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

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.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Infant Development; Mother-Infant Interaction
• Intervention / Treatment: Procedure: skin-to-skin contact

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Katrin Mehler, PD Dr.; Phone Number: 004922147885663; Email: katrin.mehler@uk-koeln.de
• Study Contact Backup: Name: Angela Kribs, PD Dr.; Phone Number: 004922147885663; Email: angela.kribs@uk-koeln.de

Study Locations

• Germany
  • Northrhine-westfalia
    • Cologne, Northrhine-westfalia, Germany, 50931
      • Recruiting
      • University hospital of Cologne, Department of Neonatology
      • Contact: Katrin Mehler, MD; Phone Number: 004922147885663; Email: katrin.mehler@uk-koeln.de
      • Contact: Angela Kribs, MD; Phone Number: 004922147885663; Email: angela.kribs@uk-koeln.de
      • Sub-Investigator: Katrin Mehler, MD
      • Principal Investigator: Angela Kribs, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard care; 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.
Experimental: skin-to-skin contact; 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.	Procedure: skin-to-skin contact; Immediately after delivery the infant will receive skin-to-skin contact with the mother.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	36 to 72 hours after birth
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.	corrected 6 months of age
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.	corrected 24 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	corrected 6 months of age
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.	corrected 3 months of age
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.	at inpatient discharge (assessed from 3 to 60 days of life), corrected 6 and 24 months of age
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.	at inpatient discharge (assessed from 3 to 60 days of life), corrected 24 months of age
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.	at inpatient discharge (assessed from 3 to 60 days of life)
breastfeeding	There will be a question about breastfeeding.	at inpatient discharge (assessed from 3 to 60 days of life) and corrected six months of age
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.	corrected 6 months of age
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.	corrected 6 and 24 months of age
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.	corrected 6 and 24 months of age
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.	36 to 72 hours after birth and corrected 24 months of age

Collaborators and Investigators

• Sponsor: University of Cologne
• Investigators: Principal Investigator: Katrin Mehler, PD Dr., University of Cologne

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 4, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: skin-to-skin contact; preterm behavioral epigenetics
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: 22-1419

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No