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Cell-Free Fetal DNA and Adverse Outcome in Low Risk Pregnancies

Stein, Werner; Müller, Sina; Gutensohn, Kai; Emons, Günter; Legler, Tobias

Obstetrical & Gynecological Survey: May 2013 - Volume 68 - Issue 5 - p 344–346
doi: 10.1097/01.ogx.0000430380.14746.b4
Obstetrics: Obstetrical Complications

ABSTRACT Preeclampsia is a common, serious pregnancy-related disorder of unknown etiology. It might be initiated by placental factors that enter the maternal circulation. Previous reports of increased free fetal DNA in maternal plasma before the clinical onset of preeclampsia have been promising. The aim of this study was to determine whether free fetal DNA in maternal plasma of the second trimester is associated with the development of preeclampsia and whether free fetal DNA could be a potential indicator of an increased risk for preeclampsia or small-for-gestational-age (SGA) infants.

A subset of a larger cohort study was used; that study was conducted during 2005 to 2007 to evaluate the feasibility of routine determination of the fetal D status from maternal plasma. A total of 1113 healthy, serologically RhD pregnant women were enrolled at up to 32 weeks’ gestation. The fetal RhD status and the quantity of cell-free fetal DNA (cff DNA) were determined through the detection of RhD-specific sequences with real-time polymerase chain reaction for RhD exon 7 using several primers after extraction of maternal and cff DNA from plasma. Inclusion criteria for this subset analysis were an RhD+ result obtained with the magnetic tips cff DNA extraction method and RhD exon 7 real-time polymerase chain reaction confirmed by postnatal serology. Ct− values of cff DNA were calculated by logistic regression. All statistical analyses were performed using SPSS software.

Of 611 women who met inclusion criteria, 44 (7.2%) developed preeclampsia. Two women had HELLP syndrome at 26 and 36 weeks’ gestation; the other women had uncomplicated preeclampsia. Of 76 preterm infants at 37 weeks’ gestation or less, 18 were born at 34 weeks or less, 10 at 32 weeks or less, and 7 at 30 weeks’ gestation or less. Of 158 cases with the newborn’s birth weight reported, SGA infants were seen in 9 women (<5th percentile) and 13 women (<10th percentile). Ct− values were not different between the groups (P = 0.905). No association was found between Ct− values as a marker for cff DNA concentration and adverse pregnancy outcome. The calculated P values ranged from 0.119 to 0.989, with 1 exception. The median Ct of 35.00 in the preterm group with a cutoff at 37 weeks’ gestation or less was slightly higher than the median Ct of 34.84 in the control group (P = 0.07), but this difference was smaller than differences between other groups and was probably a random observation.

In this study, cff DNA determined in the second trimester was not a prediction marker for complicated pregnancies because increased cff DNA levels were not associated with adverse pregnancy outcomes. Elevated levels of fetal DNA were not seen in preeclamptic pregnancies or those with SGA fetuses or preterm labor. The use of cff DNA measurement as a screening tool in maternal plasma during the second trimester thus appears to be limited.

Department of Obstetrics and Gynaecology (W.S., G.E.), University Medical Center, Göttingen, Germany; Department of Transfusion Medicine (S.M., T.L.), University Medical Center, Göttingen, Germany; and Endokrinologikum Labore Hamburg (K.G.), Hamburg, Germany

© 2013 by Lippincott Williams & Wilkins.