Prediction and prevention of preeclampsia, intrauterine growth restriction, prenatal stress and fetal programming of child's psychological development

1. Gestational weeks of 12th to 14th:
1.1. Women’s weight and blood pressure
1.2. Ultrasound examination (Doppler velocimetry)
1.3. Blood for biochemical and genetic analysis (30 ml)
1.4. Urine (10 ml)
1.5. Randomisation for the ASA and placebo groups

2. Gestational weeks of 18th to 20th and 26th to 28th :
2.1. Weight and blood pressure measurements are repeated
2.2. Ultrasound examinations (Doppler velocimetry)
2.3. Fasting blood (30 ml) and urine (10 ml) samples
2.4. A 2-hour oral glucose tolerance test (only at 26th to 28th weeks of gestation)

3. At delivery:
3.1. Information collected from the clinical records of the mother and the newborn
3.2. Blood (30 ml) and urine (10ml) samples
3.3. Cord blood sample

4. Biochemical measurements: samples are obtained at 12th to 14th, 18th to 20th and 26th to 28th weeks of gestation and within 12-24 hours after delivery. The biochemical measurements include:
4.1. Indices of antioxidant status: serum uric acid (enzymatic assay using uricase)
4.2. Indices of placental insufficiency:
4.2.1. Serum activin A
4.2.2. Inhibin A and B (two site enzyme immunoassay)
4.2.3. Serum leptin (Radioimmunoassay [RIA] or Enzyme-Linked Immunosorbent Assay [ELISA])
4.2.4. Serum Flt1 (ELISA)
4.3. Indices of endothelial function:
4.3.1. Serum asymmetric dimethylarginine (ADMA)
4.3.2. Serum fibronectin (ELISA)
4.3.3.Serum e-selectin (ELISA)
4.3.4. Serum c-reactive protein (immunotubidimetry or immunonefelometry)
4.4. Lipids:
4.4.1. Serum triglyserides (enzymatic)
4.4.2. Serum free fatty acids (enzymatic)
4.5. Glucose metabolism:
4.5.1. Serum insulin (RIA)
4.5.2. Serum glucose (enzymatic)
4.5.3. 2-hour glucose tolerance test
4.5.4. Serum Sex Hormone-Binding Globulin (SHBG) (Time-Resolved Fluorescence Immunoassay [TR-FIA])
4.6. Biochemical measurements from the cord blood
5. The biochemical compounds to be measured in the study population include:
5.1. Insulin- insulin-like growth factor system:
5.1.1. Serum insulin (RIA)
5.1.2. IGF- I (RIA)
5.1.3. IGF- II (RIA or ELISA)
5.1.4. IGF-binding proteins 1 and 2 (ELISA)
4.1.5. adiponectin (ELISA)
5.2. Hypothalamic-pituitary-adrenal axis:
5.2.1. Corticotrophin-releasing hormone
5.2.2. Cortisol (RIA or LC-MS/MS)
5.2.3. Cortisol-binding globulin (RIA)
5.3. Regulation of fetal cortisole exposure: 11β- hydroxysteroid dehydrogenase 2 (determined from placental sample) (LC-MS/MS)
6. The incidence of pre-eclampsia in ASA and placebo groups

1. To test whether infants born to mothers with preeclampsia are characterized by greater behavioral difficulty in emotional, social and cognitive domains of development than infants born to mothers without preeclampsia. The aim is also to test whether infant developmental outcomes are predicted by maternal prenatal stress, depression and anxiety measured and the mother’s stress-predisposing / buffering traits and characteristics, together or independently of preeclampsia and potential postnatal environmental factors.

2. Healthcare register study
We collect data from the following sources:
2.1. National Population Register: to identify the parents and siblings (including half-siblings)
2.2. Medication reimbursement: hypertension, coronary heart disease, cardiac insufficiency, diabetes, asthma, death register (time and cause of death)
2.3. Hospital diagnosis register: diagnosis related to cardiovascular disease and obstetrics
2.4. Birth register: birth measurements, gestational age and possible pre- and postnatal complications of siblings and half-siblings of newborn infant
2.5. Hospital records of the women and their mothers: pregnancy follow-up and newborn
2.6. Permission to collect and link the data applied by the Ministry of Social and Health Affairs