Movement-based Intervention to Promote Positive Neurodevelopmental Outcomes in Infants at Risk for Developmental Delay
Phase: NA
Conditions: Infant Development, Infant,Premature, Infant, Very Low Birth Weight, Infant, Small for Gestational Age, Infant Conditions
Sponsor: University of Southern California

 
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ClinicalTrials.gov Identifier: NCT03082313  
Date uploaded 10/20/21 
 
Version 02/10/18 
 
Leg Movement Rate before and after a Caregiver- Provided Intervention for Infants at Risk of 
Developmental Disability: A Pilot Study  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
2 
 
 
 
Protocol: Intervention: Leg Movement Rate 
 
Significance 
 
Infants with developmental delay often experience lifelong functional limitations in motor, cognitive and 
social domains. A strictly-defined, conservative estimate recently determined that ~9% of infants in the 
US are eligible for early intervention services because they are at risk for developmental delay. Diagnoses 
of developmental delay are typically made at 18 to 24 months of age1 and current practice is to provide 
infrequent, low intensity therapies or no intervention across infancy2-4. In infants born preterm, for 
example, low intensity developmental interventions have generally demonstrated short-term benefits 
that are not sustained into the school years5-8. Basic science evidence supports that early and intense 
therapy intervention is more effective at promoting optimal neuromotor structure and function9-11. Given 
this information, dosing of pediatric physical therapy intervention is a current topic of high interest in the 
field12, and researchers are starting to investigate the feasibility of different approaches for providing 
early, intense interventions13,14. Although these approaches are laudable and strongly theoretically based 
there is a fundamental gap: we do not know what amount and type of movement experience is necessary 
and sufficient to have a positive effect on the development of infant neuromotor control. This proposal 
will address this fundamental question by increasing the leg movement experience of infants at risk for 
developmental delay to an evidence-based minimum threshold for quantity and type of movement and 
measuring the association between amount of leg movement experience and motor development rate. 
 
The intervention promotes movement experience from 3 months to sitting onset, based on our pilot data 
that indicate infants at risk for developmental delay who demonstrate a leg movement rate below 1200 
movements per hour of awake time across a day are more likely to have a poor neuromotor outcome 
than infants who demonstrate a leg movement rate above 1200 movements per hour of awake time. 
Further, infants at risk for developmental delay move their legs significantly less and make a higher 
proportion of unilateral movements than infants with typical development. The goal of the intervention is 
to increase infant movement experience above the quantity threshold while consisting of the prescribed 
type (1200 movements per hour of awake time with variety of type of movement) in order to provide 
sufficient and necessary experience for learning neuromotor control. 
 
Approach 
 
Recruitment. Participants will be a representative sample of 12 infants AR recruited using 4 methods. 1) 
The infants will be recruited with fliers placed around USC campuses and public spaces such as local 
libraries. Fliers will also be distributed in person and/or electronically via email to local early 
intervention providers, on social media sites including facebook and instagram, and on the website of the 
Division of Biokinesiology and Physical Therapy. The parent or legal guardian will be asked to contact 
research staff by phone or email for further information about the research study, including further 
discussion of the inclusion criteria. When the parent or legal guardian contacts research staff, the 
research staff will give more specific information about the study and answer any questions. If they 
choose to participate after the initial contact, a written consent form will be mailed to them. This will 
allow the parents and/or legal guardians to discuss their participation with others before signing the 
written consent. 2) A licensed healthcare provider at CHLA or an early intervention provider, with the 
permission of the parent or legal guardian, will provide the research staff with the name and phone 
number of the parent of a potential infant participant who is under their professional care. Research staff 
will call the parent or legal guardian and give more specific information about the study and answer any 

 
3 
questions. If they choose to participate after the initial contact, a written consent form will be mailed to 
them. This will allow the parents and/or legal guardians to discuss their participation with others before 
signing the written consent. 3) Research staff will attend the High Risk Follow-Up Clinic at CHLA. A 
licensed healthcare provider at CHLA, with the permission of the parent or legal guardian, will introduce 
the research staff to the family. The research staff will give more specific information about the study and 
answer any questions. If they choose to participate after the initial contact, a written consent form will be 
mailed to them. This will allow the parents and/or legal guardians to discuss their participation with 
others before signing the written consent. 4) A CHLA Clinical Research Coordinator (CRC) will coordinate 
with the High Risk Follow Up Clinic and potentially the NICU to review infants' medical records for 
eligibility and speak to families of potential participants. With the permission of the parent or legal 
guardian, the CRC will provide the research staff with the contact info. Research staff will call the parent 
or legal guardian and give more specific information about the study and answer any questions. If they 
choose to participate after the initial contact, a written consent form will be mailed to them. This will 
allow the parents and/or legal guardians to discuss their participation with others before signing the 
written consent. 
 
Inclusion Criteria. Infants will be 3-6 months of adjusted age at the first visit, +/- 30 days. Infants will be 
defined as at risk in accordance with the definition below (confirmed by the PI or the CHLA CRC) 15: 
 
 
 
Exclusion Criteria. Infants with congenital malformations of the legs will be excluded.  
1.
pH%less%than%7.0%on%an%umbilical%blood%sample%or%a%blood%gas%obtained%within%one%hour%of%life)%or%an%
Apgar%score%of%less%than%or%equal%to%three%at%five%minutes%or%an%Apgar%score%less%than%5%at%10%minutes.
2.
An%unstable%infant%manifested%by%hypoxia,%acidemia,%hypoglycemia%and/or%hypotension%requiring%
pressor%support.
3.
Persistent%apnea%which%required%caffeine%or%other%simulant%medication%for%the%treatment%of%apnea%at%
discharge.
4.
Required%oxygen%for%more%than%28%days%of%hospital%stay%and%had%radiographic%finding%consistent%with%
chronic%lung%disease%(CLD).
5.
Infants%placed%on%extracorporeal%membrane%oxygenation%(ECMO).
6.
Infants%who%received%inhaled%nitric%oxide%greater%than%four%hours,%and/or%treatment%during%
hospitalization%with%sildenafil%or%other%pulmonary%vasodilatory%medications%for%pulmonary%
hypertension.%
7.
Congenital%heart%disease%requiring%surgery%or%minimally%invasive%intervention.
8.
History%of%observed%clinical%or%electroencephalograhic (EEG)%seizure%activity%or%receiving%antiepileptic%
medication(s)%at%time%of%discharge.
9.
Evidence%of%intracranial%pathology,%including%but%not%limited%to,%intracranial%hemorrhage%(grade%II%or%
worse),%white%matter%injury%including%periventricular%leukomalacia%(PVL),%cerebral%%thrombosis,%cerebral%
infarction%or%stroke,%congenital%structural%central%nervous%system%(CNS)%abnormality%or%other%CNS%
problems%associated%with%adverse%neurologic%outcome.
10. Clinical%history%and/or%physical%exam%findings%consistent%with%neonatal%encephalopathy.
11. Other%documented%problems%that%could%result%in%neurologic%abnormality,%such%as:%history%of%CNS%
infection,%documented%sepsis,%bilirubin%at%excessive%levels%concerning%for%brain%injury%as%determined%by%
NICU%medical%staff,%history%of%cardiovascular%in%stability%as%determined%by%NICU%medical%staff%due%to:%
sepsis,%congential heart%disease,%patent%ductus%arteriosus%(PDA),%necrotizing%enterocolitis,%other%
documented%conditions.%
Had$a$CCS$Program,eligible$medical$condition$in$a$CCS$Program,
approved$NICU,$regardless$of$length$of$stay,$even%if%they%were%never%CCS%
Program%Clients%during%their%stay,%(as$per$California$Code$of$Regulations,$Title$22,$
Section$41515.1$through$41518.9,$CCS$Program$Medical$Eligibility$Regulations).
OR
Data%should%be%collected%on%infants/children%under%three%years%of%age%who%meet%California%Children’s%Services%(CCS)%HRIF%medical%eligibility%criteria%and who%
met%CCS%medical%eligibility%criteria%for%Neonatal%Intensive%Care%Unit%(NICU)%care%OR had%a%CCS%eligible%medical%condition%at%some%time%during%their%stay%in%a%
CCS^approved%NICU,%even%if%they%were%never%a%CCS%client.%%Infants$are$medically$eligible$for$the$HRIF$Program$when$the$infant:
CCS$HRIF$PROGRAM$MEDICAL$ELIGIBILITY$CRITERIA
HRIF$Program$Referral$Process:
Communication$is$between$the$CCS$ProgramGapproved$NICU$and$
HRIF$Program.
1.
The%discharging/referring%NICU/Hospital%will%refer%eligible%
infants%to%the%HRIF%Program%at%the%time%of%discharge%to%
home,%and%complete%the%“Referral/Registration%(RR)%Form”%
via%the%web,based HRIF^QCI%Reporting%System.
2.
The%discharging/referring%NICU/Hospital%or%HRIF%Program%
will%submit%a%Service%Authorization%Request%(SAR)%to%the%
local%CCS%Office%for%HRIF%Services.%(Service%Code%Group%[SCG]%
06,%should%be%requested).%
http://www.dhcs.ca.gov/services/ccs/cmsnet/Pages/SARTo
ols.aspx
3.
The%discharging/referring%NICU/Hospital%%will%send%a%copy%of%
the%Discharge%Summary%to%the%HRIF%Program.%%
Medical$eligibility$for$the$HRIF$Program$is$determined$by$the$County$CCS$
Program$or$Regional$Office$staff.$The$CCS$Program$is$also$required$to$
determine$residential$eligibility.$As$the$HRIF$Program$is$a$diagnostic$service,$
there$is$no$financial$eligibility$determination$performed$at$the$time$of$referral$
to$CCS.$However,$insurance$information$shall$be$obtained$by$CCS.$An$infant$or$
child$is$eligible$for$the$HRIF$Program$from$birth$up$to$3$years$of$age.
Met$CCS$medical$eligible$criteria$for$NICU$care,$in$a$CCS$Program,
approved$NICU,$regardless$of$length$of$stay,$(as$per$Number$Letter$05G0502,$
Medical$Eligibility$in$a$CCS$ProgramGapproved$NICU$or$the$most$current$N.L.).$NOTE:$Medical%
eligibility%includes%neonates%who%require%direct%admit%to%a%CCS^approved%PICU,%who%are%
never%admitted%to%a%CCS%Program^approved%NICU,%but%who%otherwise%meet%all%medical%
eligibility%criteria%for%HRIF%services.
AND$MET$ONE$OF$THE$FOLLOWING:
OR
UPDATED'01/2017
Birth$weight ≤$1500$grams$or$the$gestational$age$at$
birth$<$32$weeks.
Birth$weight$>$1500$grams$and$the$gestational$age$at$birth$≥$32$weeks$and one$of$the$
following$criteria$was$met$during$the$NICU$stay:

 
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 Procedures. A parent or legal guardian will sign an informed consent form prior to their infant’s 
participation. They will receive the consent form to review and will have any questions answered before 
scheduling a visit. At the time of the visit, they will inspect all equipment and toys have any questions 
answered before signing the consent form. A caregiver will be present and engaged throughout the data 
collection visit, which lasts approximately 1 hour in their home, or, if they prefer, in our laboratory. 
Infants will receive $20 compensation and souvenir photos for each visit. 
 
Data Collection. All infants will be assessed in their homes once per month (+ or – 5 days), from 3-6 
months of corrected age until sitting onset (can maintain independent sitting > 30 s) or 9 months 
corrected age, whichever occurs first. We have chosen this as our intervention endpoint because 1) once 
sitting is established, the way in which infants use their legs shifts drastically (from mostly supine and 
some prone free movement to primary use as postural stability) and 2) if they are not sitting 
independently by 9 months corrected age it is straightforward clinically to identify significantly delay. 
The goal of our intervention is to get them on the “right track” early, not to provide intervention once a 
significant delay has occurred. We have chosen to start our intervention at 3 months of corrected age, as 
this is just before relationships have been observed between leg movement frequency and later 
functional outcomes (as described in the siginificance section). Sensor Data. To record leg movement rate, 
infants will wear custom leg warmers with a pocket that securely holds a movement sensor at each ankle 
from the morning visit until bedtime. The caregivers will remove the leg warmers and sensors when they 
put their infant to bed for the night (~10-12 hours later). We will return to pick them up the next day. 
Amount and type of leg movements will be determoned using our exitisting, validated software 
algorithms. Assessments. We will measure the infant’s weight, length, head circumference, thigh and 
shank lengths and circumferences. We will document medical and therapy interventions being received 
and assess motor skills using the Alberta Infant Motor Scale (AIMS), a standardized, norm-referenced 
observational scale16. We will record 5 minutes of spontaneous movement video to have a visual 
reference for data. We will record the caregiver teaching the child a novel task and assess the caregiver-
infant interaction using the Nursing Child Assessment Teaching Scale (NCAST), a evidence based 
standardized-assement tool17.  
 
Intervention. At each visit, the caregiver will be reminded of the infant’s movement. The research team 
will spend 15 minutes interacting with the caregiver to determine possible ways to achieve the goal of 
1200 movements per hour of awake time, with a variety of movements. Strategies to increase leg 
movements will be encouraged based on the infant’s developmental level and what they demonstrate a 
response to, including: shake a toy when infant moves legs, sing a line of a song when infant moves legs, 
change the position of the infant to encourage more leg movement, or lightly tickle the legs and feet of the 
infant. The intervention will use the GAME (Goals - Activity - Motor Enrichment) protocol, a motor 
learning, environmental enrichment intervention that has recently been shown to be effective for 
improving motor skills in infants at high risk of cerebral palsy compared to standard care. The 
intervention is based on the principles of active motor learning, family centred care, parent coaching and 
environmental enrichment. Intervention was customised to parent goals and enrichment style and the 
child’s motor ability. To increase the dose of motor practice families were provided with a home program 
containing suggested activities according to identified goals14,18,19. We are expanding this effective 
intervention by applying it to a new population (infants broadly at risk as opposed to specifically at risk 
for cerebral palsy) and by specifically quantifying the dose of leg movement experience (amount and 
type). Otherwise, all intervention will be consistent with the established, published protocol. A 
customized logbook of all exercises with demonstration pictures of the baby, instructions, and tracking 
(amount and type) will be provided to the family each visit. Example Intervention Strategy. The research 
team and family determine that the baby likes Mom smiling and singing “You are my sunshine”. They 
decide that every time the baby’s diaper is changed, Mom will demonstrate by assisting the baby with 

 
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producing alternating kicks while smiling and singing for 10 total alternating kicks (5 each leg) and then 
encouraging the baby to perform alternating kicks (not assisting) for 15 seconds and responding with 
singing and smiling if he or she does. Five sets will be performed each diaper change. Fidelity. Caregivers 
will keep logbooks of the amount and type of movement experience they provide. This will assist our 
efforts to create a manual of intervention strategies for future grant proposals. Despite best intentions, 
however, logbooks are often incomplete; the GAME study reported ~ 50% completion 19. Our main 
fidelity measure in this study will be the movement rate and proportion of unilateral movements 
demonstrated by the infants across days and months. We will be able to compare these data to our 
existing obervational data to measure the intervention effect size.  
 
Follow Up: Families will be contacted by email or phone every 3-4 months from after the last visit until 
24 months of corrected age for updates on their child's medical and developmental status. 
 
Statistical test and analyses were performed using SPSS (Version 24; IBM, Corporation, Armonk, NY, 
USA). We first checked all variables for normality by plotting histograms and visually inspecting the data. 
Given the sample size and visual inspection of the variables, we chose to analyze our data using non-
parametric statistics. The median and range were used to represent all descriptive statistics for the first 
and last visit. Wilcoxon Signed Ranked tests (alpha = 0.05) were used to compare the leg movement rates, 
adherence, and NCAST-Teaching total score to test for significant differences between the first and last 
visits. Spearman rank order correlations (alpha = 0.05) were used to test for significant relationships 
between quality of caregiver-child interaction and adherence to the intervention and leg movement rate 
at all visits.  
 
Sample size justification. We determined our sample size of 12 for this pilot intervention study based on 
our observational pilot data. In our pilot data, we found large effect sizes (Cohen’s d = 0.8 – 1.3) for leg 
movement quantity (movements per hour of awake time) between 12 infants with TD and 24 infants AR 
(anticipate ~12 good and ~12 poor neuromotor outcomes). With the planned primary comparison of leg 
movement of those who received intervention (N = 12) versus those who did not (N = 24), we should be 
able to detect an effect of Cohen’s d of 1.0 at 9 months, with alpha = 0.05 and 80% power.  
 
Potential Risks 
Wearable Sensors: There is a small risk of skin irritation from wearing the legwarmers all day. Parents 
will be able to visually see their infants’ feet at all times (they are not covered) and can remove the 
legwarmers briefly as desired to inspect their infant’s skin. Although the movement sensors are small, 
they are not small enough to present a choking hazard. They measure 1.4 inches by 1.9 inches, larger than 
the standard choking hazard guidelines.20  
 
 
Storage of Materials. There is a small risk of disclosure of participant’s personal information. Data 
collected from participants includes biological data of leg movement activity, video recordings and health 
status information. All information collected will be kept private and secure. Password protection and 
secure internal computer networks and REDCap, a HIPAA-compliant database system hosted by USC, will 
be used to collect and store data. Hard copies of data, including 2 backup copies on external hard drives, 
will be stored in a locked, waterproof, fireproof safe in a locked room in a secured building (keys, 
identification cards) on a secured campus (identification cards, security patrol). Unique identifier codes 
will be used to separate all data collected from any personal identifying information. Laboratory 
members will have access to data identified by code for analysis and manuscript preparation, while only 
the PI and Research Assistant (RA) will have access to identifying information for participant tracking 
purposes. 
 
Intervention. As is typical with trying to get an infant to perform any desired behavior, there is a risk that 

 
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the infant will become distressed as the caregiver attempts to get the infant to move his or her legs more 
(the intervention). Caregivers will be encouraged to soothe their infant and try the intervention again at a 
later time of the day. If the infant still becomes distressed, the caregiver will make a note of this and not 
perform the distressing activity further.  
 
References 
 
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