Biological Underpinnings of Socio-emotional Regulation in Preterm Infants and Healthy Controls

NCT05253924 | Unknown

• 1 other identifier: Id. 867
• Study Type: observational
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

Preterm infants (PT) often need to spend their first weeks of life in the Neonatal Intensive Care Unit (NICU) where they are exposed to several adverse conditions. Whereas a consistent number of studies suggest that NICU-related experiences may have effects on infant development including long-term impairments in emotional regulation, the underlying mechanisms remain partially unexplored. Spectral analysis of EEG signal has demonstrated that frontal alpha-band asymmetry represents a reliable biomarker of social-emotional functioning. In the literature, higher right frontal activation has been associated with worse emotional regulation but no study has measured this value during a condition of social-emotional stress such as the Still Face paradigm. Our hypothesis is that higher alpha activity will be recorded in right frontal areas in premature infants compared to healthy controls and that this activation will be associated with higher negative emotionality (i.e., worse socio-emotional regulation) expressed during the Still Face paradigm. Moreover, despite several changes in epigenetic patterns have already been reported in association with prematurity and early adverse experiences, the relationship between epigenetic changes and electroencephalographic patterns (i.e. frontal alpha asymmetry) remains unexplored. The investigators therefore expect to find associations between increased methylation levels of socio-emotional and stress related genes (i.e. SLC6A4, NR3C1, OXTR, Piezo1, Piezo2, TRPV1 and TRPM8) with spontaneous oscillations of neural activity at frontal sites measured by EEG (i.e. frontal alpha asymmetry). Finally, there is ample evidence that infant's socio-emotional regulation abilities are highly dependent on the behaviors of their caregivers. More recent studies have shown that behavior can be influenced by interoceptive awareness, i.e., the ability to perceive the physiological condition of one's body in this way and to represent one's internal states. Better interoceptive awareness is associated with better recognition of others' needs, more empathetic behaviors, and better emotional regulation. Therefore, with the present exploratory study, the investigators will compare the interceptive awareness of mothers of preterm infants with that of mothers of full-term infants by exploring possible associations of this dimension with the socio-emotional responses of preterm infants and healthy controls. The investigators expect that better socio-emotional regulation of infants is predicted by a higher level of interoceptive awareness in mothers, regardless of prematurity condition.

Conditions

Preterm Birth; Parent-Child Relations; Epigenetics

Keywords

At-risk Infants; Developmental Care; DNA methylation; Affectionate touch; Frontal alpha asymmetry

Outcome Measures

Primary Outcomes (2)

• Negative emotionality assessed during the Still-Face Paradigm (FFSF).

  Negative emotionality (withdrawn, protesting, complaining, being fussy or crying behaviors) will be assessed using the validated coding system Infant and Caregiver Engagement Phases - ICEP. Coders have to detect the presence or the absence of negative emotionality-related behaviors for each episode of FFSF. Then, a proportion index of negative emotionality will be obtained for each of the five episodes of FFSF dividing the total score of negative emotionality displayed in every FFSF episode for the actual length of the episode, resulting in five negative emotionality indexes. Higher indexes of negative emotionality are indicative of worse social emotional regulation.

  Once, From 6 to 12 months (CA for prematurity) of infant's life

• Frontal Alpha Asymmetry (FAA)

  Frontal Alpha Asymmetry (FAA) will be assessed by computing the difference in signal power in the alpha band recorded by two homologous electrodes (or electrode clusters) (i.e. right alpha - left alpha). The EEG signal will be recorded through the medical system eego mylab (AntNeuro), using special headphones equipped with 32 electrodes and suitable to acquire the EEG signal since early childhood. Frontal Alpha Asymmetry (FAA) will also be correlated with Negative emotionality indexes.

  Once, From 6 to 12 months (CA for prematurity) of infant's life

Secondary Outcomes (2)

• DNA methylation level of target genes

  Once, From 6 to 12 months (CA for prematurity) of infant's life

• Heartbeat Counting Task index

  Once, From 6 to 12 months (CA for prematurity) of infant's life

Study Arms (2)

Preterm children (PT)

gestational age at birth \<37

Diagnostic Test: DNA methylation of target genes; Diagnostic Test: EEG acquisition

Full-term children (FT)

gestational age at birth ≥ 37 weeks

Diagnostic Test: DNA methylation of target genes; Diagnostic Test: EEG acquisition

Interventions

DNA methylation of target genes DIAGNOSTIC_TEST

The methylation status of target genes (BDNF, SLC6A4, OXTR, NR3C1, Piezo1, Piezo2, TRPV1 andTRPM8) will be investigated. Saliva sample will be collected for PT and FT. Genomic DNA will be extracted from aliquots of 0. 4 ml of each saliva sample with the Oragene OG575 (DNA Genotek) 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)

EEG acquisition DIAGNOSTIC_TEST

Both PT and FT infants will have their EEG signal recorded during mother-baby interaction according to a modified version of the Still Face paradigm; the EEG signal will be recorded by means of the medical system eego mylab (AntNeuro), using special headphones equipped with 32 electrodes and suitable to acquire the EEG signal since early childhood. After spectral analysis of the EEG signal, the difference in signal strength in the alpha band recorded by two homologous electrodes (or electrode clusters) (i.e. right alpha - left alpha) will be calculated to obtain the FAA index. Because the alpha frequency band is associated with cortical inhibitory activity, a lower asymmetry reflects less left hemisphere activation than right hemisphere activation. The analysis of EEG data will be performed in MatLab environment using the eeglab software and algorithms developed ad hoc.

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

Eligibility Criteria

• Age: 6 Months - 1 Year
• 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 course in different hospital and nursery school 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\< 37weeks;
• gestational age ≥ 37weeks;
• 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, NR3C, Piezo1, Piezo2, TRPV1 andTRPM8) in saliva samples of preterm children (PT), compared with a sample of full term children (FT). Saliva sample will be collected for both PT and FT groups. Saliva samples will be obtained by a trained researcher.

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

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

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: February 1, 2022
• First Posted: February 24, 2022
• Study Start: July 13, 2021
• Primary Completion: March 31, 2024
• Study Completion: July 13, 2024
• Last Updated: October 18, 2023

Record last verified: 2023-10

Locations

IT (1)