Placenta DNA Methylation Adaptation to Maternal Glucose Tolerance in Pregnancy

ABSTRACTMaternal hyperglycemia during pregnancy is associated with fetal growth and adverse perinatal and developmental outcomes. Placental epigenetic maladaptation may underlie these associations. We performed an epigenome-wide association study of term placentas and prenatal maternal glucose response 2-hour post oral glucose challenge at 24-30 weeks of gestation among 448 mother-infant pairs. Maternal glucose levels post-load were strongly associated with lower DNA methylation of 4 CpGs (FDR q<0.05) within the Phosphodiesterase 4B gene (PDE4B). Additionally, three other CpGs were differentially methylated relative to maternal glucose response within the TNFRSF1B; LDLR; and BLM genes (FDR q<0.05). Methylation levels correlated with expression in placental tissue for all 4 CpG sites in PDE4B (rs: 0.26–0.35, P<0.01), LDLR (rs: 0.22, P=0.03) and at TNFRSF1B (rs: -0.25, P=0.01). Our study provides evidence that maternal glucose response during pregnancy is associated with DNA methylation of genes within the placenta that are partially under epigenetic control.

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Maternal glucose levels after a 75-g oral glucose challenge and neonatal outcome

Obstetrics and Gynecology ◽

10.1016/s0029-7844(02)01705-2 ◽

2002 ◽

Vol 99 (4) ◽

pp. S20

Author(s):

J RENAUD

Keyword(s):

Neonatal Outcome ◽

Oral Glucose ◽

Glucose Levels ◽

Glucose Challenge ◽

Maternal Glucose Levels ◽

Maternal Glucose

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Maternal Glucose Levels after a 75-g Oral Glucose Challenge and Neonatal Outcome

Obstetrics and Gynecology ◽

10.1097/00006250-200204001-00038 ◽

2002 ◽

Vol 99 (Supplement) ◽

pp. 20S

Author(s):

Jennifer A. Renaud ◽

Thomas R. Wigton

Keyword(s):

Neonatal Outcome ◽

Oral Glucose ◽

Glucose Levels ◽

Glucose Challenge ◽

Maternal Glucose Levels ◽

Maternal Glucose

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Influence of Maternal Glycemia on Intrauterine Fetal Adiposity Distribution after a Normal Oral Glucose Tolerance Test at 28 Weeks Gestation

Experimental Diabetes Research ◽

10.1155/2011/951203 ◽

2011 ◽

Vol 2011 ◽

pp. 1-6 ◽

Cited By ~ 7

Author(s):

Nadine Farah ◽

Jennifer Hogan ◽

Vicky O'Dwyer ◽

Bernard Stuart ◽

Mairead Kennelly ◽

...

Keyword(s):

Birth Weight ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Subcutaneous Tissue ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Glucose Levels ◽

Maternal Glucose Levels ◽

Maternal Glucose

Objective. To examine the relationship between maternal glucose levels and intrauterine fetal adiposity distribution in women with a normal oral glucose tolerance test (OGTT) at 28 weeks gestation.Study Design. We recruited 231 women with a singleton pregnancy. At 28 and 37 weeks gestation, sonographic measurements of fetal body composition were performed. Multiple regression analysis was used to study the influence of different maternal variables on fetal adiposity distribution.Results. Maternal glucose levels correlated with the fetal abdominal subcutaneous tissue measurements (; ) and with birth weight (; ). Maternal glucose levels did not correlate with the fetal mid-thigh muscle thickness and mid-thigh subcutaneous tissue measurements.Conclusion. We found that in nondiabetic women maternal glucose levels not only influence fetal adiposity and birth weight, but also influence the distribution of fetal adiposity. This supports previous evidence that maternal glycemia is a key determinant of intrauterine fetal programming.

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‘Normal’ Maternal Glucose Levels Up Adverse Outcomes

Family Practice News ◽

10.1016/s0300-7073(07)70838-1 ◽

2007 ◽

Vol 37 (14) ◽

pp. 1-2

Author(s):

PATRICE WENDLING

Keyword(s):

Adverse Outcomes ◽

Glucose Levels ◽

Maternal Glucose Levels ◽

Maternal Glucose

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Maternal Glycemia during pregnancy and Early Offspring Development: A Prospective Birth Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab331 ◽

2021 ◽

Author(s):

Peng Wang ◽

Jun Xie ◽

Xue-chun Jiao ◽

Shuang-shuang Ma ◽

Yang Liu ◽

...

Keyword(s):

Cohort Study ◽

Birth Cohort ◽

Plasma Glucose ◽

Birth Cohort Study ◽

Neurodevelopmental Outcomes ◽

Glucose Levels ◽

Maternal Glucose Levels ◽

Prospective Birth Cohort ◽

Maternal Glucose ◽

Prospective Birth Cohort Study

Abstract Context The association of maternal gestational diabetes mellitus (GDM) with neurodevelopmental outcomes remains controversial and evidence that maternal increasing levels of glucose during pregnancy associated with the risk for impaired neurodevelopment were limited. Objective To identify the continuous association of increasing maternal glucose levels with neurodevelopmental disorders in offspring and explore the potential contribution of cord metabolites to this association. Methods The prospective birth cohort study included 1036 mother-child pairs. Primary predictors were maternal exposure GDM and maternal glucose values at a 75-g oral-glucose-tolerance test (OGTT) at 24–28 weeks during pregnancy. Primary neurodevelopmental outcomes at 12 mo in offspring were assessed by the ASQ-3. Results Maternal GDM was associated with failing the communication domain in offspring in the adjusted models [RR with 95% CI: 1.97(1.11, 3.52)]. Increasing levels of fasting plasma glucose (FPG), 1 h plasma glucose (1-h PG) and 2 h plasma glucose (2-h PG) with one SD change were at higher risks in failing the personal social domain of ASQ [RRs with 95% CI for FPG: 1.49(1.09, 2.04); for 1-h PG: 1.70(1.27, 2.29); for 2-h PG: 1.36(1.01, 1.84)]. The linear association was also demonstrated. Compared with girls, boys exposed to higher maternal glucose levels were inclined to the failure of the personal social domain. Mediation analysis showed the contribution of maternal GDM to failure of communication domain mediated by C-peptide. Conclusions Maternal glucose levels below those diagnostic of diabetes are continuously associated with impaired neurodevelopment in offspring at 12 mo.

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