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The Effect of Perinatal Stress on the Development of Preterm Infants (RESILIENCE)

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ClinicalTrials.gov Identifier: NCT02623400
Recruitment Status : Recruiting
First Posted : December 7, 2015
Last Update Posted : May 4, 2018
Sponsor:
Collaborator:
KU Leuven
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief 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.

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.

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.


Condition or disease
Premature Birth of Newborn

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.


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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effect of Perinatal Stress on the Development of Preterm Infants
Study Start Date : July 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : September 2019

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



Primary Outcome Measures :
  1. Attachment behavior (will be assessed using questionnaires and both free and structured observations of the child-parent interaction) [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Psychomotor development (will be assessed using Infant Scales of Development) [ Time Frame: 24 months ]
  2. Cognitive development (will be assessed using Infant Scales of Development) [ Time Frame: 24 months ]
  3. Cognitive development (executive functioning will be assessed by the Snack Delay Task) [ Time Frame: 24 months ]
  4. Language development (will be assessed using Infant Scales of Development) [ Time Frame: 24 months ]
  5. Language development (will be assessed using the NCDI-2A) [ Time Frame: 24 months ]
  6. Behavioral development (will be assessed using Infant Scales of Development ) [ Time Frame: 24 months ]
  7. Behavioral development (will be assessed by questioning both parents and external caregivers) [ Time Frame: 24 months ]
  8. Physical development (will be assessed by measuring children's height) [ Time Frame: 24 months ]
  9. Physical development (will be assessed by measuring children's weight) [ Time Frame: 24 months ]
  10. Physical development (will be assessed by measuring children's head circumference) [ Time Frame: 24 months ]
  11. Emotional development (will be assessed using the Bayley Scales of Infant Development III) [ Time Frame: 24 months ]
  12. Emotional development (will be assessed by questioning both parents and external caregivers) [ Time Frame: 24 months ]

Biospecimen Retention:   Samples With DNA
saliva samples of both parents and the child, blood sample of mother and child, cord blood sample,


Information from the National Library of Medicine

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Ages Eligible for Study:   up to 34 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02623400


Contacts
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Contact: Chiara Bernagie, MD 003216340232 chiara.bernagie@uzleuven.be
Contact: Bieke Bollen, PhD

Locations
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Belgium
UZ Leuven Recruiting
Leuven, Vlaams-Brabant, Belgium, 3000
Contact: Chiara Bernagie, MD       chiara.bernagie@uzleuven.be   
Contact: Bieke Bollen, PhD         
Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven
KU Leuven
Investigators
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Principal Investigator: Gunnar Naulaers, MD, PhD UZ / KU Leuven

Publications:
Bowlby J, Attachment and Loss: Attachment V, Basic Books, 1969.
Cassidy J. The nature of the child's ties. Handbook of attachment: Theory, research, and clinical implications 2:3-22, 1999.
Sai FZ. The role of the mother's voice in developing mother's face preference: Evidence for intermodal perception at birth.
Van Beek Y, Hopkins B, Hoeksma JB. Development of communicative behaviors in preterm infants: The effects of birthweight status and gestational age. Infant Behavior and Development 17(2):107-117, 1994.
Van Belle V, Neven P, Harvey V, Van Huffel S, Suykens JA, Boyd S. Risk group detection and survival function estimation for interval coded survival methods. Neurocomputing 112:200-210, 2013.
Walton GE, Bower NJA, Bower TGR. Recognition of familiar faces by newborns. Infant Behavior and Development 15(2):265-269, 1992.
Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabé E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fèvre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gonzalez-Medina D, Gosselin R, Grainger R, Grant B, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Laden F, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Levinson D, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mock C, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O'Donnell M, O'Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leòn FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiebe N, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, AlMazroa MA, Memish ZA. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2197-223. doi: 10.1016/S0140-6736(12)61689-4. Erratum in: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added].
Luts J., Molenberghs G., Verbeke G., Van Huffel S., Suykens J.A.K. A mixed effects least squares support vector machine model for classification of longitudinal data. Statistics & Data Analysis 56(3): 611-628, 2012.
World Health Organization (2002). Iron and folate supplementation. Integrated management of pregnancy and childbirth (IMPAC). Standards for Maternal and Neonatal Care. http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/iron_folate_supplementation.pdf The Department of Making Pregnancy Safer, World Health Organization.

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Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT02623400     History of Changes
Other Study ID Numbers: S58807
First Posted: December 7, 2015    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: July 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Universitaire Ziekenhuizen Leuven:
preterm birth
perinatal stress
growth and development

Additional relevant MeSH terms:
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Premature Birth
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications