Prediction of Preeclampsia and Other Pregnancy Complications Following Combined Iterative Screening

Study Overview
=================
Brief Summary
-----------------
Preterm birth (PTB), preeclampsia (PE), fetal growth restriction (FGR) and intra-uterine fetal death (IUFD) constitutes the main causes of perinatal morbidity and mortality and are called Great Obstetrical Syndromes. Algorithms to predict those outcomes have been developed by combining maternal characteristics (history, age, BMI, blood pressure), biochemical (sFlt-1, β-hCG, PlGF, AFP) and sonographic (uterine artery Doppler, 3D of placenta, cervical length, nasal bone measurement, nuchal translucency) markers. Another prospective observational study (PREDICTION study NCT 02189148) is also ongoing, which aims to validate those algorithms at the first trimester of pregnancy. Recent data suggest that repeating the same measurements later in pregnancy could improve the detection rates, allowing closer monitoring of high-risk patients and potential therapeutics under investigation. The current study (PREDICTION2) is an ancillary study of PREDICTION and aims at validating the use of these markers in a combined iterative manner in the prediction of preeclampsia and other obstetrical outcomes.

Detailed Description
-----------------
The objective of this study is to validate the predictive values of biophysical (maternal blood pressure); biochemical (sFlt-1, β-hCG, PlGF, and AFP) and ultrasonographic (cervical length, Doppler, 3D evaluation of the placenta, 3D nasal bone) biomarkers at several timepoints for the prediction of adverse pregnancy outcomes including preterm birth, preeclampsia, fetal growth restriction and intra-uterine fetal death. These biomarkers will be evaluated at 14-16 weeks, 20-24 weeks and 30-34 weeks. Those specific gestational ages have been selected because they correspond to the typical clinical/hospital visits for prenatal blood and/or ultrasound screening.

Official Title
-----------------
Prediction of Preeclampsia and Other Pregnancy Complications Following Combined Iterative Screening

Conditions
-----------------
Preterm Birth, Intra Uterine Fetal Death, Preeclampsia, Fetal Growth Restriction

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: nulliparous pregnant women participating in Prediction study (NCT02189148) Exclusion Criteria: <18 years old at recruitment; multiple pregnancies; fetal congenital malformation; positive for HIV or hepatitis C; fetal demise at recruitment; women planning a delivery outside the participating hospitals; women not able to provide an informed consent to the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------
What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| preeclampsia | 1) de novo hypertension with systolic blood pressure ≥ 140 mmHg or diastolic blood pressure >90 mmHg on two occasions at least four hours apart, after 20 weeks of pregnancy, and 2) associated with proteinuria ≥300 mg/24 h or at least '2 +' protein on urine dipstick or an adverse conditions | >20 weeks of preeclampsia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fetal growth restriction | defined as a birth weight below the 10th centile (or below the 3rd centile for severe FGR) of Canadian reference growth charts. | neonatal weight at birth (on the day of birth) | 
| Preterm birth | defined as delivery <37 weeks of gestation. | between 20-37 weeks of gestation | 
| Intra uterine fetal death | fetal death during pregnancy | from the 20th week of gestation to the moment of birth | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pregnancy, screening, doppler, markers, PlGF, sFlt-1, placenta