Clinical trial
Epigenetics and Protective Factors in the Preterm Infant: Neural and Methylation Correlates of Developmental Care During Neonatal Intensive Care Unit Hospitalization
Name
RC2020_751
Description
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.
Trial arms
Trial start
2019-01-01
Estimated PCD
2024-04-04
Trial end
2024-09-04
Status
Recruiting
Treatment
DNA methylation of target genes
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.
Arms:
Full-term children (FT), Preterm children (PT)
Functional Magnetic Resonance Imaging (fMRI) acquisition
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.
Arms:
Full-term children (FT), Preterm children (PT)
Size
94
Primary endpoint
DNA methylation changes in PT
first 6 months (Corrected Age for PT) of infant's life
Eligibility criteria
Inclusion criteria for PT children are:
* 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.
Protocol
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Updated at
2023-10-18
1 organization
1 product
3 indications
Organization
IRCCS Eugenio MedeaProduct
DNA methylationIndication
premature birthIndication
Parent-Child RelationsIndication
Epigenetics