Validation of a Test for Fetal Malformations

Theoreo

Status: Completed

Conditions: Fetal Anomaly

Treatments: Other: Serum metabolomics profiling

Study type: Observational

Funder types: Other; Industry

Identifiers

NCT02965287

MV-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,943 estimated patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

1,943 participants in 2 patient groups

19-21 weeks' gestation

Description:

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.

Treatment:

Other: Serum metabolomics profiling

14-16 weeks' gestation

Description:

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.

Treatment:

Other: Serum metabolomics profiling