Non-invasive prenatal testing (NIPT), also referred to as non-invasive prenatal screening (NIPS), refers to the screening of free placenta-derived DNA in maternal blood serum and is a non-invasive method for detecting fetal aneuploidy (1, 2). Unlike invasive prenatal diagnosis, NIPT minimized the risk such as miscarriage or infection. Since its introduction in Hong Kong in 2011, NIPT has been adopted in over 60 countries due to its high sensitivity (3, 4) and specificity in identifying fetal chromosomal abnormalities, particularly trisomies 21, 18, and 13 (5). The American College of Medical Genetics and Genomics (ACMG) advocates for NIPT as the primary method for detecting fetal aneuploidy (6). In contrast, many other countries, including China (7) and the United Kingdom (8), consider serological screening to be the primary approach, using NIPT as a secondary screening method for high-risk pregnancies (1, 4, 5). NIPT is not utilized as the initial screening method due to its ability to detect more chromosomal abnormalities, which would result in increased expenses. Cost-effectiveness analyses indicate that utilizing NIPT as a secondary screening method following traditional prenatal scanning methods is more economically viable (5).

In 2016, the China National Health and Family Planning Commission promulgated “the technical specifications of Prenatal Screening and Diagnosis of Fetal Free DNA in Peripheral Blood of Pregnant Women,” which delineated criteria for the optimal timing, eligible and ineligible candidates for NIPT (9). The guidelines stipulated that serological prenatal screening is the primary method for detecting fetal aneuploidy, whereas NIPT is a secondary screening modality (9). Simultaneously, Chinese technical experts have achieved a consensus regarding the laboratory process of prenatal screening utilizing maternal peripheral blood fetal free DNA (10) and experts’ quality evaluation indicators for prenatal screening (11).

The Chinese government and experts attribute substantial importance to NIPT (12), manifesting in the publication of its Technical Specifications (7) and consensus on quality assessment indices (11). However, it is critical that pregnant women, being the subjects of NIPT application, comprehend the screening plan meticulously, as it forms the underpinning of its effective implementation. Documentary research revealed that scholars from multiple nations, including the United States (13), Italian (14), Croatian (15), Canada (16), Australia (17), and Hong Kong, China (18), have conducted studies on the knowledge and willingness of pregnant women regarding NIPT for fetal aneuploidy. However, heretofore, investigations regarding the awareness and inclination of pregnant women in Mainland China have not been reported. Therefore, in light of this, the present study delves into pregnant women’s cognition and standpoints pertaining to NIPT in Mainland China, thereby providing a solid foundation for facilitating its prudent utilization.

Multiple screening methods are available for screening T21, T18, and T13, such as maternal serum screening (MSS), ultrasound, and NIPT (24). However, MSS and ultrasound screening are known to have lower accuracy and higher false-positive rates (25, 26). Hence, the current common strategy in most countries involves combining these three screening methods. A meta-analysis indicated that the detection rate for T21 was 96%, 87% for T18, and 77% for T13 in the general population (27). The high accuracy of NIPT holds significant value in reducing invasive prenatal testing (28, 29). Nonetheless, despite its accuracy, NIPT has inherent constraints. Comprehension regarding the false positive rate of NIPT need to be improved. Two comprehensive reviews outlined the false positive rate for T21 via NIPT to be around 0.1% (30, 31), which was subsequently updated to 0.04% by Gil et al. (32). We believe that the study’s outcome is significantly influenced by whether the participating expectant women had previously undergone conventional MSS. Furthermore, only 33% of false-positive results for autosomal trisomy can be attributed to biological or technical factors, necessitating further research into the reasons for false positives in NIPT (33). NIPT can detect approximately 85% of fetal chromosomal abnormalities in women identified as high risk during early pregnancy screening (34). However, NIPT misses approximately 30.0% of chromosomal abnormalities that are detectable by invasive prenatal diagnostic methods (35). Despite its high accuracy, it is vital to acknowledge that NIPT is not a flawless technology. Inherent limitations and challenges persist, necessitating concomitant usage with other testing methodologies and clinical assessments for a holistic determination of fetal health (2, 36–38). Notably, NIPT hinges on free placental DNA and not – as certain literature posits – on “cell-free fetal DNA (cffDNA)” (2). The nuances of NIPT results are not thoroughly comprehended; uncertain variations may be enclosed within NIPT findings, demanding physicians proficiently relay this to expectant mothers undergoing the test (37, 39). The genesis of this research was to understand expectant women’s knowledge about NIPT, thus informing further propagation of knowledge on NIPT.

The ten knowledge questions in this study were designed based on the International Society for Prenatal Diagnosis (ISPD) Rapid Response Statement and previous related surveys (18, 40). Knowledge questions 1–5 were basic knowledge questions about NIPT, while questions 6–10 were too complex or challenging for most women to answer regarding the applicability of NIPT to special risk groups. In this study, only 60.6% of women knew that NIPT only screens for chromosomal abnormalities and that diagnostic testing requires invasive procedures. Additionally, only 76.5% of women were cognizant of the possibility of receiving an uninformative NIPT test result. In contrast, Kou et al.’s survey reported that more than 90% of pregnant women were aware of the limitations mentioned above of NIPT (18). The apparent disparity in cognizance could potentially be attributed to the varied demographics of the expectant pregnant women incorporated within our survey. Our study incorporates a significant 27.4% of pregnant women from the rural demographic; contrarily, the preponderance of contributors in Kou et al.’s investigation are derived from an urban milieu. Simultaneously, while women engaged in Kou et al.’s study—those with positive screenings who consequently proceeded with NIPT—were availed counseling and a mid-trimester abnormality scan during the questionnaire’s completion phase, we targeted expectant pregnant women demonstrating a critical risk of prevalent fetal chromosomal aneuploidy predicated upon MSS outcomes prior to initiating NIPT.

The present investigation revealed a lower rate of accurate responses to knowledge queries concerning the suitability of NIPT for special risk groups, except for the item that NIPT is only suitable for detecting single-fetal pregnancies, which was correctly answered by 54.4% of the participants. This outcome may be attributed to the technical specifications released by the China National Health and Family Planning Commission in 2016, which underscored the applicability of NIPT solely for detecting single-fetal pregnancies (9). This is consistent with the literature, which suggests that pregnant women usually have more knowledge about the practical aspects of chromosomal abnormality than the limitations and accuracy of screening (41, 42).

The study findings reveal that urban pregnant women exhibited a significantly higher rate of correct answers to two NIPT knowledge questions (K2 and K6) than their rural counterparts. Similarly, pregnant women with higher levels of education demonstrated a significantly higher rate of correct answers to three knowledge questions related to NIPT compared to those who were uneducated. Furthermore, pregnant women from higher-income households exhibited a significantly higher rate of correct answers to two NIPT knowledge questions than those from lower-income households. These results suggest that pregnant women in urban areas with higher income and higher education possess a greater understanding of NIPT, consistent with previous research (43, 44). Similar results were obtained in Women’s Perception of NIPT, where urban, high-income, and highly educated pregnant women had a significantly higher proportion in considering prenatal screening and diagnosis as the primary measure to reduce the incidence of birth defects, as compared to rural, low-income, and uneducated pregnant women.

If serum screening results suggest a high risk of chromosomal abnormalities in the subsequent pregnancy, a significant proportion of pregnant women (83.2%) would opt for NIPT to detect fetal aneuploidy. Furthermore, a considerable percentage of pregnant women (66.4%) would select NIPT as the primary method for fetal aneuploidy screening in the subsequent pregnancy. Conversely, alternative studies have reported that only approximately 30.4% of pregnant women would directly choose NIPT for fetal aneuploidy detection (18, 45). This discrepancy may be attributed to the higher income level of the surveyed households, with 60.2% of families earning a monthly income of ≥10,000 RMB. Additionally, the cost of NIPT has decreased to 1,100 RMB per test due to its increased utilization in China. In light of the potential hazards of miscarriage, a considerable majority (66.4%) of expectant mothers would opt for NIPT as their primary choice for prenatal screening in subsequent pregnancies.

The ACMG and the National Society of Genetic Counselors (NSGC) recommend that NIPT counseling should be provided by a qualified prenatal care provider, a trained designee, or a genetic counselor (46, 47). The present investigation revealed that 95.5% of pregnant women believed that medical practitioners’ recommendations are essential in selecting screening methods. A comparable inquiry discovered that women exhibited women preferred pre- and post-NIPT counseling by a midwife (48). As online information can have varying degrees of accuracy, it is vital to establish an effective prenatal screening counseling platform that provides professional and efficient counseling services to pregnant women, enabling them to make the best choice. Additionally, reducing the anxiety caused by positive results and placing the patient at the center of decision-making are crucial factors in determining the uptake of diagnostic testing (49).

NIPS is classified as a screening test rather than a diagnostic test. To ensure consistency in testing methods and procedures, prominent governing and professional organizations, including the American College of Obstetricians and Gynecologists, ACMG, NSGC, and ISPD, recommend standardization of NIPT. These organizations also advise that informed decision-making, education, and counseling should be provided before and after testing (45–47, 50). At the national level of healthcare, the government must prioritize the reduction of superfluous invasive testing and miscarriage-related outcomes, as well as the formulation of more efficacious policies for prenatal care to mitigate the prevalence of birth defects. The findings of this study indicate that, despite the strong preference of Chinese expectant mothers for NIPT, their knowledge and perception of this screening method for fetal aneuploidy is limited. Consequently, it is incumbent upon the government to implement effective measures to enhance public awareness of fetal aneuploidy screening and promote the judicious use of NIPT.

This study is subject to certain limitations. Firstly, Given that our study exclusively focused on pregnant women residing in Zhejiang Province, China, it is important to note that the generalizability of our findings is limited not only to other countries but also to the wider Chinese population. Secondly, the study was conducted in developed urban areas of China, and the sample size was relatively small, necessitating larger sample sizes and surveys across multiple cities. Finally, while the study’s questionnaire was informed by prior research, it lacked expert validation, evaluation of questionnaire applicability, and reliability. The questionnaire will be further improved in future research.

NIPS is a screening test that is distinct from a diagnostic test. Standardization of the testing methods and procedures utilized in NIPS is imperative. NIPT should be administered through informed decision-making, education, and counseling before and after testing. Chinese expectant mothers strongly prefer NIPT yet possess limited knowledge and comprehension of this screening method for fetal aneuploidy. Consequently, it is incumbent upon the government to implement effective measures to augment public awareness of fetal aneuploidy screening and promote appropriate utilization of NIPT.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by written informed consent was taken from all participants. The study was approved by the Women’s Hospital, School of Medicine, Zhejiang University Ethics Committee (approval number: IRB-20210185-R), and obtained informed consent from each participant following the Helsinki Declaration. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

YZ, ZX, YG, JZ, MH, and MJ made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas, and took part in drafting, revising or critically reviewing the article. All authors contributed to the article and approved the submitted version.