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Infants exposed to maternal type 1 diabetes: intrauterine epigenetic modifications and neurological development

Nieves Luisa González-González1, Enrique González-Dávila2, José Ramón Castro-Conde1,3

  • 1Obstetrics and Gynecology Department, Facultad de Ciencias de la Salud, Sección de Medicina. University of La Laguna (ULL), San Cristóbal de La Laguna, Tenerife, Spain.

Frontiers in Endocrinology
|February 26, 2026
PubMed

Insights

Maternal Type-1 diabetes is linked to infant neurodevelopmental changes via fetal DNA methylation. This pilot study found specific gene methylation differences associated with lower cognitive, language, and motor scores in exposed infants.

Area of Science:

  • Epigenetics
  • Developmental Neuroscience
  • Maternal Health

Background:

  • The impact of maternal Type-1 diabetes on infant neurodevelopment and its connection to fetal DNA methylation remains unexplored.
  • Investigating intrauterine epigenetic modifications in infants exposed to maternal diabetes is crucial for understanding neurodevelopmental outcomes.

Purpose of the Study:

  • To determine if neurodevelopmental outcomes in offspring of mothers with Type-1 diabetes are associated with intrauterine epigenetic changes in fetal DNA.
  • To explore the relationship between maternal diabetes, fetal DNA methylation, and infant neurodevelopment.

Main Methods:

  • A prospective, pilot case-control study comparing infants exposed to maternal Type-1 diabetes with control infants.
  • Analysis of cord blood DNA methylation using the TruSeq-Methyl-Capture-EPIC-Kit, covering over 3.3 million CpGs.
  • Assessment of infant neurodevelopment using the Bayley-III Scales and correlation with DNA methylation data.

Main Results:

  • Identified 108 differentially methylated genes in infants exposed to maternal diabetes, enriched in neurodevelopmental pathways like learning, synapse organization, and neurogenesis.
  • Significant methylation differences observed in key neurological genes including MYT1L, NRXN1, SHANK3, and KIRREL3.
  • Infants exposed to maternal diabetes showed lower Bayley-III scores in cognitive, language, and motor domains; specific gene methylation correlated with these scores.

Conclusions:

  • This study provides initial evidence supporting the hypothesis that neurodevelopmental alterations in offspring of mothers with Type-1 diabetes are linked to intrauterine DNA methylation changes.
  • These epigenetic changes, identifiable at birth, may contribute to observed neurodevelopmental differences.
  • Further research is needed to confirm these findings and elucidate the mechanisms involved.
Abstract

Keywords:
DNAcord bloodepigeneticgenematernal diabetesmethylationneurodevelopmenttype 1 diabetes

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