Overview and recent developments in cell-based noninvasive prenatal testing

Investigators have long been interested in the natural phenomenon of fetal and placental cell trafficking into the maternal circulation. The scarcity of these circulating cells makes their detection and isolation technically challenging. However, as a DNA source of fetal origin not mixed with maternal DNA, they have the potential of considerable benefit over circulating cell-free DNA-based noninvasive prenatal genetic testing (NIPT). Endocervical trophoblasts, which are less rare but more challenging to recover are also being investigated as an approach for cell-based NIPT. We review published studies from around the world describing both forms of cell-based NIPT and highlight the different approaches’ advantages and drawbacks. We also offer guidance for developing a sound cell-based NIPT protocol.     

Factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT)

Objective

To investigate factors involved in the decision to decline prenatal screening with noninvasive prenatal testing (NIPT).

Method

A questionnaire study was conducted among 219 pregnant women in the Netherlands who had declined prenatal screening with NIPT (TRIDENT-2 study). Respondents were selectively recruited from three hospitals and 19 midwifery practices, primarily located in or near socioeconomically disadvantaged neighborhoods. 44.3% of the respondents were of non-Western ethnic origin and 64.4% were religious.

Results

Most respondents (77.2%) found the decision to decline NIPT easy to make, and 59.8% had already made the decision before information about NIPT was offered. These respondents were more often religious, multigravida, and had adequate health literacy. The main reasons to decline NIPT were “I would never terminate my pregnancy” (57.1%) and “every child is welcome” (56.2%). For 16.9% of respondents, the out-of-pocket costs (175 euros) played a role in the decision, and the women in this group were more often nonreligious, primigravida, and had inadequate health literacy.

Conclusion

The primary factors involved in the decision to decline NIPT were related to personal values and beliefs, consistent with autonomous choice. Out-of-pocket costs of NIPT hinder equal access for some pregnant women.     

Commercial landscape of noninvasive prenatal testing in the United States

Cell-free fetal DNA-based noninvasive prenatal testing (NIPT) could significantly change the paradigm of prenatal testing and screening. Intellectual property (IP) and commercialization promise to be important components of the emerging debate about clinical implementation of these technologies. We have assembled information about types of testing, prices, turnaround times, and reimbursement of recently launched commercial tests in the United States from the trade press, news articles, and scientific, legal, and business publications. We also describe the patenting and licensing landscape of technologies underlying these tests and ongoing patent litigation in the United States. Finally, we discuss how IP issues may affect clinical translation of NIPT and their potential implications for stakeholders. Fetal medicine professionals (clinicians and researchers), genetic counselors, insurers, regulators, test developers, and patients may be able to use this information to make informed decisions about clinical implementation of current and emerging noninvasive prenatal tests. © 2013 John Wiley & Sons, Ltd.     

Conflict of interest related to clinical practice is underreported: The case of noninvasive prenatal testing

Authors of policy statements from the American College of Obstetricians and Gynecologists and from the Society for Maternal-Fetal Medicine do not acknowledge the potential for their clinical income to influence their opinions, or the positions of the societies they represent. These policy statements were published in Obstetrics and Gynecology and the American Journal of Obstetrics and Gynecology, again, without acknowledgment of the potential for conflict of interest. The case of noninvasive prenatal testing, which has threatened the role of maternal-fetal medicine in the practice of prenatal screening and diagnosis, and has significantly reduced the demand for invasive prenatal diagnosis, illustrates the importance of identifying this potential conflict.     

Overview of the impact of noninvasive prenatal testing on diagnostic procedures

Noninvasive prenatal testing (NIPT) has had a profound influence in the field of prenatal diagnosis since the 1997 discovery of cell-free fetal DNA in maternal blood. Research has progressed rapidly, with clinical data supporting laboratory studies showing that NIPT is highly sensitive and specific for fetal aneuploidy, resulting in marked uptake in the high-risk patient population. The superior accuracy of NIPT compared with conventional screening methods has led to significant decreases in the number of invasive diagnostic procedures, in addition to a concomitant decrease in the number of procedure-related fetal losses. Yet, NIPT has been described as a ‘disruptive innovation’ due to the considerable changes the technology has commanded on current prenatal screening and diagnostic practices. This review summarizes both institutional and global experience with NIPT uptake, its effect on reducing diagnostic invasive procedures, and the unique challenges that reduced procedural volume may have on physician and trainee proficiency, cytogenetic laboratories, and neonatal outcome. © 2015 John Wiley & Sons, Ltd.     

Cell-free DNA fetal fraction in twin gestations in single-nucleotide polymorphism-based noninvasive prenatal screening

Objectives

The performance of noninvasive prenatal screening (NIPS) for fetal aneuploidy in twin pregnancies is dependent on the amount of placentally derived cell-free DNA, the “fetal fraction (FF),” present in maternal plasma. We report FF values in monozygotic (MZ) and dizygotic (DZ) pregnancies.

Methods

We reviewed FF in pregnancies at 10 to 20 completed weeks gestational age based on single-nucleotide polymorphism (SNP)-based NIPS where zygosity was routinely established in twin pregnancies. The cohort included 121 446 (96.3%) singleton, 1454 (1.2%) MZ, and 3161 (2.5%) DZ pregnancies. For DZ twins, individual FFs were measured.

Results

Combined FF for DZ and MZ fetuses were 35% and 26% greater than singletons, respectively. The individual FF contributions from each fetus in DZ twins were, on average, 32% less than singletons. FF in DZ twin pairs were moderately correlated (Pearson correlation coefficient.66). When a threshold of 2.8% FF was applied to define uninterpretable results, 1.7% (2102/121 446) of singletons, 0.8% (11/1454) of MZ pairs, and 5.6% (178/3161) of DZ pairs were uninterpretable.

Conclusion

For optimal aneuploidy NIPS in twin pregnancies, zygosity should be established and in DZ twins FF for both fetuses should be determined to identify those cases where results can be reliably interpreted.     

Recommended pre-test counseling points for noninvasive prenatal testing using cell-free DNA: a 2015 perspective

Noninvasive prenatal testing (NIPT) using cell-free DNA is being offered to an increasing number of women. Comprehensive pre-test counseling is complicated by emerging information about the benefits and limitations of testing, as well as the potential to detect incidental findings. Genetic counselors are trained to facilitate informed decision-making; however, not all centers have access to these professionals. To aid in the informed consent process, we have summarized key points to be included in discussions with patients who are considering NIPT. © 2015 John Wiley & Sons, Ltd.