, performs comprehensive and standardized TnECHO assessments. The distinction from point of care ultrasonography (POCUS), which provides limited and brief one-time assessments, is important. Neonatal hemodynamics training is a 1-year structured program designed to optimize image acquisition, measurement analysis, and hemodynamic knowledge (physiology, pharmacotherapy) to support cardiovascular decision-making. Neonatologists with hemodynamic expertise are trained to recognize deviations from normal anatomy and appropriately refer cases of possible structural abnormalities. We provide an outline of neonatal hemodynamics training, the standardized TnECHO imaging protocol, and an example of representative echo findings in a hemodynamically significant patent ductus arteriosus.

Presented here is a protocol to perform comprehensive neonatal echocardiography by trained neonatologists in the neonatal intensive care unit. The trained individuals provide longitudinal assessments of heart function, systemic and pulmonary hemodynamics in a consultative role. The manuscript also describes the requirements to become a fully trained neonatal hemodynamics specialist.

Targeted neonatal echocardiography (TnECHO) refers to the use of comprehensive echocardiographic evaluation and physiologic data to obtain accurate, ...