Background
Laboratories offering cell-free DNA often reserve the right to share prenatal genetic data for research or even commercial purposes, and obtain this permission on the patient consent form. Although it is known that nonpregnant patients are often reluctant to share their genetic data for research, pregnant patients’ knowledge of, and opinions about, genetic data privacy are unknown.
Objective
We investigated whether pregnant patients who had already undergone cell-free DNA screening were aware that genetic data derived from cell-free DNA may be shared for research. Furthermore, we examined whether pregnant patients exposed to video education about the Genetic Information Nondiscrimination Act—a federal law that mandates workplace and health insurance protections against genetic discrimination—were more willing to share cell-free DNA-related genetic data for research than pregnant patients who were unexposed.
Study Design
In this randomized controlled trial ( ClinicalTrials.gov Identifier: NCT04420858 ), English-speaking patients with singleton pregnancies who underwent cell-free DNA and subsequently presented at 17 0/7 to 23 6/7 weeks of gestation for a detailed anatomy scan were randomized 1:1 to a control or intervention group. Both groups viewed an infographic about cell-free DNA. In addition, the intervention group viewed an educational video about the Genetic Information Nondiscrimination Act. The primary outcomes were knowledge about, and willingness to share, prenatal genetic data from cell-free DNA by commercial laboratories for nonclinical purposes, such as research. The secondary outcomes included knowledge about existing genetic privacy laws, knowledge about the potential for reidentification of anonymized genetic data, and acceptability of various use and sharing scenarios for prenatal genetic data. Eighty-one participants per group were required for 80% power to detect an increase in willingness to share data from 60% to 80% (α=0.05).
Results
A total of 747 pregnant patients were screened, and 213 patients were deemed eligible and approached for potential study participation. Of these patients, 163 (76.5%) consented and were randomized; one participant discontinued the intervention, and two participants were excluded from analysis after the intervention when it was discovered that they did not fulfill all eligibility criteria. Overall, 160 (75.1%) of those approached were included in the final analysis. Most patients in the control group (72 [90.0%]) and intervention (76 [97.4%]) group were either unsure about or incorrectly thought that cell-free DNA companies could not share prenatal genetic data for research. Participants in the intervention group were more likely to incorrectly believe that their prenatal genetic data would not be shared for nonclinical purposes than participants in the control group (28.8% in the control group vs 46.2% in the intervention; P =.03). However, video education did not increase participant willingness to share genetic data in multiple scenarios. Non-White participants were less willing than White participants to allow sharing of genetic data specifically for academic research ( P <.001).
Conclusion
Most participants were unaware that their prenatal genetic data may be used for nonclinical purposes. Pregnant patients who were educated about the Genetic Information Nondiscrimination Act were not more willing to share genetic data than those who did not receive this education. Surprisingly, video education about the Genetic Information Nondiscrimination Act led patients to falsely believe that their data would not be shared for research, and participants who identified as racial minorities were less willing to share genetic data. New strategies are needed to improve pregnant patients’ understanding of genetic privacy.
Why was this study conducted?
It is not known whether pregnant patients know or mind that their genetic data collected during prenatal genetic screening may be used and shared for research. This study explored patient knowledge and opinions about the privacy of prenatal genetic information.
Key findings
Pregnant patients have substantial misunderstandings about what commercial laboratories can and cannot do with genetic information obtained from cell-free DNA (cfDNA). Instead of increasing patient willingness to share genetic information for research, video education about existing genetic privacy legislation led patients to falsely believe that their genetic data would not be shared for research.
What does this add to what is known?
Informed consent for prenatal genetic screening is currently inadequate. Evidence-based interventions and educational resources are needed to improve pregnant patients’ understanding of genetic privacy issues before undergoing cfDNA screening.
Introduction
Prenatal genetic screening has historically relied on data sources other than actual genetic material, such as ultrasound and maternal serum analytes. In recent years, DNA-based prenatal genetic screens, such as fetal cell-free DNA (cfDNA) and carrier screening have been widely adopted. Since its introduction in 2011, cfDNA has become widely accepted for pregnancies at both high-risk and low-risk of aneuploidy, with a projected 15% annualized growth rate. Similarly, carrier screening for inherited conditions has rapidly expanded beyond the basic conditions recommended by the American College of Obstetricians and Gynecologists (ACOG). , More than 200,000 pregnant patients undergo expanded carrier screens annually in the United States, some of which test more than 1000 genes. Although these screens have great utility, their results hold sensitive information about the current and future health status of both the pregnant patient and the fetus. Specifically, even if deidentified, prenatal genetic data can be reidentified and traced back to an individual. If a party with an economic interest in a patient’s genetic health (eg, disability, life, or long-term care insurers) were to access potentially compromising genetic data, this information could be used to discriminate against the patient.
Surprisingly, these sensitive genetic data do not always belong to the patient. The commercial laboratories that perform most of this screening often reserve broad rights to retain, use, and share these sensitive data. Although the privacy policies of these companies may differ in specifics, many laboratories reserve rights to use and share patients’ data in several ways, including maintaining samples for internal quality control, sharing genetic information on publicly available databases, obtaining patient clinical and pregnancy outcome information, and sharing genetic information with third parties for the development of commercial applications. Although a minority of companies give patients granular control over their data, most do not, and many companies have genetic privacy policies that are opaque or nonexistent. It is not known whether pregnant patients understand the potential genetic privacy implications stemming from cfDNA data, much less whether they would be willing to allow their genetic data to be shared or used for nonclinical purposes. Issues surrounding genetic privacy have been studied in nonpregnant populations: patients are generally amenable to sharing genetic data for nonclinical purposes, such as research, although minorities and parents are more likely to hold misgivings about the safety of genetic data. As pregnant patients’ decisions about genetic testing affect not only themselves but also their fetus, who may be alive for many decades to come and in an era when genetic testing is even more pervasive and powerful than it is presently, it is important to examine how pregnant patients view genetic privacy.
We designed a randomized controlled trial (RCT) to investigate pregnant patients’ baseline knowledge of and attitudes about the use of prenatal genetic data for nonclinical purposes and to determine whether video-based education would affect their willingness to share their data for research. We hypothesized that pregnant patients would have unique privacy concerns regarding the retention, use, and sharing of genetic information related to themselves and their fetus and that educating them about existing legislation that protects patients’ genetic privacy would make them more willing to share their prenatal genetic data for research purposes. Furthermore, we hypothesized that demographic factors and social media activity would associate with willingness to share genetic data for nonclinical purposes.
Materials and Methods
Trial design
This double-blinded RCT enrolled patients who had undergone cfDNA and were presenting for a detailed anatomy scan at the Prenatal Diagnosis Center of Women and Infants Hospital, a tertiary maternity hospital in Providence, Rhode Island. Recruitment occurred from July 21, 2020, to October 16, 2020. The trial was approved by the institutional review board (study identification number 1500909) and was registered prospectively on ClinicalTrials.gov (Identifier: NCT04420858).
Patients
Pregnant patients were eligible if they were ≥18 years old with a singleton pregnancy and if they underwent cfDNA during the current pregnancy and subsequently presented at 17 0/7 to 23 6/7 weeks of gestation for a detailed anatomy scan. Because the video intervention was only available in English, the study excluded non–English-speaking patients. Additional exclusion criteria were (1) suboptimally dated pregnancies (defined as a pregnancy dated by an ultrasound at or after 22 0/7 weeks of gestation), (2) previous participation in the study, and (3) patients presenting for unscheduled or urgent anatomy scans.
Procedures
All patients presenting for a detailed anatomic survey were screened for eligibility. Eligible patients were approached before their ultrasound, and consenting participants were randomized 1:1 to a control or intervention group. Participants in the control group viewed a 2-page infographic about cfDNA jointly developed by ACOG, the Society for Maternal-Fetal Medicine, and the National Society of Genetic Counselors, which is freely available on the ACOG website. This infographic did not address genetic privacy. Participants in the intervention group viewed the same infographic plus a 2-minute and 30-second video about the Genetic Information Nondiscrimination Act (GINA), which was produced by the American Society of Human Genetics (ASHG) and is accessible on a popular online video streaming platform. Participants completed a 42-item electronic questionnaire using a tablet ( Supplemental Materials ). The questionnaire, which was adapted from a previously used survey, collected demographic information and knowledge and attitudes about genetic privacy concerning prenatal genetic screening. Participant responses were directly entered into a secure Research Electronic Data Capture (REDCap) database. , As screening, enrollment, randomization, education (control or intervention), and the participant survey were all administered in REDCap, timestamps for each step in this process were logged. As a quality check, the total time spent in the education module by each participant was calculated ( Supplemental Materials ; Supplemental Table ). Clinical outcomes were subsequently abstracted in duplicate by 2 different research personnel, entered into REDCap, and were compared to confirm accuracy. For more information about GINA and access to the educational interventions used in this trial, please see the Supplemental Materials .
Outcomes
There were 2 primary outcomes. The first was knowledge that commercial laboratories may share prenatal genetic data for nonclinical research purposes. The second primary outcome was willingness for commercial laboratories to share data in 3 scenarios: sharing with academic researchers, sharing with a government-funded medical research database, and sharing with other companies that might profit from this information. The secondary outcomes included knowledge about existing genetic privacy laws, knowledge about the potential for reidentification of anonymized genetic data, and willingness to retain or share maternal or fetal genetic information in several scenarios. Outcomes data were collected through the questionnaire using a Likert scale.
Statistical analysis
Of note, 81 participants per group were required for 80% power to detect an increase in willingness to share prenatal genetic data for nonclinical (ie, research) purposes from 60% to 80% (with an alpha of 0.05) between the control and intervention groups. The estimated baseline willingness-to-share rate of 60% and anticipated postintervention rate were informed by published studies that assessed willingness to use and share genetic data for research in nonpregnant populations. , , Although knowledge about the data-sharing practices of commercial laboratories that perform cfDNA screening was also a primary outcome, the study was not powered to detect a specific change in knowledge because no literature or preliminary studies were identified to inform baseline knowledge estimates.
To assess demographic differences between the control and intervention groups, continuous variables were presented as means and standard deviations or medians with interquartile ranges. Means were compared using the Wilcoxon rank-sum test. Categorical variables are presented as frequencies, and proportions were compared using the Fisher exact test. All tests were 2-tailed, and a cutoff of P <.05 was used to define statistical significance. The primary outcomes, and most secondary outcomes, were categorical variables on a Likert scale and were reported as proportions. Furthermore, we performed a planned secondary analysis to examine whether attitudes about genetic privacy differed by demographic characteristics, including age (as a continuous variable), frequency of social media browsing and posting (defined as “≤1 time per month,” “≤1 time per week,” “≤1 time per day,” “2 to 5 times per day,” “>5 times per day”), and self-reported race (White or non-White). The Spearman rank correlation test was used for comparisons between continuous variables, and the Wilcoxon rank-sum test was used for comparisons between continuous and categorical variables. Data were analyzed with Stata/SE (version 15; Stata Corp, College Station, TX) using an intention-to-treat approach.
Results
Of 213 pregnant patients who were invited to participate in this study, 163 (76.5%) agreed to participate. Of note, 1 individual in the intervention group declined to answer key outcomes, and 1 individual from each group was excluded during the analysis phase after being found to not meet the inclusion criteria, for a total of 80 participants in each group ( Figure ). Demographic and medical characteristics were similar between both groups. Participants in the control and intervention groups were similar in age, gestational age, risk of fetal aneuploidy, education level, and insurance type. Moreover, although patient race and ethnicity were similar between groups, participants were racially and ethnically diverse: overall, 25% self-identified as non-White and 20% identified as Hispanic ( Table 1 ).
| N=160 | Control group (n=80) | Intervention group (n=80) | P value |
|---|---|---|---|
| Age (y) | .38 a | ||
| Mean (SD) | 34.3 (5.1) | 33.5 (5.8) | |
| Median (IQR) | 35 (20–46) | 35 (19–45) | |
| IQR (Q1–Q3) | (32–37) | (29–37) | |
| Gestational age (wk) | .38 a | ||
| Mean (SD) | 19.6 (1.1) | 19.4 (1.5) | |
| Median (IQR) | 19.2 (17.6–23.7) | 19.1 (10.3–22.9) | |
| IQR (Q1–Q3) | (18.7–20.4) | (18.6–20.4) | |
| Race (self-reported) | .21 b | ||
| White | 65 (81.3) | 55 (68.8) | |
| Black | 5 (6.3) | 10 (12.5) | |
| All others | 10 (12.5) | 15 (18.8) | |
| Ethnicity (self-reported) | .55 b | ||
| Hispanic | 14 (17.5) | 18 (22.5) | |
| Non-Hispanic | 66 (82.5) | 62 (77.5) | |
| Education | (n=79) | .34 b | |
| College or beyond | 43 (53.8) | 49 (62.0) | |
| Less than college | 37 (46.3) | 30 (37.9) | |
| Insurance type | .86 b | ||
| Private or commercial | 58 (72.5) | 60 (75.0) | |
| Public or Medicaid | 22 (27.5) | 20 (25.0) | |
| Nulliparous | .41 b | ||
| Yes | 26 (32.5) | 32 (40.0) | |
| No | 54 (67.5) | 48 (60.0) | |
| Prenatal care provider | .62 b | ||
| General obstetrician and gynecologist | 64 (80.0) | 58 (72.5) | |
| MFM specialist | 3 (3.8) | 4 (5.0) | |
| All others | 13 (16.3) | 18 (22.5) | |
| Genetic counseling visit | 1.00 b | ||
| Yes | 27 (33.8) | 28 (35.0) | |
| No | 53 (66.3) | 52 (65.0) | |
| High risk of fetal aneuploidy c | .24 b | ||
| Yes | 58 (72.5) | 50 (62.5) | |
| No | 22 (27.5) | 30 (37.5) | |
| cfDNA company | .05 b | ||
| Integrated Genetics | 8 (10.0) | 18 (22.5) | |
| Natera | 42 (52.5) | 43 (53.8) | |
| Myriad | 29 (36.3) | 19 (23.8) | |
| Invitae | 1 (1.3) | 0 (0) |
a Wilcoxon rank-sum test was used
b The Fisher exact test was used
c Risk factors included advanced maternal age at time of delivery, ultrasound findings or serum screen with increased risk of aneuploidy, previous pregnancy affected by aneuploidy, family history of aneuploidy, and parental balanced Robertsonian translocation with increased risk of T13 or T21.
The participants in both groups expressed similar baseline knowledge of cfDNA screening and similar motivations for pursuing cfDNA screening ( Table 2 ). For example, when asked why they chose to undergo cfDNA screening, at least 95% of participants in both groups ranked early detection of Down syndrome as “somewhat” or “very” important, and more than 50% of participants in both groups ranked early detection of fetal sex as “somewhat” or “very” important.
| N=160 | Control group (n=80) | Intervention group (n=80) | P value |
|---|---|---|---|
| Discussed with physician, CNM, or GC how prenatal genetic information can be used, stored, and shared | .08 a | ||
| Yes | 17 (21.3) | 8 (10.0) | |
| No | 63 (78.8) | 72 (90.0) | |
| Importance of knowing early on whether pregnancy affected by Down syndrome | .37 a | ||
| Not important | 2 (2.5) | 0 (0) | |
| Not really important | 1 (1.3) | 4 (5.0) | |
| Somewhat important | 22 (27.5) | 22 (27.5) | |
| Very important | 55 (68.8) | 54 (67.5) | |
| Importance of prenatal care provider’s recommendation | (n=79) | (n=78) | .93 a |
| Not important | 0 (0) | 0 (0) | |
| Not really important | 5 (6.3) | 5 (6.4) | |
| Somewhat important | 27 (34.2) | 29 (37.2) | |
| Very important | 47 (59.5) | 44 (56.4) | |
| Importance of early fetal sex detection | .29 a | ||
| Not important | 14 (17.5) | 12 (15.0) | |
| Not really important | 9 (11.3) | 17 (21.3) | |
| Somewhat important | 32 (40.0) | 24 (30.0) | |
| Very important | 25 (31.3) | 27 (33.8) | |
| Previous blood draw, patient aware that multiple companies offer cfDNA testing | .74 a | ||
| Yes | 27 (33.8) | 24 (30.0) | |
| No | 53 (66.3) | 56 (70.0) | |
| Previous blood draw, patient researched cfDNA companies | (n=27) | (n=24) | 1.00 a |
| Yes | 4 (14.8) | 3 (12.5) | |
| No | 23 (85.2) | 21 (87.5) | |
| Factors that influenced selection of cfDNA screening company b | |||
| Physician, GC, or CNM recommendation | 73 (91.3) | 73 (91.3) | 1.00 a |
| Covered by insurance | 14 (17.5) | 16 (20.0) | .84 a |
| Test performance | 3 (3.8) | 4 (5.0) | 1.00 a |
| Genetic privacy concerns | 1 (1.3) | 0 (0) | 1.00 a |
| Other | 2 (2.5) | 3 (3.8) | 1.00 a |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
