Condition category
Pregnancy and Childbirth
Date applied
12/02/2019
Date assigned
25/02/2019
Last edited
01/03/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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

Medical Ethical Committee of the University Medical Center Groningen (Postbus 30.001, 9700 RG Groningen, The Netherlands; Tel: +31 (0)50 361 4204;, Email: metc@umcg.nl - approval pending

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

01/05/2019

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

government non-federal

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

Publication citations

Additional files

Editorial Notes

01/03/2019: Internal review.