Conventional first trimester prenatal screening (FTS) for chromosome anomalies combines maternal age, ultrasound markers, and maternal serum markers and reaches 80%–90% sensitivity with 5% of false positive (FP) rate. The presence of cell-free DNA (cfDNA) of fetal origin in the maternal circulation (Lo et al in 1997) has allowed the development of non-invasive testing (NIPT) based on total cfDNA sequencing for the screening of fetal aneuploidies for all chromosomes (RAs) and for the identification of segmental aneuploidies (SAs). NIPT shows a detection rate for common aneuploidies of>99% with a <0.1% FP rate and rare false-negative (FN) cases reported in large clinical series, being a more efficient screening method than FTS.
Circulating cell-free DNA in pregnant women is a mixture of maternal and placental cell-free DNA, in which the maternal fraction is on average ten times the fetal one (fetal fraction, FF). NIPT shows high sensitivity and specificity for detection of common trisomies (13, 18 and 21), however false-positive, false-negative as well as non-reportable cases exist and may raise from technical issues or may be due to biological causes of fetal origin such as low fetal fraction, fetoplacentalmosaicism, or vanishing twin. Moreover, a high risk NIPT result could potentially unravel a maternal condition such as a previously undiagnosed malignancy or an unknown chromosomal aneuploidy. Hence, NIPT remains a screening method and all professional societies recommend that pregnant women with high-risk results receive genetic counseling and are offered an invasive prenatal diagnosis to confirm the screening result. False negative NIPT results, which have the highest clinical impact on patients and clinicians, are mainly due to placental mosaicisms. Explaining the placental origin of cfDNA provides the patient with a clear view of the abilities and limitations of cfDNA-based prenatal screening. Understanding the biology behind cfDNA‐fetal karyotype discordancy is useful to counsel patients comprehensively and appropriately.
In this Research Topic we would like to provide an overview of the most recent advances in the field of discordances between non-invasive prenatal screening result and fetal karyotype. In particular, this issue will be focused on the possible biological causes of false positive/false negative NIPT results, with emphasis on fetoplacental chromosomal mosaicisms.
We welcome submissions of article types including Original Research, Methods, Clinical Trial, Case Reports, Reviews and Perspectives focused on:
- Mosaicisms, maternal copy number variants (CNV), maternal malignancy, vanishing twin, as causes of discordant NIPT results
- Fetoplacentalmosaicisms
- Benefits and pitfalls of genomewide NIPT
- RAs/SAs detected by genomewide NIPT: genetic counselling, pregnancy outcome and at-birth follow-up
- Genetic counselling and pregnancy management in case of a discordant result
Conventional first trimester prenatal screening (FTS) for chromosome anomalies combines maternal age, ultrasound markers, and maternal serum markers and reaches 80%–90% sensitivity with 5% of false positive (FP) rate. The presence of cell-free DNA (cfDNA) of fetal origin in the maternal circulation (Lo et al in 1997) has allowed the development of non-invasive testing (NIPT) based on total cfDNA sequencing for the screening of fetal aneuploidies for all chromosomes (RAs) and for the identification of segmental aneuploidies (SAs). NIPT shows a detection rate for common aneuploidies of>99% with a <0.1% FP rate and rare false-negative (FN) cases reported in large clinical series, being a more efficient screening method than FTS.
Circulating cell-free DNA in pregnant women is a mixture of maternal and placental cell-free DNA, in which the maternal fraction is on average ten times the fetal one (fetal fraction, FF). NIPT shows high sensitivity and specificity for detection of common trisomies (13, 18 and 21), however false-positive, false-negative as well as non-reportable cases exist and may raise from technical issues or may be due to biological causes of fetal origin such as low fetal fraction, fetoplacentalmosaicism, or vanishing twin. Moreover, a high risk NIPT result could potentially unravel a maternal condition such as a previously undiagnosed malignancy or an unknown chromosomal aneuploidy. Hence, NIPT remains a screening method and all professional societies recommend that pregnant women with high-risk results receive genetic counseling and are offered an invasive prenatal diagnosis to confirm the screening result. False negative NIPT results, which have the highest clinical impact on patients and clinicians, are mainly due to placental mosaicisms. Explaining the placental origin of cfDNA provides the patient with a clear view of the abilities and limitations of cfDNA-based prenatal screening. Understanding the biology behind cfDNA‐fetal karyotype discordancy is useful to counsel patients comprehensively and appropriately.
In this Research Topic we would like to provide an overview of the most recent advances in the field of discordances between non-invasive prenatal screening result and fetal karyotype. In particular, this issue will be focused on the possible biological causes of false positive/false negative NIPT results, with emphasis on fetoplacental chromosomal mosaicisms.
We welcome submissions of article types including Original Research, Methods, Clinical Trial, Case Reports, Reviews and Perspectives focused on:
- Mosaicisms, maternal copy number variants (CNV), maternal malignancy, vanishing twin, as causes of discordant NIPT results
- Fetoplacentalmosaicisms
- Benefits and pitfalls of genomewide NIPT
- RAs/SAs detected by genomewide NIPT: genetic counselling, pregnancy outcome and at-birth follow-up
- Genetic counselling and pregnancy management in case of a discordant result