NEO Rehab Program for Premature Infants at Risk for Cerebral Palsy
Phase: NA
Conditions: Cerebral Palsy, Prematurity, Early Intervention, Family Centered Care
Sponsor: University of Virginia

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Project summary 
Cerebral Palsy (CP) is the most common motor disability in children born preterm. CP can cause 
profound disability, lifelong need for extensive care and result in significant economic burden. Ideally 
interventions should be initiated while at-risk infants are still admitted in the neonatal intensive care unit 
(NICU), at a stage of rapid brain development where intervention may have an impact on synaptic 
pruning and brain rewiring. Previous studies indicate that intervention focusing on environmental 
enrichment and emotional connection between mother and infant can positively impact the 
neurodevelopmental outcomes of infants born preterm. However, whether this type of interventions can 
improve the motor outcomes of infants at risk for CP remains unknown. To address this gap in 
knowledge, we have developed a NICU-based multimodal rehabilitation program (NeoRehab) to support 
neuromuscular development in preterm infants, This multimodal program, is composed of 6 evidence-
based interventions (vocal soothing, scent exchange, comforting touch, kangaroo care, infant massage and 
physical therapy (PT)) administered in a gestational age (GA) appropriate fashion by a parent. We 
hypothesize that the NeoRehab program will positively impact short-term motor outcomes in preterm 
infants at risk for CP.  At risk infants (≤32 week’s gestation and/or ≤1500 grams birthweight) will be 
eligible for a pilot randomized controlled trial (RCT) comparing the effects of the NeoRehab program 
versus usual care on short term motor outcomes (general movements, cranial nerves, posture, movements, 
tone, and reflexes). The primary outcome is to determine the acceptability, feasibility and fidelity of 
the program by performing direct observation, weekly interviews and activity log reviews. 
Secondary short-term developmental outcomes will be measured using the Hammersmith Infant 
Neurological Examination (HINE) instruments, the general movement assessment (GMA), and the Test 
of Infant Motor Performance (TIMP) at 3 months postmentrual age (PMA). This study addresses one of 
the priorities of the National Center for Medical Rehabilitation Research to explore “multimodal 
rehabilitation approaches that promote plasticity and sensorimotor function”. Results from this study will 
provide the preliminary evidence necessary to design and implement a large, multi-center RCT to test the 
efficacy of NICU-based rehabilitation programs to improve the motor outcomes of infants born preterm.  
General Information 
Protocol title: Neonatal Rehabilitation Program for premature infants at risk for cerebral palsy 
Protocol number: R03HD097727 - 01  
FOA: PAR18-211 NCMRR Early Career Research Award (R03 clinical trial optional) 
Eunice Kennedy Shriver National Institute of Child Health & Human Development 
Rationale & Background Information 
Significance: CP is an umbrella term used to describe a spectrum of disorders related to movement and 
motor abnormalities that are non-progressive in nature. CP develops after injury to the developing fetal or 
infant brain.1 However, in some cases the underlying pathology remains unclear without a history of 
periventricular leukomalacia, intraventricular hemorrhage, birth asphyxia or neonatal stroke.1 The 
reported incidence and prevalence of CP has varied overtime but has not been mitigated by advances in 
medical care resulting in increased survival of premature and low birth weight infants. Premature infants 
are at increased risk of CP with the highest prevalence seen in those born at less than 28 weeks 
gestation.2-3  
Magnetic resonance imaging (MRI) can predict CP with high probability in severe cases, however not 
for mild-to-moderate CP, resulting in delayed diagnosis and treatment.4 As a result, the mean age for 
diagnosis of CP is 1-2 years of age.1 As such, treatment algorithms are centered on supportive and 
corrective care and are typically reserved to pre-discharge and most often post NICU discharge time 
periods. The NeoRehab program aims to address this gap by introducing intervention early during the 
NICU stay. 
09/10/2024
NEO Rehab Program for Premature Infants at Risk for Cerebral Palsy - NCT04330859 
Research protocol: part 1 

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Innovation:   
The possibility of intervention in the NICU is attractive because the brain is highly plastic and 
actively developing. Interventions at this stage may have a profound disease modifying impact.5-6 Several 
investigators have evaluated the impact of early intervention strategies on neurodevelopmental outcomes 
in preterm infants reporting a positive effect on behavioral problems, social-relatedness, and cognitive 
and language performance.7 
Infant massage represents a form of environmental enrichment that has a positive impact on multiple 
important outcomes after preterm birth including: improved weight gain, decreased stress and improved 
neurodevelopmental outcomes.8-16 Infant massage can be administered by NICU therapist (UVA has 
several therapists trained in infant massage) and the feasibility of infant massage by the mother is being 
actively investigated.17 
Similarly, early PT in the NICU leads to multiple positive outcomes including: increased bone 
mineralization and reduced incidence of motor delays in very low birth weight infants.18,19 Parent-
administered PT has recently been shown to be feasible.20 Results from a recent RCT indicate that a 10 
minute intervention twice a day for 3 weeks, from 34 to 36 weeks’ PMA resulted in improved motor 
performance at 37 weeks’ PMA. The intervention was supervised by a PT and was primarily designed to 
promote postural control, head control, and midline orientation.20  
Finally, studies have shown that interventions promoting the establishment of emotional connection 
between infant and mother, such as the Family Nurture Intervention (FNI) strategy, can positively impact 
neurodevelopmental outcomes at 18 months.7The FNI targets infants 26-34 weeks PMA and aims to 
reduce the effects that abnormal sensory inputs in the NICU have on the developing brain.21 The program 
aims to enhance the emotional connection between mothers and their premature infants.7, 21 Nurture 
specialists met with mothers on average 6.4 hours per week over the course of the NICU stay and 
continued until discharge (35-38 weeks’ PMA). Elements of the FNI include mother/infant calming 
sessions with scent cloth exchange, vocal soothing, eye contact, kangaroo care, and family-based support 
sessions. It can be implemented shortly after birth and incorporates multiple elements of routine NICU 
care, an important point for implementation 
 
References 
1. Himmelmann K. Epidemiology of cerebral palsy. 1st ed. Handb Clin Neurol. 2013;111:163-7 
2. Oskoui M, Coutinho F, Dykeman J, et al. An update on the prevalence of cerebral palsy: a systematic 
review and meta‐analysis. Dev Med Child Neurol. 2013;55(6):509–19 
3. Hack M, Costello DW. Trends in the rates of cerebral palsy associated with neonatal intensive care of 
preterm children. Clin Obstet Gynecol. 2008;51(4):763–74  
4. Herskind A, Greisen G, Nielsen JB. Early identification and intervention in cerebral palsy. Dev Med  
 
Child Neurol. 2015;57(1):29–36 
5. Kolb B, Whishaw IQ. Plasticity in the neocortex: mechanisms underlying recovery from early brain 
damage. Progress in Neurobiology. 1989. p. 235–76  
6. Duyme M, Dumaret A-C, Tomkiewicz S. How can we boost IQs of “dull children”?: A late adoption 
study. Proc Natl Acad Sci. 1999;96(15):8790–4 
7. Welch MG, Firestein, MR, Austin,J., Hane, AA., Stark, RI., Hofer, MA., Garland, M., Glickstein, SB., 
Brunelli, S., Ludwig, RJ & Myers, MM. (2015). Family Nurture Intervention in the  Neonatal 
Intensive Care Unit improves social-relatedness, atttention, and neurodevelopment of premature 
infants at 18 months in a randomized control trial. The Journal of Child Psychology and 
Psychiatry. 56:11, 1202-1211  
8. Field T, Diego M, Hernandez-Reif M. Preterm infant massage therapy research: a review. Infant Behav 
Dev. 2010;33(2):115–24 
9. Massaro AN, Hammad TA, Jazzo B, Aly H. Massage with kinesthetic stimulation improves weight 

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gain in preterm infants. J Perinatol. 2009;29(5):352–7  
10. Field T, Diego MA, Hernandez-Reif M, Deeds O, Figuereido B. Moderate versus light pressure 
massage therapy leads to greater weight gain in preterm infants. Infant Behav Dev. 
2006;29(4):574–8 
11. Hernandez-Reif M, Diego M, Field T. Preterm infants show reduced stress behaviors and activity 
after 5 days of massage therapy. Infant Behav Dev. 2007;30(4):557–61  
12. Acolet D, Modi N, Giannakoulopoulos X, et al. Changes in plasma cortisol and catecholamine 
concentrations in response to massage in preterm infants. Arch Dis Child. 1993;68(1 Spec No):29–
31 
13. Guzzetta A, D’Acunto MG, Carotenuto M, et al. The effects of preterm infant massage on brain 
electrical activity. Dev Med Child Neurol. 2011;53(SUPPL.4):46–51  
14. Guzzetta A, Baldini S, Bancale A, et al. Massage accelerates brain development and the maturation of 
visual function. J Neurosci. 2009;29(18):6042–51 
15. Procianoy RS, Mendes EW, Silveira RC. Massage therapy improves neurodevelopment outcome at 
two years corrected age for very low birth weight infants. Early Hum Dev. 2010;86(1):7–11  
16. Holopainen IE, Laurén HB. Glutamate signaling in the pathophysiology and therapy of prenatal 
insults. Pharmacol Biochem Behavior. 2012. p. 825–34  
17. Lai MM, D’Acunto G, Guzzetta A, et al. PREMM: preterm early massage by the mother: protocol of 
a randomised controlled trial of massage therapy in very preterm infants. BMC Pediatr; 
2016;16(1):146 
18. Cameron EC,Maehle V, Reid J. The Effects of an Early Physical Therapy Intervention for Very  
Preterm, Very Low Birth Weight Infants: A Randomized Controlled Clinical Trial. Pediatr Phys 
Ther. 2005;17(2):107–19 
19. Vignochi CM, Miura E, Canani LH. Effects of motor physical therapy on bone mineralization in  
 
premature infants: a randomized controlled study. J Perinatol. 2008;28(9):624–31 
20. Ustad T, Evensen KAI, Campbell SK, et al. Early Parent-Administered Physical Therapy for Preterm 
Infants: A Randomized Controlled Trial. Pediatr; 2016;138(2):e20160271–e20160271 
21. Welch MG, Hofer M a, Brunelli S a, et al. Family nurture intervention (FNI): methods and treatment 
protocol of a randomized controlled trial in the NICU. BMC Pediatr. 2012;12(1):12-14 
 
Study goals and objectives 
The goal of this project is to investigate the acceptability, feasibility and fidelity of an innovative NICU 
rehabilitation program that will include six multimodal, GA appropriate, parent-administered 
interventions (vocal soothing, scent exchange, comforting touch, kangaroo care, infant massage and 
physical therapy). We will also determine the effects of this program on short-term motor outcomes using 
the HINE, the GMA and the TIMP instruments in premature infants (≤32 week’s gestation and/or ≤1500 
grams birthweight).  
AIM 1: Enroll 60 preterm infants (<32 weeks’ gestation and/or ≤1500 grams) into a pilot RCT 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. We 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.  
 

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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 CP at discharge from the NICU and at 3 months PMA.  We 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 DESIGN 
Methodology: The design will be a RCT at a single site academic NICU-UVA Hospital in Charlottesville 
Virginia. Randomization will be stratified by birth weight (< 1000 grams and 1000-1500 grams) using a 
randomly permuted block design with random block sizes of 2 and 4.  The intervention group will receive 
a novel multisensory, multimodal rehabilitative program, which will incorporate elements from the FNI 
program (scent exchange, touch, vocal soothing) as well as infant massage and parent-administered 
physical therapy. The intervention will be adjusted to take into account the infant’s developmental stage 
and physiologic stability (See Table 1). Additionally, the intervention focuses heavily on interventions 
the parent can provide.  
 
Inclusion and exclusion criteria: 
Infants will be eligible for this study if they meet the following criteria: 
- 
GA at birth: ≤32 weeks gestation and/or birthweight ≤1500 grams 
- 
Infants 7 days or older 
- 
Parental ability to perform the interventions or identified designated surrogate (e.g. grandparent) 
- 
Abnormal writhing GMs defined by the presence of a poor repertoire pattern on 2 consecutive 
weeks or the presence of a cramped-synchronized pattern on any assessment (see Figure 1) 
 
Infants will be excluded from the study if they are clinically unstable (requiring high frequency 
mechanical ventilation, vasopressor support, need for continuous intravenous pain or sedation 
medication), if their parents do not speak English or if parental participation is hindered (e.g. 
incarceration or work/personal related issues). 
 
Figure 1: Intervention algorithm  
 

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Intervention (n=30): Parents will be provided oral as well as written (Flip book) and illustrated 
information about the interventions. Study team members will assist with demonstrating appropriate 
technique for applying interventions and will use the teach-back method to ensure comprehension and 
understanding. Interventions will be developmentally tailored to the infant’s GA (Table 1) as follows: 
1. Modified FNI portion of the bundle includes: 
a. Vocal soothing: mothers will be instructed to express their feelings to their infant in their native 
language using varying intonations 
b. Scent exchange: on initial visit, mothers will receive 2 cloths, 1 to place in her bra and 1 to place 
under her infant’s head. Cloths are subsequently exchanged at each visit.  
c. Comforting touch: mothers will be instructed to use gentle but firm and sustained touch by 
placing the infant’s arms on the chest and placing their hand on top. The other hand will be used 
to gently contain the infants’ feet, lightly drawing the knees towards the chest. 
d. Mother-Kangaroo-Care plus: kangaroo care will be combined with gentle touch, vocal soothing 
and eye contact as described above. 
2- Infant massage: mothers will be taught moderate pressure massage by PT 
3- Parent-administered PT: 10 minutes interventions promoting postural and head control as well as 
midline orientation will be conducted by the mother is recommended starting at 33 weeks’ PMA. The 
intervention will be monitored by a physical therapist for 3 consecutive sessions and weekly 
thereafter. 
 
Mothers/Fathers whose infants are randomized to the intervention group will be encouraged to be at the 
bedside and provide the GA appropriate interventions once per day, 5 days per week (5/7).  
 
Table 1: Developmental-Guided NICU based rehabilitation program 
 
Postmentrual Age (completed weeks) 
Interventions 
23-25 
26-28 
29-32 
33-36 
≥ 37 
Vocal soothing 
 
 
 
 
 
Scent exchange 
 
 
 
 
 
Comforting touch 
 
 
 
 
 
Kangaroo care plus 
 
 
 
 
 
Infant massage 
 
 
 
 
 
Parent-administered PT 
 
 
 
 
 
 
Standard of care (control group) (n=30): Parents of infants randomized to standard care will continue to 
be encouraged to touch, hold, and talk to their infants. They are also encouraged to perform kangaroo care 
based on unit guidelines. All infants in standard care will have a routine physical therapy consult at 28 
weeks gestation. The infants will continue to be followed 2-3 times per week for 10-30 minutes per 
session by PT until discharge from hospitalization. Social work actively engages with parents of infants 
admitted to the NICU which will include the intervention and standard of care group. Social work 
provides ongoing parental support and strives to alleviate barriers to visitation. At time of discharge 
standard care will resume for both groups, which includes a referral to early intervention and a NICU 
follow up appointment with developmental pediatrics at 3 months PMA. Below is the study schedule.  

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Self-report activity logs (separately uploaded documents) will be used to monitor the fidelity of the 
program. Both groups will fill out the log and document what aspects of the program were performed, the 
date, and duration of the intervention. Weekly interviews will be conducted with parental participants to 
evaluate the acceptability (satisfaction), feasibility (practicality) and fidelity (engagement) of the 
program. Weekly interviews will be done at the bedside with parental participants and a research team 
member to discuss any challenges or barrier to applying the recommended evidence based practice 
interventions. Examples of interview questions are 1) How are things going? 2) Do you have any 
questions about the interventions? 3) Are there things that are preventing you from doing the 
interventions? Additionally, research team members will perform random direct observations of 
intervention application to further evaluate feasibility and fidelity. 
 
Safety considerations 
Risk of loss of confidentiality and privacy 
Risks related to the Maternal/Designee Activities with Baby: 
Rare but serious: 
• 
During Kangaroo Care there is a rare risk that infant may fall or that a tube or line may be 
dislodged.  
• 
Injury to muscles or bones due to improperly applied infant massage 
 
General: Infants in the NICU and family members are encouraged to participate in developmentally 
appropriate activities. However, these activities are not applied in a systematic fashion. The intervention 
group is at no greater risk than the standard care group as interventions evidence based and has been applied 
in the NICU setting.  
 
Adverse events are monitored for the entirety of the study.  
 
Follow up 
Interventions will be completed upon discharge from the NICU. Usual care resumes for both groups at 
discharge. Outpatient follow up for secondary developmental outcomes will occur at 3-4 month follow up 
appointment (see study schedule).  
 
Data management and statistical analysis  
IRB approval and informed consent will be obtained prior to the start of the study. Video recorded GMA 
is standard of care in the NICU for neonates born ≤32 week’s gestation and/or ≤1500 grams birthweight. 
Videos will be reviewed and scored independently by at least 2 of the study investigators. Videos will be 
scored with only the PMA information available to the investigator at the time of review.  Inter-rater and 
intra-rater agreement will be assessed using Cohen’s kappa (kappa) and percentage agreement. In case of 

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disagreement, the videos will be reviewed by all study members trained in the GMA and a consensus will 
be obtained. 
The UVA NICU admits an average of 112 very low birth weight infants every year among which 
83 are born at 32 weeks’ gestation or less. We anticipate that, in one year of accrual, there will be 
approximately 120 infants <32 weeks gestation and/or ≤1500g birth weight. Based on a preliminary 
assessment of children in the NICU, we expect that 80% of these children will be eligible for the study. 
Recruitment acceptance rates of previous studies conducted in our NICU range from 30-50% for 
intervention studies and 80-90% for noninvasive studies. Using an acceptance rate of 80% yields an 
expected accrual of 70 patients per year.  Allowing for 10% dropout, accrual of 33 patients per group 
(power calculation below) can be completed in 1 year. 
Quantitative data will be analyzed using descriptive statistics and content analysis will be 
performed for qualitative responses.   Quantitative data will be analyzed using the newest version of SPSS. 
Due to the exploratory purpose of the specific aim, descriptive statistics will be computed for all 
quantitative variables (demographic characteristics, recruitment, refusal, retention, follow up rates, % 
completion of self-report log and number of visitations per unit log). Frequencies and rates will be 
calculated for categorical variables and means and standard deviations will be calculated for continuous 
variables.  
Qualitative analysis will included semi-structured interviews with adult participants as well as 
direct observations using qualitative description. Qualitative descriptive analysis will provide a 
comprehensive evaluation of the NICU multimodal rehabilitation program. The textual data from the 
interviews and observation notes will be analyzed by (1) immersion in the data (2) followed by line by 
line analysis and data reduction of the textual data through inductive open coding and constant 
comparative analysis.36-37  Tentative categories will be listed with each line of data and identified by 
“nodes” in the Dedoose software. (3) After line-by-line analysis of the transcripts, categories (“nodes”) 
will be grouped together to form tentative themes. 
Repeated measures models will be used to compare HINE and TIMP total scores at the time of 
discharge and at 3 months PMA between newborns in the standard care group and in the intervention 
group (NEO rehab program). F-tests based on contrasts will be used to make comparisons at the two 
specific time points. To approximate the power of the F-test for comparing the groups with respect to the 
3-month HINE scores, the results in Romeo et al.(2008) were used. Their study showed that across CP 
diagnoses, the average 3 –month HINE score was approximately 40 with an estimated standard deviation 
of 8.8. A score of below 40 is associated with the GMFCS IV and V levels while a score of 40-60 is 
associated GMFCS levels I and II at 3 months of age.  A score ≥ 73 is optimal. With 30 subjects per 
group, the two-sample t-test has 80% power, with a 2-sided significance level of 5% when the effect of 
the intervention is to increase HINE scores by 6.5 points. Allowing for 10% dropout, 33 patients per 
group are required.  Similar analyses will be used for the TIMP scores as well as subscales of the 
HINE.  For the GMA assessments, we will tabulate the proportion of children in each group classified as 
having poor repertoire, cramped/synchronized or chaotic movement abnormalities at each of the follow-
up times.  Markov models will be used to assess how the intervention affects the proportions of children 
transitioning between classifications. For all of the endpoints; this study will provide estimates of 
variation useful for planning a larger study of the rehabilitation program. Our primary analysis will be 
done as intention-to-treat. 
 
Quality assurance 
Human Subject Research Institutional Review Board approved study  
DSMB not required for this project 
 
Expected outcomes of the study 
Acceptability, feasibility and fidelity will be evaluated to ensure that the study design is sound for a future 
full-scale intervention study, Table 2.  

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• 
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 
 
Table 2: Primary outcomes  
Variable 
Concept 
Domain 
Metrics 
Acceptability 
Satisfaction 
 
Correct, consistent and continuous 
use of the program 
1. ≥75% Recruitment rates 
2. <10 % Refusal rates  
3. 75% Retention rates 
4. 90% Follow-up rates  
5. Weekly interviews with 
parental participants  
Feasibility 
Practicality  
Adequacy of the logistics a) 
determining the capability of 
carrying out the program as planned 
b) identifying difficulties in 
applying any aspect of the program  
1. Direct observations 
2. Weekly interview the 
parental participants  
Fidelity 
Adherence 
a) pro portion of the program 
content, b)methods and c) activities 
1.>75% Completion of self-
report activity log to be 
completed by parental 
participant  
3.Direct observations by 
research team member 
Fidelity 
Exposure 
a) number of sessions, b) 
attendance, c)frequency and d) 
duration 
1. Self-report activity log to be 
completed by parental 
participant 
3.Direct observations by 
research team member 
4. Administrative data (NICU 
visitation log) 
Fidelity 
Engagement 
Participation in the program 
1. Weekly interviews conducted 
by research team member with 
parental participants  
2. Administrative data (NICU 
visitation log) 
3. >75% Completeness of the 
activity logs  
 
The short-term impact of these combined interventions on motor function will be assessed using the 
HINE, theGMA and the TIMP. These instruments will be administered at time of discharge from the 
NICU and at 3 months PMA. These instruments used in combination are recommended to be 
administered to infants before 5 months PMA and provide the most predictive of risk for CP. Instruments 
will be administered by certified providers and/or therapists. Additionally, demographic characteristics of 
the sample will be collected using the medical record and include: gender, ethnicity, race, gestational age 
at birth, birth weight and head circumference, primary diagnosis, neurologic comorbidities, medication 
management of neurologic comorbidities and neonatal abstinence syndrome, NICU length of stay, 

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feeding method upon discharge, discharge head circumference, geographical region, and disposition 
(death or discharge home).  
 
Table 3: Short term developmental outcomes 
 
Instrument Measurement 
Age  
Interval 
HINE 
26 items used to assess cranial nerve function, 
posture, quality and quantity of movements, muscle 
tone, and reflexes and reactions). Each item is 
scored individually 0-3 with a sum score of all 
individuals ranging from 0-78. Lower the score the 
poorer the motor function. The HINE allows for 
identification of early signs of CP and individual 
items have demonstrated predictive value of motor 
outcome. Sensitivity 90% for prediction of motor 
outcome. 
2 and 24 months 
of age 
At time of 
discharge and 3 
months PMA 
GMA 
Writhing stage 
1) normal 
2) poor repertoire- monotonous and lack 
complexity  
3) cramped-synchronized- appear rigid and are not 
smooth or fluent in character. 
4) chaotic -characterized by abrupt, large amplitude 
movements involving all limbs.  
Fidgety stage 
1)normal 
2) abnormal fidgety movements-absent or 
abnormal (exaggerated).  
Cramped-synchronized followed by absent fidgety 
pattern, have a 98% sensitivity and specificity for 
prediction of CP 
Writing 
movements 
birth-9 weeks 
Fidgety 
movements 9-
20 weeks 
Every 2 weeks 
during 
hospitalization 
and 3 months 
PMA 
TIMP 
28 observed items of spontaneous movements and 
31 elicited items that assess the child’s motor 
responses scored 0-6. The lower the score the 
poorer the motor function. The test is sensitive to 
age-related changes in motor performance (r =0 
.83).  
32 weeks to 4 
months post 
term 
At time of 
discharge and 3 
months PMA 
 
Dissemination of results and publication policy 
Presentations at National Meetings: We plan to present our findings at national scientific meetings 
annually.   
 
Publication in Journals: We aim to publish all data and results generated from this proposal in conference 
abstracts and manuscripts. We will aim for high impact open access journals with wide readership. All 
publications will be available through PubMed Central. [http://www.ncbi.nlm.nih.gov/pmc] 
 
Communication with local authorities: Not applicable in this grant 
 
Sharing Model Organisms: Not applicable in this grant. 
 

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Genome Wide Association Studies: Not application in this grant 
 
Duration of the project 
Project period begin date 4/4/2019 
Project period end date 3/31/2022 
 
Study timeline- 24 months 
 
Months 1-2 
Finalize IRB approval   
Months 2-14 
Recruitment and data collection 
Months 14-18 
Data management and analysis 
Months 18-24 
Dissemination  
Months 18-24 
Grant preparation for next step- R01 to include 
long term motor outcomes 
 
Problems anticipated/encountered 
Due to COVID a 1 year no cost extension was obtained 
1. The concept of hospital-based NICU multi-modal rehabilitation is innovative and may not be viewed as 
“traditional rehabilitation.” However, this model of rehabilitation requires a different approach and 
consideration given the developmental age of the subjects and the unique NICU setting.  
2. To ensure patients are not lost to follow up, complimentary phone calls will be provided prior to their 
scheduled appointment. If transportation issues arise, social work is available to assist. In the future, home 
visits to perform these developmental assessments maybe more accepted then an outpatient clinic follow 
up appointment.  
3. The primary end point of this study is feasibility. However, the research team is particularly interested 
in the impact of these interventions on developmental outcomes. While short term outcomes maybe 
demonstrate significant differences between treatment arm, short term and long term outcomes will need 
to be further evaluated in subsequent studies and may incorporate other markers of health.   
 
Ethics 
HSR IRB approval (# 21502) was obtained prior to initiating any study procedures. 
This proposed research will in human subject research. Institutional Review Board will be obtained. 
Informed consent will be obtained (supplemental attachment).  
 
This proposal seeks to investigate the acceptability, feasibility, fidelity of a neonatal intensive care unit 
(NICU) rehabilitation program that will consist of gestational appropriate interventions. Additionally, we 
will determine the effects of short term motor outcomes of the program in premature infants identified to 
be at risk for cerebral palsy (CP). Will seek to enroll 60 participants.  
 
Recruitment and Retention Strategies:  Our study team has existing relationships with the academic NICU. 
The PI is a member of the Neuro NICU team.  Study participants will have the opportunity to learn about 
the research and ask questions and make suggestions.   The study participants will be meeting with a 
member of the research team weekly. Recruitment and retention rates will be monitors and considered an 
outcome measure to determine acceptability of the program.  
 
Recruitment and Informed Consent 

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Participants will be recruited after IRB approval at the University of Virginia has been obtained. Patients 
will be recruited from the NICU after meeting the outlined inclusion/exclusion criteria. Informed consent 
will be obtained for all participants. There will be opportunities to ask questions, and are informed that they 
may withdraw from any part of the study at any time.  Randomization will not occur until consent is 
obtained.  
 
Protections Again Risk 
Participants enrolled in the studies are told of the risks, benefits and alternatives before the studies start and 
are able to withdraw at any time.  Risks are minimal and every effort is made to explain things clearly to 
participants and allow the participants to ask questions.  Researchers completing analyses will have only 
de-identified data.  All data are kept locked and secure.  Names are not used on forms.   
 
 
Potential Benefits of the Proposed Research to Human Subjects 
We anticipate that the NICU-based intervention program will be well accepted and feasible. Additionally 
we hypothesize that the intervention will result in improved short term motor outcomes.  Information gained 
may help improve care of infants at risk for CP.   
 
Informed consent forms (uploaded as a supplement document)