Background
Background of the study
Why this study should be made
Methods
Step 1: identifying the research question
Step 2: identifying relevant studies
Step 3: study selection
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Population: pregnant women, parents
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Intervention: NIPT, cell-free fetal DNA (cffDNA)
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Outcome: psychological and social outcomes after NIPT
Step 4: charting the data
Step 5: collating, summarizing and reporting the results
Study | Aim of study | Data collection | Participants | Outcome measures | Limitations of the study (excerpt), conflicts of interest (COI) |
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Farrell, et al., 2014, USA [19] | To determine how pregnant women conceptualize the utility of NIPT as compared to conventional screening and diagnostic tests. | Focus groups. | N = 53 women who received prenatal care at the study clinic; n = 10 women had NIPT. Mean age (range) = 31.7 ys (21–43) (n = 53); AMAa: n = 16. | Individual quotes. | Limited sample size, women from only one community. Authors declared to have no COI. |
Lewis, et al. 2016, UK [20] | To report on a number of psychosocial outcomes including decisional uncertainty, distress and anxiety, as well as motivations for undergoing or declining NIPT and clinical service preferences. | Questionnaires at blood draw (Q1) and/or 1 month following receipt of results (Q2). | N = 582 women with a Down syndrome screening (DSS) risk > 1:1000 accepted NIPT free of charge as part of an implementation study in the UK NHS. N = 263 responded to Q1 and Q2 and were included in the analysis. Mean age (range): 35 ys (19–49) (n = 582). DSSa risk distribution: > 1:1000/medium (n = 417); > 1:150/high (n = 165). NIPT results: Negative: n = 246; Positive: n = 10; Other: n = 7 (n = 4 test failed; n = 2 declined NIPT; n = 1 inconclusive results). | State-Trait Anxiety Inventory (STAI-6), short formb; Decisional Regret Scale (DRS)c. | Only a small number of women declined NIPT, no control group that has not been offered NIPT, low response rate to Q2, absence of baseline anxiety testing. Authors declared to have no COI. |
Lo, et al., 2019, Hong Kong [21] | To assess decision outcomes (decision conflict, decision regret and anxiety) of pregnant women who are offered NIPT for high-risk Down syndrome screening results. | “first questionnaire” (Q1) and 4 weeks after Q1/after receiving NIPT results (Q2). | N = 262 women with positive Down syndrome screening results whose informed decision making about NIPT had been analyzed in a previous cohort study. Age distribution: < 35 years (n = 89); ≥35 years (n = 173). DSSa risk distribution: 1:1–125 (n = 114); 1:126–250 (n = 91). | State-Trait Anxiety Inventory (STAI-6), short formb; Decisional Regret Scale (DRS)c. | No limitations discussed. Authors declared to have no COI. |
Richmond, et al., 2017, Australia [22] | To examine the psychological impact of NIPT in women with a high-risk and low-risk result on combined first trimester screening (cFTS) and to examine factors influencing anxiety and decision-making in both risk populations. | Questionnaires at NIPT consultation and blood draw (point A) and 1 week post NIPT result (point B), then online after point B (point C). | N = 115 women requesting NIPT after combined first trimester screening (cFTS) but prior to morphology ultrasound were recruited from a genetic counsellor-led clinic (n = 2 women excluded due to failed NIPT). All n = 113 women received a negative NIPT result. Mean age (SD; range) = 36.4 ys (4.24; 27–44) (n = 113). cFTS risk distribution: ≤1:301/low (n = 50); ≥1:300/ high (n = 63). Both high-risk and low-risk cFTS groups had similar intrinsic trait anxiety levels at point A. | State-Trait Anxiety Inventory (STAI)b. | Failure to record reasons for non-participation and declining follow-up; bias against those that experience pathological anxiety; artificially inflated anxiety scores (completing STAI in a clinic environment); no control group without NIPT; cohort may demonstrate ascertainment bias towards those who both knew about and could afford NIPT; small study population. Authors declared to have no COI. |
Takeda, et al., 2018, Japan [23] | To clarify the characteristics of psychological mental distress in postpartum women after non-invasive prenatal testing (NIPT) in Japan. | Questionnaires pre-NIPT and approx. 1 month post-partum. | N = 697 women that underwent NIPT at study hospital and had negative NIPT-results and low pre-NIPT psychological mental distress (K6) were included. Cases had high post-partum mental distress, controls had low post-partum mental distress (K6). Mean age (SD; range): ‘case’ group (n = 29): 37.9 ys (±2.4; 34–43); ‘control’ group (n = 668): 37.0 ys (±2.3; 30–41). | Kessler Psychological Distress Scale (K6), Japanese versiond. | No control group with women who did not undergo NIPT, inability to adjust for the variable of neonatal abnormality. Authors declared to have no COI. |
van Schendel, et al., 2017, Netherlands [24] | To address the questions whether women feel reassured and less anxious after receiving a favorable NIPT result and whether women feel satisfied with their choice for NIPT. | Questionnaires after NIPT counseling (Q1) and/or after NIPT or invasive test results were received (Q2). | N = 682 women participating in a study on evaluation of NIPT with an elevated first-trimester combined test (FCT) risk for aneuploidy (≥1:200) or based on medical history. Mean age (range): 35.8 years (22–45) (n = 682). Negative NIPT result: n = 656; positive NIPT result: n = 26. FCTa risk distribution: ≥1:10 (n = 30); 1:11–1:100 (n = 267); 1:101–1:200 (n = 267); missing (n = 24); NA (n = 92). | Spielberger State-Trait Anxiety Inventory (STAI-6), short form; Dutch versionb; Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R scale)e; Survey on Reassurance/ Satisfaction/ Experience with NIPT. | Low response rate to post-test questionnaire, inability to perform subgroup analyses for positive NIPT results group, possible selection bias due to several reasons. COI: One middle author had been employed and one middle author had participated in clinical research sponsored by companies that offer NIPT |
Vanstone, et al., 2015, Candada [25] | To examine how Ontario women have experienced the process of publicly funded NIPT in 2014, with the aim of identifying women’s values about this process to inform future formal policy making about this new health technology. | Interviews and constructivist grounded theory. | N = 38 women at ‘high risk’ of fetal aneuploidy, identified at prenatal diagnostics unit, via advertisements, snowball sampling and personal networks until theoretical saturation was reached. Mean age at delivery = 35.4 ys (n = 38). Age classes: 25–29 ys (n = 2); 30–34 ys (n = 14); 34–39 ys (n = 16); ≥40 ys (n = 6). | Grounded theory and individual quotes. | Particular group of women, older and more educated than the average, with potentially more thorough understanding of NIPT and the available testing options. Authors declared to have no COI. |
Study | Test | Data source | Baseline (at NIPT blood draw or counselling) | After receiving tests results | Results |
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Lewis, et al. 2016, UK [20] | State anxiety (STAI-6, short form, range 20–80) | N = 263 women with either negative or positive NIPT results; questionnaires at baseline (Q1), and 1 month following receipt of results (Q2). | STAI-6 mean score (SD) = 40.1 (±15.5). | STAI-6 mean score (SD) = 34.3 (±12.6). | Decrease of anxiety. |
Richmond, et al., 2017, Australia [22] | State anxiety (STAI, range 20–90) | N = 113 women at baseline (point A); n = 83 women at least 1 week after receipt of results (point C, online); all with negative NIPT result. | STAI mean score (SD) in high-risk cFTS vs. low-risk cFTS = 42 (±11) vs. 36 (±11); p < 0.01. | STAI mean score (SD) in high-risk cFTS vs low-risk cFTS = 30 (±11) vs. 29 (±8); p = 0.61. | Whilst the high-risk cFTS population had significantly higher levels of state anxiety when they elected NIPT, both groups experienced a statistically significant reduction in state anxiety to similar final levels after they received a negative NIPT result (p < 0.01). |
van Schendel, et al., 2017, Netherlands [24] | State anxiety (STAI-6, range 20–80) | N = 656 women with negative NIPT result. | STAI-6 mean score = 44.3. | STAI-6 mean score = 28.8. | Significant reduction in state anxiety in women with negative NIPT result (p < 0.001). |
Lewis, et al. 2016, UK [20] | Elevated anxiety (STAI-6, short form, scores ≥50) | N = 263 women with either negative or positive NIPT results; questionnaires at baseline (Q1), and 1 month following receipt of results (Q2). | Rate of women: 29.9% (n = 174). | Rate of women: 13.7% (n = 36). | Significant decrease in [elevated] anxiety at time of Q2. Of the 36 women whose scores indicated elevated anxiety, 30 had a negative NIPT result, 5 had a positive NIPT result (confirmed through invasive testing) and 1 had an inconclusive result (the fetus was found to be unaffected following invasive testing). |
Lo, et al., 2019, Hong Kong [21] | Elevated anxiety (STAI-6, scores ≥50) | N = 254 women at baseline (Q1); n = 229 women 4 weeks later and after receiving results (Q2). | STAI-6 score ≥ 50: n = 142/254 women (55.9%). | STAI-6 score ≥ 50: n = 59/229 women (25.8%). | Elevated anxiety was less common after the results had been announced (p < 0.001). Elevated anxiety was not more common among NIPT decliners than acceptors (p = 0.679). |
van Schendel, et al., 2017, Netherlands [24] | Elevated anxiety (STAI-6, score ≥ 50) | N = 26 women with positive NIPT results. | (−-) | STAI-6 mean score = 54.0. | Overall, the 26 women who had received a positive NIPT result for trisomies 21, 18 or 13, or for other trisomies showed high anxiety scores after receiving test-results (M = 54.0). For 11 of 14 women who had had confirmatory invasive testing anxiety levels remained high (M ≥ 50.0) (diagnostic testing confirmed that the fetus had a trisomy in 10/11 women). |
van Schendel, et al., 2017, Netherlands [24] | Child-related anxiety (subscale of PRAQ-R3, range 4–20) | N = 656 women with negative NIPT results | PRAQ-R3 mean score = 10.8. | PRAQ-R3 mean score = 7.8. | Women with negative NIPT result showed a significant decrease in level of child-related anxiety after receiving test results (p < 0.001). |
Takeda, et al., 2018, Japan [23] | Psychological distress (K6, range 0–24, Japanese version) | N = 697 women with negative NIPT-results and low pre-NIPT psychological mental distress (K6). | Pre-NIPT K6 scores: cases (n = 29, post-partum K6 high): mean K6 score (SD, range) = 5.0 (±2.4, 0–9); controls (n = 668, post-partum K6 low: mean K6 score (SD, range) = 2.5 (±2.4, 0–9); there was no significant difference between groups. | Post-partum K6 scores: cases (n = 29, post-partum K6 high): mean K6 score (SD, range) = 12.8 (±3.6, 10–24); controls (n = 668, post-partum K6 low: mean K6 score (SD, range) = 2.0 (±2.5, 0–9); there was no significant difference between groups. | Although women may not feel mental stress before undergoing NIPT, they may develop mental distress post-partum. |
Lewis, et al. 2016, UK [20] | Decisional regret (DRS, range 0–100, no formal cut-off) | N = 263 women with either negative or positive NIPT results; 1 month following receipt of results (Q2). | (−-) | DRS mean score (SD) = 3.17 (±7.27). | Very low level of decisional regret after NIPT with none of the women scoring above the midway point (0% ≥50/100). |
Lo, et al., 2019, Hong Kong [21] | Decisional regret (DRS, score ≥ 50) | N = 223 women 4 weeks after baseline and after receiving results (Q2). | (−-) | DRS mean score [95% CI]: 15.7 [13.2–18.3]; DRS score ≥ 50: N = 13 womena. | Decisional regret (DRS score ≥ 50) was reported by n = 13 of 223 women. Among them were n = 200 NIPT acceptors and n = 23 NIPT decliners. All n = 13 women who reported decisional regret were NIPT acceptors (n = 12 had negative NIPT results, and n = 1 required invasive prenatal testing for either inconclusive or positive NIPT results). Decisional regret was more common in women with insufficient (n = 29) vs. sufficient (n = 194) knowledge about NIPT: 5/29 vs. 8/194 (p = 0.016). |
Question | Data source | Responses and/or results |
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Reassurance: ‘I felt reassured by the test-result’ (Scale: not at all applicable (1) – very much applicable (5)) | N = 656 women with negative NIPT results. | - 2.4% not at all applicable - 0.9% hardly applicable - 15.7.% somewhat applicable - 80.9% very much applicable |
Confidence: ‘I am confident that the test-result is correct’ (Scale: not at all applicable (1) – very much applicable (5)) | N = 656 women with negative NIPT results. | - 0.2% not at all applicable - 0.6% hardly applicable - 18.3% somewhat applicable - 80.9% very much applicable |
Certainty: ‘The test result offers me sufficient certainty whether my child has a disorder’ (Scale: not at all applicable (1) – very much applicable (5)) | N = 656 women with negative NIPT results. | - 0.3% not at all applicable - 1.4% hardly applicable - 34.0% somewhat applicable - 64.3% very much applicable |
Satisfaction with NIPT: (Scale: not at all applicable (1) – very much applicable (4) | N = 656 women with negative NIPT results. | 2.4% (n = 16) women would rather have had invasive testing than NIPT (shorter waiting time, more accurate results) |
Satisfaction with NIPT: (Scale: not at all applicable (1) – very much applicable (4) | N = 682 women with negative or positive NIPT results. | 97.5% had no regret on NIPT; 28.6% would have preferred to receive results earlier. |
Experience with test offer and procedure. (Scale: completely disagree (1) – completely agree (5), compressed to 3-point scale) | N = 682 women with negative or positive NIPT results. | 96.1% of participating women have been glad to have been offered NIPT, 85.9% had had sufficient time to reflect on their choice. |
Waiting time for test results. (Scale: way too long (1) – way too short (5)) | N = 682 women with negative or positive NIPT results. | Reported waiting time until NIPT result: mean = 15 days (range 5–32 days). Waiting time was considered (much) too long by 68.5% of women, for 31.5% it was neither too long nor too short. A waiting time of ≤10 days was acceptable for most women, longer was considered too long by the majority of women. |
Study | Number of participating women | Quotes of participating women | Results |
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Vanstone, et al., 2015, Candada [25] | N = 38 women at high risk for fetal aneuploidy; here, only quotes of women who clearly were interviewed after NIPT are considered. | Timing: “It took almost three weeks.. .. I was concerned because I knew the amnio had to happen at a certain time and that if we had to make any decisions regarding the pregnancy that had to happen at a certain time.” “I was already at 19 weeks, so I wanted to do it all fast, because if you did want to abort or anything, god forbid, they say you should do it before 22 weeks, so it was kind of like I had maybe a week or two, not even.” “You feel like it is ticking. It’s like, everything is just building your anxiety.” “I found out early enough that I’m able to have the two week wait [for NIPT results]. I’m still able to possibly have an amnio if I need it.” Accuracy: “Chance of not getting a result from the NIPT. .. to go through the test and to not actually have anything, you know time is ticking, so just making sure that we are going to get a reasonably good answer in a good amount of time was important.” “If it comes back negative, you’re pretty much fine not to worry about it because they are very accurate tests.” | Timing: The wait for results was typically described as very stressful, as the “deadline” for confirmatory testing and termination loomed. The idea of a deadline refers to the gestational age after which confirmatory invasive testing and pregnancy termination are no longer available. Women considering termination discussed perceptions of deadlines to make decisions about further testing or termination, describing the process of prenatal testing as a race against the clock. Women made frequent references to time pressures. Accuracy: The possibility of an inconclusive result was stressful for some women. Whereas women described a high confidence in negative NIPT results. |
Farrell, et al., 2014, USA [19] | N = 58 women in 6 focus groups, among them n = 10 had NIPT; only statements of women who clearly were recorded after NIPT are considered. | Improved accuracy without risk: One woman who had NIPT commented on how she perceived the value of NIPT in her prenatal care: “In my mind, it was just as well as diagnostic. I know it’s not. I know there is still a risk but in my mind, it made me feel better that 99% is good enough for me. If there is a 1% chance of something happening, then it’s meant to happen but 99%, I could at least breathe a little easier” Identification of Fetal sex: “That is another reason why we chose to do it because we wanted to know the sex of the baby. So I knew 5 weeks before I would have known from the ultrasound and some people (asked), ‘How do you know already?’” | The values and opinions expressed about NIPT by women who have personal experience with this technology are inconsistent with the way it is has typically been implemented in Ontario so far. A revision of the current policy should consider this evidence that women value early access to accurate tests without associated risks of miscarriage when considering how and when NIPT should be implemented into the prenatal testing care pathway. |