DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease.
Publication/Presentation Date
1-1-2025
Abstract
BACKGROUND: We lack early biomarkers for predicting neurodevelopment (ND) outcomes in children with congenital heart disease (CHD). Placentas of fetuses with CHD have abnormalities, including unbalanced fetal/placental weight ratios (F/P). Although DNA methylation profiles have revealed insights into the maternal-fetal environment (MFE), it is unknown if DNA methylation correlates to normalized F/P weight ratio groups and how these differences relate to ND outcomes.
METHODS: We prospectively recruited a cohort of pregnant women carrying a fetus with CHD. A subset of the cohort had DNA methylation performed on either umbilical cord blood or postnatal blood (45 full-term neonates). We calculated normalized F/P weight ratios, focusing on three normalized F/P ratio groups for analysis. We calculated differential methylation signals in eight ND disabilities-associated gene sets. Normalized F/P ratios were compared to 18-month Bayley Scales of Infant Development-III scores (BSID-III).
RESULTS: Unbiased gene ontology enrichment analysis of differentially methylated regions revealed enrichment for brain development-related pathways. Although there were no significant differences between normalized F/P weight ratio groups and BSID-III, disease-associated gene set pathway analysis revealed significant methylation differences between the most severely unbalanced F/P weight ratio and normal F/P weight ratio groups.
CONCLUSION: Gene ontology enrichment analysis of differential methylation regions revealed significant differences between normalized F/P weight ratio groups in neurogenesis genes. Furthermore, our data identified methylation differences between unbalanced and balanced normalized F/P weight ratio groups in gene pathways associated with ND dysfunction common in the aging CHD population suggesting converging pathways for ND disorders that should be investigated further.
Volume
20
Issue
8
First Page
0317944
Last Page
0317944
ISSN
1932-6203
Published In/Presented At
Jacobwitz, M., Xie, M., Catalano, J., Helbig, I., Gaynor, J. W., Burnham, N., Linn, R. L., Gebb, J., Russell, M. W., Hakonarson, H., Chaiyachati, B. H., & Cristancho, A. G. (2025). DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. PloS one, 20(8), e0317944. https://doi.org/10.1371/journal.pone.0317944
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
40768515
Department(s)
Department of Pediatrics
Document Type
Article