Six years after the demonstration of the presence of cell-free fetal
nucleic acids in maternal plasma, perinatal clinical applications continue to expand. The focus of this article is on advances that have occurred since the CNAPS II conference held in Hong Kong in 2001. Circulating fetal
DNA levels (fDNA) are elevated in pregnancies complicated by fetal
trisomies 13 and 21 but not 18. Measurement of fDNA levels improves the performance of the current standard maternal serum screen, by increasing the detection of
Down syndrome cases by 5% with no increase in the false-positive rate. fDNA levels are elevated in women who have developed clinical symptoms of
preeclampsia, but they are also elevated by the early second trimester in women who will eventually develop
preeclampsia. fDNA and
mRNA gamma globin measurement may have clinical utility as markers for
fetomaternal hemorrhage in the late first trimester. Cell-free fetal
DNA levels are quite high in the amniotic fluid, permitting fetal genomic isolation and analysis using comparative genomic hybridization techniques. Fetal
DNA crosses the blood-brain barrier and is detectable in maternal cerebrospinal fluid in a subset of pregnant women. The
biological implications of this are currently unknown. Review of the literature suggests that the placenta is the predominant source of the circulating fetal
nucleic acids. However, detection of
gamma globin mRNA sequences in the plasma of pregnant women suggests that fetal blood cells also contribute to the pool of
nucleic acids. Widespread incorporation of fetal
nucleic acid measurement into routine
prenatal care depends on the identification of a readily accessible gender-independent fetal marker.