Light-scattering spectroscopy differentiates fetal from adult nucleated red blood cells: may lead to noninvasive prenatal diagnosis.

Present techniques for prenatal diagnosis are invasive and present significant risks of fetal loss. Noninvasive prenatal diagnosis utilizing fetal nucleated red blood cells (fNRBC) circulating in maternal peripheral blood has received attention, since it poses no risk to the fetus. However, because of the failure to find broadly applicable identifiers that can differentiate fetal from adult NRBC, reliable detection of viable fNRBC in amounts sufficient for clinical use remains a challenge. In this Letter we show that fNRBC light-scattering spectroscopic signatures may lead to a clinically useful method of minimally invasive prenatal genetic testing.

[1]  E. Alberman,et al.  Frequency of chromosomal abnormalities in miscarriages and perinatal deaths. , 1977, Journal of medical genetics.

[2]  W. Holzgreve,et al.  Fetal cells in maternal blood , 1995, Current opinion in obstetrics & gynecology.

[3]  F. Bischoff,et al.  Isolation and genetic analysis of fetal nucleated red blood cells from maternal blood: the Baylor College of Medicine experience. , 1996, Early human development.

[4]  K. Klinger,et al.  PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies. , 1997, American journal of human genetics.

[5]  Michael B. Wallace,et al.  Observation of periodic fine structure in reflectance from biological tissue: A new technique for measuring nuclear size distribution , 1998 .

[6]  Y. Lo,et al.  Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21. , 1999, Clinical chemistry.

[7]  A Farina,et al.  Fetal nucleated erythrocyte recovery: fluorescence activated cell sorting-based positive selection using anti-gamma globin versus magnetic activated cell sorting using anti-CD45 depletion and anti-gamma globin positive selection. , 2000, Cytometry.

[8]  M. Divon,et al.  Maternal pain and anxiety in genetic amniocentesis: expectation versus reality , 2002, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[9]  P. Kroisel,et al.  Fetal nucleated red blood cells in peripheral blood of pregnant women: detection and determination of location on a slide using laser‐scanning cytometry , 2003, Prenatal diagnosis.

[10]  L. Jackson,et al.  Fetal cells and DNA in maternal blood , 2003, Prenatal diagnosis.

[11]  D. Bianchi,et al.  ROC analysis of an erythroblast morphologic scoring system to improve identification of fetal cells in maternal blood , 2004, Prenatal diagnosis.

[12]  K. Klinger,et al.  Detection of fetal cells with 47,XY,+21 karyotype in maternal peripheral blood , 1992, Human Genetics.

[13]  Irving Itzkan,et al.  Confocal light absorption and scattering spectroscopic microscopy monitors organelles in live cells with no exogenous labels , 2007, Proceedings of the National Academy of Sciences.

[14]  O. Geifman‐Holtzman,et al.  Prenatal diagnosis: update on invasive versus noninvasive fetal diagnostic testing from maternal blood , 2008, Expert review of molecular diagnostics.

[15]  D. Maddocks,et al.  Post-genomics studies and their application to non-invasive prenatal diagnosis. , 2008, Seminars in fetal & neonatal medicine.