Current controversy in prenatal diagnosis: The use of cfDNA to screen for monogenic conditions in low risk populations is ready for clinical use

Abstract

Noninvasive cfDNA testing for monogenic disorders (sgNIPT) has become integrated into the care of pregnant women at increased risk based on carrier status, known family history, or ultrasound anomalies. The availability of commercial tests for common autosomal recessive and de novo autosomal dominant conditions has led to the use of these tests in low‐risk pregnancies. However, is the technology ready for use in this low‐risk population? This report is a summary of the debate on this topic at the 27th International Conference on Prenatal Diagnosis and Therapy. Both expert debaters provided strong arguments in favor and against the use of sgNIPT in low‐risk pregnancies. The argument in favor of sgNIPT for autosomal recessive conditions is that it allows the identification of affected pregnancies without the need for involving the partner in testing. Arguments for sgNIPT for autosomal dominant conditions include identification of affected fetuses that would have either presented later in pregnancy with fetal anomalies or not been detected prenatally given normal ultrasounds, respect for patient autonomy and patient desire for information. Strong arguments were made against offering sgNIPT screening. Given that traditional carrier screening for recessive conditions can be carried out in many jurisdictions, the added value of sgNIPT has not been clearly demonstrated. Arguments against sgNIPT for autosomal dominant conditions included the total lack of clinical validation studies and the risk of false reassurance in cases of negative results and unnecessary invasive procedures in cases of false positive results. Although there is a desire to take advantage of new technologies to improve the detection of monogenic disorders in low‐risk populations, based on the discussion and the audience vote, it appears premature to offer sgNIPT to all low risk pregnant women. Further clinical validation studies are needed prior to broad implementation.

Tumor- and Fibroblast-Derived Cell-Free DNAs Differently Affect the Progression of B16 Melanoma In Vitro and In Vivo

“…The study of circulating cell-free DNA (cfDNA) has gained significant momentum in recent decades, with tens of thousands of cfDNA studies being published each year [1][2][3][4][5]. Most of these studies have focused on the applications of cfDNA in medicine, such as liquid biopsies, sources of prognostic biomarkers, and the development of cfDNA-based test systems, including noninvasive prenatal testing [3,5,6]. Another important area of research is devoted to the origin, composition, and effects of cfDNA on cells and organisms, as well as other related aspects [7,8].…”

Highlights of the 27th ISPD annual conference hosted in the historic and atmospheric city of Edinburgh

“…Issues such as test validation, potential for increasing invasive testing as well as the value of this test to screen populations who do not or cannot access carrier screening were all factors raised in the debate. 2 The need for detailed pretest counseling and family studies when undergoing NIPT screening for monogenic conditions was stressed in a COL1A1 case report presented at the meeting. 3 Analysis and new applications of cfDNA remain reasonably "hot" topics and we heard more on approaches to confirming abnormal results, 4 the challenges of delivering NIPT for aneuploidy in underserved low resource settings from an enlightening patient perspective 5 and applications for screening for other pregnancy complications such as preeclampsia.…”