Trial to Improve Multisensory Neural Processing, Language & Motor Outcomes in Preterm Infants

Study Overview
=================
Brief Summary
-----------------
Every year, almost all of ½ million infants born prematurely in the US and 15 million worldwide suffer from abnormal brain maturation resulting from interactions between immaturity and atypical sensory experiences after birth. The current proposal uses rigorous scientific methods to measure the effects and determine the mechanisms of action of a parent-supported multisensory neurorehabilitative intervention for preterm infants, adaptable to a wide variety of neonatal environments, even when parents cannot be at their child's bedside. The intervention aims to improve brain multisensory processing, reactions to sensory stimulation in the home and long term language and motor development.

Detailed Description
-----------------
The proposed is a randomized controlled trial design with intent-to-treat analysis in hospitalized preterm infants between 32 and 36 weeks post-menstrual age. Both the control and intervention groups will receive routine neonatal intensive care unit care (i.e., skin-to-skin care by parent when available and daily sessions of exposure to recorded parent's voice). In addition to routine care, the parent-supported multisensory intervention consists of sessions of standardized, therapist-administered, auditory-tactile stimulation that combines contingent recorded mother's voice delivered using a pacifier-activated system, during holding with supportive tactile containment against the therapist's chest, covered by cloth imprinted with mother's scent. Possible covariates, multi- and uni-sensory processing, will be measured at entry into the study and immediately after the treatment phase. Event-related potential (ERP) testing will be performed prior to the prior to intervention and after intervention is complete, which occurs at 36 weeks postmenstrual age (PMA) on average. ERP testing will take approximately 30 to 40 minutes. All infants will be seen at the neonatal intensive care unit (NICU) Follow-Up Program clinics at 9-12 months PMA (Year 1) and 22-24 months PMA (Year 2), where neurodevelopmental outcomes will be assessed using standardized methods. Parents will also have the opportunity to consent separately to a secondary part to the study in which their infant would participate in one additional ERP testing session in the NICU between 34-36 weeks PMA and one additional visit to the clinical laboratory for ERP testing between 3-4 months PMA. This optional, secondary part of the study is observational only and does not influence randomization for the main trial. For the secondary part of the study, the population will be 40 of the 230 participants. All parents who are approached for the study prospectively and are randomized to control group will be asked if they would like to participate in the secondary part. Enrollment for this secondary part of the study will stop when 40 participants are reached.

Official Title
-----------------
Randomized Controlled Trial to Improve Multisensory Neural Processing, Language & Motor Outcomes in Preterm Infants

Conditions
-----------------
Preterm Infant

Intervention / Treatment
-----------------
* Behavioral: Therapist skin-to-skin Care
* Device: Contingent parent's voice exposure
* Behavioral: Parental skin-to-skin care
* Device: Recorded parent's voice


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Hospitalization at a study location Postmenstrual age of 32 weeks 0 days gestation to 36 weeks 0 days gestation Exclusion Criteria: Ventilation using an endotracheal tube Major congenital malformations Family history of genetic hearing loss Use of sedatives or seizure medications Secondary Study Inclusion Criteria: Enrolled in the control group of the main study

Ages Eligible for Study
-----------------
Minimum Age: 32 Weeks
Maximum Age: 36 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized controlled trial design with intent-to-treat analysis in hospitalized preterm infants between 32 and 36 weeks post-menstrual age. Both the control and intervention groups will receive routine neonatal intensive care protocols (including skin-to-skin care by parent when available and daily sessions of exposure to recorded parent's voice). In addition to routine care, the parent-supported multisensory intervention consists of 10 sessions of standardized, therapist-administered, auditory-tactile stimulation that combines contingent recorded mother's voice delivered using a pacifier-activated system, during holding with supportive tactile containment against the therapist's chest, covered by cloth imprinted with mother's scent. Possible covariates, multi- and uni- sensory processing, will be measured at entry into the study and immediately after the treatment phase. Sensory reactivity will be measured at 1 year and language and motor outcomes will be assessed at 2 years.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multisensory Intervention<br>Preterm infants in the NICU who are randomized to receive a multisensory intervention, in addition to the standard of care. The multisensory intervention uses recordings of the parents' voices and nurturing touch administered in the NICU during 12 to 23 sessions of standardized, therapist-administered, auditory-tactile stimulation, dispersed over a 2 to 3 week period. The intervention includes 2 components: (1) holding and light pressure containment of the infant against the hospital-gown covered chest of the therapist for tactile and non-specific auditory stimulation simultaneous with (2) playing of mother's voice contingent on infant pacifier sucking. Additionally, a gauze square scented with parent's skin will be used to provide olfactory stimulation. | Behavioral: Therapist skin-to-skin Care<br>* Skin-to-skin (STS) holding is part of the multisensory intervention where the therapist will wear a clean 100% cotton T-shirt with a clean hospital gown on top of the shirt and wrap the kangaroo positioner securely over the gown. A gauze square scented with parent's skin will be used to provide olfactory stimulation. Therapist STS sessions occur with simultaneous playing of mother's voice contingent on infant pacifier sucking.<br>Device: Contingent parent's voice exposure<br>* The Pacifier Activated Lullaby® (PAL®) device, is a digital music delivery system that integrates a sensor, a pacifier routinely used in the NICU, and a receiver. It delivers a predetermined 10 seconds of recorded parent's voice singing lullabies upon detection of a suck that meets a preset pressure threshold. The original systems were modified for research use by decreasing the lower limit of activation thresholds for delivering the recording. Minimal effort is required to trigger the device. However, the settings ensure that regular attempts are needed to continue to receive continual presentation of the recording of mother's voice by requiring another suck after 10 seconds. The auditory stimulation with PAL will be provided when the infants are still awake (i.e., at the beginning of the session).<br>* Other names: Pacifier Activated Lullaby® (PAL®);Behavioral: Parental skin-to-skin care<br>* The standard of care includes parental skin-to-skin care and exposure to parent's voice. During parental skin-to-skin care, infants are placed in a prone position with head positioned over the sternum, allowing transmission of breath and heart sounds to the developing ear. Deeper pressure is applied to offer support and feedback to the child's bottom. Session length is set to a minimum of 45 minutes per unit protocols.<br>Device: Recorded parent's voice<br>* Per standard of care, preterm infants in the NICU currently receive noncontingent recorded parents' voice during two 20 minute sessions per day. Recordings are standardized and are played through a sterilizable device (DINO-egg).<br>* Other names: DINO-egg;|
| Other: Standard of Care<br>Preterm infants in the NICU who are randomized to receive the standard of care. The standard care for preterm infants in the NICU currently follows medical protocols of skin-to-skin holding and exposure to recordings of parent's voice. | Behavioral: Parental skin-to-skin care<br>* The standard of care includes parental skin-to-skin care and exposure to parent's voice. During parental skin-to-skin care, infants are placed in a prone position with head positioned over the sternum, allowing transmission of breath and heart sounds to the developing ear. Deeper pressure is applied to offer support and feedback to the child's bottom. Session length is set to a minimum of 45 minutes per unit protocols.<br>Device: Recorded parent's voice<br>* Per standard of care, preterm infants in the NICU currently receive noncontingent recorded parents' voice during two 20 minute sessions per day. Recordings are standardized and are played through a sterilizable device (DINO-egg).<br>* Other names: DINO-egg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Latency of response to auditory and tactile stimuli on EEG/ERP | Change from baseline event related potential multisensory response at term-equivalent age (up to 42 weeks gestation) | at enrollment up to 36 weeks gestation and at intervention completion up to 42 weeks gestation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Baby Care Questionnaire (BCQ) Score | The Baby Care Questionnaire (BCQ) is a parent parent-report instrument assessing the degree of parental structure (regularity and routines in infant care) and parental attunement (using infant cues and close contact) for infant care domains of sleeping, feeding, and soothing. The tool is validated for parents expecting a baby through 24 months of age. Parents are asked to indicate their feelings about each statement by circling strongly agree (SA), agree (A), disagree (D), or strongly disagree (SD). Items are scored on a 4-point Likert-type scale where strongly disagree = 1 and strongly agree = 4. Scores are averaged to provide separate scores for structure and attunement. The total scores range from 1 to 4 and higher scores indicate greater endorsement of structure or attunement in parenting. | 4 months, 1 year, 2 years | 
| Hammersmith Neonatal Neurological Examination (HNNE) Score | The HNNE is a neonatal neurological examination consisting of 34 items to assess tone, tone patterns, reflexes, movements, abnormal signs, and behavior. The items are scored 1 - 5 and these raw scores are converted to optimality scores based on a population distribution. Items above the 10th percentile are scored as 1, items between the 5th and 10th percentile are scored as 0.5, and items below the 5th percentile are scored as 0. Total optimality scores range from 0 to 34 with higher scores being more favorable. | prior to discharge (up to 42 weeks gestational age) | 
| Change in Parenting Styles and Dimensions Questionnaire (PSDQ) - Short Version Score | The PSDQ - Short Version is a 32-item parent questionnaire that assesses parenting style based on a series of items scored by parents along a 5-point Likert-type scale, where 1 = never and 5 = always. Three parenting styles are assessed: authoritative (15 items), authoritarian (12 items), or permissive (5 items). The average score for each of the three styles is calculated so that parenting style scores range from 1 to 5 and higher scores indicate more of that parenting style being expressed. | 1 year, 2 years | 
| Infant/Toddler Sensory Profile (ITSP) Score | The Infant/Toddler Sensory Profile (ITSP), for ages 7 to 36 months, is a 48-item questionnaire, completed by caregivers, and is used to measure sensory reactivity and adaptation to the environment. The ITSP assesses five sensory processing sections (Auditory, Visual, Tactile, Vestibular, and Oral Sensory Processing) and a General measure. Responses are given on a 5-point scale where 1 = almost always and 5 = almost never. For children 7 to 36 months there are four quadrant scores and one combined quadrant score available. For children 12 months corrected age, the four quadrant score ranges are as follows: Low Registration: 11-55 (typical performance is 46-54) Sensation Seeking: 14-70 (typical performance is 19-35) Sensory Sensitivity: 11-55 (typical performance is 41-52) Sensation Avoiding: 12-60 (typical performance is 45-56) Low Threshold (combined quadrant score): 23-115 (typical performance is 87-107) | at 12 months corrected age | 
| Change in Bayley Scales of Infant and Toddler Development - 3rd Edition (Bayley III) Score | The Bayley-III is a standardized comprehensive assessment tool for assessing child development in children one month to 42 months old. The highest possible scaled score on each subtest is 19, and the lowest possible score is 1. Scores from 8 to 12 are considered average. Composite scores for motor and language domains are derived from sums of the subtest scaled scores. Composite scores range from 40-160. | 12 and 24 months corrected age | 
| Change in Preschool Language Scales - 5th Edition (PLS-5) Score | The PLS-5 is a language assessment tool administered by a trained professional in which children point or verbally respond to pictures or objects. It assesses both receptive (auditory comprehension) and expressive language skills in young children, and a total language score is also calculated. Total scores for Auditory Comprehension, Expressive Communication, and Total Language are standardized with a mean of 100 and a standard deviation of 15. Scores below 100 indicate below average performance while scores above 100 indicate better than average performance. | 2 Years (22-26 months corrected age) | 
| Child Behavior Checklist (CBCL) | The CBCL is a 113-question standardized checklist used to detect social-emotional and behavioral concerns in young children. The form is filled out by parents and uses a 3-point Likert-type scale where 0 = Not True, 1 = Somewhat or Sometimes True, 2 = Very True or Often True. Total raw scores are converted to t-scores with a mean of 50 and standard deviation of 10. Higher scores indicative of better behavior and fewer problems. | 2 Years (22-26 months corrected age) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
auditory, tactile, mother's voice, multisensory