High levels of fetal cell-free DNA in maternal serum: a risk factor for spontaneous preterm delivery.
OBJECTIVE
This study was conducted to determine whether there is a relationship between the concentration of fetal cell-free DNA in maternal serum and the duration of pregnancy in women who are at high risk for preterm delivery because of either preterm labor or preterm premature rupture of the membranes.


METHODS
Sera were collected and frozen from 71 women with a male fetus. Maternal serum fetal cell-free DNA concentration was measured with the use of real-time polymerase chain reaction amplification of DYS1. Fetal cell-free DNA concentrations were converted to multiples of the median. The following groups were studied: group 1: women with preterm labor and intact membranes who were delivered at > or = 36 weeks of gestation (n = 21); group 2: women with preterm labor who were delivered at <36 weeks of gestation (n = 29); and group 3: women with preterm premature rupture of the membranes in labor (n = 20) or not in labor (n = 1) who were delivered prematurely (<36 weeks of gestation). Kaplan-Meier and Cox regression analyses were used to analyze the relationship between fetal cell-free DNA concentrations and the likelihood of preterm delivery.


RESULTS
A cut-off value for fetal cell-free DNA of 1.82 multiples of the median was chosen for analysis. The cumulative rate of early preterm delivery (<30 weeks of gestation) was significantly higher for women with fetal cell-free DNA concentrations of > or = 1.82 multiples of the median than those with fetal cell-free DNA concentrations below this cut-off (45% [95% CI, 36%-74%] vs 18% [95% CI, 11%-25%]; P = .008]. The cumulative rate of preterm delivery (<36 weeks of gestation) was also significantly higher at > or = 1.82 multiples of the median (73% [95% CI, 52%-93%] vs 66% [95% CI, 54%-79%]; P = .02). After adjustment for covariates, Cox analysis showed that fetal cell-free DNA at > or = 1.82 multiples of the mechanisms of disease that are associated with a mean hazard rate of delivery of 1.57 (P = .005).


CONCLUSIONS
High concentrations of fetal cell-free DNA in maternal serum are associated with an increased risk of spontaneous preterm delivery. This observation may have implications for the understanding of the mechanisms of disease that is associated with preterm labor.
Farina
Antonio
A
Department of Embryology, Obstetrics and Gynecology, Prenatal Medicine Unit, University of Bologna, Bologna, Italy.
LeShane
Erik S
ES
Romero
Roberto
R
Gomez
Ricardo
R
Chaiworapongsa
Tinnakorn
T
Rizzo
Nicola
N
Bianchi
Diana W
DW
D003430:Cross-Sectional Studies; D004247:DNA / Q000097:blood*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000097:blood* / Q000453:epidemiology*; D005333:Fetus / Q000502:physiology*; D005865:Gestational Age; D006801:Humans; D007752:Obstetric Labor, Premature / Q000097:blood* / Q000453:epidemiology*; D011247:Pregnancy; D016016:Proportional Hazards Models; D012307:Risk Factors
D004247:DNA