High levels of fetal DNA are associated with increased risk of spontaneous preterm delivery

Jakobsen, Tanja Roien; Clausen, Frederik Banch; Rode, Line; Dziegiel, Morten Hanefeld; Tabor, Ann

doi:10.1002/pd.3917

Cited by 68 publications

(69 citation statements)

References 25 publications

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“…Two studies examined women presenting with contractions and/or premature rupture of membranes and reported a correlation between fetal cfDNA levels and subsequent delivery [42,43]. A cohort study of women undergoing routine fetal RHD genotyping at 25 weeks' gestation reported that if the fetal cfDNA levels were above the 95th percentile there was a 16-fold increase in risk for SPB before 34 weeks [44]. In contrast, a study examining women with short cervical length at 22-24 weeks reported no significant difference in the level of fetal cfDNA between those that delivered before 37 weeks compared to those delivering at term [45].…”

Section: Discussionmentioning

confidence: 99%

Maternal Plasma Cell-Free Fetal and Maternal DNA at 11-13 Weeks' Gestation: Relation to Fetal and Maternal Characteristics and Pregnancy Outcomes

Poon

Musci²,

Song³

et al. 2013

Fetal Diagn Ther

200

101

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Objective: To examine the possible relationship between maternal and fetal characteristics and pregnancy outcomes on fetal and maternal cell-free (cf) DNA in maternal plasma at 11-13 weeks' gestation. Methods: cfDNA was extracted from maternal plasma of 1,949 singleton pregnancies and chromosome-selective sequencing was used to determine the proportion of cfDNA and total cfDNA counts which was of fetal and maternal origin. Multivariate regression analysis was used to determine whether specific maternal and fetal characteristics and pregnancy complications, such as preeclampsia (PE), early spontaneous preterm birth (SPB) and delivery of small for gestational age (SGA) neonates, were significant predictors of fetal and maternal cfDNA in maternal plasma. Results: The fetal and maternal cfDNA plasma concentration increased with serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin level, was higher in women of Afro-Caribbean and East-Asian racial origin than in Caucasians, and lower in smokers, but it was not significantly altered in pregnancies complicated by PE, SPB or SGA. The fetal cfDNA level was inversely related to maternal weight and uterine artery pulsatility index, and maternal cfDNA increased with maternal weight. Conclusions: The fetal and maternal cfDNA level in maternal plasma is affected by maternal and fetal characteristics, but it is not altered in pregnancy complications.

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Section: Discussionmentioning

confidence: 99%

Maternal Plasma Cell-Free Fetal and Maternal DNA at 11-13 Weeks' Gestation: Relation to Fetal and Maternal Characteristics and Pregnancy Outcomes

Poon

Musci²,

Song³

et al. 2013

Fetal Diagn Ther

200

101

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“…It has been shown that the placenta is the major source of circulating cell-free fetal nucleic acids in maternal plasma (5)(6)(7). Significantly elevated levels of total cell-free DNA and selected placenta-specific RNA transcripts have also been reported in the maternal plasma of women with PE (8)(9)(10)(11), restricted fetal growth (12), and preterm birth (13)(14)(15), supporting a role for cell-free nucleic acids as a noninvasive tool for placental monitoring. Previous studies have attempted to provide a comprehensive assessment of maternal plasma nucleic acids by microarray analysis, massively parallel transcriptomic, or methylomic sequencing (16)(17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 94%

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Tsang

Vong

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

259

267

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The human placenta is a dynamic and heterogeneous organ critical in the establishment of the fetomaternal interface and the maintenance of gestational well-being. It is also the major source of cell-free fetal nucleic acids in the maternal circulation. Placental dysfunction contributes to significant complications, such as preeclampsia, a potentially lethal hypertensive disorder during pregnancy. Previous studies have identified significant changes in the expression profiles of preeclamptic placentas using whole-tissue analysis. Moreover, studies have shown increased levels of targeted RNA transcripts, overall and placental contributions in maternal cell-free nucleic acids during pregnancy progression and gestational complications, but it remains infeasible to noninvasively delineate placental cellular dynamics and dysfunction at the cellular level using maternal cell-free nucleic acid analysis. In this study, we addressed this issue by first dissecting the cellular heterogeneity of the human placenta and defined individual cell-type-specific gene signatures by analyzing more than 24,000 nonmarker selected cells from full-term and early preeclamptic placentas using large-scale microfluidic single-cell transcriptomic technology. Our dataset identified diverse cellular subtypes in the human placenta and enabled reconstruction of the trophoblast differentiation trajectory. Through integrative analysis with maternal plasma cell-free RNA, we resolved the longitudinal cellular dynamics of hematopoietic and placental cells in pregnancy progression. Furthermore, we were able to noninvasively uncover the cellular dysfunction of extravillous trophoblasts in early preeclamptic placentas. Our work showed the potential of integrating transcriptomic information derived from single cells into the interpretation of cell-free plasma RNA, enabling the noninvasive elucidation of cellular dynamics in complex pathological conditions. single-cell transcriptomics | cell-free RNA | noninvasive prenatal testing | placenta | preeclampsia

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“…Alarmins are interesting candidate as their release represents an initiating step in sterile inflammation following an injury, and because most preterm births happen without any evidence of infection, which raises interrogations about what factor (or group of factors) initiates pro-labor pathways in women with preterm labor and no infection. Accordingly, it is reported that sterile intra-amniotic inflammation is observed significantly more often than microbial-associated intra-amniotic inflammation in patients with preterm labor and intact membranes , and recent advances have found increased expressions of alarmins, namely cffDNA (Leung et al 1998, Farina et al 2005, Jakobsen et al 2012, HMGB1 (Bredeson et al 2014), interleukin-1 (Romero et al 1989, Puchner et al 2011, uric acid (Roberts et al 2005, Homer et al 2008) and S100B (Friel et al 2007), in maternal serum or gestational tissue of women at risk of preterm labor or having delivered preterm. This increase in alarmins could be a link between numerous causes of preterm labor wherein tissue injury and cell death are implicated, and the initiation of a pro-inflammatory, pro-labor response.…”

Section: Preterm Labormentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

216

161

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Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

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High levels of fetal DNA are associated with increased risk of spontaneous preterm delivery

Abstract: High levels of cffDNA at 25 weeks are associated with increased risk of spontaneous preterm delivery.

Cited by 68 publications

References 25 publications

Maternal Plasma Cell-Free Fetal and Maternal DNA at 11-13 Weeks' Gestation: Relation to Fetal and Maternal Characteristics and Pregnancy Outcomes

Maternal Plasma Cell-Free Fetal and Maternal DNA at 11-13 Weeks' Gestation: Relation to Fetal and Maternal Characteristics and Pregnancy Outcomes

Integrative single-cell and cell-free plasma RNA transcriptomics elucidates placental cellular dynamics

Sterile inflammation and pregnancy complications: a review

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