Validation of a Test for Fetal Malformations

Study Overview
=================
Brief Summary
-----------------
The investigators have developed a diagnostic test for the evaluation of the presence of fetal malformations through metabolomic analysis of maternal peripheral blood serum by chromatographic techniques and mass spectrometry, and subsequent mathematical modeling analysis of the data by means of multivariate mathematical models specifically developed for this purpose. The study aims at determining the performance parameters (specificity, sensibility, positive predictive value (PPN), negative predictive value (NPV), etc.) of the test and its applicability. To do this, the investigators will use the serum samples of the patients enrolled in New Zealand in the SCOPE Study (www.scopestudy.net), an international study conducted between years 2004-2008.

Detailed Description
-----------------
The test has been developed in a case-control study. In this clinical trial the investigators will test it in a large cohort that is likely to resemble a real population. The purpose of validation is to see if the test is able to recognize the few malformed fetuses in the entire population and especially its specificity in real conditions. In addition, the investigators will check whether particular maternal conditions (such as preeclampsia, gestational diabetes, etc.) or fetal conditions (Small for gestational age, Large for gestational age, etc.) affect the test results.

Official Title
-----------------
Blind Validation of a Metabolomics Based Test for the Non-invasive Screening of Fetal Malformations

Conditions
-----------------
Fetal Anomaly

Intervention / Treatment
-----------------
* Other: Serum metabolomics profiling


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria were the ones designed by SCOPE Study: - Nulliparous women, with a singleton pregnancy, between 14wks, 0 days and 16wks, 6 days gestation who give informed consent to participate in SCOPE. Exclusion criteria were the ones designed by SCOPE Study: Unsure of last menstrual period (LMP) Unwilling to have ultrasound scan at ≤20 weeks ≥3 miscarriages ≥3 terminations Essential hypertension treated pre-pregnancy Moderate-severe hypertension at booking ≥160/100 mmHg Diabetes Renal disease Systemic lupus erythematosus Anti-phospholipid syndrome Sickle cell disease HIV positive Major uterine anomaly Cervical suture Knife cone biopsy Ruptured membranes now Long term steroids Treatment low-dose aspirin Treatment calcium (>1g/24h) Treatment eicosapentanoic acid (fish oil) Treatment vitamin C ≥1000 mg & Vit E ≥400 iu Treatment heparin/low molecular weight heparin
Sexes Eligible for Study
-----------------
Female

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

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 19-21 weeks' gestation<br>The test validation will be performed on the 1943 serum samples of pregnant women at 19-21 weeks' gestation recruited in New Zealand for the SCOPE Study. All the samples will be analyzed to extract and purify the whole metabolome. Metabolites will be characterized through mass spectrometric techniques. These data will be interpreted by means of a bioinformatic algorithm specifically designed for this purpose. | Other: Serum metabolomics profiling<br>* The serum samples will be used to get a metabolomic profile<br>|
| 14-16 weeks' gestation<br>Five hundred subjects at 14-16 weeks gestation were randomly selected from the whole cohort of patients. The serum samples collected at 14-16 weeks gestation will be used to test the diagnostic performance at this earlier gestational phase. | Other: Serum metabolomics profiling<br>* The serum samples will be used to get a metabolomic profile<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic test performance evaluation in dichotomic classification at 19-21 weeks' gestation | Assessment of the sensitivity, likelihood ratios and performances (diagnostic accuracy) in the identification of a malformed fetus through the analysis of a serum sample from a mother at 19-21 weeks' gestation | 6 months | 
| Diagnostic test performance evaluation in the individuation of the exact diagnosis of fetal malformation at 19-21 weeks' gestation | Assessment of the sensitivity, likelihood ratios and performances (diagnostic accuracy) in the identification of the type of malformation through the analysis of a serum sample from a mother at 19-21 weeks' gestation | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic test performance evaluation in dichotomic classification at 14-16 weeks gestation | Assessment of the sensitivity, likelihood ratios and performances (diagnostic accuracy) in the identification of a malformed fetus through the analysis of a serum sample from a mother at 19-21 weeks' gestation | 6 months | 
| Diagnostic test performance evaluation in the individuation of the exact diagnosis of fetal malformation at 14-16 weeks gestation | Assessment of the sensitivity, likelihood ratios and performances (diagnostic accuracy) in the identification of the type of malformation through the analysis of a serum sample from a mother at 14-16 weeks gestation | 6 months |