Fetal aneuploidy detection by maternal plasma DNA sequencing: a technology assessment

The American College of Obstetricians and Gynecologists currently recommends that all pregnant women be offered screening for chromosomal abnormalities, regardless of maternal age. Traditional screening tests have detection rates ranging from 85% to 90% and false-positive rates of 3% to 5%. A woman with an abnormal noninvasive test is offered a diagnostic test, but diagnostic tests are associated with a risk of pregnancy loss. Recently, analysis of cell-free fetal DNA (cffDNA) in maternal blood has been shown to have potential for the accurate detection of some of the common fetal autosomal aneuploidies. As part of a technology assessment for the California Technology Assessment Forum, we critically reviewed the evidence for the use of cffDNA as a prenatal screening test. We evaluated the evidence for its use as either a ‘primary’ or an ‘advanced’ screening test and for its use in screening for three different trisomies: 21, 18, and 13. We evaluated whether the use of cffDNA met established technology assessment criteria and established conclusions about evidence-based use of this new technology. © 2013 John Wiley & Sons, Ltd.     

Fetal cells and DNA in maternal blood

Although fetal cells have been known to escape to the maternal circulation for a number of years, research attempts to use them for prenatal diagnosis have not had any consistent success. This review attempts to trace the history of such attempts and to document their progress and reasons for success or failure. The opinions of recent conferences including that of the US National Institute of Child Health and Human Development, a sponsor of major US research in the field, are reported and discussed. It is concluded that although basic work has demonstrated the biologic availability of both fetal cells and their free DNA representatives in the maternal circulation at gestational ages relevant to prenatal diagnosis, much work remains to develop practical technology for their consistent recovery and assay. Copyright © 2003 John Wiley & Sons, Ltd.     

First-trimester maternal serum alphafetoprotein and chorionic gonadotropin in aneuploid pregnancies

First-trimester maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels were measured in samples from 29 women with cytogenetically abnormal pregnancies and 145 women with cytogenetically normal pregnancies matched for gestational age, race, and sample storage time. All patients had a risk of fetal aneuploidy greater than or equal to that of a mother 35 years of age. AFP was significantly lower in samples from pregnancies affected with trisomy 21 (0.67 MoM;p <0.05), while HCG values were no different from those of matched controls. Trisomies 13 and 18 could not be distinguished from matched controls by AFP. However, levels of HCG were significantly lower in such pregnancy samples, with median values of 0.65 MoM in trisomy 13 and 0.32 MoM in trisomy 18 (p<0.05). Variations in AFP and HCG levels suggest that expressed differences between autosomal aneuploidies include differences in fetal and placenta! protein production in the first trimester.