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Continuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants (COSY)

Primary Purpose

Preterm Birth, Mother-Infant Interaction, Infant Development

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
skin-to-skin contact
Sponsored by
University of Cologne
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Preterm Birth focused on measuring preterm behavioral epigenetics, skin-to-skin contact

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: preterm birth between gestational age of 32 0/7 and 36 6/7 weeks first child vaginal delivery singleton informed consent before birth Exclusion Criteria: malformations or syndromes of the infant resuscitation of the infant maternal psychological or severe physical illness lack of German language skills

Sites / Locations

  • University hospital of Cologne, Department of NeonatologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

No Intervention

Experimental

Arm Label

Standard care

skin-to-skin contact

Arm Description

After delivery the infant will be separated from the mother and placed on a primary care unit in another room to monitor the cardiopulmonary adaption for at least 20 minutes.

After delivery the infant will be put skin-to-skin on the mother's breast in comfort position for 60 minutes. The cardiopulmonary adaption will be monitored and supervised by the attending neonatologist and nurse.

Outcomes

Primary Outcome Measures

gene expression in candidate genes of the stress signalling pathway
DNA will be extracted from peripheral white blood cells and mucosal epithelial cells. The expression of candidate genes of the stress signaling pathways are investigated. The candidate genes are glucocorticoid receptor (NR3C1), corticotropin releasing hormone (CRH), corticotropin-releasing hormone receptor 1 and 2 (CRHR1/2), serotonin transporter (slc6a4), vasopressin and brain-derived neurotrophic factor.
gene expression in candidate genes of the stress signalling pathway
DNA and RNA will be extracted from mucosal epithelial cells. The expression of candidate genes of the stress signaling pathways are investigated. The candidate genes are glucocorticoid receptor (NR3C1), corticotropin releasing hormone (CRH), corticotropin-releasing hormone receptor 1 and 2 (CRHR1/2), serotonin transporter (slc6a4), vasopressin and brain-derived neurotrophic factor. Furthermore a whole-genome methylation will be analysed.
gene expression in candidate genes of the stress signalling pathway
DNA will be extracted from mucosal epithelial cells. The expression of candidate genes of the stress signaling pathways are investigated. The candidate genes are glucocorticoid receptor (NR3C1), corticotropin releasing hormone (CRH), corticotropin-releasing hormone receptor 1 and 2 (CRHR1/2), serotonin transporter (slc6a4), vasopressin and brain-derived neurotrophic factor.

Secondary Outcome Measures

mother-child-interaction
Mother-child-interaction is investigated using Mannheim Rating Scales. Therefore a five-minute-videotape of the mother changing the infant's diapers and playing with the infant is used. Mannheim Rating Scales is a good validated standardized observation instrument. Stimulation and response from the mother as well from the infant are being recorded. Different communication channels can be used by mother and child (vocal, facial or motor). All behaviors are analysed at intervals of five seconds (event coding). Then the values are formed from the sum of the coded events. The scale ranges from 0 to 60. If there is no interaction, the scale is 0. If there is an interaction in each interval (every 5 seconds in a 5 minute videotape), the scale is 60. The mother-child interaction is better if the scale is higher.
General Movements
The early infant development will be analyzed by general movements assessment by Prechtl. It is a validated diagnostic tool for the functional assessment of the young nervous system.
maternal depression
Maternal depression is assessed with the German long form of the Center for Epidemiological Studies Depression Scale (CES-D). It is a self-report questionnaire to measure depressive symptoms and it consists of 20 questions. For each question the response choice are assigned point values (how often a symptom occurred during the last week). The point values are summed to a total measure score. The score ranges from 0 to 60. Zero points represents no symptoms of depression, a score of 15 or higher is interpreted to indicate a risk of depression.
social support
Social support is assessed with the short version of the German questionnaire for social support (Fragebogen zur sozialen Unterstützung, questionnaire on social support) scale (F-SozU K-22). The questionnaire records the subjectively perceived or anticipated support from the social environment. There are 22 items and the test person can indicate the degree of agreement on a five-level Likert scale (from 1 = does not apply to 5 = applies completely). The scale ranges from a minimum of 22 points to a maximum of 110 points. The higher the score, the better the subjectively perceived or anticipated support.
socio-economic status
There will be a question to the household income per month and the parents' highest school-leaving certificate as well as the housing situation.
breastfeeding
There will be a question about breastfeeding.
impact of event scale
Symptoms for post-traumatic stress is assessed with the impact of event scale - revised (IES-R). It is a self-report questionnaire and consists of 22 questions. For each question the response choice are assigned point values (how often a symptom occurred during the last week). The sub-scale values are summed by the corresponding sub-scale items. The three sub-scales are: intrusion, avoidance and hyperarousal. The overall result is calculated by a formula. The score ranges from -4,36 to 2,99. A result above 0 is interpreted to indicate a risk of post-traumatic stress disorder.
Parental Bonding
Parental Bonding is assessed with the parental bonding questionnaire (PBQ). It consists of 25 items and each item is rated on a scale from 0 to 3 points (response range from "very like" to "very unlike"). There are four sub-scales and the point values of each sub-scale are summed to a total measure score. The four sub-scales are: impaired bonding, rejection and anger, anxiety about care, risk of abuse. The higher the score, the higher the risk of a disorder in each area of the sub-scale.
Parental Stress
Parental stress is assessed with the German form of the parenting stress index (PSI). It consists of 48 items. The test person can indicate the degree of agreement on a five-level Likert scale (from 1 = does not apply to 5 = applies completely). There are 12 subscales, each consisting of 4 items and the points on the Likert scale are added. In each subscale there can be a minimum of 4 and a maximum of 20 points. The higher the score, the higher the parental stress.
reactivity of hypothalamic-pituitary-adrenal-axis
Salivary cortisol is measured before and 20 minutes after heel lance, respectively after a stressful testing. The saliva is collected by a small cotton roll, which is placed in the infants' mouth. The cortisol is assayed in duplicate using an immunoassay, which is a validated test.

Full Information

First Posted
July 13, 2023
Last Updated
August 4, 2023
Sponsor
University of Cologne
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1. Study Identification

Unique Protocol Identification Number
NCT05975203
Brief Title
Continuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants
Acronym
COSY
Official Title
Continuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 4, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Cologne

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this randomized controlled trial is to compare the effect of direct skin-to-skin contact in moderate and late preterm infants. The main questions it aims to answer are: does skin-to-skin contact in moderate and late preterm infants influence gene expression in the stress signaling pathway? does skin-to-skin contact in moderate and late preterm infants improve the short- and long-term outcome? Participants will either get immediate separation after vaginal birth or receive immediate skin-to-skin contact. Researchers will compare these two groups to answer the proposed questions.
Detailed Description
The planned study investigates prospectively the effect of early intervention (skin-to-skin contact in the delivery room) in moderate and late preterm infants on neonatal programming by determining gene expression in the stress signaling pathway. The working hypothesis of our project is that the intervention will affect gene expression in a way that subsequently leads to better long-term psycho-social and neurological development of these preterm infants. The study aims to improve the understanding of the correlation of behavioral and epigenetic parameters and prove the underlying hypothesis of a novel mechanistic link between immediate skin-to-skin contact in the delivery room and life-long stress tolerance.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preterm Birth, Mother-Infant Interaction, Infant Development
Keywords
preterm behavioral epigenetics, skin-to-skin contact

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Due to the nature of the intervention blinding of participant and care provider is not possible. The investigators are part of the care providing team.
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard care
Arm Type
No Intervention
Arm Description
After delivery the infant will be separated from the mother and placed on a primary care unit in another room to monitor the cardiopulmonary adaption for at least 20 minutes.
Arm Title
skin-to-skin contact
Arm Type
Experimental
Arm Description
After delivery the infant will be put skin-to-skin on the mother's breast in comfort position for 60 minutes. The cardiopulmonary adaption will be monitored and supervised by the attending neonatologist and nurse.
Intervention Type
Procedure
Intervention Name(s)
skin-to-skin contact
Intervention Description
Immediately after delivery the infant will receive skin-to-skin contact with the mother.
Primary Outcome Measure Information:
Title
gene expression in candidate genes of the stress signalling pathway
Description
DNA will be extracted from peripheral white blood cells and mucosal epithelial cells. The expression of candidate genes of the stress signaling pathways are investigated. The candidate genes are glucocorticoid receptor (NR3C1), corticotropin releasing hormone (CRH), corticotropin-releasing hormone receptor 1 and 2 (CRHR1/2), serotonin transporter (slc6a4), vasopressin and brain-derived neurotrophic factor.
Time Frame
36 to 72 hours after birth
Title
gene expression in candidate genes of the stress signalling pathway
Description
DNA and RNA will be extracted from mucosal epithelial cells. The expression of candidate genes of the stress signaling pathways are investigated. The candidate genes are glucocorticoid receptor (NR3C1), corticotropin releasing hormone (CRH), corticotropin-releasing hormone receptor 1 and 2 (CRHR1/2), serotonin transporter (slc6a4), vasopressin and brain-derived neurotrophic factor. Furthermore a whole-genome methylation will be analysed.
Time Frame
corrected 6 months of age
Title
gene expression in candidate genes of the stress signalling pathway
Description
DNA will be extracted from mucosal epithelial cells. The expression of candidate genes of the stress signaling pathways are investigated. The candidate genes are glucocorticoid receptor (NR3C1), corticotropin releasing hormone (CRH), corticotropin-releasing hormone receptor 1 and 2 (CRHR1/2), serotonin transporter (slc6a4), vasopressin and brain-derived neurotrophic factor.
Time Frame
corrected 24 months of age
Secondary Outcome Measure Information:
Title
mother-child-interaction
Description
Mother-child-interaction is investigated using Mannheim Rating Scales. Therefore a five-minute-videotape of the mother changing the infant's diapers and playing with the infant is used. Mannheim Rating Scales is a good validated standardized observation instrument. Stimulation and response from the mother as well from the infant are being recorded. Different communication channels can be used by mother and child (vocal, facial or motor). All behaviors are analysed at intervals of five seconds (event coding). Then the values are formed from the sum of the coded events. The scale ranges from 0 to 60. If there is no interaction, the scale is 0. If there is an interaction in each interval (every 5 seconds in a 5 minute videotape), the scale is 60. The mother-child interaction is better if the scale is higher.
Time Frame
corrected 6 months of age
Title
General Movements
Description
The early infant development will be analyzed by general movements assessment by Prechtl. It is a validated diagnostic tool for the functional assessment of the young nervous system.
Time Frame
corrected 3 months of age
Title
maternal depression
Description
Maternal depression is assessed with the German long form of the Center for Epidemiological Studies Depression Scale (CES-D). It is a self-report questionnaire to measure depressive symptoms and it consists of 20 questions. For each question the response choice are assigned point values (how often a symptom occurred during the last week). The point values are summed to a total measure score. The score ranges from 0 to 60. Zero points represents no symptoms of depression, a score of 15 or higher is interpreted to indicate a risk of depression.
Time Frame
at inpatient discharge (assessed from 3 to 60 days of life), corrected 6 and 24 months of age
Title
social support
Description
Social support is assessed with the short version of the German questionnaire for social support (Fragebogen zur sozialen Unterstützung, questionnaire on social support) scale (F-SozU K-22). The questionnaire records the subjectively perceived or anticipated support from the social environment. There are 22 items and the test person can indicate the degree of agreement on a five-level Likert scale (from 1 = does not apply to 5 = applies completely). The scale ranges from a minimum of 22 points to a maximum of 110 points. The higher the score, the better the subjectively perceived or anticipated support.
Time Frame
at inpatient discharge (assessed from 3 to 60 days of life), corrected 24 months of age
Title
socio-economic status
Description
There will be a question to the household income per month and the parents' highest school-leaving certificate as well as the housing situation.
Time Frame
at inpatient discharge (assessed from 3 to 60 days of life)
Title
breastfeeding
Description
There will be a question about breastfeeding.
Time Frame
at inpatient discharge (assessed from 3 to 60 days of life) and corrected six months of age
Title
impact of event scale
Description
Symptoms for post-traumatic stress is assessed with the impact of event scale - revised (IES-R). It is a self-report questionnaire and consists of 22 questions. For each question the response choice are assigned point values (how often a symptom occurred during the last week). The sub-scale values are summed by the corresponding sub-scale items. The three sub-scales are: intrusion, avoidance and hyperarousal. The overall result is calculated by a formula. The score ranges from -4,36 to 2,99. A result above 0 is interpreted to indicate a risk of post-traumatic stress disorder.
Time Frame
corrected 6 months of age
Title
Parental Bonding
Description
Parental Bonding is assessed with the parental bonding questionnaire (PBQ). It consists of 25 items and each item is rated on a scale from 0 to 3 points (response range from "very like" to "very unlike"). There are four sub-scales and the point values of each sub-scale are summed to a total measure score. The four sub-scales are: impaired bonding, rejection and anger, anxiety about care, risk of abuse. The higher the score, the higher the risk of a disorder in each area of the sub-scale.
Time Frame
corrected 6 and 24 months of age
Title
Parental Stress
Description
Parental stress is assessed with the German form of the parenting stress index (PSI). It consists of 48 items. The test person can indicate the degree of agreement on a five-level Likert scale (from 1 = does not apply to 5 = applies completely). There are 12 subscales, each consisting of 4 items and the points on the Likert scale are added. In each subscale there can be a minimum of 4 and a maximum of 20 points. The higher the score, the higher the parental stress.
Time Frame
corrected 6 and 24 months of age
Title
reactivity of hypothalamic-pituitary-adrenal-axis
Description
Salivary cortisol is measured before and 20 minutes after heel lance, respectively after a stressful testing. The saliva is collected by a small cotton roll, which is placed in the infants' mouth. The cortisol is assayed in duplicate using an immunoassay, which is a validated test.
Time Frame
36 to 72 hours after birth and corrected 24 months of age

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: preterm birth between gestational age of 32 0/7 and 36 6/7 weeks first child vaginal delivery singleton informed consent before birth Exclusion Criteria: malformations or syndromes of the infant resuscitation of the infant maternal psychological or severe physical illness lack of German language skills
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Katrin Mehler, PD Dr.
Phone
004922147885663
Email
katrin.mehler@uk-koeln.de
First Name & Middle Initial & Last Name or Official Title & Degree
Angela Kribs, PD Dr.
Phone
004922147885663
Email
angela.kribs@uk-koeln.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katrin Mehler, PD Dr.
Organizational Affiliation
University of Cologne
Official's Role
Principal Investigator
Facility Information:
Facility Name
University hospital of Cologne, Department of Neonatology
City
Cologne
State/Province
Northrhine-westfalia
ZIP/Postal Code
50931
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katrin Mehler, MD
Phone
004922147885663
Email
katrin.mehler@uk-koeln.de
First Name & Middle Initial & Last Name & Degree
Angela Kribs, MD
Phone
004922147885663
Email
angela.kribs@uk-koeln.de
First Name & Middle Initial & Last Name & Degree
Katrin Mehler, MD
First Name & Middle Initial & Last Name & Degree
Angela Kribs, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
31423649
Citation
Mehler K, Hucklenbruch-Rother E, Trautmann-Villalba P, Becker I, Roth B, Kribs A. Delivery room skin-to-skin contact for preterm infants-A randomized clinical trial. Acta Paediatr. 2020 Mar;109(3):518-526. doi: 10.1111/apa.14975. Epub 2019 Sep 16.
Results Reference
background
PubMed Identifier
33027708
Citation
Hucklenbruch-Rother E, Vohlen C, Mehdiani N, Keller T, Roth B, Kribs A, Mehler K. Delivery room skin-to-skin contact in preterm infants affects long-term expression of stress response genes. Psychoneuroendocrinology. 2020 Dec;122:104883. doi: 10.1016/j.psyneuen.2020.104883. Epub 2020 Sep 24.
Results Reference
background

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Continuous Delivery Room Skin-to-skin-study for Moderate and Late Preterm Infants

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