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

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

Interventions

DIAGNOSTIC_TEST

DNA methylation of target genes

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.

DIAGNOSTIC_TEST

EEG acquisition

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.

Sponsors & Collaborators

• IRCCS Eugenio Medea

  lead OTHER

Eligibility

Min Age

6 Months

Max Age

1 Year

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2021-07-13

Primary Completion

2024-03-31

Completion

2024-07-13

Countries

• Italy

Study Locations