CELL-FREE DNA-BASED PRENATAL SCREENING FOR MONOGENIC AND CHROMOSOMAL DISORDERS

Background: Since its first description in 1997, cell-free fetal DNA in maternal plasma has emerged as two distinct, but related clinical applications: population level screening for the most common fetal aneuploidies and clinical testing for a limited number of monogenic disorders in families who have known risks. Although the two applications share a biological basis, they are often mentioned separately in the literature. 
Aim: This review is intended to synthesise these two aspects and summarise the current state of each application, its true shortcomings, and its areas where the evidence is weak. 
Method: A narrative literature review was performed, searching PubMed, Embase and the Cochrane Library for articles published between 1997 and December 2024 and hand searching and retrieval of professional guidance documents. Large prospective cohort studies, meta-analyses and systematic reviews were prioritised.
Result: There is a strong evidence base to support chromosomal screening, especially for the detection of trisomy 21, with pooled detection rates consistently over 99% and with a low false positive rate in unselected populations. While monogenic diagnosis is technically more challenging, is available at a handful of specialist laboratories and relies heavily on the prior characterisation of the familial mutation. 
Conclusion: There are clear and persistent gaps in access to health care and the common misconception that screening results are communicated with greater certainty than the statistics warrant are the most pressing unanswered.