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Premature Birth of NewbornRESILIENCENCT02623400

The Effect of Perinatal Stress on the Development of Preterm Infants

An observational study of Premature Birth of Newborn, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In this project, the investigators will study a cohort of preterm infants, together with their parents, during NICU hospitalization and follow their developmental trajectory until the age of two. Read more about this study

Who is it for?
Ages Up to 34 weeks
Conditions the study is for
Premature Birth of Newborn
How many people
174 participants
Where
1 siteBelgium
Study dates
Jul 2016to Dec 2025
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 34 weeks
  • All sexes
  • No healthy volunteers
  • Child

Study population: The investigators will approach parents of preterm infants born before 34 weeks gestational age and/or with a birth weight lower than 1500g. Ideally, pregnant women admitted to the maternal intensive care (MIC) for preterm labor will be informed about the study together with their partner, and asked for consent. But in a number of preterm infants prenatal inclusion will not be possible (e.g. birth in another hospital, preterm premature rupture of the membranes,…) . Parents of infants in this subgroup, who are admitted to the Neonatal Intensive Care Unit (NICU) at the University Hospitals Leuven, will be informed and asked for consent within 3 days after birth.

Who may be able to join

  • Preterm infants born before 34 weeks gestational age and/or with a birth weight lower than 1500g and their parents

Who cannot join

  • Age < 18yr.
  • Unable to speak and understand Dutch, French or English
  • Unstable medical (somatic and/or psychiatric) disease in the parent(s)
  • The presence of a major congenital malformation in the preterm infant

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • UZLEUVEN

    Leuven, Vlaams-Brabant, 3000

Other trials in Belgium

About this study

In this project, the investigators will study a cohort of preterm infants, together with their parents, during NICU hospitalization and follow their developmental trajectory until the age of two.

An important first scientific goal of the project is to identify objective stress markers that can be obtained easily and non-invasively in preterm infants during NICU hospitalization. This will include the development of novel techniques to measure stress related heart rate variability (HRV) and EEG maturation, as well as sleep stage markers for preterm infants.

Read more

Secondly, the investigators will study the emotional and bonding processes in parents of preterm infants. Parental distress in terms of depressive symptoms, anxiety, perceived stress and parent-infant bonding will be measured at multiple measuring points. This will enable the validation of psychometric instruments in the specific population of parents of preterm infants. Also, the investigators can investigate the effect and predictive value of the course of parental depression, anxiety and stress scores on child's developmental outcome and on parent-infant bonding and attachment.

Thirdly, studies on epigenetic changes due to prenatal stress are still scarce in humans. In this study, the investigators will include a cohort of mothers experiencing profound prenatal stress due to preterm labor, which will complement the earlier work that has been carried out in a low-risk population. The investigators expect more profound changes in methylation state of the NR3C1 and other promotor regions in their cohort of mothers exposed to important prenatal stress. Secondly, the methylation of oxytocin receptor regions will be studied in relation to attachment and bonding.

An important overall goal of the project is to develop a Perinatal Stress Calculator that studies the value of the different neonatal, endocrinological, psychological and physiological stress-related parameters to predict differences in psychomotor, cognitive, behavioral, and emotional development. This longitudinal study design will enable the investigators to use the perinatal stress calculator to study the relation between the perinatal stress parameters and later developmental disabilities such as motor impairment, cognitive deficits, language delay but also social and behavioral problems such as attentional deficits and emotional self-regulation dysfunction.

Read the detailed description

Project goals and their impact on societal challenges:

Objective 1: The first goal of the project is to identify objective stress markers that can be obtained easily and non-invasively in preterm infants during NICU hospitalization. This will include the development of novel techniques to measure stress related heart rate variability (HRV) and EEG maturation, as well as sleep stage markers. On a societal and economical level, reliable measures of the degree of distress in a hospitalized preterm infant will enable the evaluation of the direct effects of stress-reducing interventions such as NICU architecture changes and early intervention programs in cost benefit analyses. (Work package 1)

Objective 2: Second, the investigators aim to study the emotional and bonding processes in parents of preterm infants. Parental distress in terms of depressive symptoms, anxiety, perceived stress and parent-infant bonding will be measured at multiple time points. This will lead to the validation of psychometric instruments in the specific population of parents of preterm infants. Also, the investigators will investigate the effect and predictive value of the course of parental depression, anxiety and stress on children's developmental outcome and on parent-infant bonding and attachment. Knowledge about the short and long term risks of parental emotional distress are important to implement sufficient and tailored support to parents. (Work package 2)

Objective 3: Third, studies on epigenetic changes due to prenatal stress are still scarce in humans. Recently, preliminary evidence was found that prenatal stress affects the methylation state of the NR3C1promotor regions (Hompes et al., 2013). In this study, the investigators will include a cohort of mothers experiencing profound prenatal stress due to preterm labor, which will complement the earlier work that has been carried out in a low-risk population. The investigators expect more profound changes in methylation state of the NR3C1 and other promotor regions in this cohort. The methylation of oxytocin receptor genes will also be studied in relation to attachment and bonding. On a societal level, knowledge about the impact of adverse maternal psychological well-being during pregnancy on the epigenome is important, for example to justify prevention campaigns. (Work package 3)

Overall objective: An important overall goal of the project is to develop a Perinatal Stress Calculator that combines the values of the different neonatal, endocrinological, psychological and physiological stress-related parameters to predict differences in psychomotor, cognitive, behavioural, and emotional development (Work package 5). This prospective longitudinal study design will enable the investigators to use the perinatal stress calculator to study the relation between the perinatal stress parameters and later developmental disabilities such as motor impairment, cognitive deficits, and language delay but also social and behavioural problems such as attentional deficits and emotional self-regulation dysfunction (Work package 4). The investigators will not only be able to weigh perinatal infant characteristics in the model, but also parental characteristics such as distress, resilience and personality as well as bonding and attachment measures. On a societal and economic level, the results of the project will be important for health policy decision-making. Improved prediction of the developmental trajectory of preterm infants could lead to earlier and targeted interventions to decrease maladaptive outcomes.

Keywords
preterm birth, perinatal stress, growth and development
Medical subject headings
Premature Birth

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02623400
Study groupRoleWhat they receive
Preterm infants and their parentsPreterm infants born before 34 weeks gestational age and/or with a birth weight lower than 1500g and their parents.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Attachment behavior (will be assessed using questionnaires and both free and structured observations of the child-parent interaction)

    Measured: 24 months

Secondary outcomes (12)
  1. Psychomotor development (will be assessed using Infant Scales of Development)

    Measured: 24 months

  2. Cognitive development (will be assessed using Infant Scales of Development)

    Measured: 24 months

  3. Cognitive development (executive functioning will be assessed by the Snack Delay Task)

    Measured: 24 months

  4. Language development (will be assessed using Infant Scales of Development)

    Measured: 24 months

  5. Language development (will be assessed using the NCDI-2A)

    Measured: 24 months

  6. Behavioral development (will be assessed using Infant Scales of Development )

    Measured: 24 months

  7. Behavioral development (will be assessed by questioning both parents and external caregivers)

    Measured: 24 months

  8. Physical development (will be assessed by measuring children's height)

    Measured: 24 months

  9. Physical development (will be assessed by measuring children's weight)

    Measured: 24 months

  10. Physical development (will be assessed by measuring children's head circumference)

    Measured: 24 months

  11. Emotional development (will be assessed using the Bayley Scales of Infant Development III)

    Measured: 24 months

  12. Emotional development (will be assessed by questioning both parents and external caregivers)

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Dec 2015 (estimated)
  2. Study startJul 2016
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
174 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02623400
Sponsor's protocol ID
S58807
Acronym
RESILIENCE
Status last verified
Jul 2024
First submitted
23 Nov 2015
Last updated
3 Jul 2024
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • Aarnoudse-Moens CS, Weisglas-Kuperus N, van Goudoever JB, Oosterlaan J. Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics. 2009 Aug;124(2):717-28. doi: 10.1542/peds.2008-2816. Epub 2009 Jul 27.

    PubMed 19651588
  • Andre M, Lamblin MD, d'Allest AM, Curzi-Dascalova L, Moussalli-Salefranque F, S Nguyen The T, Vecchierini-Blineau MF, Wallois F, Walls-Esquivel E, Plouin P. Electroencephalography in premature and full-term infants. Developmental features and glossary. Neurophysiol Clin. 2010 May;40(2):59-124. doi: 10.1016/j.neucli.2010.02.002. Epub 2010 Mar 16.

    PubMed 20510792
  • Bosmans G, De Raedt R, Braet C. The invisible bonds: does the secure base script of attachment influence children's attention toward their mother? J Clin Child Adolesc Psychol. 2007 Oct-Dec;36(4):557-67. doi: 10.1080/15374410701662717.

    PubMed 18088214
  • Bosmans G, Braet C, Koster E, De Raedt R. Attachment security and attentional breadth toward the attachment figure in middle childhood. J Clin Child Adolesc Psychol. 2009 Nov;38(6):872-82. doi: 10.1080/15374410903258926.

    PubMed 20183670
  • Bowlby J, Attachment and Loss: Attachment V, Basic Books, 1969.

  • Braeken MA, Kemp AH, Outhred T, Otte RA, Monsieur GJ, Jones A, Van den Bergh BR. Pregnant mothers with resolved anxiety disorders and their offspring have reduced heart rate variability: implications for the health of children. PLoS One. 2013 Dec 10;8(12):e83186. doi: 10.1371/journal.pone.0083186. eCollection 2013.

    PubMed 24340091
  • Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Circulation. 1996 Mar 1;93(5):1043-65. No abstract available.

    PubMed 8598068
  • Carpenter LL, Carvalho JP, Tyrka AR, Wier LM, Mello AF, Mello MF, Anderson GM, Wilkinson CW, Price LH. Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol Psychiatry. 2007 Nov 15;62(10):1080-7. doi: 10.1016/j.biopsych.2007.05.002. Epub 2007 Jul 27.

    PubMed 17662255
  • Cassidy J. The nature of the child's ties. Handbook of attachment: Theory, research, and clinical implications 2:3-22, 1999.

  • Cecchini M, Baroni E, Di Vito C, Piccolo F, Lai C. Newborn preference for a new face vs. a previously seen communicative or motionless face. Infant Behav Dev. 2011 Jun;34(3):424-33. doi: 10.1016/j.infbeh.2011.04.002. Epub 2011 May 8.

    PubMed 21550665
  • Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009 Jul;5(7):374-81. doi: 10.1038/nrendo.2009.106. Epub 2009 Jun 2.

    PubMed 19488073
  • Coolen MW, Statham AL, Gardiner-Garden M, Clark SJ. Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Res. 2007;35(18):e119. doi: 10.1093/nar/gkm662. Epub 2007 Sep 13.

    PubMed 17855397
  • Dykas MJ, Ehrlich KB, Cassidy J. Links between attachment and social information processing: examination of intergenerational processes. Adv Child Dev Behav. 2011;40:51-94. doi: 10.1016/b978-0-12-386491-8.00002-5.

    PubMed 21887959
  • Feldman R, Gordon I, Zagoory-Sharon O. Maternal and paternal plasma, salivary, and urinary oxytocin and parent-infant synchrony: considering stress and affiliation components of human bonding. Dev Sci. 2011 Jul;14(4):752-61. doi: 10.1111/j.1467-7687.2010.01021.x. Epub 2010 Dec 16.

    PubMed 21676095
  • Feldman R, Weller A, Zagoory-Sharon O, Levine A. Evidence for a neuroendocrinological foundation of human affiliation: plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding. Psychol Sci. 2007 Nov;18(11):965-70. doi: 10.1111/j.1467-9280.2007.02010.x.

    PubMed 17958710

Questions about this trial

What is this clinical trial studying?

An observational study of Premature Birth of Newborn, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Attachment behavior (will be assessed using questionnaires and both free and structured observations of the child-parent interaction) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02623400, which also lists 58 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2024.

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