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.

Epigenetic patterns inherited from both parents significantly influence gene expression and disease susceptibility in their offspring, with particularly negative effects in gestational diabetes, as indicated in animal and observational studies. However, human studies are limited due to the complexity and ethical concerns of collecting samples from fetuses and newborns. Invasive fetal sampling methods carry a risk of pregnancy loss, but the discovery of fetal cell-free DNA in maternal blood has revolutionized prenatal diagnostics by providing a non-invasive alternative. Recent advancements have made it possible to use cell-free DNA analyses also for epigenetic characterizations. The primary objective of this project is to elucidate the bidirectional epigenetic interactions between maternal gestational metabolism and the fetal epigenome, with a focus on identifying and understanding the biological impacts of epigenetic modifications in both the mother and fetus. Additionally, the research seeks to uncover epigenetic biomarkers that are linked to gestational diabetes and to assess the influence of parental epigenetic marks on the fetus. It will examine how parental epigenetics and parental glucose metabolism affects these modifications, facilitating a detailed analysis of the origins and mechanisms of epigenetic transmission.

We will recruit couples between gestational weeks 24 and 28, with and without gestational diabetes, and perform metabolic characterizations. Maternal cell-free DNA (including fetal DNA), maternal nuclear DNA, and paternal nuclear and cell-free DNA will be collected for methylation analyses.

Inclusion Criteria:

• 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
• No known underlying diseases
• Understanding and voluntary signing of a consent form before study- related examinations

Exclusion Criteria:

• 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])
• Current depression or other psychiatric disorders
• Eating disorders
• Regular use of medication during pregnancy
• Pre-existing cardiovascular disease
• Drug and/or alcohol abuse
• Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m²
• C-reactive protein > 10 mg/l
• Transaminase elevation of 2 times the upper norm
• No consent to be informed about incidentally discovered pathological findings
• Any other (clinical) condition that would endanger participants safety or question scientific success according to the physicians opinion.

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.