NEO Rehab Program for Premature Infants at Risk for Cerebral Palsy

The goal of this project is to investigate the acceptability, feasibility and fidelity of an innovative NICU rehabilitation program that will include six multimodal, gestational age (GA) appropriate, parent-administered interventions (vocal soothing, scent exchange, comforting touch, kangaroo care, infant massage and physical therapy). Using the general movement assessment (GMA) instrument, the investigators will determine the effects of this program on short-term motor outcomes (general movements (GMs), cranial nerves, posture, movements, tone, and reflexes) in premature infants (≤32 week's gestation and/or ≤1500 grams birthweight) identified as at-risk for CP. The short-term motor outcomes will be measured using the GMA, the Test of Infant Motor Performance (TIMP) and the Hammersmith Infant Neurological Examination (HINE) instruments. This novel program will be applied during the neonatal intensive care unit (NICU) hospitalization when the brain is highly plastic and actively developing with the goal to mitigate severity of brain injury and its impact on development.

Study Overview

• Status: Completed
• Conditions: Cerebral Palsy; Prematurity; Early Intervention; Family Centered Care
• Intervention / Treatment: Other: NeoRehab Bundle; Other: Routine care

Detailed Description

The two following specific aims will be tested:

Aim 1: Enroll 60 preterm infants (<32 weeks' gestation and/or ≤1500 grams) with abnormal GMA into a pilot randomized control trial to evaluate the acceptability, feasibility (practicality) and fidelity (adherence, exposure and engagement) of a multimodal GA appropriate rehabilitation program during NICU hospitalization compared to standard of care. The investigators will evaluate:

• Acceptability using recruitment, refusal, retention, and follow-up rates as well as weekly interviews with parental participants
• Feasibility (practicality) using direct observations and weekly interviews with parental participants
• Fidelity (adherence, exposure and engagement) using visitation data, activity logs, direct observations, and weekly interviews.

Aim 2: Examine the effect of a multimodal NICU-based rehabilitation program on short-term motor outcomes (general movements, cranial nerves, posture, movements, tone, and reflexes) of premature infants at risk for cerebral palsy (CP) at discharge from the NICU and at 3 months corrected age. The investigators hypothesize that this type of GA appropriate multimodal NICU-based rehabilitation program will positively impact short-term motor outcomes by normalizing general movements and improving TIMP and HINE scores.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 7 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• GA at birth: ≤32 weeks gestation and/or birthweight ≤1500 grams
• Infants 7 days or older
• Ability of parents or identified designated surrogate (e.g. grandparent) to perform the interventions
• Abnormal writhing GMs defined by the presence of a poor repertoire pattern on 2 consecutive assessments or the presence of a cramped-synchronized pattern on any assessment

Exclusion Criteria:

• Clinically unstable (requiring high frequency mechanical ventilation, vasopressor support, need for continuous intravenous pain or sedation medication)
• If their parents do not speak English
• If parental participation is hindered (e.g. incarceration).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Parent-driven intervention bundle of 6 evidence-based elements: vocal soothing, scent exchange, comforting touch, kangaroo care, infant massage and physical therapy	Other: NeoRehab Bundle; The NICU rehabilitation program includes six multimodal, GA appropriate, parent-administered interventions (vocal soothing, scent exchange, comforting touch, kangaroo care, infant massage and physical therapy)
Placebo Comparator: Routine care; Routine care per unit guidelines	Other: Routine care; Routine NICU care including talking, touching and holding the participant per unit guideline as well as physical therapy, occupational therapy, and speech therapy per unit guideline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acceptability	The following measure will be used to measure study acceptability: % Recruitment rates during enrollment period	from day 1 of study screening through end of screening (approximately 1 year and3 months).
Retention Rates	The following measure will be used to assess the retention rate of study participants: - Rate of follow-up at the 3 month outpatient visit	From discharge to 3 months follow-up
Adherence Rates	Adherence rates were monitored by daily activity logs of interventions from enrollment day 1 to discharge for each visit day	from study enrollment (day 1) to study discharge
Impact of the NeoRehab Bundle on Motor Performance Using the Test of Infant Motor Performance (TIMP)	Motor outcomes will be assessed at NICU discharge and at 3 months using the Test of Infant Motor Performance (TIMP); 3 months outcome reported. TIMP score range = 0-142; lower scores indicate worse motor performance	3 months
Impact of the NeoRehab Bundle on Neurologic Function as Assessed by the Hammersmith Infant Neurological Examination (HINE).	Neurologic function will be assessed at NICU discharge and at 3 months postmenstrual age using the Hammersmith Infant Neurological Examination (HINE) instrument, 3 months outcome reported. The HINE is a 26 items scale that evaluates cranial nerve function, posture, quality and quantity of movements, muscle tone, and reflexes and reactions. Lower the score the poorer the motor function. HINE score range = 0-78 (with lower score indicating lower motor performance). The HINE has a sensitivity of 90% for prediction of motor outcome.	3 months
Percent Abnormal General Movements	The impact of the intervention on the infants' general movement will be assessed at NICU discharge and at 3 months postmenstrual age using the general movement assessment (GMA) tool. The GMA has been shown to reliably identify infants at high risk for CP and can be implemented shortly after birth making it an ideal screening tool for preterm infants. Cramped-synchronized writhing general movements followed by absent fidgety general movements is a movement pattern that has been shown to be highly specific of later development of cerebral palsy.	3 months

Collaborators and Investigators

• Sponsor: University of Virginia
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: santina zanelli, MD, University of Virginia

Publications and helpful links

General Publications

• Letzkus L, Conaway M, Miller-Davis C, Darring J, Keim-Malpass J, Zanelli S. A feasibility randomized controlled trial of a NICU rehabilitation program for very low birth weight infants. Sci Rep. 2022 Feb 2;12(1):1729. doi: 10.1038/s41598-022-05849-w.

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2019
• Primary Completion (Actual): October 10, 2020
• Study Completion (Actual): August 1, 2021

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: October 9, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: prematurity; early intervention; cerebral palsy; motor outcome; brain plasticity; parent-driven
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Cerebral Palsy; Premature Birth; Paralysis
• Other Study ID Numbers: UVirginia; R03HD097727 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No