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Cell free DNA fetal fraction and preterm birth

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发表于 2016-8-24 08:50:06 | 显示全部楼层 |阅读模式

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Cell free DNA fetal fraction and preterm birth

Background

Cell-free deoxyribonucleic acid (DNA) is increasingly being used to screen for fetal aneuploidy. The majority of fetal cell-free DNA in the maternal blood results from release from the syncytiotrophoblast as a result of cellular apoptosis and necrosis. Elevated levels of fetal cell-free DNA may be indicative of underlying placental dysfunction, which has been associated with preterm birth. Preliminary studies have demonstrated that fetal cell-free DNA is increased in pregnancies complicated by spontaneous preterm birth. There are limited data on the association between fetal cell-free DNA levels and fetal fraction and preterm birth in asymptomatic women in the first and second trimesters. Preliminary studies have failed to find an association between first-trimester cell-free DNA levels and preterm birth, whereas there is conflicting evidence as to whether elevated second-trimester cell-free DNA is associated with a subsequent spontaneous preterm birth clinical event.

Objective

The objective of the study was to evaluate the association between first- and second-trimester cell-free DNA fetal fraction and preterm birth.

Study Design

This was a retrospective cohort study of women with singleton pregnancies at increased risk for aneuploidy who had cell-free DNA testing at 10–20 weeks’ gestation between October 2011 and May 2014. The cohort was subdivided by gestational age at the time of cell-free DNA testing (10–14 weeks or 14.1–20 weeks). The primary outcome was preterm birth less than 37 weeks’ gestation, and the secondary outcomes were preterm birth at less than 34 weeks’ gestation and spontaneous preterm birth at less than 37 and 34 weeks’ gestation.

Results

Among 1349 pregnancies meeting inclusion criteria 119 (8.8 %) had a preterm birth prior to 37 weeks with 49 cases (3.6 %) delivering prior to 34 weeks. Whereas there was no significant association between fetal fraction and the preterm birth outcomes for those who underwent cell-free DNA testing at 10–14 weeks’ gestation, there were significant associations among those screened at 14.1–20.0 weeks’ gestation. Fetal fraction greater than or equal to the 95th percentile at 14.1–20.0 weeks’ gestation was associated with an increased risk for preterm birth less than 37 and 34 weeks’ gestation (adjusted odds ratio, 4.59; 95% confidence interval, 1.39–15.2; adjusted odds ratio, 22.0; 95% confidence interval, 5.02–96.9).

Conclusion

Elevated fetal fraction levels at 14.1–20.0 weeks’ gestation were significantly associated with an increased incidence of preterm birth. Our findings warrant future exploration including validation in a larger, general population and investigation of the potential mechanisms that may be responsible for the initiation of preterm labor associated with increased fetal cell-free DNA.

Key words
cell-free deoxyribonucleic acid; fetal fraction; preterm birth
This study was supported by the Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania.

The authors report no conflict of interest.

Cell free DNA fetal fraction and preterm birth

Cell free DNA fetal fraction and preterm birth


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