IDENTIFY Study: Natural History of Maternal Neoplasia

Background:

• Starting in 2011, analysis of circulating cell-free DNA (cfDNA) in the plasma 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 is referred to as noninvasive prenatal testing (NIPT) or noninvasive prenatal screening (NIPS). 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 test results, 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 high-risk result that is suggestive of aneuploidy. A diagnostic test such as an amniocentesis or a chorionic villus sampling (CVS) should be performed. However, if the fetus has a normal karyotype or

chromosome microarray (CMA),there are no guidelines for the 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 or CMA.

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.

• 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 "non-reportable" or multiple aneuploidies inconsistent with a viable fetus.
• Normal-appearing fetus or fetuses on ultrasound examination and/or a normal fetal or neonatal karyotype. If a fetal anomaly is present but does not explain entirely the NIPT results, or there is a continuing concern for maternal cancer, the individual is still eligible for participation.
• Study enrollment may occur during pregnancy or up to two years postpartum.
• Ability to travel to NIH.
• Ability of subject to understand and the willingness to sign a written informed consent document.

Exclusion criteria

-The following NIPT results will be excluded:

--Abnormal results that have been associated previously with an increased risk for hematologic malignancy, including but not limited to, Trisomy 8, 20delq, 5delq.