DOI: 10.1002/pd.4594
ORIGINAL ARTICLE
A first look at women’s perspectives on noninvasive prenatal testing to detect sex chromosome aneuploidies and microdeletion syndromes Patricia K. Agatisa1, Mary Beth Mercer1, Angela C. Leek1, Marissa B. Smith2, Elliot Philipson3 and Ruth M. Farrell1,2,3* 1
Department of Bioethics, Cleveland Clinic, Cleveland, OH, USA Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA 3 Department of Obstetrics & Gynecology, Cleveland Clinic Women’s Health Institute, Cleveland, OH, USA *Correspondence to: Ruth M. Farrell. E-mail: [email protected] 2
ABSTRACT 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. © 2015 John Wiley & Sons, Ltd.
Funding sources: This project was supported in part by Research Grant No. 12-FY13-293 from the March of Dimes Foundation. Conflicts of interest: Dr. Farrell is an advisor for EMMI Solutions which develops educational materials for patients.
INTRODUCTION Noninvasive prenatal testing (NIPT) is a screening test that utilizes cell-free fetal DNA in maternal blood to offer pregnant women risk assessment for Trisomies 21, 18, and 13. It has superior detection and lower false-positive rates than conventional screening tests for these conditions.1–5 Currently, NIPT is recommended for a subset of pregnant patients, as the test’s sensitivity and specificity have been validated among women who are at increased risk for fetal aneuploidy due to maternal age, abnormal ultrasound or serum analyte findings, or reproductive history.6–8 Expanded indication for low-risk pregnant women is considered by many to be imminent as research and validation of NIPT technology progresses.3,9–12 Moreover, NIPT has the capability to detect sex chromosome aneuploidies (SCAs),13–15 which conventional screening tests cannot. SCAs, including Turner syndrome and Klinefelter syndrome, are the most frequently occurring aneuploidies, observed in approximately 1/400 births.16–18 Of note, unlike Trisomies 21, 18, and 13, the incidence of SCAs is not related Prenatal Diagnosis 2015, 35, 1–7
to maternal age.17,18 Thus, the availability of screening for SCAs has important implications for all pregnant women. An emerging application of NIPT is to the option to screen for fetal genomic microdeletion syndromes that are restricted to genomic regions with clinical phenotypes.4,19–23 These conditions are not associated with advanced maternal age, have variable phenotypes, and, in general, are rare at a population level.21 Microdeletion syndromes assessed vary by commercial testing company, but most include 22q11.2 deletion syndrome, 5p minus syndrome, 1p36 deletion syndrome, and microdeletion of the proximal 15q11.2 region. While NIPT technology can assess risk of these conditions, the paucity of published literature on sensitivities, specificities, false-positive and false-negative rates has led many in the genetics, maternal-fetal medicine, and obstetrics/gynecology communities to question whether this option should be offered before adequate data and resources are in place to support such testing. However, companies that offer NIPT for microdeletion syndromes provide the clinician an ‘opt in or © 2015 John Wiley & Sons, Ltd.
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opt out’ for this service, allowing for patient choice to acquire this information. Advancements in NIPT technology, including assessment of the full cell-free fetal DNA karyotype or microarray are currently a focus of research.19–23 Little is known about pregnant women’s receptivity to the use of NIPT to detect SCAs and microdeletion syndromes and how they will perceive the value of NIPT when used for this purpose in their prenatal care decisions. We conducted a qualitative study to examine women’s knowledge and attitudes about the use of NIPT to identify fetal SCAs and their views regarding emerging applications of NIPT to detect microdeletion syndromes.
METHODS Women’s perspectives about using NIPT for the detection of SCAs and microdeletion syndromes were explored using qualitative methods. Inclusion criteria included English-speaking women who were either pregnant or recently delivered, 18 to 45 years of age, and able to provide informed consent for research participation. Participants were recruited from a sample of 68 women who had taken part in previous focus groups or semi-structured interviews about the use of NIPT as a screening tool for common autosomal aneuploidies including Trisomies 21, 18, and 13.24 Given the advancements in NIPT technology, follow-up focus groups were held to specifically explore the participants’ perspectives on the use of NIPT to identify SCAs and microdeletion syndromes, topics which had not been investigated in prior discussions. Furthermore, these focus groups were convened to confirm previous findings and to explore whether these findings hold true with the addition of SCAs and microdeletion syndromes to NIPT’s platform. All study procedures and materials were approved by the Cleveland Clinic Institutional Review Board. Three focus groups with 9–12 participants per group were facilitated by a single moderator who led discussions regarding familiarity with conditions resulting from SCAs and microdeletion syndromes. Additional probes explored participants’ attitudes and perceptions of the utility of screening for SCAs and microdeletion syndromes, approaches to the counseling process, and how assessment of these conditions might impact decision making about the use of NIPT. Prior to the focus groups, participants provided informed consent and completed a brief demographic and reproductive history questionnaire. In addition, a brief educational review of NIPT’s capability to identify common autosomal aneuploidies, SCAs, and microdeletion syndromes currently offered by commercial laboratories was presented (Table 1). The presentation was developed with experts in genetic counseling, obstetrics, and maternal–fetal medicine. Focus groups were digitally recorded, transcribed verbatim, and verified for accuracy by the research team. Using an inductive approach, data analysis consisted of an iterative process of data immersion, coding, memoing, and theme identification, consistent with interpretative description.25,26 The research team identified content domains to create a coding tree and codebook used to systematically organize the data. The data analyst coded the transcripts using NVivo while composing memos to record insights and interpretations Prenatal Diagnosis 2015, 35, 1–7
Table 1 Topics discussed in educational session 1) What is noninvasive prenatal testing (NIPT)? a. Noninvasive blood test that uses maternal blood sample to assess fetal DNA for: i. Common autosomal trisomies, including Trisomy 21, 13, and 18 ii. Abnormalities in number of sex chromosomes iii. Determination of fetal sex b. Current recommendation to women of advanced maternal age or considered at high risk (based on prior screening test, reproductive history, or personal or family history of genetic condition) 2) What are chromosomes? a. Normal number of chromosomes b. Abnormalities in number of sex chromosomes i. Most common sex chromosome abnormalities (SCAs) 1. Description of Turner Syndrome: genotype and phenotype 2. Description of Klinefelter Syndrome: genotype and phenotype ii. Range of phenotypic expression iii. SCAs not associated with advanced maternal age c. Microdeletion sydromes i. Missing genes or changes on certain chromosomes ii. Not detected by conventional screening tests iii. Rare but often associated with variable phenotypic expression 3) What NIPT can and cannot do a. Sensitivity and specificity for assessing common autosomal trisomies b. Assess presence of sex chromosome aneuploidy i. Determine fetal sex c. Need for confirmatory invasive testing if NIPT result is positive d. Does not assess presence of all genetic conditions nor structural abnormalities
of the data and emergent themes.27 The research team met weekly to monitor progress, review coding and memos to identify areas of consensus, themes, and incorporate clinical perspectives throughout the analytic process.
RESULTS A total of 31 women attended three focus groups. The majority (80.6%) had prenatal screening or testing in their recent or current pregnancy, including 10 who reported having NIPT. Nearly two-thirds delivered in the past six months. Demographic and reproductive history characteristics are listed in Table 2. Major themes and recommendations that emerged during the focus group discussions are summarized in the subsequent discussion and presented in Table 3.
Sex chromosome aneuploidies The utilization of NIPT to identify SCAs was considered an important but secondary test benefit. Participants were knowledgeable of Trisomies 21, 18, and 13 and generally unfamiliar with SCAs. Participants suggested that greater awareness of Trisomies 21, 18, and 13 reflected that these conditions have been a primary focus of prenatal testing for decades. One participant stated: ‘I think there is more publicity about Down syndrome… That is where everyone’s focus is’ (Focus group [FG] 3). Given that the risk of SCAs is not associated with © 2015 John Wiley & Sons, Ltd.
Women’s perspectives on NIPT to detect SCAs and microdeletion syndromes
Table 2 Demographic and reproductive characteristics of participants
Table 3 Focus group themes and participants’ recommendations Theme
Characteristic
N = 31 n (%)
Age (years)
Mean [standard deviation (SD)]: 32.4 (4.8) Range: 24–41
Advanced maternal age
11(35.5)
Had prenatal screening/testing
25 (80.6)
Specific tests: NIPT 1st trimester screening test
10 (32.3)
7(22.6)
Chorionic villus sampling
1(3.2)
Months from delivery Currently pregnant
White Other/multi-ethnic
Familiarity with conditions being assessed by noninvasive prenatal testing (NIPT) affects patients’ perceptions of the value of testing.
SCAs and microdeletion syndromes are less familiar to patients than Trisomy 21, 18, and 13.
The counseling process should inform patients about each condition being assessed by NIPT during pre-test counseling.
The identification of fetal sex is of value but should be considered secondary to screening for SCAs.
Patients readily recognize that NIPT can identify fetal sex but less familiar with the capability to provide information about SCAs.
Clinicians should delineate in the counseling process that the purpose of NIPT is to assess the risk of Trisomy 21, 18, 13, and SCAs and that the identification of fetal sex is secondary to detecting SCAs.
Learning about conditions with variable or unknown phenotypic expression influences patients’ perceptions of the utility of using NIPT to gain this information.
Patients may be uncertain about the utility and actionability of receiving information about microdeletion syndromes. Patients support the ability to opt in or opt out of testing for certain conditions based on the value they assign acquiring such information.
The counseling process should involve a component where the clinician informs patients’ about what conditions can be identified using NIPT, then inquires about what information is sought by the patient, and then offer only those tests desired by the patients.
Obstetric clinicians are considered the primary and most reliable source of information about NIPT.
Patients trust their obstetric clinicians and rely on them to provide the information required to make informed decisions about NIPT. Patients recognize that clinicians have limited time and resources for patient education and counseling in addition to a responsibility to being informed healthcare consumers.
Clinicians should continue to provide accurate and unbiased information in the clinical encounter, in addition to developing a pool of resources [including genetic counselors and selfdirected educational resources (websites, printed materials, e-learning modules)] to provide additional information about the varied conditions identifiable using NIPT.
29 (93.5) Mean: 6.4 months 2 (6.5)
Race/ethnicity Black or African American
Recommendations
19(61.3)
2nd trimester screening test
Postpartum
Issue
7 (22.6) 21 (67.7) 3 (9.7)
Education High school graduate or GED Community college
2 (6.5) 6 (19.4)
College graduate
10 (32.3)
Advanced degree
13 (41.9)
advanced maternal age, participants questioned why NIPT is not available to all pregnant women, as articulated by one participant: ‘What I think is interesting is that [Turner and Klinefelter syndromes] are both not associated with advanced maternal age but this test is only offered to women who are’ (FG 1). Participants perceived the capability of NIPT to detect prenatal conditions, such as SCAs that may not be obvious at birth, as a key difference between NIPT and other prenatal screening tests. One participant described this distinction: ‘[SCAs] seem really different from something like Down syndrome, where you would know right away at birth anyway versus something that you could possibly have for many years and nobody would know and now it is becoming a subject of inquiry during pregnancy’ (FG 1). Despite having less familiarity with conditions resulting from SCAs, participants supported using NIPT for their identification. They strongly advocated that clinicians present information about NIPT’s ability to detect these conditions prior to testing. Participants expressed strong interest in learning fetal sex and having early access to this information. However, they stated that an emphasis should be placed on the purpose of NIPT – to identify specific aneuploidies – and that fetal sex identification is a secondary benefit. As described by a participant: ‘I think [clinicians] should not even Prenatal Diagnosis 2015, 35, 1–7
say that it tests for the sex because it’s not testing the sex. As a result of testing [for] the sex abnormality you can know the sex’ (FG 2). Without knowledge of NIPT’s assessment of SCAs, participants voiced concern regarding a pregnant woman’s ability to make an informed choice about utilizing NIPT. Furthermore, they noted that women would be unprepared for a positive test result and their post-test options.
Microdeletions and microdeletion syndromes Participants were even less familiar with chromosomal microdeletions and the syndromes resulting from them. Additionally, they expressed concerns about the utilization of NIPT to detect these conditions. Participants valued NIPT to detect Trisomies © 2015 John Wiley & Sons, Ltd.
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21, 18, and 13 based on awareness of these conditions and their physical and cognitive disabilities. In contrast, participants were less certain about the utility and actionability of information about microdeletion syndromes. These perceptions, in part, reflected hesitancy about the benefit of learning of conditions with variable or unknown phenotypic expression. As one participant described:
Everyone wants to know everything. But, what are you going to do with this information? I feel … if somebody tells you your child has Down syndrome or they have Turner syndrome or Klinefelter, we have a list of the things that might happen…pictures of these kids that have this syndrome… But some of these microdeletions…What does that mean? (FG 1) Yet, some participants perceived value in using NIPT to obtain information about a growing number of fetal genetic abnormalities. As one participant voiced: ‘Knowledge is power’ (FG1). Furthermore, participants recognized that the capability of NIPT to identify microdeletions and other non-aneuploidrelated conditions requires new approaches and increased efforts to ensure pregnant women have the information and resources needed to make informed choices about its use.
Challenges to education and counseling Participants acknowledged that the growing capabilities of NIPT would increase the volume of information that must be conveyed during the counseling process. They deliberated about the best approaches to educate patients about NIPT, given its ability to identify a host of genetic abnormalities. They recognized that healthcare providers may not be able to provide all the necessary information for women to make an informed decision during a clinical encounter. Participants recommend that, at a minimum, clinicians provide brief verbal and written information about all conditions being assessed prior to testing so that patients would not be blindsided by a positive result. They also recommended that clinicians suggest reputable resources, such as websites, so patients may access information outside of the clinical setting. As discussed by two participants:
Participant 1 I knew I was being tested for these things. I knew one of them was Down syndrome and then there were a couple other things that I wasn’t really that familiar with but I knew they were being tested too. In my opinion, I don’t think it is a good use of resources to sit down and have a lecture about Klinefelter syndrome with every person who is going to have this test. Participant 2 Especially if they don’t end up having it (FG 1). There was consensus among participants that their clinician is their trusted and main source of information about prenatal testing. They also agreed that women should be proactive in obtaining all the necessary information to make informed decisions. As this participant noted: ‘The patient has a responsibility, too, to research and educate themselves’ (FG 1). Another participant expressed a similar viewpoint: Prenatal Diagnosis 2015, 35, 1–7
I feel like a doctor’s job is to give me information: These [conditions] are what we can test for. Here is what the test is. Here is what it is going to look at. And then I think it’s our responsibility as a patient to take that information and think about it and make an informed decision and ask the questions ahead of time and not just kind of go with the flow… As the patient, it is our responsibility to be that active partner (FG 2). Overall, participants perceived the value of NIPT on a continuum based on the conditions the test assesses and their perceptions of the usefulness of test results. Participants generally saw the value of screening for Trisomies 21, 18, and 13 but less for SCAs and questioned the utility of screening for microdeletion syndromes. This was due, in part, to uncertainties associated with these conditions, given their range of phenotypic expression. Furthermore, in light of the expanding capabilities of NIPT, some participants thought that women should be able to choose the conditions assessed. As described by this participant:
I think that giving the information on what can be looked at… and then options for each person’s personal preference on what you do or don’t want to know and what options are available to you for further information… Everyone is different, and saying we are going to tell you everything, blanket-wise, doesn’t work for everyone (FG 1). DISCUSSION Noninvasive prenatal testing has quickly become integrated into prenatal care. Its capability to assess the presence of SCAs and applications for microdeletion syndromes will present challenges to clinicians who offer the test and to patients who must decide if this information is of value to them, their partners, and their families. NIPT has rapidly been embraced by clinicians and high-risk patients24,28–32 as a more sensitive and specific screening tool for fetal aneuploidies than conventional screening tests. This study offers a first look at women’s perspectives about the increasing scope of conditions assessed by NIPT, including SCAs and microdeletion syndromes. Discussions about Trisomies 21, 18, and 13 have been the core of prenatal counseling for decades. Participants in this study were well versed about the use of prenatal testing to assess the presence of Trisomies 21, 18, and 13, the utility of NIPT as a screening test, and the need for diagnostic testing to confirm the presence or absence of a condition. The majority were less familiar with SCAs, and the capability and limitations of NIPT to identify them. Most viewed learning fetal sex as a benefit of NIPT and valued gaining that knowledge earlier than during the second-trimester anatomical ultrasound. Having this information earlier in the pregnancy in and of itself was perceived as an advantage, although studies suggest that fetal sex information may be sought by some women for the purpose of making key decisions about the pregnancy.33,34 However, when considering the capability of NIPT to identify SCAs, participants had comparatively less knowledge of the medical and cognitive issues associated with such conditions. © 2015 John Wiley & Sons, Ltd.
Women’s perspectives on NIPT to detect SCAs and microdeletion syndromes
Identification of conditions resulting from SCAs was desired by participants. This is in agreement with a study which reported that at the time of NIPT, while approximately 25% of pregnant women considered disabilities resulting from SCAs to be less than that resulting from Down syndrome, nearly all wanted to know if a SCA was suspected.35 Due to existing counseling practices and paradigms of obstetric risk that preceded the integration of NIPT, pregnant women may have less exposure to conditions associated with SCAs compared with other aneuploidies. Counseling about the chance of fetal aneuploidy has centered on fetal risk assessments based on maternal age. SCAs and microdeletion syndromes are not associated with advanced maternal age and can occur in women traditionally considered low risk based upon this criterion. The introduction of NIPT into prenatal care intensifies an ongoing debate to update how risk is framed in the context of pregnancy and risk-benefit analysis when considering prenatal genetic testing.7,36,37 Pre-test and post-test NIPT counseling is an important topic that needs to be addressed as this technology becomes further integrated into clinical practice. It is critical that clinicians educate patients about their screening and testing options, test benefits and limitations, as well as results and implications. This includes a discussion of the lower sensitivity and specificity of NIPT for SCAs compared with those for autosomal aneuploidies.38,39 To make an informed choice about NIPT, pregnant women must have information that addresses all conditions assessed by the selected testing platform. This includes information about the ability of NIPT to provide information about sex chromosome aneuploidies, not only fetal sex. One aspect of counseling that warrants consideration is that the clinical expression of these conditions is highly variable, and these conditions may be undiagnosed at birth and identified later in childhood or adult life.18 To foster an informed decision, participants suggested that pregnant women understand the capability and accuracy of NIPT for each condition. For now, this includes autosomal and SCAs; in the near future, this will include microdeletion syndromes. The counseling process should also address how pregnant women would integrate fetal genetic information into their framework of values and preferences. This counseling approach should be continually expanded to address the growing number of fetal genetic conditions detectable with advances in noninvasive molecular diagnostics. With increased capabilities will come the need for specific strategies to communicate large and complex amounts of information to patients. As seen in the context of prenatal microarray testing, studies show that patients find information regarding variants of unknown significance particularly concerning40 and can lead to increased levels of anxiety for the duration of the pregnancy and into the postpartum period.41 It is critical that information regarding all conditions being evaluated is disclosed before prenatal testing, as the post-test period is not the time for women to consider an abnormal result and the impact of that information on their pregnancy.42 It is well accepted that the breadth of information that must be conveyed to support informed decision making for conventional screening tests poses challenges of both Prenatal Diagnosis 2015, 35, 1–7
time and resources to the clinician–patient encounter. This will be exacerbated in the context of NIPT, as parents are generally unprepared for the diagnosis of a SCA.18 Studies show healthcare providers vary in the manner in which they present information about SCAs to pregnant women, both in terms of the accuracy of the information and potential biases introduced in the counseling process.43 Furthermore, obstetric providers’ self-reported level of knowledge and confidence in prenatal counseling are low, a finding noted prior to the introduction of NIPT.44 For this reason, genetic counselors are well versed in this regard and should play a central role in educating patients about their testing options, although it is widely recognized their numbers are too few to meet the needs of the obstetric population. Yet, participants in our study emphasized the importance of acquiring information and guidance from their obstetric provider. Thus, these findings, as well as prior studies, warrant efforts that ensure clinicians are aware of pregnant women’s preferences regarding the use of NIPT paired with the education and skills to prepare patients to make informed choices about this and other testing options.24 Given the scope of these issues and the realities of clinical practice, we recognize that there is not a single approach to address the challenges inherent in the counseling process. Instead, advances in prenatal testing call for a combination of resources utilized by clinicians and patients. This includes educational tools and decision aids that present information about the testing process and assist pregnant patients to explore their values and beliefs. Ideally, these materials would be available to patients prior to and following prenatal testing discussions to support informed decisions about NIPT. The growth of electronic information provides another opportunity for clinicians to identify high-quality web-based or app-based resources to supplement the educational process.45 These resources may also be made available in clinical areas. As NIPT capabilities expand, information can be grouped into broad discussion categories of conditions in the pre-test counseling session, as used during the early days of microarray analysis.46 Such strategies will require the coordinated efforts of obstetricians, and maternal–fetal medicine and genetic specialists to work together across disciplines and institutions to implement such plans. This study provides valuable insight into women’s views about present and future applications of NIPT. We acknowledge potential study limitations. This study cohort had participated in our previous research on NIPT,24 and their opinions and experiences may not represent that of the general pregnant population. In addition, one-third utilized NIPT during their current/recent pregnancy and thus had firsthand experience with the testing process. The educational session was provided to allow other participants to gain foundational knowledge about NIPT, so they could formulate their views regarding the use of current and future applications of NIPT. Furthermore, participants were queried about the utilization of NIPT to identify microdeletion syndromes, although this application is not widely available. Given the emerging application of NIPT for this purpose, it was suitable to explore in this study. This research provides a first look into © 2015 John Wiley & Sons, Ltd.
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women’s perspectives about advancements in NIPT technology and warrants further evaluation of pregnant women’s preferences and perspectives about the utility of SCA and microdeletion testing using NIPT.
CONCLUSIONS NIPT is rapidly gaining acceptance as a valuable tool to assess risk of fetal aneuploidies in high-risk women. In time, as validation of the test’s performance in low-risk women is accepted by the medical community, NIPT may replace conventional analyte screening tests and be offered to all pregnant women who wish to undergo prenatal testing. The additional assessment of fetal sex chromosomes and microdeletion syndromes will further alter the prenatal testing paradigm, both in terms of how pregnant women and clinicians conceptualize the risks and benefits of testing, and how the counseling process unfolds to prepare pregnant women to make informed choices. The time has come to address the challenges that translation of this new genetic technology into clinical care will pose upon clinicians who must maintain their competency in genetic medicine, so they can
effectively educate their patients to make informed decisions about prenatal testing. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • Noninvasive prenatal testing (NIPT) has gained acceptance as a valuable tool to assess the risk of common autosomal aneuploidies in high-risk women. • Advancements of NIPT technology will allow assessment of sex chromosome aneuploidies and microdeletion syndromes.
WHAT DOES THIS STUDY ADD? • Pregnant women are unfamiliar with sex chromosome aneuploidies and microdeletions. • Pregnant women should be educated about the full testing platform of NIPT to avoid being unprepared for an abnormal finding from NIPT. • The expanded scope of NIPT for sex chromosome aneuploidies and microdeletion syndromes will introduce new challenges for clinicians to ensure patients make informed decisions about undergoing testing for all applications of NIPT.
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31. Chetty S, Garabedia MJ, Norton ME. Uptake of noninvasive prenatal testing (NIPT) in women following positive aneuploidy screening. Prenat Diagn 2013;33(6):542–6. 32. Haymon L, Simi E, Moyer K, et al. Clinical implementation of noninvasive prenatal testing among maternal fetal medicine specialists. Prenat Diagn 2014;34(5):416–23. 33. Chandrasekharen S, Minear MA, Hung A, Allyse M. Noninvasive prenatal testing goes global. Sci Transl Med 2014;6(231):231fs15. 34. Chapman AR, Benn PA. Noninvasive prenatal testing for early sex identification. A few benefits and many concerns. Perspect Biol Med 2014;56(4):530–47. 35. Lau TK, Chan MK, Salome Lo PS, et al. Non-invasive prenatal screening of fetal sex chromosomal abnormalities: perspective of pregnant women. J Matern Fetal Neonatal Med 2012;25(12):2616–9. 36. Lyerly AD, Mitchell LM, Armstrong EM, et al. Risks, values, and decision making surrounding pregnancy. Obstet Gynecol 2007; 109(4):979–84. 37. Devers PL, Cronister A, Ormond KE, et al. Noninvasive prenatal testing/noninvasive prenatal diagnosis: the position of the National Society of Genetic Counselors. J Genet Couns 2013; 22(3):291–5. 38. Bianchi DW, Platt LD, Goldberg JD, et al. Genome-wide fetal aneuploidy detection by maternal plasma DNA sequencing. Obstet Gynecol 2012;119:890–901.
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39. Song Y, Liu C, Qi H, et al. Noninvasive prenatal testing of fetal aneuploidies by massively parallel sequencing in a prospective Chinese population. Prenat Diagn 2013;33:700–6. 40. Hillman SC, Skelton J, Quinlan-Jones E, et al. “If it helps…” The use of microarray technology in prenatal testing: patient and partners reflections. Am J Med Genet A 2013;161A:1619–27. 41. Bernhardt BA, Soucier D, Hanson K, et al. Women’s experiences receiving abnormal prenatal chromosomal microarray testing results. Genet Med 2013;15:139–45. 42. Metcalfe A, Hippman C, Pastuck M, Johnson JA. Beyond trisomy 21: additional chromosomal anomalies detected through routine aneuploidy screening. J Clin Med 2014;3(2):388–415. 43. Abramsky L, Hall S, Levitan J, Marteau TM. What parents are told after prenatal diagnosis of a sex chromosome abnormality: interview and questionnaire study. BMJ 2001;322(7284):463–6. 44. Cleary-Goldman J, Morgan MA, Malone FD, et al. Screening for Down syndrome: practice patterns and knowledge of obstetricians and gynecologists. Obstet Gynecol 2006;107(1):11–7. 45. Mercer MB, Agatisa PK, Farrell RM. What patients are reading about noninvasive prenatal testing: an evaluation of Internet content and implications for patient-centered care. Prenat Diagn 2014;34(10):986–93. 46. Darilek S, Ward P, Pursley A, et al. Pre-and postnatal genetic testing by array-comparative genomic hybridization: genetic counseling perspectives. Genet Med 2008;10(1):13–8.
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ORIGINAL ARTICLE
A first look at women’s perspectives on noninvasive prenatal testing to detect sex chromosome aneuploidies and microdeletion syndromes Patricia K. Agatisa1, Mary Beth Mercer1, Angela C. Leek1, Marissa B. Smith2, Elliot Philipson3 and Ruth M. Farrell1,2,3* 1
Department of Bioethics, Cleveland Clinic, Cleveland, OH, USA Genomic Medicine Institute, Cleveland Clinic, Cleveland, OH, USA 3 Department of Obstetrics & Gynecology, Cleveland Clinic Women’s Health Institute, Cleveland, OH, USA *Correspondence to: Ruth M. Farrell. E-mail: [email protected] 2
ABSTRACT 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. © 2015 John Wiley & Sons, Ltd.
Funding sources: This project was supported in part by Research Grant No. 12-FY13-293 from the March of Dimes Foundation. Conflicts of interest: Dr. Farrell is an advisor for EMMI Solutions which develops educational materials for patients.
INTRODUCTION Noninvasive prenatal testing (NIPT) is a screening test that utilizes cell-free fetal DNA in maternal blood to offer pregnant women risk assessment for Trisomies 21, 18, and 13. It has superior detection and lower false-positive rates than conventional screening tests for these conditions.1–5 Currently, NIPT is recommended for a subset of pregnant patients, as the test’s sensitivity and specificity have been validated among women who are at increased risk for fetal aneuploidy due to maternal age, abnormal ultrasound or serum analyte findings, or reproductive history.6–8 Expanded indication for low-risk pregnant women is considered by many to be imminent as research and validation of NIPT technology progresses.3,9–12 Moreover, NIPT has the capability to detect sex chromosome aneuploidies (SCAs),13–15 which conventional screening tests cannot. SCAs, including Turner syndrome and Klinefelter syndrome, are the most frequently occurring aneuploidies, observed in approximately 1/400 births.16–18 Of note, unlike Trisomies 21, 18, and 13, the incidence of SCAs is not related Prenatal Diagnosis 2015, 35, 1–7
to maternal age.17,18 Thus, the availability of screening for SCAs has important implications for all pregnant women. An emerging application of NIPT is to the option to screen for fetal genomic microdeletion syndromes that are restricted to genomic regions with clinical phenotypes.4,19–23 These conditions are not associated with advanced maternal age, have variable phenotypes, and, in general, are rare at a population level.21 Microdeletion syndromes assessed vary by commercial testing company, but most include 22q11.2 deletion syndrome, 5p minus syndrome, 1p36 deletion syndrome, and microdeletion of the proximal 15q11.2 region. While NIPT technology can assess risk of these conditions, the paucity of published literature on sensitivities, specificities, false-positive and false-negative rates has led many in the genetics, maternal-fetal medicine, and obstetrics/gynecology communities to question whether this option should be offered before adequate data and resources are in place to support such testing. However, companies that offer NIPT for microdeletion syndromes provide the clinician an ‘opt in or © 2015 John Wiley & Sons, Ltd.
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opt out’ for this service, allowing for patient choice to acquire this information. Advancements in NIPT technology, including assessment of the full cell-free fetal DNA karyotype or microarray are currently a focus of research.19–23 Little is known about pregnant women’s receptivity to the use of NIPT to detect SCAs and microdeletion syndromes and how they will perceive the value of NIPT when used for this purpose in their prenatal care decisions. We conducted a qualitative study to examine women’s knowledge and attitudes about the use of NIPT to identify fetal SCAs and their views regarding emerging applications of NIPT to detect microdeletion syndromes.
METHODS Women’s perspectives about using NIPT for the detection of SCAs and microdeletion syndromes were explored using qualitative methods. Inclusion criteria included English-speaking women who were either pregnant or recently delivered, 18 to 45 years of age, and able to provide informed consent for research participation. Participants were recruited from a sample of 68 women who had taken part in previous focus groups or semi-structured interviews about the use of NIPT as a screening tool for common autosomal aneuploidies including Trisomies 21, 18, and 13.24 Given the advancements in NIPT technology, follow-up focus groups were held to specifically explore the participants’ perspectives on the use of NIPT to identify SCAs and microdeletion syndromes, topics which had not been investigated in prior discussions. Furthermore, these focus groups were convened to confirm previous findings and to explore whether these findings hold true with the addition of SCAs and microdeletion syndromes to NIPT’s platform. All study procedures and materials were approved by the Cleveland Clinic Institutional Review Board. Three focus groups with 9–12 participants per group were facilitated by a single moderator who led discussions regarding familiarity with conditions resulting from SCAs and microdeletion syndromes. Additional probes explored participants’ attitudes and perceptions of the utility of screening for SCAs and microdeletion syndromes, approaches to the counseling process, and how assessment of these conditions might impact decision making about the use of NIPT. Prior to the focus groups, participants provided informed consent and completed a brief demographic and reproductive history questionnaire. In addition, a brief educational review of NIPT’s capability to identify common autosomal aneuploidies, SCAs, and microdeletion syndromes currently offered by commercial laboratories was presented (Table 1). The presentation was developed with experts in genetic counseling, obstetrics, and maternal–fetal medicine. Focus groups were digitally recorded, transcribed verbatim, and verified for accuracy by the research team. Using an inductive approach, data analysis consisted of an iterative process of data immersion, coding, memoing, and theme identification, consistent with interpretative description.25,26 The research team identified content domains to create a coding tree and codebook used to systematically organize the data. The data analyst coded the transcripts using NVivo while composing memos to record insights and interpretations Prenatal Diagnosis 2015, 35, 1–7
Table 1 Topics discussed in educational session 1) What is noninvasive prenatal testing (NIPT)? a. Noninvasive blood test that uses maternal blood sample to assess fetal DNA for: i. Common autosomal trisomies, including Trisomy 21, 13, and 18 ii. Abnormalities in number of sex chromosomes iii. Determination of fetal sex b. Current recommendation to women of advanced maternal age or considered at high risk (based on prior screening test, reproductive history, or personal or family history of genetic condition) 2) What are chromosomes? a. Normal number of chromosomes b. Abnormalities in number of sex chromosomes i. Most common sex chromosome abnormalities (SCAs) 1. Description of Turner Syndrome: genotype and phenotype 2. Description of Klinefelter Syndrome: genotype and phenotype ii. Range of phenotypic expression iii. SCAs not associated with advanced maternal age c. Microdeletion sydromes i. Missing genes or changes on certain chromosomes ii. Not detected by conventional screening tests iii. Rare but often associated with variable phenotypic expression 3) What NIPT can and cannot do a. Sensitivity and specificity for assessing common autosomal trisomies b. Assess presence of sex chromosome aneuploidy i. Determine fetal sex c. Need for confirmatory invasive testing if NIPT result is positive d. Does not assess presence of all genetic conditions nor structural abnormalities
of the data and emergent themes.27 The research team met weekly to monitor progress, review coding and memos to identify areas of consensus, themes, and incorporate clinical perspectives throughout the analytic process.
RESULTS A total of 31 women attended three focus groups. The majority (80.6%) had prenatal screening or testing in their recent or current pregnancy, including 10 who reported having NIPT. Nearly two-thirds delivered in the past six months. Demographic and reproductive history characteristics are listed in Table 2. Major themes and recommendations that emerged during the focus group discussions are summarized in the subsequent discussion and presented in Table 3.
Sex chromosome aneuploidies The utilization of NIPT to identify SCAs was considered an important but secondary test benefit. Participants were knowledgeable of Trisomies 21, 18, and 13 and generally unfamiliar with SCAs. Participants suggested that greater awareness of Trisomies 21, 18, and 13 reflected that these conditions have been a primary focus of prenatal testing for decades. One participant stated: ‘I think there is more publicity about Down syndrome… That is where everyone’s focus is’ (Focus group [FG] 3). Given that the risk of SCAs is not associated with © 2015 John Wiley & Sons, Ltd.
Women’s perspectives on NIPT to detect SCAs and microdeletion syndromes
Table 2 Demographic and reproductive characteristics of participants
Table 3 Focus group themes and participants’ recommendations Theme
Characteristic
N = 31 n (%)
Age (years)
Mean [standard deviation (SD)]: 32.4 (4.8) Range: 24–41
Advanced maternal age
11(35.5)
Had prenatal screening/testing
25 (80.6)
Specific tests: NIPT 1st trimester screening test
10 (32.3)
7(22.6)
Chorionic villus sampling
1(3.2)
Months from delivery Currently pregnant
White Other/multi-ethnic
Familiarity with conditions being assessed by noninvasive prenatal testing (NIPT) affects patients’ perceptions of the value of testing.
SCAs and microdeletion syndromes are less familiar to patients than Trisomy 21, 18, and 13.
The counseling process should inform patients about each condition being assessed by NIPT during pre-test counseling.
The identification of fetal sex is of value but should be considered secondary to screening for SCAs.
Patients readily recognize that NIPT can identify fetal sex but less familiar with the capability to provide information about SCAs.
Clinicians should delineate in the counseling process that the purpose of NIPT is to assess the risk of Trisomy 21, 18, 13, and SCAs and that the identification of fetal sex is secondary to detecting SCAs.
Learning about conditions with variable or unknown phenotypic expression influences patients’ perceptions of the utility of using NIPT to gain this information.
Patients may be uncertain about the utility and actionability of receiving information about microdeletion syndromes. Patients support the ability to opt in or opt out of testing for certain conditions based on the value they assign acquiring such information.
The counseling process should involve a component where the clinician informs patients’ about what conditions can be identified using NIPT, then inquires about what information is sought by the patient, and then offer only those tests desired by the patients.
Obstetric clinicians are considered the primary and most reliable source of information about NIPT.
Patients trust their obstetric clinicians and rely on them to provide the information required to make informed decisions about NIPT. Patients recognize that clinicians have limited time and resources for patient education and counseling in addition to a responsibility to being informed healthcare consumers.
Clinicians should continue to provide accurate and unbiased information in the clinical encounter, in addition to developing a pool of resources [including genetic counselors and selfdirected educational resources (websites, printed materials, e-learning modules)] to provide additional information about the varied conditions identifiable using NIPT.
29 (93.5) Mean: 6.4 months 2 (6.5)
Race/ethnicity Black or African American
Recommendations
19(61.3)
2nd trimester screening test
Postpartum
Issue
7 (22.6) 21 (67.7) 3 (9.7)
Education High school graduate or GED Community college
2 (6.5) 6 (19.4)
College graduate
10 (32.3)
Advanced degree
13 (41.9)
advanced maternal age, participants questioned why NIPT is not available to all pregnant women, as articulated by one participant: ‘What I think is interesting is that [Turner and Klinefelter syndromes] are both not associated with advanced maternal age but this test is only offered to women who are’ (FG 1). Participants perceived the capability of NIPT to detect prenatal conditions, such as SCAs that may not be obvious at birth, as a key difference between NIPT and other prenatal screening tests. One participant described this distinction: ‘[SCAs] seem really different from something like Down syndrome, where you would know right away at birth anyway versus something that you could possibly have for many years and nobody would know and now it is becoming a subject of inquiry during pregnancy’ (FG 1). Despite having less familiarity with conditions resulting from SCAs, participants supported using NIPT for their identification. They strongly advocated that clinicians present information about NIPT’s ability to detect these conditions prior to testing. Participants expressed strong interest in learning fetal sex and having early access to this information. However, they stated that an emphasis should be placed on the purpose of NIPT – to identify specific aneuploidies – and that fetal sex identification is a secondary benefit. As described by a participant: ‘I think [clinicians] should not even Prenatal Diagnosis 2015, 35, 1–7
say that it tests for the sex because it’s not testing the sex. As a result of testing [for] the sex abnormality you can know the sex’ (FG 2). Without knowledge of NIPT’s assessment of SCAs, participants voiced concern regarding a pregnant woman’s ability to make an informed choice about utilizing NIPT. Furthermore, they noted that women would be unprepared for a positive test result and their post-test options.
Microdeletions and microdeletion syndromes Participants were even less familiar with chromosomal microdeletions and the syndromes resulting from them. Additionally, they expressed concerns about the utilization of NIPT to detect these conditions. Participants valued NIPT to detect Trisomies © 2015 John Wiley & Sons, Ltd.
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21, 18, and 13 based on awareness of these conditions and their physical and cognitive disabilities. In contrast, participants were less certain about the utility and actionability of information about microdeletion syndromes. These perceptions, in part, reflected hesitancy about the benefit of learning of conditions with variable or unknown phenotypic expression. As one participant described:
Everyone wants to know everything. But, what are you going to do with this information? I feel … if somebody tells you your child has Down syndrome or they have Turner syndrome or Klinefelter, we have a list of the things that might happen…pictures of these kids that have this syndrome… But some of these microdeletions…What does that mean? (FG 1) Yet, some participants perceived value in using NIPT to obtain information about a growing number of fetal genetic abnormalities. As one participant voiced: ‘Knowledge is power’ (FG1). Furthermore, participants recognized that the capability of NIPT to identify microdeletions and other non-aneuploidrelated conditions requires new approaches and increased efforts to ensure pregnant women have the information and resources needed to make informed choices about its use.
Challenges to education and counseling Participants acknowledged that the growing capabilities of NIPT would increase the volume of information that must be conveyed during the counseling process. They deliberated about the best approaches to educate patients about NIPT, given its ability to identify a host of genetic abnormalities. They recognized that healthcare providers may not be able to provide all the necessary information for women to make an informed decision during a clinical encounter. Participants recommend that, at a minimum, clinicians provide brief verbal and written information about all conditions being assessed prior to testing so that patients would not be blindsided by a positive result. They also recommended that clinicians suggest reputable resources, such as websites, so patients may access information outside of the clinical setting. As discussed by two participants:
Participant 1 I knew I was being tested for these things. I knew one of them was Down syndrome and then there were a couple other things that I wasn’t really that familiar with but I knew they were being tested too. In my opinion, I don’t think it is a good use of resources to sit down and have a lecture about Klinefelter syndrome with every person who is going to have this test. Participant 2 Especially if they don’t end up having it (FG 1). There was consensus among participants that their clinician is their trusted and main source of information about prenatal testing. They also agreed that women should be proactive in obtaining all the necessary information to make informed decisions. As this participant noted: ‘The patient has a responsibility, too, to research and educate themselves’ (FG 1). Another participant expressed a similar viewpoint: Prenatal Diagnosis 2015, 35, 1–7
I feel like a doctor’s job is to give me information: These [conditions] are what we can test for. Here is what the test is. Here is what it is going to look at. And then I think it’s our responsibility as a patient to take that information and think about it and make an informed decision and ask the questions ahead of time and not just kind of go with the flow… As the patient, it is our responsibility to be that active partner (FG 2). Overall, participants perceived the value of NIPT on a continuum based on the conditions the test assesses and their perceptions of the usefulness of test results. Participants generally saw the value of screening for Trisomies 21, 18, and 13 but less for SCAs and questioned the utility of screening for microdeletion syndromes. This was due, in part, to uncertainties associated with these conditions, given their range of phenotypic expression. Furthermore, in light of the expanding capabilities of NIPT, some participants thought that women should be able to choose the conditions assessed. As described by this participant:
I think that giving the information on what can be looked at… and then options for each person’s personal preference on what you do or don’t want to know and what options are available to you for further information… Everyone is different, and saying we are going to tell you everything, blanket-wise, doesn’t work for everyone (FG 1). DISCUSSION Noninvasive prenatal testing has quickly become integrated into prenatal care. Its capability to assess the presence of SCAs and applications for microdeletion syndromes will present challenges to clinicians who offer the test and to patients who must decide if this information is of value to them, their partners, and their families. NIPT has rapidly been embraced by clinicians and high-risk patients24,28–32 as a more sensitive and specific screening tool for fetal aneuploidies than conventional screening tests. This study offers a first look at women’s perspectives about the increasing scope of conditions assessed by NIPT, including SCAs and microdeletion syndromes. Discussions about Trisomies 21, 18, and 13 have been the core of prenatal counseling for decades. Participants in this study were well versed about the use of prenatal testing to assess the presence of Trisomies 21, 18, and 13, the utility of NIPT as a screening test, and the need for diagnostic testing to confirm the presence or absence of a condition. The majority were less familiar with SCAs, and the capability and limitations of NIPT to identify them. Most viewed learning fetal sex as a benefit of NIPT and valued gaining that knowledge earlier than during the second-trimester anatomical ultrasound. Having this information earlier in the pregnancy in and of itself was perceived as an advantage, although studies suggest that fetal sex information may be sought by some women for the purpose of making key decisions about the pregnancy.33,34 However, when considering the capability of NIPT to identify SCAs, participants had comparatively less knowledge of the medical and cognitive issues associated with such conditions. © 2015 John Wiley & Sons, Ltd.
Women’s perspectives on NIPT to detect SCAs and microdeletion syndromes
Identification of conditions resulting from SCAs was desired by participants. This is in agreement with a study which reported that at the time of NIPT, while approximately 25% of pregnant women considered disabilities resulting from SCAs to be less than that resulting from Down syndrome, nearly all wanted to know if a SCA was suspected.35 Due to existing counseling practices and paradigms of obstetric risk that preceded the integration of NIPT, pregnant women may have less exposure to conditions associated with SCAs compared with other aneuploidies. Counseling about the chance of fetal aneuploidy has centered on fetal risk assessments based on maternal age. SCAs and microdeletion syndromes are not associated with advanced maternal age and can occur in women traditionally considered low risk based upon this criterion. The introduction of NIPT into prenatal care intensifies an ongoing debate to update how risk is framed in the context of pregnancy and risk-benefit analysis when considering prenatal genetic testing.7,36,37 Pre-test and post-test NIPT counseling is an important topic that needs to be addressed as this technology becomes further integrated into clinical practice. It is critical that clinicians educate patients about their screening and testing options, test benefits and limitations, as well as results and implications. This includes a discussion of the lower sensitivity and specificity of NIPT for SCAs compared with those for autosomal aneuploidies.38,39 To make an informed choice about NIPT, pregnant women must have information that addresses all conditions assessed by the selected testing platform. This includes information about the ability of NIPT to provide information about sex chromosome aneuploidies, not only fetal sex. One aspect of counseling that warrants consideration is that the clinical expression of these conditions is highly variable, and these conditions may be undiagnosed at birth and identified later in childhood or adult life.18 To foster an informed decision, participants suggested that pregnant women understand the capability and accuracy of NIPT for each condition. For now, this includes autosomal and SCAs; in the near future, this will include microdeletion syndromes. The counseling process should also address how pregnant women would integrate fetal genetic information into their framework of values and preferences. This counseling approach should be continually expanded to address the growing number of fetal genetic conditions detectable with advances in noninvasive molecular diagnostics. With increased capabilities will come the need for specific strategies to communicate large and complex amounts of information to patients. As seen in the context of prenatal microarray testing, studies show that patients find information regarding variants of unknown significance particularly concerning40 and can lead to increased levels of anxiety for the duration of the pregnancy and into the postpartum period.41 It is critical that information regarding all conditions being evaluated is disclosed before prenatal testing, as the post-test period is not the time for women to consider an abnormal result and the impact of that information on their pregnancy.42 It is well accepted that the breadth of information that must be conveyed to support informed decision making for conventional screening tests poses challenges of both Prenatal Diagnosis 2015, 35, 1–7
time and resources to the clinician–patient encounter. This will be exacerbated in the context of NIPT, as parents are generally unprepared for the diagnosis of a SCA.18 Studies show healthcare providers vary in the manner in which they present information about SCAs to pregnant women, both in terms of the accuracy of the information and potential biases introduced in the counseling process.43 Furthermore, obstetric providers’ self-reported level of knowledge and confidence in prenatal counseling are low, a finding noted prior to the introduction of NIPT.44 For this reason, genetic counselors are well versed in this regard and should play a central role in educating patients about their testing options, although it is widely recognized their numbers are too few to meet the needs of the obstetric population. Yet, participants in our study emphasized the importance of acquiring information and guidance from their obstetric provider. Thus, these findings, as well as prior studies, warrant efforts that ensure clinicians are aware of pregnant women’s preferences regarding the use of NIPT paired with the education and skills to prepare patients to make informed choices about this and other testing options.24 Given the scope of these issues and the realities of clinical practice, we recognize that there is not a single approach to address the challenges inherent in the counseling process. Instead, advances in prenatal testing call for a combination of resources utilized by clinicians and patients. This includes educational tools and decision aids that present information about the testing process and assist pregnant patients to explore their values and beliefs. Ideally, these materials would be available to patients prior to and following prenatal testing discussions to support informed decisions about NIPT. The growth of electronic information provides another opportunity for clinicians to identify high-quality web-based or app-based resources to supplement the educational process.45 These resources may also be made available in clinical areas. As NIPT capabilities expand, information can be grouped into broad discussion categories of conditions in the pre-test counseling session, as used during the early days of microarray analysis.46 Such strategies will require the coordinated efforts of obstetricians, and maternal–fetal medicine and genetic specialists to work together across disciplines and institutions to implement such plans. This study provides valuable insight into women’s views about present and future applications of NIPT. We acknowledge potential study limitations. This study cohort had participated in our previous research on NIPT,24 and their opinions and experiences may not represent that of the general pregnant population. In addition, one-third utilized NIPT during their current/recent pregnancy and thus had firsthand experience with the testing process. The educational session was provided to allow other participants to gain foundational knowledge about NIPT, so they could formulate their views regarding the use of current and future applications of NIPT. Furthermore, participants were queried about the utilization of NIPT to identify microdeletion syndromes, although this application is not widely available. Given the emerging application of NIPT for this purpose, it was suitable to explore in this study. This research provides a first look into © 2015 John Wiley & Sons, Ltd.
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women’s perspectives about advancements in NIPT technology and warrants further evaluation of pregnant women’s preferences and perspectives about the utility of SCA and microdeletion testing using NIPT.
CONCLUSIONS NIPT is rapidly gaining acceptance as a valuable tool to assess risk of fetal aneuploidies in high-risk women. In time, as validation of the test’s performance in low-risk women is accepted by the medical community, NIPT may replace conventional analyte screening tests and be offered to all pregnant women who wish to undergo prenatal testing. The additional assessment of fetal sex chromosomes and microdeletion syndromes will further alter the prenatal testing paradigm, both in terms of how pregnant women and clinicians conceptualize the risks and benefits of testing, and how the counseling process unfolds to prepare pregnant women to make informed choices. The time has come to address the challenges that translation of this new genetic technology into clinical care will pose upon clinicians who must maintain their competency in genetic medicine, so they can
effectively educate their patients to make informed decisions about prenatal testing. WHAT’S ALREADY KNOWN ABOUT THIS TOPIC? • Noninvasive prenatal testing (NIPT) has gained acceptance as a valuable tool to assess the risk of common autosomal aneuploidies in high-risk women. • Advancements of NIPT technology will allow assessment of sex chromosome aneuploidies and microdeletion syndromes.
WHAT DOES THIS STUDY ADD? • Pregnant women are unfamiliar with sex chromosome aneuploidies and microdeletions. • Pregnant women should be educated about the full testing platform of NIPT to avoid being unprepared for an abnormal finding from NIPT. • The expanded scope of NIPT for sex chromosome aneuploidies and microdeletion syndromes will introduce new challenges for clinicians to ensure patients make informed decisions about undergoing testing for all applications of NIPT.
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