From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth

<div><p>Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (<i>SLC6A4</i>). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and <i>SLC6A4</i> methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. <i>SLC6A4</i> methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of <i>SLC6A4</i> methylation at NICU discharge. Moreover, higher <i>SLC6A4</i> discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in <i>SLC6A4</i> methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.</p></div

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth - Fig 2

<p><b>Brain MRI segmentation: A. axial and B. coronal view T1 images.</b> Note. Colors highlight anterior temporal lobe (ATL) lateral part left (ATL-LPL, yellow) and right (ATL-LPR, dark blue) as well as ATL medial part left (ATL-M;PL, light blue) and right (ATL-MPR, pink).</p

Effects of brain volumes on GMDS Personal-Social scale.

<p>Effects of brain volumes on GMDS Personal-Social scale.</p

Descriptive statistics for the included subjects.

<p>Descriptive statistics for the included subjects.</p

Effects of NICU-related stress and SLC6A4 methylation on brain volumes.

<p>Effects of NICU-related stress and SLC6A4 methylation on brain volumes.</p

Schematic time-line of the longitudinal project, limitedly to the variables of interest.

<p>Note. NICU, Neonatal Intensive Care Unit; <i>SLC6A4</i>, serotonin transporter gene; <i>Δ</i>_<i>met</i>, mean change in <i>SLC6A4</i> methylation from birth to NICU discharge at CpG chr17: 28562786–28562787; ATL, anterior temporal lobe; MRI, Magnetic Resonance Imaging; GMDS, Griffith Mental Development Scales; PCA, Post-Conceptional Age; TEA, term-equivalent age; CA, Corrected Age for prematurity.</p

Data_Sheet_1_Start a Neonatal Extracorporeal Membrane Oxygenation Program: A Multistep Team Training.docx

<p>Background: Extracorporeal membrane oxygenation (ECMO) is a complex life-saving support for acute cardio-respiratory failure, unresponsive to medical treatment. Emergency events on ECMO are rare but require immediate and proficient management. Multidisciplinary ECMO team members need to acquire and maintain over time cognitive, technical and behavioral skills, to safely face life-threatening clinical scenarios.</p><p>Methods: A multistep educational program was delivered in a 4-year period to 32 ECMO team members, based on guidelines from the Extracorporeal Life Support Organization. A first traditional module was provided through didactic lectures, hands-on water drills, and laboratory animal training. The second phase consisted of a multi-edition high-fidelity simulation-based training on a modified neonatal mannequin (SimNewB®). In each session, participants were called to face, in small groups, ten critical scenarios, followed by debriefing time. Trainees underwent a pre-test for baseline competency assessment. Once completed the full training program, a post-test was administered. Pre- and post-test scores were compared. Trainees rated the educational program through survey questionnaires.</p><p>Results: 28 trainees (87.5%) completed the full educational program. ECMO staff skills improved from a median pre-test score of 7.5/18 (IQR = 6–11) to 14/18 (IQR = 14–16) at post-test (P < 0.001, Wilcoxon rank test). All trainees highly rated the educational program and its impact on their practice. They reported high-fidelity simulations to be beneficial to novice learners as it increased self-confidence in ECMO-emergencies (according to 100% of surveyed), theoretical knowledge (61.5%) and team-work/communicative skills (58%).</p><p>Conclusions: The multistep ECMO team training increased staff' knowledge, technical skills, teamwork, and self-confidence, allowing the successful development of a neonatal respiratory ECMO program. Conventional training was perceived as relevant in the early phase of the program development, while the active learning emerged to be more beneficial to master ECMO knowledge, specific skills, and team performance.</p