Epigenetics and Protective Factors in the Preterm Infant

  • STATUS
    Recruiting
  • End date
    Jun 30, 2022
  • participants needed
    94
  • sponsor
    IRCCS Eugenio Medea
Updated on 7 September 2021

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.

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:

  1. number of pain-related stress procedures (e.g.: number of withdrawals, central insertions, invasive and non-invasive mechanical ventilation) obtained from the patient's medical record;
  2. time spent doing DC procedures (e.g.:, total time spent in which the child is attached to the mother's breast, total time spent in holding, total time spent in kangaroo care) obtained through the use of the "closeness diary" implemented in electronic format, in the form of an APP.

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.

Details
Condition Premature Birth, Parent-Child Relations, Epigenetic Process, Epigenetics, Premature, Pre-Term, preterm delivery, preterm birth, premature delivery
Treatment Functional Magnetic Risonance Imaging (fMRI) acquisition, DNA methylation of target genes, Functional Magnetic Resonance Imaging (fMRI) acquisition
Clinical Study IdentifierNCT04804280
SponsorIRCCS Eugenio Medea
Last Modified on7 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

gestational age: 26+0 to 31+6 weeks
absence of documented neurological pathology
absence of sensory deficits
absence of malformative syndromes and/or major malformations
Inclusion criteria for FT infants are
gestational age 37weeks
birth weight 2,500g
APGAR 5' 7 - delivery without any complications for the child and/or mother
no pre/postnatal/postnatal clinical conditions
no hospitalizations at the time of birth or postpartum
absence of malformative syndromes and/or major malformations
Inclusion criteria for mothers are
mothers of Italian nationality
mother over 18 years of age
mother with absence of manifest psychiatric and/or cognitive pathologies (must be previously diagnosed major psychiatric pathologies)
non-addicted/no habitual use of psychotropic medications, drugs, alcohol no smoking
non-single-parent families

Exclusion Criteria

refer to inclusion criteria
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note