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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]

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

Neurodevelopment and psychosocial development in surgical neonates and infants

Condition category

Condition code

Anaesthesiology

Pain management

Physical Medicine / Rehabilitation

Physiotherapy

Neurological

Studies of the normal brain and nervous system

Reproductive Health and Childbirth

Complications of newborn

Mental Health

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]

Not applicable

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

3, 4, 8, 12 (primary endpoint) months corrected age.

Secondary outcome [1]

Cognition/problem-solving will be assessed using the Ages and Stages Questionnaire, and the Bayley's Scale for Infant and Toddler Development.

Timepoint [1]

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]

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]

During admission in neonatal intensive care unit

Secondary outcome [3]

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]

At discharge from NICU; 3 and 12 months corrected age

Secondary outcome [4]

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]

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]

Fine Motor Skills - will be assessed by the Ages and Stages Questionnaire, and Bayley's scale of Infant and Toddler Development

Timepoint [5]

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]

Receptive and Expressive Language will be assessed using the Ages & Stages Questionnaire, and Bayley's scale of Infant and Toddler Development

Timepoint [6]

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]

Personal/Social Skills will be assessed using the Ages and Stages Questionnaire

Timepoint [7]

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?

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

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

The Children's Hospital at Westmead - Westmead

Recruitment postcode(s) [1]

2145 - Westmead

Funding & Sponsors

Funding source category [1]

University

Name [1]

Macquarie University

Address [1]

Department of Health Professions
75 Talavera Road
Macquarie University NSW 2109

Country [1]

Australia

Funding source category [2]

Hospital

Name [2]

Grace Centre for Newborn Care, Children's Hospital at Westmead

Address [2]

Corner Hawkesbury Road and Hainsworth Street, Westmead NSW 2145

Country [2]

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]

Hospital

Name [1]

Grace Centre for Newborn Care, Children's Hospital at Westmead

Address [1]

Corner Hawkesbury Road and Hainsworth Street, Westmead NSW 2145

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Sydney Children's Hospital Network Human Research Ethics Committee

Ethics committee address [1]

Corner Hawkesbury Road and Hainsworth Street
Locked Bag 4001
Westmead NSW 2145
Sydney Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/10/2018

Approval date [1]

28/10/2018

Ethics approval number [1]

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

Prof Julia Hush

Address

Department of Health Professions
Ground Floor, 75 Talavera Road
Macquarie University NSW 2109
Australia

Country

Australia

Phone

+61 2 9850 6619

Fax

julia.hush@mq.edu.au

Contact person for public queries

Name

Emre Ilhan

Address

Department of Health Professions
Ground Floor, 75 Talavera Road
Macquarie University NSW 2109
Australia

Country

Australia

Phone

+61 2 9850 6619

Fax

emre.ilhan@hdr.mq.edu.au

Contact person for scientific queries

Name

Emre Ilhan

Address

Department of Health Professions
Ground Floor, 75 Talavera Road
Macquarie University NSW 2109
Australia

Country

Australia

Phone

+61 2 9850 6619

Fax

emre.ilhan@hdr.mq.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.

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