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

NCT03232931 | Completed Results DMC FDA Device

• 4 other identifiers: STUDY00003034R01HD093706IRB17-00025/IRB18-005792024P007108
• Study Type: interventional
• Target: 248
• Locations: 1 country
• Sites: 3

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. This study 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.

Conditions

Preterm Infant

Keywords

auditory; tactile; mother's voice; multisensory

Outcome Measures

Primary Outcomes (1)

• Index of Multisensory Processing (IMP)

  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).

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

Secondary Outcomes (3)

• Infant/Toddler Sensory Profile (ITSP) Score

  at 12 months corrected age

• Change in Bayley Scales of Infant and Toddler Development - 3rd Edition (Bayley III) Score

  12 and 24 months corrected age

• Change in Preschool Language Scales - 5th Edition (PLS-5) Score

  2 Years (22-26 months corrected age)

Study Arms (2)

Multisensory Intervention

EXPERIMENTAL

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; Device: Contingent parent's voice exposure; Behavioral: Parental skin-to-skin care; Device: Recorded parent's voice

Standard of Care

OTHER

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; Device: Recorded parent's voice

Interventions

Therapist skin-to-skin Care BEHAVIORAL

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.

Multisensory Intervention

Contingent parent's voice exposure DEVICE

The parent's voice recording is delivered via a pacifier-activated music player (PAM). 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).

Also known as: Pacifier Activated Lullaby® (PAL®)

Multisensory Intervention

Parental skin-to-skin care BEHAVIORAL

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.

Multisensory Intervention; Standard of Care

Recorded parent's voice DEVICE

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).

Also known as: DINO-egg

Multisensory Intervention; Standard of Care

Eligibility Criteria

• Age: 32 Weeks - 36 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Hospitalization at a study location
• Postmenstrual age of 32 weeks 0 days gestation to 36 weeks 0 days gestation

You may not qualify if:

• Ventilation using an endotracheal tube
• Major congenital malformations
• Family history of genetic hearing loss
• Use of sedatives or seizure medications
• Enrolled in the control group of the main study

Sponsors & Collaborators

• Emory University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Nationwide Children's Hospital: collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (3)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (2)

• 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.

  PMID: 34710395 DERIVED

• 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.

  PMID: 30890132 DERIVED

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Results Point of Contact

• Title: Dr. Nathalie Maitre
• Organization: Emory University

nathalie.linda.maitre@emory.edu

404-712-8920

Study Officials

• Nathalie L Maitre, MD, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Except for parent reports, all measures will be administered by masked examiners.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 3, 2017
• First Posted: July 28, 2017
• Study Start: October 29, 2018
• Primary Completion: February 20, 2023
• Study Completion: April 25, 2025
• Last Updated: March 17, 2026
• Results First Posted: March 19, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)