Trial Outcomes & Findings for Trial to Improve Multisensory Neural Processing, Language & Motor Outcomes in Preterm Infants (NCT NCT03232931)

Last Updated: 2025-05-13

Results Overview

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).

Recruitment status

COMPLETED

Study phase

Target enrollment

248 participants

Primary outcome timeframe

At enrollment up to 36 weeks gestation (prior to intervention), and at intervention completion up to 42 weeks gestation

Results posted on

2025-05-13

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Multisensory Intervention 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.	Standard of Care 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 Study STARTED	126	122
Overall Study COMPLETED	112	116
Overall Study NOT COMPLETED	14	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Multisensory Intervention 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.	Standard of Care 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 Study Physician Decision	1	1
Overall Study Withdrawal by Subject	6	0
Overall Study Discharged before completing study activities per protocol	4	2
Overall Study Parent did not record voice	1	2
Overall Study Research and staffing limitations during the Coronavirus Disease 2019 (COVID-19) pandemic	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Multisensory Intervention n=112 Participants 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.	Standard of Care n=116 Participants 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 n=228 Participants Total of all reporting groups
Age, Continuous	34.22 Weeks postmenstrual age (PMA) STANDARD_DEVIATION 1.22 • n=5 Participants	34.14 Weeks postmenstrual age (PMA) STANDARD_DEVIATION 1.18 • n=7 Participants	34.18 Weeks postmenstrual age (PMA) STANDARD_DEVIATION 1.15 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	61 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	55 Participants n=7 Participants	111 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	109 Participants n=5 Participants	113 Participants n=7 Participants	222 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	50 Participants n=5 Participants	56 Participants n=7 Participants	106 Participants n=5 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants	55 Participants n=7 Participants	105 Participants n=5 Participants
Race (NIH/OMB) More than one race	9 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	112 Participants n=5 Participants	116 Participants n=7 Participants	228 Participants n=5 Participants
Gestational age at birth	28.84 Weeks postmenstrual age (PMA) STANDARD_DEVIATION 2.79 • n=5 Participants	28.81 Weeks postmenstrual age (PMA) STANDARD_DEVIATION 2.91 • n=7 Participants	28.82 Weeks postmenstrual age (PMA) STANDARD_DEVIATION 2.85 • n=5 Participants

PRIMARY outcome

Timeframe: At enrollment up to 36 weeks gestation (prior to intervention), and at intervention completion up to 42 weeks gestation

Population: 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.

Outcome measures

Outcome measures
Measure	Multisensory Intervention n=98 Participants 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.	Standard of Care n=105 Participants 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.
Index of Multisensory Processing (IMP) After the intervention	35.6 percentage of time Standard Deviation 47	18.8 percentage of time Standard Deviation 37
Index of Multisensory Processing (IMP) Prior to the intervention	31.4 percentage of time Standard Deviation 47	49.0 percentage of time Standard Deviation 48

SECONDARY outcome

Timeframe: at 12 months corrected age

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)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 and 24 months corrected age

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 Years (22-26 months corrected age)

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.

Outcome measures

Outcome data not reported

Adverse Events

Multisensory Intervention

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Standard of Care

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Multisensory Intervention n=126 participants at risk 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.	Standard of Care n=122 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Hospital admission due to respiratory distress	0.00% 0/126 • 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).	0.82% 1/122 • 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).

Other adverse events

Other adverse events
Measure	Multisensory Intervention n=126 participants at risk 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.	Standard of Care n=122 participants at risk 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.
Surgical and medical procedures Participant needed resuscitation measures while in NICU	1.6% 2/126 • 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).	0.82% 1/122 • 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).
Cardiac disorders Multiple mild bradycardia/desaturation events during a session, while in NICU	1.6% 2/126 • 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).	0.00% 0/122 • 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).
Respiratory, thoracic and mediastinal disorders Major event needing vigorous stimulation and free flow oxygen (blow by) to resolve, while in NICU	0.79% 1/126 • 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).	0.00% 0/122 • 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).
Infections and infestations Emergency department visit for respiratory distress due to respiratory syncytial virus (RSV)	0.79% 1/126 • 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).	0.00% 0/122 • 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).

Additional Information

Dr. Nathalie Maitre

Emory University

Phone: 404-712-8920

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place