Women and prenatal genetic testing in the 21st century.

Author:Farrell, Ruth M.
Position:New Technologies, New Challenges: Women and Prenatal Genetic Testing in the 21st Century


With over four million women presenting for prenatal care in the United States annually and current recommendations to offer aneuploidy testing to all, there is no doubt that advances in prenatal genetic testing will have an important impact on the health and well-being of women and their children. Translational genomic research over the past decade has vastly increased our knowledge of human health and disease, bringing the promise of improving the lives of patients through new medical technology. Initially used in adult testing indications, many of these technologies are finding a place in obstetrics as pregnant women and their partners now have access to a vast array of fetal testing options that dramatically influence the delivery of prenatal care. With the development of new molecular testing modalities, fetal cells can now be analyzed for dozens of genetic mutations in a single pass and provide rich genomic information that would be undetectable using conventional testing methods. (1) The ability to conduct genetic tests on cell-free fetal

DNA in the maternal blood stream is paving the way for non-invasive diagnostic tests to become part of routine prenatal care. Direct-to-consumer test offerings have become increasingly visible and accessible in conjunction with these advances, expanding the avenues by which women can obtain information about their pregnancies. (2) It is not just innovation in clinical genetics that has affected antenatal care. Parallel advances in the fields of maternal-fetal medicine and neonatology are also influencing how new genetic tests become incorporated into the care of the pregnant woman, establishing new boundaries for optimizing in utero health using genetic science.

The recent explosion of genetic science and technology has allowed innovative approaches for identifying and treating disease to become a clinical reality. While aimed at improving and preserving health, these advances produce some of the most profound ethical, legal, and social questions about how to integrate new technology into the healthcare and lives of patients. These questions are twofold, as they pertain not only to understanding the significance of personal genetic information but also to how such information can and should be used to guide fundamental choices about the self and family. Information about one's genetic makeup leads to a host of interlaced ethical and pragmatic ramifications that spring from our limited understanding of how the presence of a mutation plays out over the course of one's life. Despite a more sophisticated understanding of the human genome, it is striking that many of the ethical and practical challenges of genetic testing remain unresolved, such as the interpretation of personal risk from the identification of a genetic mutation, the privacy and confidentiality of genetic information, and the prediction of quality of life for those living with disease or disability.

These existing dilemmas have magnified implications in women's reproductive health and prenatal genetic testing. While genomic research has opened up new possibilities to assess fetal health, the sheer volume of information generated by prenatal testing it as amplified the fundamental ethical, legal, and social conundrums that already exist for genetic testing in other areas of medicine. In the context of pregnancy, decisions regarding genetic testing of the developing fetus involve a complex calculus based largely on conjecture and uncertainty. As in the case of genetic testing for adults, it is necessary for the pregnant woman to weigh the benefits of accessing genetic information about the fetus against the disadvantages and limitations of that information. She must consider the well-being of the unborn child and, as such, must integrate a host of unknowns about disease severity, progression, and quality of life for her future child. (3) Given the rapid advance of medical technology, she is also faced with considering what therapies or other resources that do not exist in the present may be available in the future that could alleviate any pain or suffering resulting from a genetic condition. It is based on these considerations that she must make the critical decision to continue a pregnancy while planning for the birth of a child with a genetic condition, to take part in an experimental procedure that may influence neonatal outcomes, or to end the pregnancy.

Because of the special maternal-fetal dyad of pregnancy, women are uniquely affected by fetal genetic information and the decisions this information invites. Choices about prenatal genetic testing are often a collaborative effort between expecting parents. Yet, due to the biology of reproduction and pregnancy, women have a distinct role and a specific interest in the integration of these tests into clinical practice. Although prenatal genetic tests are conducted to assess the health of the fetus, they are performed on the pregnant woman and, as a result, have direct implications for her health and well-being. It is critical to recognize that these implications extend far beyond collecting a maternal blood sample or fetal cells though an invasive in utero procedure. The decision to proceed with testing has the potential to produce a cascade of downstream tests and procedures during the pregnancy to further evaluate or manage fetal genetic findings. Additionally, as the fields of perinatology and neonatology are advancing in conjunction with genetic science, the decision to undergo testing may also affect intrapartum management in the delivery suite. Finally, genetic information or procedures conducted in response to that information may also influence future reproductive decision-making.

Women are uniquely affected by advances in prenatal genetic tests in another significant way. The decision to proceed with or to decline testing is a very personal choice that weaves a woman's most personal values and beliefs about self, pregnancy, and parenthood into her healthcare choices. However, these individualized choices about the pregnancy are often influenced by factors external to her. Many of a woman's reproductive decisions are bound by laws, policies, clinical practice guidelines, and public opinion about what a pregnant woman should and can do during the pregnancy. Given the ramifications of all of these issues, it is critical to understand how advances in genetic technologies affect the health and lives of women.


    To understand the evolution and salience of these issues, it is important to first understand how genetic technologies have evolved over the past fifty years. One category of prenatal genetic testing that has undergone important changes is the screening test. Screening tests provide information about the chance that a fetus has Down syndrome or other related chromosomal abnormalities. (4) The advantage of screening tests is that they are performed by drawing a sample of blood from the mother without the use of more invasive procedures; thus, the pregnant woman can bypass the uncommon but real risks associated with chorionic villus sampling (CVS) and amniocentesis. (5) When used as a triage mechanism, screening tests help to determine which women might benefit from definitive diagnostic testing, thus reducing the potential number of iatrogenic losses of chromosomally normal fetuses that could occur with generalized use of these procedures. Screening tests also have limitations. One limitation is the ability of the screen to detect all fetuses with...

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