Effects of Touch on Brain Connectivity and Metabolic Biomarkers in Preterm Infants

Study Overview
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Brief Summary
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Improving the quality of life of preterm children by 2035 is the top priority of worldwide health organisations, including the WHO. Every year, 15 million preterm infants, particularly those under 32 weeks of age, are at significant risk of neurocognitive impairments with adverse health consequences (disability, developmental delay, disease), exacerbated by the lack of post-hospital care for newborns. Intervening on the health of the preterm newborn through certain types of touch from its first days of life to activate its cutaneous senses permits, in reality, a significant improvement in the clinical state of the infant, hence promoting its growth, development, and social behaviour. In the neonatal period, during which significant neurological development occurs, tactile interactions and close physical proximity between infants and caregivers have significant short-term effects on the health of premature infants (weight gain, brain and vision development) and medium- to long-term effects on their development and expression of sociability. The likelihood that a premature newborn may develop attention and autism spectrum disorders, brain, gastrointestinal, and respiratory difficulties, as well as sleep disorders during the preschool years, is so high that clinical and social settings must prioritise care. Utilizing functional magnetic resonance imaging (fRMI), computerized electroencephalogram (EEG), and metabolomics, the research aims to explore the effects of touch, including physiotherapy and manual therapy (OMT) approaches, on brain activity. This research intends to examine the impact of touch on premature infants' brain activity (physical biomarker) and metabolic activity (biological biomarker).

Official Title
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Effects of Affective Touch, Therapeutic Touch (OMT), and Static/Nonspecific Touch on Brain Connectivity and Metabolic Biomarkers in Preterm Infants

Conditions
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Preterm, Infant ALL, Premature, Disease

Intervention / Treatment
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* Other: osteopathic manipulative treatment
* Other: Active comparator
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm birth, between 32.0 and 33.6 weeks gestational age (GA); Absence of comorbidities that could affect the stability of vital parameters, and therefore represent a contraindication to the proposed intervention. Comorbities include sepsis, pathologies pertaining to surgery, respiratory or cardiovascular instability, birth from a drug-addicted or HIV-positive mother) or known congenital pathologies; Obtaining informed consent for participation in this research project from parents or legal guardians. Exclusion Criteria: Preterm infants born before 32.0 weeks of GA and after 34 weeks and with respiratory and neurological pathologies and any additional comorbities. Children whose parents will not read and sign or in case of failure to obtain informed consent will be excluded from the study.

Ages Eligible for Study
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Minimum Age: 32 Weeks
Maximum Age: 34 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Therapeutic touch<br>The intervention will be based on 2 phases: 1) assessment to identify areas following the NAME procedure, 2) treatment to improve the function of the area identified | Other: osteopathic manipulative treatment<br>* The intervention will be based on the specific assessment and treatment of the preterm developed by the team and validated through different studies.<br>|
| Active Comparator: Affective touch<br>Participants will receive an affective touch intervention following the standardised procedure for affective touch | Other: Active comparator<br>* Application of affective touch<br>|
| Placebo Comparator: Static touch<br>Participants will receive a static touch intervention following the standardised procedure for static touch | Other: Placebo<br>* Application of static touch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| brain changes | pre-post changes in BOLD levels among different brain areas | 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| electroencephalogram (EEG) changes | pre-post changes from baseline in the EEG power in slow delta waves band at the end of the treatment period | 10 days | 
| Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) at T1 | pre-post changes in urinary metabolites as assessed by 1H NMR at T1 | 1 hour | 
| Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) at T2 | pre-post changes in urinary metabolites as assessed by 1H NMR at T2 | 4 days | 
| Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) at T3 | pre-post changes in urinary metabolites as assessed by 1H NMR at T3 | 8 days | 
| Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) at T4 | pre-post changes in urinary metabolites as assessed by 1H NMR at T4 | 12 days | 
| Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR) at T5 | pre-post changes in urinary metabolites as assessed by 1H NMR at T5 | 40 weeks | 
| Mass Spectrometry combined with Liquid Chromatography (CL-MS)at T1 | pre-post changes in urinary metabolites as assessed by CL-MS at T1 | 1 hour | 
| Mass Spectrometry combined with Liquid Chromatography (CL-MS)at T2 | pre-post changes in urinary metabolites as assessed by CL-MS at T2 | 4 days | 
| Mass Spectrometry combined with Liquid Chromatography (CL-MS)at T3 | pre-post changes in urinary metabolites as assessed by CL-MS at T3 | 8 days | 
| Mass Spectrometry combined with Liquid Chromatography (CL-MS)at T4 | pre-post changes in urinary metabolites as assessed by CL-MS at T4 | 12 days | 
| Mass Spectrometry combined with Liquid Chromatography (CL-MS)at T5 | pre-post changes in urinary metabolites as assessed by CL-MS at T5 | 40 weeks | 
| Mass Spectrometry combined with Gas Chromatography (CG-MS) at T1 | pre-post changes in urinary metabolites as assessed by CG-MS at T1 | 1 hour | 
| Mass Spectrometry combined with Gas Chromatography (CG-MS) at T2 | pre-post changes in urinary metabolites as assessed by CG-MS at T2 | 4 days | 
| Mass Spectrometry combined with Gas Chromatography (CG-MS) at T3 | pre-post changes in urinary metabolites as assessed by CG-MS at T3 | 8 days | 
| Mass Spectrometry combined with Gas Chromatography (CG-MS) at T4 | pre-post changes in urinary metabolites as assessed by CG-MS at T4 | 12 days | 
| Mass Spectrometry combined with Gas Chromatography (CG-MS) at T5 | pre-post changes in urinary metabolites as assessed by CG-MS at T5 | 40 weeks |