Plain English Summary
Background and study aims
Premature birth has many effects during childhood, such as delayed growth and developmental and behavioral problems. Being admitted to a Neonatal Intensive Care Unit and encountering many stressful circumstances may be a contributing factor. In the last decades, evidence has emerged concerning stress and its long-lasting effects with chemical modifications of DNA. The aim of this study is to identify the most stressful stimuli and lead to a better understanding of potential targets for early intervention. Moreover, we aim to investigate the associations between stress and childhood outcomes.
Who can participate?
Anyone who is admitted to the Neonatal Intensive Care Unit of the University Medical Center Groningen can take part.
What does the study involve?
The study involves participants being monitored closely during NICU stay and during the follow-up period of 1 year after birth. Data on stress exposure during NICU stay will be collected from medical files and from rating by nurses. Children will be videotaped twice to study general movements in relation to stress exposure. Biological samples will be collected regularly to investigate the epigenetic profile in relation to stress exposure. Parents will be asked to complete several questionnaires during the first year of life, to study the effects of stress on childhood outcomes.
What are the possible benefits and risks of participating?
The possible benefits of this cohort study that eventually we will find targets for stress reduction and neurodevelopmental improvement. We do not expect any burdens or risks for participants, as the study is purely observational.
Where is the study run from?
Neonatal Intensive Care Unit of the University Medical Center Groningen, Hanzeplein 1, Groningen, Netherlands
When is the study starting and how long is it expected to run for?
March 2019 until March 2021
Who is funding the study?
Universitair Medisch Centrum Groningen (University Medical Center Groningen)
Who is the main contact?
Hanneke van Dokkum
n.h.van.dokkum@umcg.nl
Trial website
Contact information
Type
Scientific
Primary contact
Miss Hanneke van Dokkum
ORCID ID
Contact details
Hanzeplein 1
Groningen
9713GZ
Netherlands
+31(0)50 361 4215
n.h.van.dokkum@umcg.nl
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
Nil known
Study information
Scientific title
STRess and Outcomes in NICU Graduates (STRONG): Studying the effects of stress exposure on preterm infants’ epigenetic profile and early childhood outcomes
Acronym
STRONG
Study hypothesis
To investigate the effects of stress exposure in preterm infants on their epigenetic profile, in particular, the NR3C1 and SLC6A4 genes, and evaluate the development of the epigenetic profile over time.
Ethics approval
Approved 30/07/2019, Medical Ethical Committee of the University Medical Center Groningen (Postbus 30.001, 9700 RG Groningen, The Netherlands; Tel: +31 (0)50 361 4204; metc@umcg.nl), ref: 2019.128
Study design
Observational cross-sectional cohort study with 1-year follow-up
Primary study design
Observational
Secondary study design
Cohort study
Trial setting
Hospitals
Trial type
Other
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet.
Condition
Stress exposure during Neonatal Intensive Care Treatment
Intervention
Participants in this observational cohort study will be treated according to usual care, we will collect data from medical files (stress measures) and ask nurses to rate stress. Children will be videotaped twice (i.e. during NICU stay and at 3 months when they are at home) to study the general movements. Moreover, we will ask parents to complete several questionnaires during stay in the Neonatal Intensive Care Unit (NICU) and during the follow-up period of 1 year after birth. Finally, we will non-invasively collect placenta, cord blood and stool during NICU stay and in the first year of life to determine the epigenetic profile. The duration of observation will thus be the NICU stay period and follow-up will last 1 year.
Intervention type
Other
Phase
Drug names
Primary outcome measure
DNA methylation pattern of our primary stress-related candidate gene (NR3C1 gene), measured in gastro-intestinal cells, cord blood and placenta using pyrosequencing, in relation to stress exposure measured at birth, before discharge, 3, 6, 9 and 12 months of age.
Secondary outcome measures
1. DNA methylation patterns of our other stress-related candidate genes measured in gastro-intestinal cells, cord blood and placenta using pyrosequencing, in relation to stress exposure
2. Stress levels of the child, measured by the neonatal infant stressor scale each day during stay in the neonatal intensive care unit,
3. Stress levels of the child according to the neonatal nurses, using a Likert scale each shift and using the COMFORT neo scores each shift.
4. Short-term neurological outcome, as assessed by General Movements Assessment at two weeks and three months of age
5. Long-term neurological outcome, as assessed by the Ages and Stages Questionnaire at 12 months of age
6. Infant quality of life, as assessed by the Infant Quality of Life Instrument at 3, 6, 9 and 12 months of age
Overall trial start date
01/09/2018
Overall trial end date
30/06/2022
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Gestational age below 30 weeks and/or birth weight below 1000 grams
2. Admittance to Neonatal Intensive Care Unit of the University Medical Center Groningen
3. Written informed consent from both parents
Participant type
Patient
Age group
Neonate
Gender
Both
Target number of participants
108
Participant exclusion criteria
1. Inability of parents to speak/understand Dutch
Recruitment start date
01/09/2019
Recruitment end date
01/03/2021
Locations
Countries of recruitment
Netherlands
Trial participating centre
University Medical Center Groningen
Hanzeplein 1
Groningen
9713GZ
Netherlands
Sponsor information
Organisation
Universitair Medisch Centrum Groningen
Sponsor details
Hanzeplein 1
Groningen
9713GZ
Netherlands
+31 (0)50 361 4215
n.h.van.dokkum@umcg.nl
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
University/education
Funder name
Universitair Medisch Centrum Groningen
Alternative name(s)
University Medical Center Groningen, UMCG
Funding Body Type
government organisation
Funding Body Subtype
Local government
Location
Netherlands
Results and Publications
Publication and dissemination plan
We plan to publish our results in high-impact peer-reviewed journals.
IPD sharing statement:
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request
Intention to publish date
30/06/2023
Participant level data
Available on request
Basic results (scientific)
Publication list