SLC9B1 methylation predicts fetal intolerance of labor

Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data...

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Main Authors: Anna K. Knight, Karen N. Conneely, Varun Kilaru, Dawayland Cobb, Jennifer L. Payne, Samantha Meilman, Elizabeth J. Corwin, Zachary A. Kaminsky, Anne L. Dunlop, Alicia K. Smith
Format: Article
Language:English
Published: Taylor & Francis Group 2018-01-01
Series:Epigenetics
Subjects:
Online Access:http://dx.doi.org/10.1080/15592294.2017.1411444
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author Anna K. Knight
Karen N. Conneely
Varun Kilaru
Dawayland Cobb
Jennifer L. Payne
Samantha Meilman
Elizabeth J. Corwin
Zachary A. Kaminsky
Anne L. Dunlop
Alicia K. Smith
author_facet Anna K. Knight
Karen N. Conneely
Varun Kilaru
Dawayland Cobb
Jennifer L. Payne
Samantha Meilman
Elizabeth J. Corwin
Zachary A. Kaminsky
Anne L. Dunlop
Alicia K. Smith
author_sort Anna K. Knight
collection DOAJ
description Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24–32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18–36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value <8.9 × 10−9, FDR <0.05) in gene SLC9B1, a Na+/H+ exchanger, were associated with fetal intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24–32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24–32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.
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spelling doaj.art-3d048e6a529c454892b9612c2bdd5f042023-09-21T13:09:20ZengTaylor & Francis GroupEpigenetics1559-22941559-23082018-01-01131333910.1080/15592294.2017.14114441411444SLC9B1 methylation predicts fetal intolerance of laborAnna K. Knight0Karen N. Conneely1Varun Kilaru2Dawayland Cobb3Jennifer L. Payne4Samantha Meilman5Elizabeth J. Corwin6Zachary A. Kaminsky7Anne L. Dunlop8Alicia K. Smith9Emory UniversityEmory UniversityEmory UniversityEmory UniversityJohns Hopkins School of MedicineJohns Hopkins School of MedicineEmory UniversityJohns Hopkins School of MedicineEmory UniversityEmory UniversityFetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24–32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18–36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value <8.9 × 10−9, FDR <0.05) in gene SLC9B1, a Na+/H+ exchanger, were associated with fetal intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24–32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24–32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.http://dx.doi.org/10.1080/15592294.2017.1411444biomarker, complicationdeliveryfetal distress; nhedc1; pregnancy; slc9b1; sodium hydrogen exchanger
spellingShingle Anna K. Knight
Karen N. Conneely
Varun Kilaru
Dawayland Cobb
Jennifer L. Payne
Samantha Meilman
Elizabeth J. Corwin
Zachary A. Kaminsky
Anne L. Dunlop
Alicia K. Smith
SLC9B1 methylation predicts fetal intolerance of labor
Epigenetics
biomarker, complication
delivery
fetal distress; nhedc1; pregnancy; slc9b1; sodium hydrogen exchanger
title SLC9B1 methylation predicts fetal intolerance of labor
title_full SLC9B1 methylation predicts fetal intolerance of labor
title_fullStr SLC9B1 methylation predicts fetal intolerance of labor
title_full_unstemmed SLC9B1 methylation predicts fetal intolerance of labor
title_short SLC9B1 methylation predicts fetal intolerance of labor
title_sort slc9b1 methylation predicts fetal intolerance of labor
topic biomarker, complication
delivery
fetal distress; nhedc1; pregnancy; slc9b1; sodium hydrogen exchanger
url http://dx.doi.org/10.1080/15592294.2017.1411444
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