Epigenetics and Protective Factors in the Preterm Infant (EPIC)
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ClinicalTrials.gov Identifier: NCT04804280 |
Recruitment Status :
Recruiting
First Posted : March 18, 2021
Last Update Posted : October 18, 2023
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Tracking Information | |||||
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First Submitted Date | March 8, 2021 | ||||
First Posted Date | March 18, 2021 | ||||
Last Update Posted Date | October 18, 2023 | ||||
Actual Study Start Date | January 1, 2019 | ||||
Estimated Primary Completion Date | April 4, 2024 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures |
DNA methylation changes in PT [ Time Frame: first 6 months (Corrected Age for PT) of infant's life ] Correlation between DNA methylation changes of target genes (BDNF, SLC6A4, OXTR, NR3C1) and the duration of Developmental Care practice that involved proximity and pyisical contact during the NICU stay measured by a specific APP.
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Original Primary Outcome Measures |
DNA methylation and Developmental Care procedures in NICU [ Time Frame: immediately after child birth and up to 6 months post-partum ] Correlation between the duration of Developmental Care practice that involved proximity and phisical contact during the NICU stay measured by a specific APP and level of DNA methylation at discarge of target genes (BDNF, SLC6A4, OXTR, NR3C1) in PT.
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Change History | |||||
Current Secondary Outcome Measures |
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Original Secondary Outcome Measures |
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Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title | Epigenetics and Protective Factors in the Preterm Infant | ||||
Official Title | Epigenetics and Protective Factors in the Preterm Infant: Neural and Methylation Correlates of Developmental Care During Neonatal Intensive Care Unit Hospitalization | ||||
Brief Summary | Preterm infants (PT) spend their first weeks of life in the Neonatal Intensive Care Unit (NICU) where they are exposed to unfavorable conditions with different effects on child development including long-term alterations in epigenetic regulation (DNA methylation). Recent studies document that these epigenetic changes are associated with behavioral modifications, such as altered stress reactivity at 3 months and 4 years. A growing number of studies suggest that protective Developmental Care (DC) procedures (e.g., breastfeeding, skin-to-skin contact (SSC), maternal holding) positively impact neurophysiological and behavioral adaptation of PT with long-term effects. Additionally, a neuro-imaging study reported that parental support in the NICU is associated with improved brain connectivity. While in term (FT) infants, parental interpersonal touch (breastfeeding, affectionate touch) is associated with reduced methylation and activation of specific brain areas associated with affective interpersonal touch, to date no study has investigated whether DC practices and maternal care in NICU (specifically, SSC) buffer methylation and support the brain response to affectionate physical touch in PT. The present study investigates the association between DC procedures in NICU, DNA methylation, and brain responses to affectionate touch, investigated through the use of MRI, at 2 months of age (corrected for prematurity), controlling for: (1) birth status (PT vs FT); (2) the duration of SSC during the NICU stay; (3) parental affectionate touch in the home environment and during mother-child interaction. | ||||
Detailed Description | Background: preterm infants (PT) spend their first weeks of life in the Neonatal Intensive Care Unit (NICU) where they are exposed to conditions with different effects on child development including long-term alterations in epigenetic regulation. Recent studies document that these epigenetic changes are associated with behavioral modifications, such as altered stress reactivity at 3 months and 4 years. A growing number of studies suggest that protective Developmental Care (DC) procedures (e.g., breastfeeding, skin-to-skin contact (SSC), maternal containment) positively impact neurophysiological and behavioral adaptation of PTs with long-term effects. Moreover, structural factors of the NICU, such as the organization of the unit space based on Open-Bay rather than Single Family Rooms could impact the child's neurobehavioral development and the parent's well-being. For example, a study on the impact of the Single Family Room shows improved medical and neurobehavioral outcomes for the infant at discharge and increased maternal involvement. However, the Single Family Room literature also reports mixed results with some studies finding increased parent involvement but no effect on child growth and some showing increased parent stress. Primary aim: to evaluate the methylation status of target genes (e.g., BDNF, SLC6A4, OXTR, NR3C1) in association with exposures to DC practices during NICU hospitalization in PT children, compared with a sample of FT children. Secondary aim: to investigate the relationship between preterm/term birth, DC practices (PT only), maternal touch in the postnatal period, epigenetic status and brain response to soft/soft stimulation during fMRI, at 2 months of age (corrected for prematurity in PT children), controlling for characteristics of the NICU of provenance (NICU Hospital of Monza: Single Family Room vs NICU Hospital of Lecco: Open-Bay). Planned Activities: Methods The project is characterized as observational, micro-longitudinal and is structured in two phases: - PHASE 1: FROM BIRTH TO DISCHARGE FOR PT CHILDREN; TIME OF BIRTH FOR FT CHILDREN) At the time of birth, both PT and FT will have their cord blood collected (methylation at birth) using non-invasive methods. Only for PTs at the time of discharge will be performed a second blood draw at the same time as the routine pre-discharge checks. In addition, at this stage, the mother will fill out some questionnaires about her mood and will be obtained information on pregnancy and childbirth (gestational age, birth weight, length and head circumference of the child at birth, type of delivery, duration of hospitalization, presence of perinatal diseases) and socio-anagraphic variables. Finally, only for the PT group, during hospitalization in the NICU, the following data will be collected on the negative and positive experiences to which PTs are exposed during hospitalization, specifically:
At the end of the NICU admission, only for PT children, a second peripheral blood sampling (methylation at discharge) will be performed at the same time as routine pre-discharge checks. At the end of hospitalization, mothers of PTs will complete the same questionnaires completed at birth and in addition will be asked to complete questionnaires on the experience of stress and support received from staff during hospitalization in the NICU. - PHASE 2: AROUND 2 MONTHS OF AGE OF THE CHILD (CORRECTED AGE FOR PT) The children of both groups (PT and FT) and their mothers will go to the IRCCS "E. Medea" for a Functional Magnetic Resonance Imaging (fMRI) examination. The fMRI session will be conducted according to a recent study on the neural correlates of maternal affective touch in FT infants. The fMRI scan will be conducted by researchers and clinicians experienced in the use of MRI in pediatric settings. Prior to the fMRI session, all parents will be adequately briefed with respect to the MRI-related procedure and the scanning protocol will be viewed with the parents and staff will confirm the absence of safety risks. To minimize the potential risk and harm to infants caused by unnecessary sedation, fMRI will be performed during natural sleep and no sedation will be performed. Infants will be wrapped, fed, and scanned. To promote falling asleep, infants will be changed and fed by their mother and given time for them to fall asleep and then moved into the scanner. All infants will be fitted with hearing protection. In the event that the infant wakes up during the scan, the mother will be asked to attempt to put the infant back to sleep and if this occurs, the scan will be attempted again. Standard hearing protection will be given to the parents who will be allowed to remain in the scanning room for the duration of the acquisition session. The scan will be observed by control room staff. The entire procedure was structured in accordance with the guidelines for conducting fMRI in healthy child samples. After the fMRI, a 10-minute video recording of the mother-child interaction will be made. During the video recording, the child will be placed in a comfortable infant seat and the mother will be asked to sit in front of the child and interact with him/her for 5 min. Baby and mother's behavior and interaction will be coded using the Global Rating Scales mother-child interaction coding system and maternal touch coding using the Maternal Touch Coding System. |
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Study Type | Observational | ||||
Study Design | Observational Model: Case-Control Time Perspective: Prospective |
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Target Follow-Up Duration | Not Provided | ||||
Biospecimen | Retention: Samples With DNA Description: The study will investigate the methylation status of target genes (such as BDNF, SLC6A4, OXTR, NR3C1) in preterm children (PT), compared with a sample of full term children (FT). Cord blood will be collected at birth for both PT and FT groups and, only for PT infants, a peripheral blood sample will be collected at hospital discharge, following routine clinical procedures. Blood samples will be obtained by trained nurses.
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Sampling Method | Non-Probability Sample | ||||
Study Population | Preterm infants. Preterm infants infants will be pre-screened for medical status variables by the NICU neonatologists of different hospital in Lombardy. Following a letter outlining the general research, parents will be meet per person in NICU or contacted by telephone and asked to voluntarily participate. Full-term infants. Mothers and their infants will be enrolled during the prenatal/ postnatal parenting coursein different hospital in Lombardy. Following a letter outlining the general research, parents will be contacted by telephone and asked to voluntarily participate. |
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Intervention |
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Study Groups/Cohorts |
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status | Recruiting | ||||
Estimated Enrollment |
94 | ||||
Original Estimated Enrollment | Same as current | ||||
Estimated Study Completion Date | September 4, 2024 | ||||
Estimated Primary Completion Date | April 4, 2024 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria | Inclusion criteria for PT children are:
Inclusion criteria for FT infants are:
Inclusion criteria for mothers are:
Exclusion criteria: refer to inclusion criteria. |
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Sex/Gender |
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Ages | up to 30 Minutes (Child) | ||||
Accepts Healthy Volunteers | Yes | ||||
Contacts |
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Listed Location Countries | Italy | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number | NCT04804280 | ||||
Other Study ID Numbers | RC2020_751 | ||||
Has Data Monitoring Committee | Not Provided | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement | Not Provided | ||||
Current Responsible Party | IRCCS Eugenio Medea | ||||
Original Responsible Party | Same as current | ||||
Current Study Sponsor | IRCCS Eugenio Medea | ||||
Original Study Sponsor | Same as current | ||||
Collaborators | Not Provided | ||||
Investigators | Not Provided | ||||
PRS Account | IRCCS Eugenio Medea | ||||
Verification Date | October 2023 |