Research
Obstetrics
First-trimester maternal plasma cell-free fetal DNA and preeclampsia

https://doi.org/10.1016/j.ajog.2009.05.025Get rights and content

Objective

The purpose of this study was to determine whether, in pregnancies that experience preeclampsia, plasma cell-free fetal DNA (cffDNA) at 11-13 weeks of gestation is increased and whether this increase is related to the uterine artery pulsatility index (PI).

Study Design

Plasma cffDNA and uterine artery PI were measured in 44 cases with preeclampsia, which included 11 cases that required delivery at <34 weeks of gestation and 176 normal control subjects. All fetuses were male, and cffDNA was assessed by amplification of the DYS14 gene. The association between cffDNA and uterine artery PI was assessed by regression analysis.

Results

Median cffDNA was higher in early preeclampsia (median, 95.5 genome equivalents/mL; interquartile range, 72.7-140.9 genome equivalents/mL), but not late preeclampsia (median, 50.8 genome equivalents/mL; interquartile range, 25.0-103.8 genome equivalents/mL), than control subjects (median, 51.5 genome equivalents/mL; interquartile range, 31.1-84.9 genome equivalents/mL). There was a significant association between cffDNA and uterine artery PI (P = .038) but not in the control subjects (P = .174).

Conclusion

The increase in plasma cffDNA in pregnancies that experience preeclampsia is associated with the degree of impairment in placental perfusion.

Section snippets

Study population

This was a case-control study in singleton pregnancies. In our center, we perform screening for hypertensive complications of pregnancy in women who attend for their routine first hospital visit in pregnancy. In this visit, which is held at 11+0-13+6 weeks of gestation, all women have an ultrasound scan (1) to confirm gestational age from the measurement of the fetal crown-rump length, (2) to diagnose any major fetal abnormalities, and (3) to measure fetal nuchal translucency thickness as part

Results

Maternal blood was collected between March 2006-March 2007 and analyzed at a median interval of 20.6 months (range, 13.3–25.0 months). The maternal characteristics of each of the outcome groups are compared in Table 2. In the preeclampsia group, compared with the control group, the BMI was higher, and more women had a personal or family history of preeclampsia and chronic hypertension. In the preeclampsia group, the median uterine artery PI was significantly higher than in the control group,

Comment

The findings of this study confirm the association of preeclampsia with increased cffDNA in maternal blood and demonstrate that (1) the increased cffDNA is evident from 11-13 weeks of gestation and (2) the level of cffDNA is associated with the degree of impairment in placental perfusion and severity of preeclampsia. Significantly increased levels of cffDNA and uterine artery PI were observed in severe early-onset preeclampsia that required delivery at <34 weeks of gestation rather than in

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      The ongoing interest in the use of ffDNA as a predictive marker or diagnostic test for adverse pregnancy outcomes is because of the need to better understand disease processes and to enable improved treatments to be developed and appropriately targeted. When considering usefulness in clinical practice, several authors have suggested that ffDNA does not enhance currently available pre-eclampsia screening.[9,21] Some have come to this conclusion for PTB too.[43]

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    Cite this article as: Sifakis S, Zaravinos A, Maiz N, et al. First-trimester maternal plasma cell-free fetal DNA and preeclampsia. Am J Obstet Gynecol 2009;201:472.e1-7.

    This study was supported by a Grant from the Fetal Medicine Foundation (UK Charity no. 1037116).

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