Prenatal screening for Down syndrome using cell-free DNA
- Glenn E Palomaki, PhD
Glenn E Palomaki, PhD
- Associate Professor of Pathology and Laboratory Medicine
- Alpert Medical School of Brown University
- Geralyn M Messerlian, PhD
Geralyn M Messerlian, PhD
- Professor of Pathology & Laboratory Medicine
- Alpert Medical School of Brown University
- Jacquelyn V Halliday, MS
Jacquelyn V Halliday, MS
- Genetic Counselor, Prenatal Diagnosis Center
- Women and Infants Hospital
Prenatal screening for trisomy 21 (Down syndrome), trisomy 18, trisomy 13, and sex chromosome aneuploidies can be performed using next-generation sequencing of cell-free DNA (cfDNA) in the maternal circulation. Circulating cfDNA is derived from both the mother and the fetus, although most "fetal" DNA is thought to be derived from the placenta [1-3] and cleared from the maternal circulation soon after delivery . Although this approach is often called "noninvasive prenatal screening" or "noninvasive prenatal testing," these terms are nonspecific, as conventional serum screening is also noninvasive.
The cfDNA test provides excellent performance – 98 to 99 percent of Down syndrome pregnancies are identified prenatally with less than 1 percent of women called screen-positive – but it is considered a screening test due to infrequent false-positive and false-negative results. An invasive procedure (eg, amniocentesis or chorionic villus sampling) to determine the fetal karyotype is considered the gold standard diagnostic test and is recommended for women who screen positive by cfDNA testing, particularly those who are considering pregnancy termination.
This topic will discuss prenatal aneuploidy screening via sequencing of cfDNA. Other issues related to prenatal screening for Down syndrome and other aneuploidies are reviewed separately:
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- CELL-FREE DNA
- Fetal fraction
- SCREENING PERFORMANCE
- Trisomy 21, 18, and 13
- Sex chromosome aneuploidies
- Rates and reasons for cell-free DNA test failures
- Reasons for false-positive and false-negative results
- - False-positive cell-free DNA test results
- - False-negative cell-free DNA test results
- Predictive value
- CLINICAL USE
- Secondary screening
- Primary screening
- Implementation issues
- Confirmatory diagnostic testing
- SCREENING FOR MICRODELETION/DUPLICATION SYNDROMES
- RECOMMENDATIONS OF PROFESSIONAL SOCIETIES
- SUMMARY AND RECOMMENDATIONS