A New Prenatal Blood Test for Down Syndrome

Study Overview
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Brief Summary
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The study will examine the sensitivity and specificity of a circulating cell-free nucleic acid test (DNA/RNA) to identify Down syndrome between about 10 weeks and 21 weeks 6 days gestation. In addition, the new test may be used to identify trisomy 13 and 18 as part of a more complete laboratory developed test. We hypothesize that the new circulating cell-free fetal NA-based test will accurately and precisely measure specific fetal markers in maternal circulation and that measurement will lead to the ability to noninvasively identify with high sensitivity and specificity, fetal chromosome abnormalities, such as Down syndrome.

Detailed Description
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The RNA study is an observational trial whose primary aim is to document the performance (sensitivity and specificity) of one or more laboratory developed test (LDT) using circulating cell-free fetal nucleic acids from maternal plasma to identify Down syndrome. Multiple test modalities are being pursued, including massively parallel sequencing and those utilizing differential methylation. The population being studied is women already having a diagnostic test (e.g., amniocentesis, CVS) between 10 weeks and 21 weeks 6 days gestation, and whose pregnancy is at high risk for having Down syndrome. The women provide informed consent. The karyotype will provide the gold standard against which the LDT test is judged. Samples and karyotypes will be collected from up to 25 prenatal diagnostic centers around the world and tested in several laboratories in the United States. The secondary aim is to develop a nucleic acid sample bank to allow documentation of subsequent improvements or new methodologies to identify fetal aneuploidy using circulating cell-free fetal nucleic acids.

Official Title
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The RNA (RNA-Based Noninvasive Aneuploidy) Study

Conditions
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Down Syndrome, Trisomy 21

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women between about 10 weeks and 21 weeks 6 days gestation who are undergoing a diagnostic procedure (i.e., chorionic villus sampling or amniocentesis) for karyotype analysis who have, on average, a high prevalence of Down syndrome (about 1:30 to 1:50). Three main sources are pregnancies screen positive for: the combined test at 10 to 13 weeks (NT, PAPP-A and hCG) the second trimester quadruple test at 15 to 18 weeks gestation integrated screening (PAPP-A and the quadruple test, with or without NT). Variations of the integrated test such as sequential testing will also be acceptable. Other, less common high risk groups would be women having diagnostic testing because of maternal age of 38 years or older at delivery, pregnancies with an abnormal ultrasound highly suggestive of a chromosome abnormality (e.g., major heart defect, clenched fist), and women with an inherited form of Down syndrome (Robertsonian translocation). Exclusion Criteria: Nonpregnant women and women at relatively low risk for a Down syndrome baby.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Down syndrome<br>Women having CVS or amniocentesis who, as a group, have a high prevalence of Down syndrome. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The RNA study is an observational trial whose primary aim is to document the performance (sensitivity and specificity) of a laboratory developed test (LDT), using fetal nucleic acid in maternal plasma to identify Down syndrome in early pregnancy. |  | Within 1st and 2nd trimesters | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The secondary aim is to develop a sample bank to allow documentation of subsequent improvements in the existing LDT or documenting performance of new methodologies. |  | Late1st and early 2nd trimesters | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Down Syndrome, trisomy 21, prenatal testing, pregnant women