Gestational Diabetes Mellitus: Placental-maternal Crosstalk and Future Health

Study Overview
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Brief Summary
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The GaP study is designed to close important knowledge gaps by: exploring placental health and cellular ageing in GDM and the association with neonatal outcome evaluating the effectiveness of current and novel maternal health follow-up strategies after GDM

Detailed Description
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The incidence of gestational diabetes mellitus (GDM) is increasing. GDM has potential adverse short and long term health effects for both the women and her offspring, and involves dysfunctional interaction between placenta and the maternal body. The burden for the individual, the health system and society warrants further investigations into the placental-maternal crosstalk in GDM in order to improve personalized pregnancy surveillance and follow-up. In Oslo county, nearly twice as many women who give birth suffer from GDM (5.7%) than from preeclampsia (2.3%). The large obstetric department at Ullevål provides an optimal environment for novel translational studies and clinical practical aspects of GDM. The GaP study is designed to close important knowledge gaps by: exploring placental health and cellular ageing in GDM and the association with neonatal outcome evaluating the effectiveness of current and novel maternal health follow-up strategies after GDM

Official Title
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The GaP Study: Gestational Diabetes Mellitus: Placental-maternal Crosstalk and Future Health

Conditions
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Gestational Diabetes, Cardiovascular Diseases, Placenta Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women >18 years with GDM giving birth at Oslo University hospital Ullevål. Control group of gestational age matched euglycemic, normotensive pregnancies Exclusion Criteria: reduced fetal movements, epilepsy thyroidea dysfunction hypertensive disorder of pregnancy non-communicable disease Communicable disease (such as HIV) type 1 or type 2 diabetes. not able to understand Norwegian or English. under legal guardianship.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Women with gestational diabetes<br>Any treatment. N=200. | |
| Control group<br>Gestational-age matched, euglycemic, normotensive pregnant women (n=150) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of women with altered levels of circulating senescence markers | Levels of maternal circulating senescence markers, e.g. SAA1, free thiol and related markers, in case group compared to controls | 4 years | 
| Number of women with altered levels of tissue-based senescence markers | Expression of markers of senescence in placental tissue, as assesed by immunohistochemistry (e.g. IL-6, p21, p16 and related markers) in case group compared to controls | 4 years | 
| Number of women with increased values for postpartum surrogate markers for impaired cardiovascular function | As assessed by circulating maternal levels of cardiovascular biomarkers, e.g. HDL (mmol/l), LDL (mmol/l) and related markers in case group compared to controls | 4 years | 
| Number of women with increased values for postpartum surrogate markers for impaired cardiovascular function | As assessed by circulating maternal levels of cardiovascular biomarkers, e.g. GDF-15 (ng/l), NT-pro BNP (ng/l), Troponin (ng/l) and related markers in case group compared to controls | 4 years | 
| Number of neonates with adverse neonatal outcome | A composite measure for neonatal outcome will be created using information on fetal acidemia, Apgar-score, asphyxia, intra-/postpartum fetal death, neonatal intubation/mechanical ventilation, meconium aspiration syndrome, netonatal hypoxic-ishcemic encephalopathy, therapeutic hypothermia of the neonate, rate of acute cesarean section (due to suspected fetal distress) and compared in case group and controls | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with operative vaginal delivery due to suspected fetal distress | Rates of operative vaginal deliveries (forceps/vacuum/combined; due to suspected fetal distress) in case and control groups | 4 years | 
| Percentage of participants with pathological placenta histology findings in case and control groups | As assessed by a senior perinatal pathologist using predefined criteria | 4 years |