Randomized controlled trial protocol to improve multisensory neural processing, language and motor outcomes in preterm infants

Abstract

Background: Premature infants are at risk for abnormal sensory development due to brain immaturity at birth and atypical early sensory experiences in the Neonatal Intensive Care Unit. This altered sensory development can have downstream effects on other more complex developmental processes. There are currently no interventions that address rehabilitation of sensory function in the neonatal period.

Methods: This study is a randomized controlled trial of preterm infants enrolled at 32-36 weeks postmenstrual age to either standard care or standard care plus multisensory intervention in order to study the effect of multisensory intervention as compared to standard care alone. The study population will consist of 100 preterm infants in each group (total n = 200). Both groups will receive standard care, consisting of non-contingent recorded parent's voice and skin-to-skin by parent. The multisensory group will also receive contemporaneous holding and light pressure containment for tactile stimulation, playing of the mother's voice contingent on the infant's pacifier sucking for auditory stimulation, exposure to a parent-scented cloth for olfactory stimulation, and exposure to carefully regulated therapist breathing that is mindful and responsive to the child's condition for vestibular stimulation. The primary outcome is a brain-based measure of multisensory processing, measured using time locked-EEG. Secondary outcomes include sensory adaptation, tactile processing, speech sound differentiation, motor and language function, measured at one and two years corrected gestational age.

Discussion: This is the first randomized controlled trial of a multisensory intervention using brain-based measurements in order to explain the causal effects of the multisensory intervention on neural processing changes to mediate neurodevelopmental outcomes in former preterm infants. In addition to contributing a critical link in our understanding of these processes, the protocolized multisensory intervention in this study is therapist administered, parent supported and leverages simple technology. Thus, this multisensory intervention has the potential to be widely implemented in various NICU settings, with the opportunity to potentially improve neurodevelopment of premature infants.

Trial registration: NIH Clinical Trials ( clinicaltrials.gov ): NCT03232931 . Registered July 2017.

Keywords: Event-related potential; Intervention; Multisensory; Neurodevelopment; Preterm; Sensory function.

Fig. 1

Study process flow. (Bayley III, Bayley Scales of Infant and Toddler Development Third ed.; CA, corrected age; ERP, Event-related Potential measurement; HINE, Hammersmith Infant Neurological Exam; ITSP, Infant Toddler Sensory Profile; PLS-5, Preschool Language Scales-5; PMA, post menstrual age)

Fig. 2

Mediation analysis model. The a-path is the main effect of treatment on the ERP measure of multisensory processing. The b-path is the association of the ERP measure of multisensory processing with the outcome controlling for the treatment group. The indirect effect (a-path coefficient * b-path coefficient) will be tested for significance in this study. (ERP, Event related potential; MS, multisensory)