We identified a total of 2488 records. After removal of duplicates, 2007 titles and abstracts were screened; subsequently, the full-texts of 99 articles were assessed. 7 studies have been included (see PRISMA flow chart in Fig. 1).
Characteristics of the included studies and women therein
Five studies assessed anxiety, psychological distress and/or decisional regret with validated psychological tests like the Spielberger State-Trait Anxiety Inventory (STAI or short form STAI-6), the Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R), the Kessler Psychological Distress Scale (K6) or the Decisional Regret Scale (DRS) [20,21,22,23,24]. Questionnaires usually were administered at baseline (i.e. at NIPT blood draw or counseling) and after receiving NIPT results. One study conducted a survey on satisfaction and experience with NIPT . Two studies assessed women’s experiences with and feelings after NIPT in interviews or focus groups [19, 25]. For more details, see Table 1.
The studies were published between 2014 and 2018 with data being assessed from 2013 until 2016 on. Two studies each were conducted in Europe [20, 24], Asia [21, 23] or North America [19, 25], one study was from Australia . Four studies were single center studies [19, 22, 23, 25], three studies were multi-centric [20, 21, 24]. Five studies assessed outcomes with self-administered questionnaires [20,21,22,23,24], one study conducted interviews , and one study worked with focus groups .
The number of participating women in the studies assessing outcomes with questionnaires ranged from 115 to 697; in the two studies that conducted interviews or focus groups, 38 and 53 women participated [19, 25].
Five studies reported a mean age of participating women [19, 20, 22, 23]: The mean age of all included women over those five studies was 35.9 years, with the youngest and oldest age of 19 and 49 (extremities of range reported; standard deviation not reported in all studies). One study only reported the mean age of women when giving birth of 35.4 years and age classes in steps of 5 years (25–29; 30–34; 34–39; ≥40) , the other study reported women’s age in two groups (< 35; ≥35) , with the majority of women in those two studies being 35 years or older.
Most studies recruited women with an elevated Down syndrome screening (DSS) risk (medium and/or high risk, cut-offs vary, range from > 1:1000 to 1:1–125) [20,21,22, 24, 25], two studies recruited from an unselected population regarding DSS [19, 23].
In all studies, psychological or social consequences of women who had NIPT were assessed (e.g. anxiety, distress after NIPT or experiences with NIPT); two studies also comprised women who had not undergone NIPT [19, 21]. See below for a detailed description of the outcomes.
Takeda et al. only included women with negative NIPT results , in the study of Richmond et al. all women received negative NIPT results (n = 113 (of 115) women received a negative result, n = 2 women were excluded due to failed NIPT) . Lewis et al., Lo et al., and van Schendel et al. included women with either negative or positive NIPT results [20, 21, 24]. Farrell et al. and Vanstone et al. did not report on NIPT results [19, 25].
All studies except one  reported limitations, for example, lack of control group (i.e. without NIPT), low response rates (i.e. to initial recruiting or second questionnaires), or origin of participating women from a selected community (i.e. older and highly educated).
Description of the assessed outcomes
Four studies assessed anxiety with the Spielberger State-Trait Anxiety Inventory (STAI or short form STAI-6) [20,21,22, 24].
In the studies of Lewis et al., Richmond et al., and van Schendel et al. women experienced a decrease in state anxiety from baseline to the time point after receiving NIPT results (reported by a decrease in STAI mean scores). Richmond et al. (n = 113) and van Schendel et al. (n = 656) report the decrease in state anxiety for women with negative NIPT results, the women in Lewis et al.’s study (n = 263) received either negative or positive NIPT results.
Richmond et al. compared state anxiety in two subgroups of women: women with a high-risk combined first trimester screening (cFTS) result were significantly more anxious at baseline compared to women with a low-risk cFTS result; nevertheless, both groups experienced similar levels of state anxiety 1 week after receiving NIPT results.
The rate of women experiencing elevated anxiety (i.e. a STAI-6 score ≥ 50/80) significantly decreased from baseline to the time point after receiving NIPT results in the studies of Lewis et al. (n = 263) and Lo et al. (n = 254). Van Schendel et al. reported that the subgroup of women receiving positive NIPT results (n = 26) experienced high levels of anxiety after receiving those.
Van Schendel et al. (n = 656) assessed child-related anxiety with a subscale of the Pregnancy-Related Anxiety Questionnaire-Revised (PRAQ-R). Women who received negative test results experienced significantly lower levels of child-related anxiety after receiving negative test results compared to baseline. For more details, see Table 2.
One study assessed psychological distress with the Kessler Psychological Distress Scale (K6) after NIPT in a case-control setting . All women in Takeda et al.’s study (n = 697) had received negative NIPT-results and experienced low psychological distress (i.e. low K6 scores) at baseline. The women who were assigned to the case group (n = 29) experienced psychological distress after giving birth (i.e. high post-partum K6 scores), the women in the control group (n = 668) did not experience psychological distress after giving birth (i.e. low post-partum K6 scores). Factors that contributed to psychological distress in women post-partum were for example low birth weight or primiparity. For more details, see Table 2.
Two studies assessed decisional regret (i.e. distress or remorse) after women’s decision for NIPT with the Decisional Regret Scale (DRS) [20, 21]. In the study of Lewis et al. (n = 263) decisional regret was very low among women after receiving (positive or negative) NIPT test results. In the study of Lo et al. (n = 223) decisional regret was low: among the n = 13 women experiencing decisional regret, n = 12 had received negative NIPT results. Women with insufficient knowledge about NIPT experienced decisional regret more commonly. For more details see Table 2.
Experiences with NIPT
Van Schendel et al. assessed experiences with NIPT in questionnaires . Either a group of women with only negative NIPT results or a group of women with negative or positive results were queried. Women with negative NIPT results (n = 656) mostly felt sufficiently reassured by the test result and were confident that the result was correct and that their child was not affected by a disorder. Some of the women with negative NIPT results (n = 16) would have preferred invasive testing over NIPT because of a shorter waiting time and more accurate results.
Of the women with either negative or positive NIPT results (n = 682), the majority had no regret about NIPT. About a third of those women would have preferred to receive results earlier; the reported mean waiting time of 15 days (range 5–32 days) was considered too long by about two thirds of women. A waiting time of ≤10 days would have been acceptable for most women. For more details, see Table 3.
Vanstone et al. interviewed n = 38 women with the aim of identifying their values about publicly funded NIPT to inform future formal policy making . Here, we only considered statements that had clearly been made after NIPT. Due to anonymization, we cannot tell from how many different women the quotes originate. Waiting time for results was an aspect that was described as very stressful, especially for women who considered either confirmatory invasive testing or pregnancy termination, both of which are only available at a certain gestational age. The possibility of an inconclusive result was also stressful for some women, whereas they described a high confidence in negative NIPT results. For more details, see Table 4.
Among the n = 58 women who participated in the focus groups of Farrell et al., only n = 10 had NIPT. Here again, we only considered statements that were clearly made after NIPT. One woman stated that the diagnostic accuracy of NIPT was sufficiently reassuring for her and that she almost considered it as confirmative. One woman reported that she had known the fetal sex of her unborn child 5 weeks earlier than would have been possible with ultrasound. This latter aspect was the only one we could find on social aspects among all the included studies. For more details, see Table 4.