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Trial registered on ANZCTR


Registration number
ACTRN12619000404123
Ethics application status
Approved
Date submitted
7/03/2019
Date registered
13/03/2019
Date last updated
3/12/2020
Date data sharing statement initially provided
13/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The impact of persisting pain following surgery in neonates
Scientific title
The biopsychosocial impact of the persisting need for pain relief in infants following major surgery during the neonatal period: a prospective cohort study with one year follow-up
Secondary ID [1] 297642 0
None
Universal Trial Number (UTN)
U1111-1229-6222
Trial acronym
pSPIN
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Persistent surgical pain 311914 0
Neurodevelopment and psychosocial development in surgical neonates and infants 311915 0
Condition category
Condition code
Anaesthesiology 310497 310497 0 0
Pain management
Physical Medicine / Rehabilitation 310500 310500 0 0
Physiotherapy
Neurological 310501 310501 0 0
Studies of the normal brain and nervous system
Reproductive Health and Childbirth 310502 310502 0 0
Complications of newborn
Mental Health 310552 310552 0 0
Learning disabilities

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study will be a prospective cohort study with one year follow-up of infants who underwent major surgery before 28 days of age. Major surgery is defined as an open (e.g., gastroschisis) or opening of a major body cavity including the head, thorax, and abdomen. The exposure the study is interested in is the impact of the persisting need for analgesia, operationalised as the duration of treated pain, during NICU admission. Pain in the infant will be measured using the Modified Pain Assessment Tool as well as the Echelle Douleur Inconfort Nouveau-ne (English version called the EDIN or Newborn Pain Scale). Details about infants' analgesia requirements will also be gathered during their admission in the NICU.
Intervention code [1] 313876 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319359 0
Gross motor skills
This will primarily be assessed using the Alberta Infant Motor Scale (AIMS-2) at 4, 8, and 12 months corrected age. Parents' perception of infant gross motor skill development will be assessed using the Ages & Stages Questionnaire at 4, 8, and 12 months. Because the Bayley's Scale of Infant and Toddler Development is a commonly used neurodevelopmental assessment tool, we will also collect data from this assessment at 3 and 12 months corrected age.
Timepoint [1] 319359 0
3, 4, 8, 12 (primary endpoint) months corrected age.
Secondary outcome [1] 367886 0
Cognition/problem-solving will be assessed using the Ages and Stages Questionnaire, and the Bayley's Scale for Infant and Toddler Development.

Timepoint [1] 367886 0
Ages and Stages Questionnaire: 4, 8, and 12 months corrected age.
Bayley's Scale for Infant and Toddler Development: 3 and 12 months corrected age.
Secondary outcome [2] 367887 0
Complications following surgery which include:
a) Incidence of iatrogenic neonatal abstinence syndrome or opioid withdrawal syndrome
b) Time to first suck
c) Difficulty gaining weight
d) Length of stay
e) Time to extubation
f) Mortality
This information will be gathered by looking at the infant's medical records during admission to the NICU.
Timepoint [2] 367887 0
During admission in neonatal intensive care unit
Secondary outcome [3] 367888 0
Growth will be assessed using:
a. Weight percentile
b. Head circumference percentile
c. Length percentile (only at birth, three and 12 months)
This information will be gathered by looking at the infant's medical records during admission to the NICU. Follow-up data will be collected during routine follow-up clinics at 3 and 12 months corrected age.
Timepoint [3] 367888 0
At discharge from NICU; 3 and 12 months corrected age
Secondary outcome [4] 367889 0
Psychosocial functioning will be assessed using three tools:

1. Infant-to-Parent Attachment Questionnaire (IPAQ)
2. Infant Quality of Life Questionnaire (QUALIN)
3. Revised Infant Behaviour Questionnaire (IBQ-R)
Timepoint [4] 367889 0
Infant-to-Parent Attachment Questionnaire (IPAQ): during admission
Infant Quality of Life Questionnaire (QUALIN) and Revised Infant Behaviour Questionnaire (IBQ-R): 4, 8, 12 months corrected age
Secondary outcome [5] 368053 0
Fine Motor Skills - will be assessed by the Ages and Stages Questionnaire, and Bayley's scale of Infant and Toddler Development
Timepoint [5] 368053 0
Ages and Stages Questionnaire: 4, 8, and 12 months corrected age
Bayley's scale of Infant and Toddler Development: 3 and 12 months corrected age
Secondary outcome [6] 368056 0
Receptive and Expressive Language will be assessed using the Ages & Stages Questionnaire, and Bayley's scale of Infant and Toddler Development
Timepoint [6] 368056 0
Ages & Stages Questionnaire: 4, 8, and 12 months corrected age
Bayley's scale of Infant and Toddler Development: 3 and 12 months corrected age
Secondary outcome [7] 368057 0
Personal/Social Skills will be assessed using the Ages and Stages Questionnaire
Timepoint [7] 368057 0
4, 8, and 12 months corrected age

Eligibility
Key inclusion criteria
i. Had at least one major surgery less than 28 days of age. Major surgery is defined as an open (e.g., gastroschisis) or opening of a major body cavity including the head, thorax, and abdomen;
ii. Were admitted to the neonatal intensive care unit;
iii. Have at least one parent/caregiver who is able to understand written and spoken English in order to participate.
Minimum age
0 Hours
Maximum age
5 Months
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
i. Are diagnosed with neonatal abstinence syndrome from maternal drug use, or
ii. Are known to the Family and Community Services.
iii. Neonates who are expected to undergo cardiopulmonary bypass.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Multiple regression analysis (ANCOVA) or logistic regression analysis will be used to analyse the data.
Subgroup analysis with be performed for those neonates who are determined to be at risk of cerebral palsy by routine developmental follow-up. At GCNIC, the HINE and GMs are used at three months corrected age to screen for infants at high risk of cerebral palsy. Risk of neurological impairment will be determined by scores on these assessments.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/03/2019
Actual
27/03/2019
Date of last participant enrolment
Anticipated
31/12/2021
Actual
Date of last data collection
Anticipated
31/03/2021
Actual
Sample size
Target
138
Accrual to date
44
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 13320 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 25920 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 302173 0
University
Name [1] 302173 0
Macquarie University
Country [1] 302173 0
Australia
Funding source category [2] 302219 0
Hospital
Name [2] 302219 0
Grace Centre for Newborn Care, Children's Hospital at Westmead
Country [2] 302219 0
Australia
Primary sponsor type
University
Name
Macquarie University
Address
Department of Health Professions
75 Talavera Road
Macquarie University NSW 2109
Country
Australia
Secondary sponsor category [1] 302014 0
Hospital
Name [1] 302014 0
Grace Centre for Newborn Care, Children's Hospital at Westmead
Address [1] 302014 0
Corner Hawkesbury Road and Hainsworth Street, Westmead NSW 2145
Country [1] 302014 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302855 0
Sydney Children's Hospital Network Human Research Ethics Committee
Ethics committee address [1] 302855 0
Corner Hawkesbury Road and Hainsworth Street
Locked Bag 4001
Westmead NSW 2145
Sydney Australia
Ethics committee country [1] 302855 0
Australia
Date submitted for ethics approval [1] 302855 0
17/10/2018
Approval date [1] 302855 0
28/10/2018
Ethics approval number [1] 302855 0
LNR/18/SCHN/446

Summary
Brief summary
Clinicians and researchers agree that neonates (infants between 0 and 27 days old following birth) admitted to the neonatal intensive care unit (NICU) experience pain. In addition to being a source of immediate distress and agitation for neonates, pain may also have consequences for neonates during their admission and also extending beyond discharge from the NICU. Researchers have hypothesised that early-life exposure to pain may alter the development of the brain, and thus hinder an infant’s ability to reach age-appropriate developmental milestones. Indeed, acute pain, or procedure-related pain, has been shown to result in long-lasting impacts on developmental outcomes such as brain development (neurodevelopment), growth, and psychosocial functioning. Specifically, researchers have suggested a dose-response relationship between pain in the NICU and poor long-term outcomes. Studies have shown that a greater frequency of painful procedures in the NICU may result in poor cognitive and motor development at eight and 18 months of age, poor cognitive outcomes at school age, increased sensitivity to pain in early childhood, higher rate of internalising behaviours at school age such as fearfulness and social withdrawal, and low weight and head circumference. Furthermore, the impact of painful experiences on the infant’s social wellbeing is unknown. In particular, the role of ongoing pain on the infant-to-parent relationship at such a critical period of relationship formation has not been investigated.

Depending on their underlying medical condition, neonates and infants in the NICU undergo a wide range of interventions, some of which may contribute to ongoing pain and distress. It has been difficult to establish whether pain has a direct impact on the developmental trajectory of infants. In order to elucidate whether there is a dose-response relationship between pain experience and developmental outcomes, it is important to determine if there is an impact of the duration of treated pain on the developing infant.

The primary objective of this study is to determine whether the persisting need for analgesia, operationalised as the duration of treated pain, during NICU admission has an impact on gross motor skills after discharge. Secondary objectives of this study are to determine whether the duration of treated pain during NICU admission has an impact on 1) other neurodevelopmental outcomes including cognition/problem-solving, fine motor skills, receptive and expressive language, and personal-social skills, 2) complications following surgery, 3) growth, and 4) psychosocial functioning, of the infant.
Trial website
None
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 91618 0
Prof Julia Hush
Address 91618 0
Department of Health Professions
Ground Floor, 75 Talavera Road
Macquarie University NSW 2109
Australia
Country 91618 0
Australia
Phone 91618 0
+61 2 9850 6619
Fax 91618 0
Email 91618 0
[email protected]
Contact person for public queries
Name 91619 0
Emre Ilhan
Address 91619 0
Department of Health Professions
Ground Floor, 75 Talavera Road
Macquarie University NSW 2109
Australia
Country 91619 0
Australia
Phone 91619 0
+61 2 9850 6619
Fax 91619 0
Email 91619 0
[email protected]
Contact person for scientific queries
Name 91620 0
Emre Ilhan
Address 91620 0
Department of Health Professions
Ground Floor, 75 Talavera Road
Macquarie University NSW 2109
Australia
Country 91620 0
Australia
Phone 91620 0
+61 2 9850 6619
Fax 91620 0
Email 91620 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Considering the population under study, we believe that sharing of individual data would be without the consent of the individuals and families involved in the research would be unethical.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.