IDENTIFY Study: Natural History of Maternal Neoplasia

Study Overview
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Brief Summary
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Background: Pregnant women can get a DNA analysis of their blood. The test tells a woman and her doctor about the DNA of her unborn baby. But some women get test results that are abnormal or not reportable. Researchers want to learn more about the relationship between these test results and cancer. Objective: To better understand prenatal DNA test results and how they can predict cancer, if present, in pregnant women. Eligibility: Women 18 and older who got prenatal DNA test results that were abnormal or not reportable and suggested the abnormality was in the woman and not her baby. <TAB> Design: Potential participants will be screened by phone or in person. They will talk about their medical history and send copies of their medical records. Eligible participants will have a physical exam and medical history. They will give blood and stool samples. They may have a Pap smear. They will talk to a specialist about the test results they got when they were pregnant. Participants will have magnetic resonance imaging (MRI). They will lie on a table that slides in and out of a metal tube, taking pictures. Participants will complete a paper or electronic survey. It will assess their emotional well-being. Participants will get a list of any possible diagnoses and treatment options. Participants may be followed for up to 5 years. They may give blood samples and copies of their medical records. This can be done without traveling to the NIH. In some cases, people might come back to the NIH in one year to see if anything has changed.

Detailed Description
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Background: Starting in 2011, analysis of circulating cell-free DNA (cfDNA) in the blood of pregnant women began to be offered clinically as a prenatal screen for trisomies 13, 18, and 21. Owing to its superior sensitivity and positive predictive values compared to serum biochemistry and ultrasound markers, the cfDNA test became rapidly incorporated into prenatal clinical care. By 2013, however, reports began to appear that described examples of false-positive test results. cfDNA analysis is performed on maternal plasma samples taken any time between 10 and 40 weeks of gestation and called noninvasive prenatal testing (NIPT). The maternal plasma contains circulating DNA from the placenta (which serves as a proxy for the fetus) as well as the maternal hematopoietic system. Retrospective studies evaluated the DNA profiles of women in whom a clinical diagnosis of malignancy was already known. Solid tumors shed cfDNA into the circulation. With increased understanding of maternal malignancy as the underlying basis for unusual cfDNA analysis, case reports have been published that suggest that the tumor cfDNA is the underlying basis for the false-positive test results. Prenatal genomic testing provides proof-of-principle that cfDNA analysis works as a screen to detect neoplasia, even when it was not designed to do so; and, clinical sequencing laboratories can find the women who are potentially at risk. There are clear and consistent professional guidelines regarding follow-up of the fetus with a diagnostic test such as an amniocentesis or a chorionic villus sampling (CVS). However, if the fetus has a normal karyotype, there are no guidelines as to follow-up of the pregnant woman. We propose here a study to determine the best approach for clinical follow-up if the test results are suggestive of cancer. Objective: - To study the natural history of women with prenatal testing results that suggest an incidental detection of maternal neoplasia Eligibility: - Women who had prenatal cfDNA tests during pregnancy to screen for fetal chromosomal aneuploidies,with non-reportable or abnormal results inconsistent with a viable fetus. Follow up testing shows a normal-appearing fetus on ultrasound examination and/or a normal fetal or neonatal karyotype. Design: Participants will undergo an initial evaluation at the Clinical Center to diagnose possible neoplasia. All collected information will be discussed in multidisciplinary meetings. If neoplasia is discovered, the results will be shared with participants and referring physicians. Participants will be followed to collect all available medical information.

Official Title
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Incidental Detection of Maternal Neoplasia Through Non-invasive Cell-Free DNA Analysis (IDENTIFY), a Natural History Study

Conditions
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Maternal Neoplasia

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Women, age >= 18 years. Pregnancy for which the following applies: -- Underwent blood noninvasive prenatal testing (NIPT) during pregnancy to screen for fetal chromosomal aneuploidies and had unusual results that either led to an interpretation of test failure or multiple aneuploidies inconsistent with a viable fetus. Follow up testing shows a normal-appearing fetus or fetuses on ultrasound examination and/or a normal fetal or neonatal karyotype. Women undergoing active treatment or surveillance for known malignancy may enroll, so that their DNA profiles will serve as positive controls. Study enrollment may occur during pregnancy or up to two years postpartum. Ability to travel to NIH, unless undergoing active treatment for known malignancy. Ability of subject to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: - None

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1/Cohort 1<br>Women with prenatal testing results that suggest an incidental detection of maternal neoplasia | |
| 2/Cohort 2<br>Women undergoing active treatment or surveillance for known malignancy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To study the natural history of women with prenatal testing results that suggest an incidental detection of maternal neoplasia | Natural history of women with prenatal testing results that suggest an incidental detection of maternal neoplasia | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prenatal Clinical Care, Prenatal Screen, Pregnant Women, Predictive Values, Natural History, Cell-Free DNA (cfDNA) test