NCT04617587

Novel Epigenetic Biomarker for Prematurity Related Neurodevelopmental Disorders in Childhood

Structural Variations of the Neural Genome as Prognostic Biomarkers for Prematurity Related Neurodevelopmental Disorders in Childhood

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 104 (actual)
• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Academic / Other
• Sex: All
• Age: 24 Weeks – 32 Weeks
• Healthy volunteers: Not accepted

Summary

Preterms are early exposed to a stressful environment (i.e. excessive sensory stimulation and paucity of parental contact) with subsequent detrimental effects on brain maturation and neurodevelopmental outcomes. In contrast, early interventions seem to reduce stress exposure and promote neurodevelopment. The brain functional plasticity in response to environmental experiences can be partly attributed to changes in DNA methylation. In this context, LINE-1 (L1) promoter (18% of human genome) methylation/demethylation has been associated with L1 somatic mobilization in the brain genomes, contributing to experience-driven brain plasticity; this mechanism being deregulated in important neurological disease. This study aims at identifying and characterizing the role of L1 DNA repeats as a novel biomarker to predict long-term neurodevelopmental outcome in preterm infants. In addition, the study's secondary goal will be to define a preventive approach, based on early intervention strategies, for improving long-term neurodevelopmental outcomes.

Detailed description

Around 25-50% of very preterm infants suffer from neurodevelopmental delays (motor, cognitive and behavioral problems), which are most likely related to brain micro-structural defects and impaired neuronal maturation and connectivity. These alterations in brain maturation occurring during the neonatal period may be implicated in long-term neurobehavioral disorders later experienced by preterm babies. There is increasing evidence that also stressful events (excessive sensory stimulation, paucity of parental contact and painful procedures) experienced in the Neonatal Intensive Care Unit (NICU) by preterm neonates can affect neurodevelopment through epigenetic mechanisms. The brain is a genomic mosaic, owing to somatic mutations that arise throughout development. It is already established that mobile genetic elements, including LINE-1 (L1), are one source of somatic mosaicism, inducing copy number variations in neural genome. Environmental experiences can drive brain plasticity at a molecular level, with changes in DNA methylation. In particular, L1 promoter methylation/demethylation is already associated with L1 mobilization in the brain genomes and its deregulation is linked with important neurological diseases. A preliminary study has shown the correlation between L1 promoter methylation levels and preterm birth. In addition, maternal care during early life has been reported to drive variability in L1 mobilization and methylation of the neural hippocampal genome in mice models. Several studies have reported how individualized developmental care in the NICU can ameliorate preterm infants' medical outcome and subsequent neurodevelopment. More recently, early intervention (EI) strategies based on parental training and multisensory stimulation, such as infant massage and visual stimulation, have been demonstrated to enhance child's neurodevelopment. These programs have the greatest potential to reduce environmental stress in preterms, promoting brain plasticity, optimizing dyadic interaction and ameliorating neurodevelopmental outcomes.

Conditions

• Premature Birth

Interventions

Type	Name	Description
BEHAVIORAL	Early Intervention	The early intervention (EI) is delivered during the NICU stay. It is a multisensory intervention which consists in three parts: parental training, massage therapy and visual interaction. The EI is first focused on parental training, according to PremieStart Protocol, in order to train parents to: recognize signs of infant stress and alert-available behavior through the identification of infant's behavioral states; adopt principles of graded stimulation; sustain infant's attention and respond to infant's cues; optimize interactions and avoid overwhelming infants through facilitation strategies. The program is held in eight main sessions and one additional post-discharge session. In addition, parents are trained and invited to daily promote preterm baby massage therapy and visual interaction (visual fixation/tracking and visual attention).

Timeline

• Start date: 2020-12-03
• Primary completion: 2025-03-21
• Completion: 2025-03-30
• First posted: 2020-11-05
• Last updated: 2025-05-01

Locations

1 site across 1 country: Italy