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Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants
Camilla Fontana1, Federica Marasca2, Livia Provitera3
1Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
Insights
Early intervention for preterm infants can restore LINE-1 (L1) methylation, improving neurodevelopment. This study highlights L1 activity as a novel predictor for prematurity-related outcomes.
Area of Science:
- Neuroscience
- Epigenetics
- Developmental Biology
Background:
- Preterm birth impacts 9-11% of newborns, causing neurodevelopmental disabilities.
- Retrotransposons like LINE-1 (L1) contribute to genomic mosaicism and are implicated in neurological disorders.
- Early life experiences can modulate L1 activity, particularly in neuronal cells.
Purpose of the Study:
- To investigate the impact of early intervention on L1 methylation in preterm infants.
- To explore the relationship between L1 methylation and neurodevelopmental outcomes.
- To examine L1 epigenetic regulation in the developing mouse brain.
Main Methods:
- Randomized controlled trial comparing standard care with early intervention for very preterm infants.
- Measurement of L1 promoter methylation at birth and hospital discharge.
- Neurodevelopmental assessment at 12 and 36 months using Griffiths Scales.
- Analysis of L1 methylation and copy number variations (CNVs) in mouse brain tissues.
Main Results:
- Preterm infants exhibited hypomethylation of the L1 promoter at birth.
- Early intervention normalized L1 methylation levels, similar to healthy newborns.
- Intervention ameliorated childhood neurodevelopmental outcomes.
- L1 activity is dynamically regulated in the perinatal mouse brain, indicating a critical window for epigenetic programming.
Conclusions:
- Early intervention can positively impact L1 methylation and neurodevelopment in preterm infants.
- L1 methylation serves as a potential molecular marker for predicting neurodevelopmental outcomes in prematurity.
- This research opens avenues for novel molecular strategies targeting L1 activity to improve infant neurodevelopment.
Background:
Preterm birth affects almost 9-11% of newborns and is one of the leading causes of childhood neurodevelopmental disabilities; the underlying molecular networks are poorly defined. In neurons, retrotransposons LINE-1 (L1) are an active source of genomic mosaicism that is deregulated in several neurological disorders; early life experience has been shown to regulate L1 activity in mice.
Methods:
Very preterm infants were randomized to receive standard care or early intervention. L1 methylation was measured at birth and at hospital discharge. At 12 and 36 months, infants' neurodevelopment was evaluated with the Griffiths Scales. L1 methylation and CNVs were measured in mouse brain areas at embryonic and postnatal stages.
Results:
Here we report that L1 promoter is hypomethylated in preterm infants at birth and that an early intervention program, based on enhanced maternal care and positive multisensory stimulation, restores L1 methylation levels comparable to healthy newborns and ameliorates neurodevelopment in childhood. We further show that L1 activity is fine-tuned in the perinatal mouse brain, suggesting a sensitive and vulnerable window for the L1 epigenetic setting.
Conclusions:
Our results open the field on the inspection of L1 activity as a novel molecular and predictive approach to infants' prematurity-related neurodevelopmental outcomes.
Trial Registration:
ClinicalTrial.gov ( NCT02983513 ). Registered on 6 December 2016, retrospectively registered.
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