STRess and Outcomes in Neonatal Intensive Care Unit Graduates (STRONG)
| ISRCTN | ISRCTN62164166 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN62164166 |
- Submission date
- 12/02/2019
- Registration date
- 25/02/2019
- Last edited
- 25/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
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
Contact information
Scientific
Hanzeplein 1
Groningen
9713GZ
Netherlands
| Phone | +31(0)50 361 4215 |
|---|---|
| n.h.van.dokkum@umcg.nl |
Study information
| Study design | Observational cross-sectional cohort study with 1-year follow-up |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Other |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | STRess and Outcomes in NICU Graduates (STRONG): Studying the effects of stress exposure on preterm infants’ epigenetic profile and early childhood outcomes |
| Study acronym | STRONG |
| Study objectives | 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(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| 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 study start date | 01/09/2018 |
| Completion date | 30/06/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Both |
| Target number of participants | 108 |
| Total final enrolment | 45 |
| Key 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 |
| Key exclusion criteria | 1. Inability of parents to speak/understand Dutch |
| Date of first enrolment | 01/09/2019 |
| Date of final enrolment | 01/03/2021 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Groningen
9713GZ
Netherlands
Sponsor information
Hospital/treatment centre
Hanzeplein 1
Groningen
9713GZ
Netherlands
| Phone | +31 (0)50 361 4215 |
|---|---|
| n.h.van.dokkum@umcg.nl | |
"ROR" |
https://ror.org/03cv38k47 |
Funders
Funder type
University/education
Government organisation / Local government
- Alternative name(s)
- University Medical Center Groningen, UMCG
- Location
- Netherlands
Results and Publications
| Intention to publish date | 30/06/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | We plan to publish our results in high-impact peer-reviewed journals. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | Course of stress | 09/12/2021 | 10/07/2023 | Yes | No |
| Results article | 02/07/2021 | 25/04/2025 | Yes | No | |
| Results article | Quality of life | 08/04/2024 | 25/04/2025 | Yes | No |
Editorial Notes
25/04/2025: Publication references added.
10/07/2023: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
01/08/2019: The ethics approval was added.
17/07/2019: The recruitment start date was changed from 01/05/2019 to 01/09/2019.
01/03/2019: Internal review.
