The personal utility of cfDNA screening: Pregnant patients' experiences with cfDNA screening and views on expanded cfDNA panels.

Prenatal cell-free DNA screening (cfDNA) provides more genetic risk information about the fetus than has ever been possible. At the same time, the rapid expansion of new cfDNA panels raises important questions about how to structure patient-centered discussions that best support patients' decision-making about its use. To address this question, we conducted interviews with pregnant patients to identify decision-making needs and preferences with respect to cfDNA in patient-centered healthcare discussions, given its evolving capability to identify a range of fetal variants. Personal utility was a core concept guiding decision-making. Participants spoke of how their deeply personal values and beliefs about maternal responsibility, actionability, and tolerance of uncertainty framed their view of the personal utility of cfDNA screening. While discussing their notions of personal utility with their healthcare provider, participants also had concerns about potential ramifications for the provider-patient relationship and shared decision-making when disclosing values and preferences regarding disability, quality of life, and termination-particularly as it becomes possible to identify variants with different disease-associated severity and outcomes. The complexities associated with the introduction of genomics in prenatal care present unique challenges to structuring effective shared decision-making discussions between patients and their healthcare providers. While efforts are underway to determine how to best educate patients about the medical aspects of cfDNA, it is equally important to develop approaches in healthcare communication that enable patients to make informed, values-based decisions about the use of cfDNA and its impact on their pregnancy.

Balancing Needs and Autonomy: The Involvement of Pregnant Women's Partners in Decisions About cfDNA.

Cell-free fetal DNA (cfDNA) screening is used to identify the presence of fetal genetic variants early in pregnancy. Patients' informed decision-making is central to the success of this new screen in clinical practice. Although research has focused on pregnant women's decision-making, little is known about partners' role and preferences as a member of the decision-making dyad. Using a grounded theory approach, this study analyzed 23 in-depth interviews to examine partners' perspectives about cfDNA screening and preferences with respect to their role in the decision-making process. Participants wished to be actively involved in testing decisions. They articulated a distinct set of needs and preferences in the decision-making process. Such involvement was hindered by several biological and logistical barriers. This study demonstrates the need to develop mechanisms that foster informed decision-making for cfDNA screening and related new reproductive genetic technologies that focus on not just the pregnant woman but also the decision-making dyad that includes her partner as well.

Genetic Counselors' Perspectives About Cell-Free DNA: Experiences, Challenges, and Expectations for Obstetricians.

The expansion of cell-free fetal DNA (cfDNA) screening for a larger and diverse set of genetic variants, in addition for use among the low-risk obstetric population, presents important clinical challenges for all healthcare providers involved in the delivery of prenatal care. It is unclear how to leverage the different members of the healthcare team to respond to these challenges. We conducted interviews with 25 prenatal genetic counselors to understand their experience with the continued expansion of cfDNA screening. Participants supported the use of cfDNA screening for the common autosomal aneuploidies, but noted some reservations for its use to identify fetal sex and microdeletions. Participants reported several barriers to ensuring that patients have the information and support to make informed decisions about using cfDNA to screen for these different conditions. This was seen as a dual-sided problem, and necessitated additional education interventions that addressed patients seeking cfDNA screening, and obstetricians who introduce the concepts of genetic risk and cfDNA to patients. In addition, participants noted that they have a professional responsibility to educate obstetricians about cfDNA so they can be prepared to be gatekeepers of counseling and education about this screening option for use among the general obstetric population.

The use of noninvasive prenatal testing in obstetric care: educational resources, practice patterns, and barriers reported by a national sample of clinicians.

OBJECTIVE: The aim of this study was to identify how physicians develop their knowledge base and practice patterns regarding noninvasive prenatal testing (NIPT). METHODS: A survey was used to assess physicians' informational sources and practice patterns regarding NIPT. RESULTS: While most of the 258 participants acquire knowledge about NIPT from the medical literature or didactic educational programming, 74 (28.7%) cite commercial laboratories as an initial source and 124 (47.8%) as a way to keep current with changes in NIPT. About one-third (n = 94, 36.4%) seek information about ethical issues related to NIPT. Half of the OB/GYN respondents (n = 136, 52.7%) provide pretest counseling; fewer refer to a genetic counselor or maternal fetal medicine specialist (MFM) (n = 94, 34.6%, n = 29, 11.2%, respectively). Pretest counseling content and the comfort with which participants discuss topics pertinent to patients' utilization of NIPT varied between OB/GYNs and MFMs. CONCLUSIONS: Advances in cff DNA technology emphasize the need for effective strategies for physicians to develop competency and practice patterns regarding NIPT. Study findings speak to the need for effective educational resources for obstetric providers, not just early adopters of NIPT but also for primary OB/GYNs as they serve in the role of the first point of contact for women considering their prenatal testing options. © 2016 John Wiley & Sons, Ltd.

A first look at women's perspectives on noninvasive prenatal testing to detect sex chromosome aneuploidies and microdeletion syndromes.

OBJECTIVE: The aim of this study is to explore women's opinions about the use of noninvasive prenatal testing (NIPT) to assess the risk of sex chromosome aneuploidies and microdeletion syndromes. METHODS: Focus groups were conducted with women who were currently pregnant or had recently delivered. Qualitative analysis using interpretive description was used to generate study findings. RESULTS: Thirty-one women (mean age 32.4 years) participated in the focus groups. Participants were unfamiliar with sex chromosome aneuploidies but expressed support for the use of NIPT to detect these conditions. Participants were uncertain about the utility and actionability of receiving information about microdeletion syndromes with variable or unknown phenotypic expression. Participants voiced their desire to be informed of all conditions assessed by NIPT prior to testing. They considered clinicians to be the key provider of such information, although stated that patients have a responsibility to be knowledgeable prior to testing in order to support informed decision making. CONCLUSIONS: The use of NIPT to identify sex chromosome aneuploidies and microdeletion syndromes will introduce new challenges for clinicians to ensure pregnant women have the information and resources to make informed choices about NIPT when used for these conditions.

Patient-centered prenatal counseling: aligning obstetric healthcare professionals with needs of pregnant women.

The first trimester aneuploidy screen (FTS) continues to be a leading approach to identify the risk of fetal aneuploidy. This study evaluated how obstetric (OB) professionals counsel women about FTS as one of a growing number of options to assess fetal health. A survey was completed by OB professionals (board-certified obstetrician/gynecologists and certified nurse midwives) between February and March 2011: (1) to identify knowledge and practice patterns with regard to FTS, and (2) to compare pregnant women's educational needs and decision-making preferences with clinicians' perceptions of these factors. A total of 216 surveys (11 percent) were completed by OB professionals and analyzed. Several barriers to effective patient counseling were identified, including gaps in obstetric professionals' mastery of the screening test characteristics and variable approaches to discuss concepts of aneuploidy risk. OB participants reported limited confidence in discussing patient-valued topics, specifically post-screen options and pregnancy termination. Discordance was identified between OB professionals' perceptions of pregnant women's educational needs and decision-making preferences specific to FTS and historical data recently collected from 139 pregnant women who underwent the FTS. Study findings illustrate the need for clinician-targeted strategies to support pregnant women as they formulate informed decisions about the tests that may have a salient impact on their prenatal care decisions.

What women want: lead considerations for current and future applications of noninvasive prenatal testing in prenatal care.

BACKGROUND: Noninvasive prenatal testing (NIPT) will change the delivery of prenatal care for all women, including those considered low risk for fetal chromosomal abnormalities. This study investigated pregnant women's attitudes, informational needs, and decision-making preferences with respect to current and future applications of NIPT. METHODS: A survey instrument was used to identify aspects of the decision-making process for NIPT among low-risk and high-risk populations. RESULTS: Both low-risk and high-risk women (n = 334) expressed interest in incorporating NIPT as a screening test into their prenatal care. Information specific to NIPT's detection rate (86%), indications (77%), and performance in comparison with conventional screens and diagnostic tests (63%) were identified as lead factors when considering its use. The future availability of NIPT as a diagnostic test increased women's willingness to undergo testing for fetal aneuploidy, cancer susceptibility, and childhood-onset and adult-onset diseases. Despite its noninvasive aspects, participants expressed the need for a formal informed consent process (71%) to take place before testing. CONCLUSIONS: This study demonstrates that NIPT will introduce new challenges for pregnant women and their health care practitioners who will be charged with supporting informed decision making about its use. It is critical that obstetric professionals are prepared to facilitate a patient-centered decision-making process as its clinical application rapidly changes.

Emerging ethical issues in reproductive medicine: are bioethics educators ready?

Advocates for the professionalization of clinical bioethics argue that bioethics professionals play an important role in contemporary medicine and patient care, especially when addressing complex ethical questions that arise in the delivery of reproductive medicine. For bioethics consultants to serve effectively, they need adequate training in the medical and ethical issues that patients and clinicians will face, and they need skills to facilitate effective dialog among all parties. Because clinical ethics consultation is a "high-stakes endeavor" that can acutely affect patient care, efforts are under way to ensure that bioethics consultants have the competence to provide such guidance. Yet to date, no studies have examined whether the training of bioethics consultants meets the needs of health care professionals who are on the front lines of such issues. In fact, limited information is available on the reproductive health issues that bioethics training programs address or the degree to which these programs meet the needs of patients confronting reproductive health decisions and their clinicians. It is therefore important to answer this key question: What are the primary ethical issues encountered in reproductive medicine that currently affect patient care? Equally important, are bioethics training programs prepared to address those issues? To begin to answer these questions, we conducted parallel surveys of directors of graduate bioethics training programs and obstetrician-gynecologists. The goal of this project is to lay the groundwork to establish a working partnership between bioethics educators and reproductive medicine practitioners to address the often troubling and frequently complex ethical issues in reproductive medicine.

Meeting patients' education and decision-making needs for first trimester prenatal aneuploidy screening.

OBJECTIVE: First trimester aneuploidy screening introduces unique challenges to patient education and informed decision-making. Our study assessed the decision-making process among those pregnant patients presenting for this new form of aneuploidy screening. METHOD: A survey instrument was used to assess components of decision-making among women who presented for first trimester aneuploidy screening. Knowledge and leading factors in the decision-making process were measured. RESULTS: Participants (n = 139) demonstrated understanding of the etiology of Down syndrome, but less understanding of its cognitive (65.2%) and physical manifestations (58.7%). Few were able to determine risk from first trimester screen results (36.7%). Participants were more familiar with amniocentesis (84.2%) than chorionic villus sampling (73.4%), though less familiar with procedural risks (29.5% and 28.1%, respectively). The majority of participants ranked the following as key information in their decision: knowledge of their intentions about the outcome of the pregnancy based on the test results (92.4%), knowledge of chorionic villus sampling to evaluate an abnormal result (92.0%), and values and beliefs about termination (89.1%). CONCLUSION: First trimester aneuploidy screening generates education and decision-making benchmarks for patients and providers. It is important to address these barriers as this new screen becomes a growing part of current prenatal genetic testing offerings.

Framing the diagnosis and treatment of absolute uterine factor infertility: Insights from in-depth interviews with uterus transplant trial participants.

BACKGROUND: Despite procedural innovations and increasing numbers of uterus transplant attempts worldwide, the perspectives of uterus transplant (UTx) trial participants are lacking. METHODS: We conducted a mixed-methods study with women with absolute uterine factor infertility (AUFI). Participants included women who had previously contacted the Cleveland Clinic regarding the Uterine Transplant Trial and met the initial eligibility criteria for participation. In-depth interviews were conducted in conjunction with FertiQoL, a validated and widely used tool to measure the impact of infertility on the quality of life of infertility patients. RESULTS: All (n = 19) rated their overall health as good; some experienced grief and social isolation. AUFI is a life-framing experience that influences acceptance by family, partners, peers, and one's self. UTx is a means to gain control of reproductive autonomy. UTx allows family-building and the ability to play an active role in prenatal health and well-being. Establishing and maintaining a supportive relationship is a key issue of AUFI and when considering UTx. Risks of UTx are perceived relative to risks to self/child/family posed by adoption/surrogacy. Participants had no overall preference regarding living or deceased donor. CONCLUSIONS: The ways in which women with AUFI conceptualize this condition in their lives and choices around UTx and participating in a study of the procedure are multifaceted and textured. These perspectives are critical to understanding its ethical, legal, and social implications.

Patient-Centered Obstetric Care in the Age of Cell-Free Fetal DNA Prenatal Screening.

PURPOSE: The clinical introduction of innovative prenatal genetic technologies challenges patients and providers to find new ways of fostering informed decision-making in a setting characterized by complexity and uncertainty. As prenatal genetic technology advances, important questions remain about how to structure patient-centered conversations that effectively prepare pregnant patients to make informed choices about the different genetic conditions for which this new form screening may be used. METHODS: Focus groups were conducted with 23 pregnant women to identify informational needs and decision-making preferences regarding emerging and anticipated applications of cell-free fetal DNA screening, the newest form of prenatal genetic screening. RESULTS: Participants were in favor of obtaining more genetic information about the fetus than provided by conventional screens but acknowledged the challenges inherent in navigating the unique complexities of the decision-making process. The provider-patient relationship was seen as an important resource to navigate the associated uncertainties at each stage of the screening process. Participants emphasized the need for initiatives to support a personalized, accurate, and unbiased discussion about prenatal genetic risk and assessment. CONCLUSION: Continued advances in prenatal genetic screening call for new approaches to structure patient-centered communication to facilitate increasingly complex decisions about fetal genetic risk and assessment.

Coronary and aortic calcification in women with a history of major depression.

BACKGROUND: Although depression is a well-documented risk factor for clinical heart disease, its association with subclinical atherosclerosis is unclear. We hypothesized that middle-aged women with a history of recurrent major depression would show evidence of atherosclerosis. METHODS: Coronary and aortic calcification was measured by electron beam tomography in 58 African American and 152 white healthy middle-aged women. Women were administered the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and a self-report measure of current depressive symptoms. RESULTS: Coronary calcification was found in 103 women (49%) and aorta calcification in 144 women (54%); high calcification scores were set at approximately 75% of the sample distribution (ie, at >/=10 for the coronary calcium score [n = 49 women] and at >100 for the aorta calcium score [n = 53 women]). Women with a history of recurrent major depression (n = 53) were more likely to have any coronary calcification or calcification in the high category at either site compared with women with a history of a single episode of depression or no depression. After stepwise forward adjustment for cardiovascular risk factors and sociodemographic characteristics, a history of recurrent major depression, compared with a single episode or no history, was associated with odds ratios (ORs) of 2.46 (95% confidence interval [CI], 1.06-5.67) for any coronary calcification, 2.71 (95% CI, 1.08-6.81) for high coronary calcification, and 3.39 (95% CI, 1.34-8.63) for high aortic calcification. Further adjustments for waist-hip ratio reduced the association between history of recurrent depression and any calcification (OR, 2.24; 95% CI, 0.94-5.32) and high calcification (OR, 2.31; 95% CI, 0.89-5.99). CONCLUSIONS: In this sample of asymptomatic middle-aged women without known coronary disease, recurrent major depression was independently associated with coronary and aortic calcification. Waist-hip ratio in part mediated the association. Our findings suggest that recurrent major depression may be a risk factor for early atherosclerosis in women.

Online direct-to-consumer messages about non-invasive prenatal genetic testing.

Non-invasive prenatal testing (NIPT) has been integrated into clinical care at a time when patients and healthcare providers increasingly utilize the internet to access health information. This study evaluated online direct-to-consumer information about NIPT produced by commercial laboratories accessible to both patients and healthcare providers. A coding checklist captured areas to describe content and assess concordance with clinical guidelines. We found that the information presented about NIPT is highly variable, both within a single website and broadly across all websites. Variability was noted in how NIPT is characterized, including test characteristics and indications. All laboratories offer NIPT to test for common sex chromosome aneuploidies, although there is a lack of consistency regarding the conditions offered and information provided about each. Although indicated for a subset of women at increased risk of aneuploidy, some laboratories describe the use of NIPT for all pregnant women. A subset of laboratories offers screening for microdeletions, although clinical practice guidelines do not yet recommend for general use for this indication. None of the online materials addressed the ethical issues associated with NIPT. This study highlights the need for clear, consistent, and evidence-based materials to educate patients and healthcare providers about the current and emerging applications of NIPT.

It's More Than a Blood Test: Patients' Perspectives on Noninvasive Prenatal Testing.

Noninvasive prenatal testing (NIPT) offers pregnant women a new risk assessment tool for fetal aneuploidy that is superior to conventional screening tests. We conducted focus groups with women who were currently pregnant or had recently delivered in the past year to characterize their perspectives about NIPT and to explore factors they would consider during decision making about its use. Women identified accuracy, early timing, testing ease, and determination of fetal sex as advantages of NIPT over other screens, and the noninvasive method of NIPT as an advantage over diagnostic tests. False positive and false negative results, anxiety, cost and insurance coverage were seen as disadvantages of NIPT. Women who do not want fetal aneuploidy information most likely will not undergo NIPT, despite its advantages over other screening tests. However, given its advantages, the decision to have NIPT is straightforward for women who want genetic information about the fetus. Women emphasized the need to make autonomous, private, and informed choices about NIPT, as they would with any prenatal genetic testing option. These perspectives may guide clinicians to conduct effective and clinically relevant counseling with pregnant women who consider utilizing this new genetic technology.

Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk.

Preeclampsia is a disorder of pregnancy diagnosed by gestational hypertension and proteinuria. Epidemiological evidence suggests that women who experience preeclampsia are at a greater risk of hypertension and heart disease later in life compared with women who had normal pregnancies. Our objective was to determine whether endothelial function is impaired in postpartum women with a history of preeclampsia in their first pregnancy. We measured forearm blood flow (FBF) by venous occlusion plethysmography in 50 healthy women: 16 with prior preeclampsia, 14 with a prior normotensive pregnancy, and 20 never pregnant controls. The postpartum women participated 6-12 mo after delivery. Heart rate (HR) and blood pressure (BP) were concurrently monitored on the contralateral arm. Hemodynamic variables were assessed at baseline and during a mental stress test known to elicit endothelium-dependent vasodilatation. We found that baseline FBF, HR, systolic BP, and diastolic BP did not significantly differ among the groups, whereas mean arterial pressure in the preeclamptic group was greater than that of the normal pregnancy group (P = 0.03). Stress-induced FBF (percent change over baseline) was reduced in the preeclamptic group compared with both the normal pregnancy and never pregnant groups (P = 0.06) and was significantly attenuated compared with women with prior normal pregnancies (91% vs. 147%, P = 0.006). These data demonstrate that women with a history of preeclampsia exhibit impaired endothelial function up to 1 yr postpartum. This observation may explain their increased risk for hypertension and cardiovascular disease.

The Trp64Arg polymorphism of the beta3-adrenergic receptor is not increased in women with preeclampsia.

OBJECTIVE: Insulin resistance is greater and obesity is more common in women with preeclampsia. The Trp64Arg polymorphism in the beta(3)-adrenergic receptor is associated with these metabolic changes. This study investigated whether the Trp64Arg polymorphism is more common in women with preeclampsia. STUDY DESIGN: beta(3)-Adrenergic receptor genotypes were determined in 177 women with a history of preeclampsia and in 179 normal pregnancies. We also compared prepregnancy body mass index (BMI), length of gestation, baby weight percentile, and glucose values during an oral tolerance test in women with and without the polymorphism. RESULTS: The genotypes and allele frequency did not differ significantly between women with preeclamptic and normal pregnancies (P=.17). Women with and without the polymorphism had similar prepregnancy BMI, glucose at 1-hour screening, gestational age at delivery, and adjusted baby weight. CONCLUSION: The Trp64Arg polymorphism of the beta(3)-receptor does not predispose to preeclampsia, and it is it not associated with obesity and carbohydrate intolerance in a population of young pregnant women.