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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Preterm Birth, Mother-Infant Interaction, Infant Development

Intervention / Treatment
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* Procedure: skin-to-skin contact


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard care<br>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<br>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<br>* Immediately after delivery the infant will receive skin-to-skin contact with the mother.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm behavioral epigenetics, skin-to-skin contact