Epigenetics and Protective Factors in the Preterm Infant

NCT04804280 | Unknown

• 1 other identifier: RC2020_751
• Study Type: observational
• Target: 94
• Locations: 1 country
• Sites: 1

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.

Conditions

Preterm Birth; Parent-Child Relations; Epigenetics

Keywords

At-risk Infants; Developmental Care; DNA methylation; affectionate touch; Insular cortex

Outcome Measures

Primary Outcomes (1)

• DNA methylation changes in PT

  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.

  first 6 months (Corrected Age for PT) of infant's life

Secondary Outcomes (2)

• Insular cortex and somatosensory cortex activation in PT and FT infants

  when the infants is 2 months-old (Corrected Age for PT)

• Developmental Care procedures in NICU and insular cortex/somatosensory cortex activation in preterm infants

  first 2 months (Corrected Age for PT) of infant's life

Study Arms (2)

Preterm children (PT)

* gestational age at birth: 26+0 to 31+6 weeks; * absence of documented neurological pathology; * absence of sensory deficits; * absence of malformative syndromes and/or major malformations.

Genetic: DNA methylation of target genes; Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI) acquisition

Full-term children (FT)

* gestational age at birth ≥ 37 weeks; * birth weight ≥ 2,500g; * APGAR 5' ≥ 7 * delivery without any complications for baby and/or mother; * no prenatal and/or postnatal clinical conditions; * no hospitalizations at the time of birth or postpartum; * absence of malformative syndromes and/or major malformations.

Genetic: DNA methylation of target genes; Diagnostic Test: Functional Magnetic Resonance Imaging (fMRI) acquisition

Interventions

DNA methylation of target genes GENETIC

The methylation status of target genes (BDNF, SLC6A4, OXTR, NR3C1) will be investigated. Cord blood will be collected at birth for PT and FT, only for PT a peripheral blood sample will be collected at hospital discharge, during routine clinical procedures. Genomic DNA will be extracted from aliquots of 0. 2 ml of each blood sample with the GeneElute Blood Genomic DNA kit (Sigma) and stored at -20°C. Aliquots of 250 ng of each DNA will be edited for methylation analysis with the EZ DNA Methylation Lightning kit (Zymo Research). Amplification of samples and their preparation for NGS sequencing will be performed. Samples will be sequenced on NextSeq 500 (Illumina). Individual processed sequences (PE reads) will be independently aligned to reference sequences using a parallel Smith-Waterman algorithm. Only reads that consistently align to the same reference sequence will be retained. At each CpG site in each analyzed sequence, the frequencies of the four bases will be evaluated.

Full-term children (FT); Preterm children (PT)

Functional Magnetic Resonance Imaging (fMRI) acquisition DIAGNOSTIC_TEST

Infants will undergo an MRI exam with a 3 Tesla Philips Achieva scanner and a 32-channel head coil. a trained experimenter will apply tactile stimulation associated with affective touch characteristics to the child with a soft brush on the right anterior tibial region in proximal and distal directions. The length of the stimulated area will be measured to cover approximately 15 cm, and tactile stimulations will be applied at a rate of 5 cm/s for 15s, with randomized intervals between stimuli of 10-15s (resulting in 5 stimulations in a 15s block). A regular audio signal will help the researcher to keep a constant stroke velocity. Audio commands will also be used to direct the experimenter. Infant must be asleep (natural sleep) during the fMRI acquisition.

Full-term children (FT); Preterm children (PT)

Eligibility Criteria

• Age: Up to 30 Minutes
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• IRCCS Eugenio Medea: lead

Study Sites (1)

Associalzione La Nostra Famiglia - IRCCS Eugenio Medea

Bosisio Parini, Lecco, 23842, Italy

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

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.

MeSH Terms

Conditions

Premature Birth

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Central Study Contacts

Rosario Montirosso

CONTACT

+39031877494; rosario.montirosso@lanostrafamiglia.it

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 18, 2021
• Study Start: January 1, 2019
• Primary Completion: April 4, 2024
• Study Completion: September 4, 2024
• Last Updated: October 18, 2023

Record last verified: 2023-10

Locations

IT (1)