Fetal expressed gene analysis in maternal blood: a new tool for noninvasive study of the fetus.

Abstract

Noninvasive approaches to prenatal diagnosis can avoid the risk of fetal loss associated with invasive procedures such as chorionic villus sampling, amniocentesis, and cordocentesis. Isolation of fetal cells from maternal blood requires further improvements before it can be applied in a clinical setting (1), but the reliability of cell-free fetal DNA analysis in maternal plasma or serum is now well established (2)(3)(4). As a result, it is currently used in specialized centers for the determination of fetal sex and fetal RhD status for the management of pregnant women at risk for X-linked disorders (5) or RhD alloimmunization (6). Because fetal DNA in maternal serum is circulating in an excess background of maternal DNA, clinical applications are restricted mainly to the detection of fetal sequences distinct from the mother’s DNA sequences. Fetal RNA in maternal blood may be an alternative source of fetal nucleic acids. Al-Mufti et al. (7) detected specific RhD mRNA in mononuclear fetal cells isolated from blood of RhD-negative pregnant women, and Lo’s group demonstrated the presence of Y-chromosome-specific ( ZFY ) mRNA in maternal plasma of women carrying a male fetus (8). These two applications, however, again require fetal sequences that differ from the mother’s. We have investigated the presence in maternal blood of fetal transcripts that may have the same sequence as that of the mother. Human chorionic gonadotropin (hCG) mRNA is a good candidate because it is a pregnancy-specific polypeptide hormone produced by the placenta and is specifically expressed in the fetal syncytiotrophoblast. We studied 43 pregnant women and 20 nonpregnant women who had previously given birth to at least one neonate. After receiving informed consent, we collected blood (2.5 mL) into PAXgeneTM tubes to reduce RNA degradation (9). All pregnancy samples were obtained before …