DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease.
<h4>Background</h4>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 re...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0317944 |
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| author | Marin Jacobwitz Michael Xie Jamie Catalano Ingo Helbig J William Gaynor Nancy Burnham Rebecca L Linn Juliana Gebb Mark W Russell Hakon Hakonarson Barbara H Chaiyachati Ana G Cristancho |
| author_facet | Marin Jacobwitz Michael Xie Jamie Catalano Ingo Helbig J William Gaynor Nancy Burnham Rebecca L Linn Juliana Gebb Mark W Russell Hakon Hakonarson Barbara H Chaiyachati Ana G Cristancho |
| author_sort | Marin Jacobwitz |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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. |
| format | Article |
| id | doaj-art-9d5d2f1d6bfb4c2c8f111fb6e96a1f2d |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-9d5d2f1d6bfb4c2c8f111fb6e96a1f2d2025-08-23T05:32:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01208e031794410.1371/journal.pone.0317944DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease.Marin JacobwitzMichael XieJamie CatalanoIngo HelbigJ William GaynorNancy BurnhamRebecca L LinnJuliana GebbMark W RussellHakon HakonarsonBarbara H ChaiyachatiAna G Cristancho<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0317944 |
| spellingShingle | Marin Jacobwitz Michael Xie Jamie Catalano Ingo Helbig J William Gaynor Nancy Burnham Rebecca L Linn Juliana Gebb Mark W Russell Hakon Hakonarson Barbara H Chaiyachati Ana G Cristancho DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. PLoS ONE |
| title | DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. |
| title_full | DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. |
| title_fullStr | DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. |
| title_full_unstemmed | DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. |
| title_short | DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease. |
| title_sort | dna methylation differences stratified by normalized fetal placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease |
| url | https://doi.org/10.1371/journal.pone.0317944 |
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