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

• ClinicalTrials.gov Identifier: NCT03232931
• Recruitment Status: Active, not recruiting
• First Posted: July 28, 2017
• Results First Posted: March 19, 2024
• Last Update Posted: March 19, 2024
• Sponsor: Emory University
• Collaborators: National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Nationwide Children's Hospital
• Information provided by (Responsible Party): Nathalie Maitre, Emory University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Preterm Infant
• Interventions: Behavioral: Therapist skin-to-skin Care; Device: Contingent parent's voice exposure; Behavioral: Parental skin-to-skin care; Device: Recorded parent's voice
• Enrollment: 248

Participant Flow

Recruitment Details	Participants were recruited from Nationwide Children's Hospital in Columbus, Ohio, and Grady Memorial Hospital and Emory University Hospital Midtown in Atlanta, Georgia, USA. Participant enrollment began October 29, 2018 and data collection for the assessments occurring at up to 42 weeks gestational age was completed by February 20, 2023.
Pre-assignment Details

Arm/Group Title	Multisensory Intervention	Standard of Care
Arm/Group Description	Preterm infants in the neonatal intensive care unit (NICU) 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.	Preterm infants in the NICU 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.
Period Title: Overall Study
Started	126	122
Completed [1]	112	116
Not Completed	14	6
Reason Not Completed
Physician Decision	1	1
Withdrawal by Subject	6	0
Discharged before completing study activities per protocol	4	2
Parent did not record voice	1	2
Research and staffing limitations during the Coronavirus Disease 2019 (COVID-19) pandemic	2	1
[1] Completed the NICU portion of the study lasting up to 42 weeks gestational age.

Baseline Characteristics

Arm/Group Title		Multisensory Intervention	Standard of Care	Total
Arm/Group Description		Preterm infants in the NICU 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.	Preterm infants in the NICU 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.	Total of all reporting groups
Overall Number of Baseline Participants		112	116	228
Baseline Analysis Population Description		The Baseline Analysis includes participants who completed the trial up to 42 weeks gestational age.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Weeks postmenstrual age (PMA)
	Number Analyzed	112 participants	116 participants	228 participants
		34.22 (1.22)	34.14 (1.18)	34.18 (1.15)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants	116 participants	228 participants
	Female	56 50.0%	61 52.6%	117 51.3%
	Male	56 50.0%	55 47.4%	111 48.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants	116 participants	228 participants
	Hispanic or Latino	3 2.7%	3 2.6%	6 2.6%
	Not Hispanic or Latino	109 97.3%	113 97.4%	222 97.4%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	112 participants	116 participants	228 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	3 2.7%	3 2.6%	6 2.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	50 44.6%	56 48.3%	106 46.5%
	White	50 44.6%	55 47.4%	105 46.1%
	More than one race	9 8.0%	1 0.9%	10 4.4%
	Unknown or Not Reported	0 0.0%	1 0.9%	1 0.4%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	112 participants	116 participants	228 participants
		112 100.0%	116 100.0%	228 100.0%
Gestational age at birth; Mean (Standard Deviation); Unit of measure: Weeks postmenstrual age (PMA)
	Number Analyzed	112 participants	116 participants	228 participants
		28.84 (2.79)	28.81 (2.91)	28.82 (2.85)

Outcome Measures

1. Primary Outcome

Title	Index of Multisensory Processing (IMP)
Description	Cortical processing is measured as the percentage of time spent in Event Related Potential (ERP) response patterns that have been previously characterized as typical in healthy infants born at full term. ERP is assessed through high-density functional electroencephalogram (EEG) in the NICU. The Index of Multisensory Processing (IMP) is calculated as the percentage of time that the topographical pattern of the participant's ERP to multisensory stimuli is most like template map of a full term infant. The IMP is expressed as a percentage from 100% (samples show nearly-typical activation all of the time) to 0% (samples show nearly-typical activation none of the time).
Time Frame	At enrollment up to 36 weeks gestation (prior to intervention), and at intervention completion up to 42 weeks gestation

Outcome Measure Data

Analysis Population Description

This analysis includes participants who completed the study and had analyzable event related potential (ERP) data for both study time points. ERP data were not collected for 9 participants in the Multisensory Intervention group and 10 participants in the Standard of Care group. ERP data were collected were not analyzable for 5 participants in the Multisensory Intervention group.

Arm/Group Title	Multisensory Intervention	Standard of Care
Arm/Group Description:	Preterm infants in the NICU 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.	Preterm infants in the NICU 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.
Overall Number of Participants Analyzed	98	105
Mean (Standard Deviation); Unit of Measure: percentage of time
Prior to the intervention	31.4 (47)	49.0 (48)
After the intervention	35.6 (47)	18.8 (37)

2. Secondary Outcome

Title	Infant/Toddler Sensory Profile (ITSP) Score
Description	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)
Time Frame	at 12 months corrected age

Outcome Measure Data Not Reported

3. Secondary Outcome

Title	Change in Bayley Scales of Infant and Toddler Development - 3rd Edition (Bayley III) Score
Description	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.
Time Frame	12 and 24 months corrected age

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Change in Preschool Language Scales - 5th Edition (PLS-5) Score
Description	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.
Time Frame	2 Years (22-26 months corrected age)

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Information on adverse events was collected beginning at the baseline assessment and is continuing through the final assessment at Year 2 (22-26 months corrected age).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Multisensory Intervention	Standard of Care
Arm/Group Description	Preterm infants in the NICU 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.	Preterm infants in the NICU 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.
All-Cause Mortality
	Multisensory Intervention	Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/126 (0.00%)	1/122 (0.82%)
Serious Adverse Events
	Multisensory Intervention	Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/126 (0.00%)	1/122 (0.82%)
Respiratory, thoracic and mediastinal disorders
Hospital admission due to respiratory distress * [1]	0/126 (0.00%)	1/122 (0.82%)
* Indicates events were collected by non-systematic assessment; [1] Hospitalization occurred after NICU discharge and before the 9-12 month follow-up.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Multisensory Intervention	Standard of Care
	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/126 (4.76%)	1/122 (0.82%)
Cardiac disorders
Multiple mild bradycardia/desaturation events during a session, while in NICU * [1]	2/126 (1.59%)	0/122 (0.00%)
Infections and infestations
Emergency department visit for respiratory distress due to respiratory syncytial virus (RSV) * [2]	1/126 (0.79%)	0/122 (0.00%)
Respiratory, thoracic and mediastinal disorders
Major event needing vigorous stimulation and free flow oxygen (blow by) to resolve, while in NICU * [3]	1/126 (0.79%)	0/122 (0.00%)
Surgical and medical procedures
Participant needed resuscitation measures while in NICU * [3]	2/126 (1.59%)	1/122 (0.82%)
* Indicates events were collected by non-systematic assessment; [1] Possibly related to the study intervention; [2] After NICU discharge, before 9-12 month follow-up; not study related; [3] Not study related

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Nathalie Maitre
• Organization: Emory University
• Phone: 404-712-8920
• EMail: nathalie.linda.maitre@emory.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Richard C, Jeanvoine A, Stark AR, Hague K, Kjeldsen C, Maitre NL. Randomized Trial to Increase Speech Sound Differentiation in Infants Born Preterm. J Pediatr. 2022 Feb;241:103-108.e3. doi: 10.1016/j.jpeds.2021.10.035. Epub 2021 Oct 25.

Neel ML, Yoder P, Matusz PJ, Murray MM, Miller A, Burkhardt S, Emery L, Hague K, Pennington C, Purnell J, Lightfoot M, Maitre NL. Randomized controlled trial protocol to improve multisensory neural processing, language and motor outcomes in preterm infants. BMC Pediatr. 2019 Mar 19;19(1):81. doi: 10.1186/s12887-019-1455-1.

• Responsible Party: Nathalie Maitre, Emory University
• ClinicalTrials.gov Identifier: NCT03232931
• Other Study ID Numbers: STUDY00003034; R01HD093706 ( U.S. NIH Grant/Contract ); IRB17-00025/IRB18-00579 ( Other Identifier: Nationwide Children's Hospital )
• First Submitted: February 3, 2017
• First Posted: July 28, 2017
• Results First Submitted: February 19, 2024
• Results First Posted: March 19, 2024
• Last Update Posted: March 19, 2024