scholarly journals Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yoshifumi Kasuga ◽  
Tomoko Kawai ◽  
Kei Miyakoshi ◽  
Yoshifumi Saisho ◽  
Masumi Tamagawa ◽  
...  

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Esther H. G. Park ◽  
Frances O’Brien ◽  
Fiona Seabrook ◽  
Jane Elizabeth Hirst

Abstract Background There is increasing pressure to get women and babies home rapidly after birth. Babies born to mothers with gestational diabetes mellitus (GDM) currently get 24-h inpatient monitoring. We investigated whether a low-risk group of babies born to mothers with GDM could be defined for shorter inpatient hypoglycaemia monitoring. Methods Observational, retrospective cohort study conducted in a tertiary maternity hospital in 2018. Singleton, term babies born to women with GDM and no other risk factors for hypoglycaemia, were included. Capillary blood glucose (BG) testing and clinical observations for signs of hypoglycaemia during the first 24-h after birth. BG was checked in all babies before the second feed. Subsequent testing occurred if the first result was < 2.0 mmol/L, or clinical suspicion developed for hypoglycaemia. Neonatal hypoglycaemia, defined as either capillary or venous glucose ≤ 2.0 mmol/L and/or clinical signs of neonatal hypoglycaemia requiring oral or intravenous dextrose (lethargy, abnormal feeding behaviour or seizures). Results Fifteen of 106 babies developed hypoglycaemia within the first 24-h. Maternal and neonatal characteristics were not predictive. All babies with hypoglycaemia had an initial capillary BG ≤ 2.6 mmol/L (Area under the ROC curve (AUC) 0.96, 95% Confidence Interval (CI) 0.91–1.0). This result was validated on a further 65 babies, of whom 10 developed hypoglycaemia, in the first 24-h of life. Conclusion Using the 2.6 mmol/L threshold, extended monitoring as an inpatient could have been avoided for 60% of babies in this study. Whilst prospective validation is needed, this approach could help tailor postnatal care plans for babies born to mothers with GDM.


2020 ◽  
Vol 24 (23) ◽  
pp. 13899-13912 ◽  
Author(s):  
Weiqiang Zhu ◽  
Yupei Shen ◽  
Junwei Liu ◽  
Xiaoping Fei ◽  
Zhaofeng Zhang ◽  
...  

Author(s):  
David Song ◽  
James C Hurley ◽  
Maryanne Lia

Background: We investigated the treatment effects of tight glycaemic targets in a population universally screened according to the International Association of Diabetes and Pregnant Study Groups (IADPSG)/World Health Organisation (WHO) gestational diabetes mellitus (GDM) guidelines. As yet there, have been no randomized control trials evaluating the effectiveness of treatment of mild GDM diagnosed under the IADPSG/WHO diagnostic thresholds. We hypothesize that tight glycaemic control in pregnant women diagnosed with GDM will result in similar clinical outcomes to women just below the diagnostic thresholds. Methods: A multiple cut-off regression discontinuity study design in a retrospective observational cohort undergoing oral glucose tolerance tests (OGTT) (n = 1178). Treatment targets for women with GDM were: fasting capillary blood glucose (CBG) of ≤5.0 mmol/L and the 2-h post-prandial CBG of ≤6.7 mmol/L. Regression discontinuity study designs estimate treatment effects by comparing outcomes between a treated group to a counterfactual group just below the diagnostic thresholds with the assumption that covariates are similar. The counterfactual group was selected based on a composite score based on OGTT plasma glucose categories. Results: Women treated for GDM had lower rates of newborns large for gestational age (LGA), 4.6% versus those just below diagnostic thresholds 12.6%, relative risk 0.37 (95% CI, 0.16–0.85); and reduced caesarean section rates, 32.2% versus 43.0%, relative risk 0.75 (95% CI, 0.56–1.01). This was at the expense of increases in induced deliveries, 61.8% versus 39.3%, relative risk 1.57 (95% CI, 1.18–1.9); notations of neonatal hypoglycaemia, 15.8% versus 5.9%, relative risk 2.66 (95% CI, 1.23–5.73); and high insulin usage 61.1%. The subgroup analysis suggested that treatment of women with GDM with BMI ≥30 kg/m2 drove the reduction in caesarean section rates: 32.9% versus 55.9%, relative risk 0.59 (95%CI, 0.4–0.87). Linear regression interaction term effects between non-GDM and treated GDM were significant for LGA newborns (p = 0.001) and caesarean sections (p = 0.015). Conclusions: Tight glycaemic targets reduced rates of LGA newborns and caesarean sections compared to a counterfactual group just below the diagnostic thresholds albeit at the expense of increased rates of neonatal hypoglycaemia, induced deliveries, and high insulin usage.


2019 ◽  
Vol 20 (23) ◽  
pp. 5828 ◽  
Author(s):  
Stephanie Dias ◽  
Sumaiya Adam ◽  
Paul Rheeder ◽  
Johan Louw ◽  
Carmen Pheiffer

Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM.


2012 ◽  
Vol 97 (2) ◽  
pp. 217-222 ◽  
Author(s):  
Juana A. Flores-le Roux ◽  
Enric Sagarra ◽  
David Benaiges ◽  
Elisa Hernandez-Rivas ◽  
Juan J. Chillaron ◽  
...  

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2792
Author(s):  
Monika Słupecka-Ziemilska ◽  
Piotr Wychowański ◽  
Monika Puzianowska-Kuznicka

Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and may result in short-term and long-term consequences for offspring. The present review highlights evidence of epigenetic programming, mostly from human studies, which occurs in offspring exposed to maternal GDM during different stages of development, paying special attention to the differences in sensitivity of offspring to maternal hyperglycemia as a result of sex-related factors. We also aim to answer the following question: If these epigenetic changes are constant throughout the lifetime of the offspring, how do they present phenotypically?


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