From the Guidelines
Abnormal cell-free deoxyribonucleic acid (DNA) results imply a significant risk of chromosomal abnormalities, such as trisomies 13,18, and 21, and sex chromosomal abnormalities, which can have major implications for morbidity, mortality, and quality of life. When interpreting these results, it is crucial to consider the accuracy of the screening, which varies depending on the condition and platform used, as well as factors like the amount of fetal DNA present and the a priori chance of a chromosomal abnormality based on maternal age or other screening results 1. Some key points to consider include:
- The probability of aneuploidy is often reported, with some laboratories stating a probability of >99% in high-risk patients and <1/10,000 in low-risk patients, although this is a population statistic and not a guarantee for individual results 1.
- A positive result for any aneuploidy confers a chance that the fetus is affected, particularly in lower-risk patients, and further evaluation may be necessary to confirm the diagnosis 1.
- False-positive results can occur due to various biologic phenomena, such as confined placental mosaicism or a cotwin death, and may require additional testing, including karyotyping of the mother to rule out a mosaic chromosomal abnormality 1.
- In some cases, false-positive results have been linked to maternal malignancies with chromosomal abnormalities, highlighting the potential benefit of further evaluation for maternal malignancy in women with false-positive results, although the clinical utility and yield of such an evaluation are currently unknown 1. Given the potential implications of abnormal cell-free DNA results, it is essential to approach these results with caution and consider further evaluation and testing to confirm the diagnosis and determine the best course of action.
From the Research
Implications of Abnormal Cell-Free DNA Results
Abnormal cell-free deoxyribonucleic acid (DNA) results can have significant implications in various clinical applications, including:
- Non-invasive prenatal testing (NIPT) for fetal aneuploidy detection 2, 3
- Cancer diagnostics and genetic profiling 4, 5
- Detection of pregnancy-associated diseases, such as preeclampsia, fetal growth restriction, and gestational diabetes 6
Causes of Aberrant Results
Aberrant cell-free DNA results can be caused by:
- Biological factors, including fetal or maternal factors, such as insufficient or absent fetal fraction, fetoplacental mosaicism, and the presence of a vanishing twin 3
- Technical issues, such as pre-analytical, analytical, and biological factors that interfere with cell-free DNA concentration and analysis 5
- Placental biology, which can affect the accuracy of cell-free DNA-based prenatal screening 3
Clinical Applications and Limitations
Cell-free DNA analysis has several clinical applications, including:
- Non-invasive prenatal testing for fetal aneuploidy detection, which can reduce the need for invasive testing, such as amniocentesis or chorionic villus sampling 4, 2
- Cancer diagnostics and genetic profiling, which can provide valuable information for treatment and follow-up 4, 5
- Detection of pregnancy-associated diseases, which can improve prenatal care and outcomes 6 However, cell-free DNA analysis also has limitations, including:
- False-positive and false-negative results, which can have significant clinical implications 3
- Variability in cell-free DNA concentration and analysis, which can affect the accuracy of results 5