Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis.
BACKGROUND
Fetal genetic material is detectable in the maternal circulation and has been used for noninvasive prenatal diagnosis. However, few data are available concerning its quantity and natural history during gestation.


METHODS
This study prospectively characterized the kinetics of cellular and cell-free fetal DNA in the circulation of 25 healthy women during and after uncomplicated pregnancy. Real-time kinetic PCR was used to quantitate human Y-chromosome sequences, and liquid oligomer hybridization with (32)P-labeled probes was used to verify the identity of amplified products.


RESULTS
In all male pregnancies, but no female pregnancies, low-level fetal Y-chromosome DNA was detected in both cellular and cell-free compartments beginning at 7 to 16 weeks but increasing steadily after 24 weeks and reaching a peak at parturition. The fetal DNA decreased rapidly after birth.


CONCLUSIONS
Fetal genetic material can be detected throughout pregnancy, and its quantity is a function of gestational age and of whether the plasma or cellular compartment is examined. Both the absolute quantity of fetal DNA and its ratio to total DNA (maternal + fetal) are greater in the plasma than in the cellular compartment. Fetal DNA is cleared rapidly from both compartments after parturition, which suggests that turnover is dynamic. Because they provide prospective and quantitative data concerning fetal DNA levels, these observations and kinetic PCR methods may have implications for noninvasive prenatal diagnosis. Further studies will be needed to determine the immunologic implications of fetal-maternal DNA exchange and cellular microchimerism.
Ariga
H
H
Blood Centers of the Pacific, San Francisco, CA 94118, USA.
Ohto
H
H
Busch
M P
MP
Imamura
S
S
Watson
R
R
Reed
W
W
Lee
T H
TH
D000328:Adult; D004247:DNA / Q000097:blood*; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005865:Gestational Age; D006801:Humans; D007700:Kinetics; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011247:Pregnancy / Q000097:blood / Q000235:genetics*; D011296:Prenatal Diagnosis / Q000379:methods; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D014998:Y Chromosome / Q000235:genetics
D004247:DNA