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The offering and acceptance of expanded carrier screening is increasing among pregnant women including women without an increased risk based on race, ethnicity or family history. The chances of a positive screening test have been reported to be as high as 24 % when multiple conditions are screened. Yet, little is known about the way these tests are offered and how patients are affected by a positive test result. To explore this area of genetic testing, interviews (n = 17) were conducted among women who received positive expanded carrier results in the context of obstetric care. A content analysis was conducted on the transcript data from the interviews. Outcomes of this research suggest that educational interventions are needed to improve maternal understanding of positive carrier screening results. Most of the participants in this study confused the results with other prenatal screening test options. In addition, the way the results were discussed varied greatly, and influenced participants’ thoughts about reproductive decisions that led to a range of emotional uncertainty. Our data suggests that genetic counseling improved participants’ understanding of positive results. More research is needed to further understand if our results are consistent within a larger, more diverse sample, and to explore how to best provide education about expanded carrier screening.
With the introduction of next generation sequencing (NGS), carrier screening for Mendelian disorders has become increasingly available and sophisticated. NGS, also known as high-throughput sequencing, now allows sequencing to be conducted more quickly, and for less cost, with more conditions than before. Due to these advances in molecular testing, carrier screening is now offered for over 100 disorders in a single, low-cost test to the general population of pregnant women (Edwards et al. 2015).
Although the American College of Medical Genetics (ACMG) has written guidelines for the appropriate use of carrier screening (2013), no national organizations have at this time advocated for NGS use as a primary screening test (Grody et al. 2013). In 2011, the American College of Obstetrics and Gynecology (ACOG), which supported screening for cystic fibrosis (CF), subtly changed their recommendations to offer CF carrier screening to women regardless of ethnicity (ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis, 2011). Traditionally, women who were pregnant or planning a pregnancy were only offered carrier screening if they were at an increased risk based on their race, ethnicity, or family history. However, it has been increasingly recognized that self-reports of racial or ethnic heritage are not necessarily accurate, nor are the clinician’s assessment of racial/ethnic background. Furthermore, ethnic based carrier screening places the burden on the provider to understand what specific screens should be offered based on ethnicity.
As expanded carrier screening is increasingly offered to a broader population it raises major challenges. A primary concern is how to empower providers to best educate and counsel the volume of screened individuals. These carrier panels are marketed to providers as well as directly to consumers. The size of these panels and the relatively low cost means that many couples may choose screening despite little knowledge about the genetic conditions. As a result, an increased number of women will receive positive screening results. For example, after screening 23,453 individuals of diverse ethnic background with the Counsyl panel of 108 conditions, Lazarin et al. (2013) reported that approximately 24 % of the sample screened positive for at least one condition, and 5.2 % screened positive for multiple disorders (Lazarin et al. 2013). The majority of these women likely would not have undergone carrier screening based only on risk factor.
Some authors question whether offering expanded carrier screening to everyone unnecessarily increases anxiety and stress during pregnancy given the higher probability of carrier detection on expanded panels but the low probability of both parents being carriers for the same condition (Ormond et al. 2007; Wienke et al. 2014). For example, most of the conditions follow autosomal recessive inheritance and therefore, both parents have to carry a mutation for the same disorder for there to be a risk of affected children. Further, assessment of risk is a problem when a pregnant woman is found to be a carrier but her partner is unavailable for testing. Finally, some carriers may experience concerns over their own health if they do not have a clear understanding of the implications of carrier status, creating additional challenges to education (Lewis 2013).
There is substantial uncertainty about how information about carrier screening can be effectively conveyed to couples. Most carrier screening tests are conducted through private companies (Wienke et al. 2014) and as such, carrier testing can be accessed directly by consumers without help or advice from health care professionals. Direct to consumer testing with pregnant women creates additional challenges with this vulnerable population because private companies are more driven by technological advancement and cost effectiveness instead of condition-specific screening (Borry et al. 2011). Even more, there is limited research on how pregnant women and their partners understand the purpose of carrier screening and the meaning of positive carrier results. In one of the few studies, assessing understanding in pregnant women who received cystic fibrosis carrier screening, initial knowledge of carrier screening and the genetic conditions they target was low and was heavily influenced by education level (Ioannou et al. 2014). In this same research, results indicated that 2 to 3 weeks after receiving the results of carrier screening, the majority of those screened did not understand the concept of residual risk for future pregnancies, believing that a negative test result meant they had no chance having a child with cystic fibrosis (Ioannou et al. 2014). These results indicate a need for more comprehensive education to help participants understand difficult genetic concepts. Furthermore, little is known on how individuals are offered and receive results or on how individuals who receive positive carrier results understand the results. These problems of communication, education, and consent associated with carrier screening may be magnified enormously when large panel screens are used. In this study, we conducted interviews to explore the experiences of women who received positive results from expanded carrier screening tests in the context of obstetric care.
Before any research activity was initiated, institutional review board approval was obtained from the corresponding university. A retrospective medical chart review of women who received a positive carrier result in the past 3–6 months at a single clinic within a university hospital was conducted. A research assistant (RA) was trained by the clinic’s genetic counselor to query basic demographic data on potential participants. Letters were mailed to these individuals by the RA with an opt-in postcard to return if they were interested in participating in this study. The first round of mailings (n = 80) were sent out in May 2015 and 11 interviews took place in June 2015. Two additional postcards were returned, but interviews were not conducted due to the inability to contact the respondents. The second round of recruitment mailings were sent out in August 2015 (n = 74) and 6 more interviews were completed that same month. One additional postcard was returned but the interview was not conducted because the interviewer was unable to reach the respondent. This resulted in a 12 % response rate for opt-in (including the three individuals who were unable to be contacted). All of the participants had insurance, only one participant was still pregnant, none of the participants, when asked, self-reported positive results on other prenatal tests (unverified by chart review). Remaining demographic data are provided in Table 1. Laboratory referral for expanded carrier screening at the university prenatal clinic in this study for all cases is Counsyl, Inc., which screens for greater than 100 disorders, the majority of which are autosomal recessive.
On average the interviews (n = 17) lasted 20 min with a range of 15 min to 45 min. The questions asked during the interviews focused on the process and communication for carrier screening including the return of results, how the partner was included in the process, reactions to the positive results, and impact on reproductive decisions. See Table 1 for a list of questions. Each respondent who completed an interview was mailed a $20 gift card for her participation.
All of the telephone interviews were audio recorded, transcribed and verified for accuracy by one of the researchers. Upon completion of this step, the data were moved into matrices for analyzing. A content analysis was conducted on the data matrices. This provided a systematic way to include the process from the offer to return of results for inclusion in the analysis (Miles and Huberman 1994). The transcript data and interview questions were read to develop codes, and systematically applied to the data. The codes were then linked together to form categories based on degree of similarity. This approach to qualitative descriptive research has been well supported in the literature and accurately captures self-reported participant experiences by using data and codes that closely reflect the actual statements of the participants (Rothwell et al. 2012; Sandelowski 2000). The researchers also used the approach of reflexivity during the data analysis to limit personal bias into the interpretation (Baillie 2015). This resulted in five categories from the interview data.
The categories presented below are based on telephone interviews from women who received positive prenatal expanded carrier screening results. The results were categorized into five areas that include: 1) confusion with other prenatal test results, 2) influences of positive results on the individual, future offspring and other family members, 3) emotional impact of the positive results, 4) the impact of clinical involvement and 5) communication process of carrier screening.
Participants were asked questions to describe their understanding for why and how carrier screening was conducted. The most common reason reported for why they opted for carrier screening was “preparation.” When asked to describe what was meant as preparation, most respondents reported it was to decide to terminate or not terminate the pregnancy. Many individuals stated they were aware of some genetic condition in their family and wanted to know their risk. Another participant mentioned it would be preparation for adoption. Further, many of the descriptions represented other types of prenatal screening. For example, over half of the participants reported that they did screening to identify genetic conditions such as “Down syndrome” or “missing chromosomes”. When participants were asked follow-up questions about how the tests were conducted, the answers varied significantly and several participants stated that tests were conducted through blood work with other tests such as ultrasounds. One participant stated it was conducted with newborn screening and she received the results after the baby was born in the hospital (“My daughter had newborn screening…she came back with an auto marker that’s when we found out we were screened for carriers.”). Another participant reported that the carrier screening was done through chorionic villus sampling. Of the seven who reported speaking with a genetic counselor for return of results, their answers more accurately reflected their understanding of carrier screening (“I would have to be a carrier and he [husband] would have to be a carrier of the same condition to have the risk of having an affected child.”). None of the participants reported pre-test counseling within this study.
About half of the participants stated that the results influenced their reproductive decisions. Two individuals mentioned that if the results were more serious then they would consider termination. Two quotes that represent this concern: “If we’d have been matched carriers for some of the more serious disorders, then we would not have had children;” and “Abortion or anything for getting rid of a baby for any type of reason is frowned upon so we were relieved [to have no serious positive results].” Two other participants stated that even though results were unsettling, they considered termination but decided to continue the pregnancy (“If you have a child that has a disability, just don’t give up”; and “We can’t prove that [the baby] doesn’t have the condition which is one of the reason why we chose not to go through with the abortion.”).
Participants also noted the importance of knowing if the child was a carrier or not. Some participants stated that it was important for their children to be informed about their health when they got older: “When our kids get older, we have to explain to them, that they’re going to have to keep in mind when they’re choosing their life partner from now on. Because if somebody is a carrier as well then their children run the risk of having this disease where people are still dying from it today.”
Participants were asked to describe their reaction to the test results. Many of the participants stated they were surprised that they were found to have a positive result: “I had no idea that being from a white background you had a much higher chance, and that there were millions of silent carriers out there with these genetics that could mean life or death for your children.”; and “I was surprised to hear I was a carrier of these diseases that I don’t show any sign of.” Others reported that they were relieved. Some representative quotes included: “I was relieved to hear that I wasn’t a carrier for anything more serious [more serious disease on the panel]. So overall it was very comforting.”; “I was 36 when I was pregnant and had some anxiety about being older mom. The testing put some of the anxiety aside.”; and “My reaction was a sense of relief, because I wasn’t a carrier for anything significant.”
However, most participants did report that the positive result was anxiety inducing. For example, one participant described the experience as an “emotional roller coaster.” Another representative quote included: “I was surprised that I was a carrier and kind of nervous what that meant and what the risks were to the baby but the genetic counselor did a good job explain everything so there wasn’t a lot of questions.”
Two participants stated that it was not worrisome to have a positive result because everyone is likely to be a carrier of something, however, it was frustrating to not choose what they could be tested for on these carrier panels and/or the high number of conditions. For example, one participants stated: “I think one of the things that was frustrating was that I actually didn’t want the whole panel of 100 plus disorders, cause a lot of those don’t matter, and I really wanted availability of just the top 12 genetic disorders.
Of the participants who stated they spoke with a genetic counselor in-person in the clinic (n = 7) for return of results, all reported high satisfaction with the testing process. Some representative quotes include: “It was a positive thing because just sitting with the [genetic] counselor and chatting about how it works. I don’t remember too much from my high school classes.”; “I feel like the counselor was really great. She had visual examples when we were talking, and she was really good at explaining.”; and “The counselor was very patient, and I had like a hundred questions, so she answered all of the questions and she helped alleviate a lot of our fears.” Many of the participants reported that they wished their obstetrician knew more. (“She wasn’t really familiar with the whole process. She didn’t know if she could do the screening in her office.”; “Well, I think that doctors should be more on top of things.”; and “If the testing is being done in OB/GYN offices that they really ought to have good resources if the screening comes back positive and can answer questions.”)
When asked how they originally learned about carrier screening, only seven participants mentioned they heard about it in the doctor’s office and three of these participants asked for carrier screening themselves (“I went to my OB and specifically asked her about it.”). Other participants heard about it through their professional work, family or could not remember. In regard to return of results, the most common method was over the telephone by a variety of providers and less than half of the participants reported talking to a genetic counselor. The other remaining participants stated return of results were provided by a geneticist, intern, a pediatrician with the newborn screening test results or they did not know who the provider was who returned the results. See Table 1 for a summary of the communication methods for an offer of carrier screening and return of results. Finally, only nine of the seventeen participants (53 %) reported that their partner completed carrier screening.
This is one of the few studies to interview women who received positive prenatal carrier screening tests. The results in this study highlight the confusion that exists among pregnant women about what a positive carrier screening test indicates and to a lesser extent, when and how the tests are actually conducted. One of the most concerning outcomes of this study is the confusion with other prenatal screening tests and the self-reports of considering termination from the carrier results. None of the participants received pre-test counseling and without education in the pre-test phase, there may be confusion about the purpose of carrier screening as compared to other prenatal screening options (Tables 2 and and33).
Pre-testing education is one of the most notable barriers to the implementation of expanded carrier screening by next-generation screening and informed patient decision-making. As highlighted in this study, offers for prenatal screening occur outside the context of genetic counseling and tend to be determined based on the obstetrician and/or access to information outside of the clinical setting. According to a recent systematic review of Cystic Fibrosis carrier screening studies (Ioannou et al. 2014), between 50 and 94 % of the population received an offer of screening from their general practitioner. Additionally, consultation with the general practitioner resulted in higher uptake of screening (25 %), as compared to those who were told about screening options in a dedicated group information session (9–12 %). These results were consistent with this study in that a medical professional is the primary source for information about screening. Medical professionals are highly influential in the uptake and understanding of carrier screening and will need to help navigate the screening process and patient needs in the pre-test phase.
Other difficulties for adequately explaining carrier screening to the general population of pregnant women is that many obstetricians are unfamiliar with carrier screening guidelines and unprepared for informing their patients or interpreting test results (Darcy et al. 2011). In this study, several participants reported that their obstetricians were unfamiliar with carrier screening, and the participants stated they wanted their obstetricians to know more about carrier screening because carrier screening was completed early in the pregnancy. However, this stated reason for wanting the obstetricians to know more about carrier screening could be a by –product of the confusion with other prenatal screening options that are offered during the first trimester. It might be useful to identify education interventions that promote informed patient decision-making prior to the acceptance of carrier screening and that are not dependent on time-limited obstetric appointments that have other competing clinical demands.
One intervention targeting Ashkenazi Jews found positive outcomes with pre-test education (Warsch et al. 2014). For this intervention, 412 young Ashkenazi Jewish men and women attended oral presentations by a medical geneticist conveying general concepts and causes of genetic disease and inheritance, specific information about Ashkenazi Jewish genetic diseases, sensitivity of screening tests and interpretation of results, reproductive options, and ethical considerations. At the conclusion, attendees were offered the opportunity to be tested at that time (free-of-charge) or schedule an appointment. In addition to overall knowledge significantly increasing, there was also a significant increase in the percentage of participants who stated the test results would influence their reproductive behavior (Warsch et al. 2014). However, with the increase in the number of conditions being screened for, there is more information to convey and national recommendations do not encourage education about each disease for expanded carrier screening (Edwards et al. 2015). Additionally, unlike other prenatal screening options, the additional testing of the partner for carrier screening is necessary for accurate results.
Traditionally, clinical protocols call for the woman to be screened first, followed by the partner if the woman is a carrier. In this study, the women mostly screened first and then out of the 17 positive carrier results, 8 partners did not undergo testing. If the partner is unavailable or unwilling to be screened, a woman who tested positive for a particular condition is faced with a dilemma. For example, with CF, if her partner is of Northern European ancestry, the probability that he is a CF carrier is about 1 in 28. The probability that the baby will be affected with CF becomes 1 in 112. Should she undergo prenatal diagnosis? In this scenario, ACOG recommends that the woman be referred for genetic counseling. Genetic counselors are trained to communicate complex genetic information in a non-directive manner and can help provide opportunities for the woman to consider all of the options before making her decision.
Additional research should explore the impact of disclosing the basis for the selection of disorders on expanded carrier screening panels. This study did not formally evaluate knowledge but asked for self-reports about the participants’ understanding of the purpose of carrier screening. The information provided about disorders with mild phenotypes, variable expression, low penetrance, and/or characterized by an adult onset should also be explained clearly, allowing patients to opt out of receiving these test results. Patients also must be made aware of the concept of residual risk following negative test results (Grody et al. 2013). In this study, some participants expressed frustration over the high number of screening tests in the one panel and the inability to choose the type of diseases included on the panel. As noted above, positive carrier results are more likely to happen with expanded carrier screening and may cause unnecessary stress or anxiety during pregnancy.
In summary, these results among women who received positive carrier results support other findings in this area of research in that there is a need for improved carrier screening education of both providers and patients, including education about how to deal with the challenges presented when the partner of a woman who received positive results does not undergo carrier testing. Results from this study also indicate confusion with other tests, and the increase in anxiety after testing positive for non-serious disorders. Future research should include a larger more quantitative study to assess if the results of this study are consistent with other populations and which type of patient is most vulnerable to misunderstanding of carrier results. Finally, developing an educational intervention is imperative because of the higher rates of positive results with expanded carrier screening compared to other genetic testing.
This was a qualitative descriptive research study with self-selected participants, all of which had insurance and may have better access to healthcare and higher socioeconomic status than individuals who do not have insurance. All participants received positive test results within a university-based obstetric care setting. More detailed demographic data is needed, including number of children. This self-selected sample limits generalizability of the results. In addition, only one participant was still pregnant and all of the participants, when asked, stated that they did not receive positive results from other possible prenatal screening tests, but this was not verified through medical chart review. The interview was purposively designed to ask how they were informed about carrier screening and did not elaborate on how it differed from other prenatal screening options. Although this is a limitation, it is also an important finding in that despite getting a positive result and the participants’ stated emotional impact, they still confused it with other prenatal screening. This result supports our argument that educational interventions are needed as expanded carrier screening is offered to the general population of women. Other limitations include the small sample, use of a single screening company, and the lack of formal assessment regarding knowledge about prenatal carrier screening before and after screening.
There is a need to improve education about prenatal expanded carrier screening with the limited number of genetic counselors. This is critical as pregnant women are increasingly accessing genetic testing from a variety of contexts outside the clinical setting. Identifying ways to inform pregnant couples about the purpose of expanded carrier screening and how it differs from other prenatal screening tests is essential. The use of pre-test education may help address these concerns, potentially allowing pregnant woman and couples to choose specific-condition screening rather than expanded carrier screening. Also, it will be important to educate providers and patients about the difficulties arising when the partner is not available for testing.
Future research among a larger more diverse population is needed to garner attitudes and knowledge about prenatal expanded carrier screening from those who received positive results. An educational intervention should address the chances that positive results may cause anxiety, reasons why a couple would undergo this type of testing, and potential implications it has on the family. It may also be important to assess perceptions of positive results when a woman is still pregnant and after birth. This study included primarily women who had already given birth; their relief from not having an affected child may have influenced results. Further, the type of positive test result will be important to include when examining how expanded carrier screening impacts perceptions of the pregnancy.
This research was funded by the Utah Center for Excellence in Ethical, Legal and Social Implication Research (UCEER) (NIH; P20 HG007249).
Conflict of Interest Erin Rothwell has no conflict of interest. Erin Johnson has no conflict of interest.
Amber Mathiesen has no conflict of interest.
Kylie Golden has no conflict of interest.
Audrey Metcalf has no conflict of interest.
Nancy C. Rose has no conflict of interest.
Jeffrey R. Botkin has no conflict of interest.
Human Studies and Informed Consent All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
Animal Studies No animal studies were carried out by the authors for this article.