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BMC Medicine
Published in: BMC Medicine 1/2021

Open Access 01-12-2021 | Care | Research article

Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants

Authors: Camilla Fontana, Federica Marasca, Livia Provitera, Sara Mancinelli, Nicola Pesenti, Shruti Sinha, Sofia Passera, Sergio Abrignani, Fabio Mosca, Simona Lodato, Beatrice Bodega, Monica Fumagalli

Published in: BMC Medicine | Issue 1/2021

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Abstract

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.
Appendix
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Metadata
Title
Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants
Authors
Camilla Fontana
Federica Marasca
Livia Provitera
Sara Mancinelli
Nicola Pesenti
Shruti Sinha
Sofia Passera
Sergio Abrignani
Fabio Mosca
Simona Lodato
Beatrice Bodega
Monica Fumagalli
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Care
Published in
BMC Medicine / Issue 1/2021
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-020-01896-0

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