This clinical trials aims to investigate the impact of parental metabolism during pregnancy on fetal epigenetic signatures.
The metabolic profiles of both parents will be evaluated through a blood sample collected from the father and an oral glucose tolerance test administered to the pregnant mother. Additionally, epigenetic signatures will be assessed using parental blood samples. Fetal epigenetic signatures can be identified by analyzing fetal cell-free DNA that circulates in the mother's bloodstream.
Pregnant women between 20 and 28 weeks of gestation
The father of the child is known and willing to participate in the study
No known underlying medical conditions in either parent
No fetal abnormalities detected in first-trimester screening, detailed fetal anatomy ultrasound, non-invasive prenatal testing (NIPT), or any additional prenatal examinations performed, if applicable
Age < 18 years
Type 1 or type 2 diabetes mellitus
Pharmacological treatment affecting blood glucose levels (e.g., steroids, insulin)
Endocrine disorders (e.g., hyperthyroidism, polycystic ovary syndrome [PCOS])
Participants will be recruited from the outpatient clinic of the department of obstetrics and gynaecology at Ulm University Hospital as well as from as well as through public advertisements posted at Ulm University.
Family-based
Cross-sectional
Metabolic and epigenetic characterization of parents ans fetuses
Other interventionPregnant women will undergo an oral glucose tolerance test to characterize metabolism and assess the presence of gestational diabetes. Moreover, they will undergo blood sampling to assess the mothers' epigenetic signatures and the fetal epigenetic signatures based on circulating fetal cell-free DNA. Fathers will undergo (if possible fasting) blood sample to characterize metabolism and epigenetic signatures
Epigenetic profiles of parents and fetuses
Methylation pattern of CpG sites in fathers, mothers and fetuses assessed from blood samples from the father and the mother. Genome-wide DNA methylation will be quantified as 5-methylcytosine (5mC) levels at CpG sites in maternal and paternal nuclear DNA from peripheral blood. Long-read sequencing will be used to detect genomic sequences and base modifications. Fetal DNA methylation will be assessed from fetal cell-free DNA isolated from maternal plasma using long-read sequencing. Allelic phasing will be applied to assign epigenetic modifications to parental origin. Deconvolution analysis will be used to subtract blood cell-derived epigenetic patterns and infer tissue-of-origin signals.
Epigenetic signatures of gestational diabetes
Differentially methylated regions will be computed across parental genomic DNA and fetal cell-free DNA between women with and without gestational diabetes. Differentially methylated regions will be bioinformatically annotated to candidate genes and pathogenic pathways.
Correlation of epigenetic signatures and glycemia
Glucose level assessed from glucose measurements from fasting blood sample or oral glucose tolerance test.
Correlation of epigenetic signatures and insulin sensitivity
Insulin sensitivity assessed by Homeostasis Model Assessment of insulin resistance based on glucose and insulin measurements from fasting blood sample or oral glucose tolerance test.
Correlation of epigenetic signatures and insulin secretion
Insulin secretion assessed by Homeostasis Model Assessment of beta-cell function based on glucose and insulin measurements from fasting blood sample and oral glucose tolerance test.
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