Cell-free fetal DNA in maternal blood: kinetics, source and structure

Bischoff, Farideh Z.; Lewis, Dorothy E.; Simpson, Joe Leigh

doi:10.1093/humupd/dmh053

Cited by 147 publications

(124 citation statements)

References 97 publications

(85 reference statements)

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“…The release of cffDNA is a physiological process present in all mammals, but its possible roles and implications in normal pregnancy (and more importantly parturition) remain poorly understood. Placental growth involves proliferation, differentiation and syncytial fusion of cytotrophoblasts, which is associated with significant release (grams per day) of microvesicles-encapsulated, cffDNA-containing apoptotic trophoblasts content into maternal circulation (Nelson 1996, Huppertz et al 1998, Huppertz & Kingdom 2004, Bischoff et al 2005, Taglauer et al 2014. These microparticles, also referred to as syncytiotrophoblast microvesicles (SCTMs), were first described more than 100 years ago in lung capillaries of women who died from preeclampsia (Schmorl 1893) and were later described as a feature of normal pregnancy, although increased in preeclampsia (Johansen et al 1999).…”

Section: Cell-free Dnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

213

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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Section: Cell-free Dnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

213

161

View full text Add to dashboard Cite

show abstract

“…It is also possible for the absolute quantity to actually change in opposition to relative abundance. Recently, we reported that particles from maternal plasma, which may be derived from apoptotic cells, stained positive for acridine orange (AO), a nucleic acid dye (Bischoff et al, 2004). We sorted the AO+ apoptotic bodies and PCR amplified male specific Y sequences, demonstrating that they contain male fetal DNA (Bischoff et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, we reported that particles from maternal plasma, which may be derived from apoptotic cells, stained positive for acridine orange (AO), a nucleic acid dye (Bischoff et al, 2004). We sorted the AO+ apoptotic bodies and PCR amplified male specific Y sequences, demonstrating that they contain male fetal DNA (Bischoff et al, 2004). For such analysis of subcellular apoptotic bodies, accurate quantitation is needed to determine the optimum amount of staining reagent required.…”

Section: Introductionmentioning

confidence: 99%

A general method for bead-enhanced quantitation by flow cytometry

Montes

Jaensson

Orozco

et al. 2006

Journal of Immunological Methods

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Flow cytometry provides accurate relative cellular quantitation (percent abundance) of cells from diverse samples, but technical limitations of most flow cytometers preclude accurate absolute quantitation. Several quantitation standards are now commercially available which, when added to samples, permit absolute quantitation of CD4+ T cells. However, these reagents are limited by their cost, technical complexity, requirement for additional software and/or limited applicability. Moreover, few studies have validated the use of such reagents in complex biological samples, especially for quantitation of non-T cells. Here we show that addition to samples of known quantities of polystyrene fluorescence standardization beads permits accurate quantitation of CD4+ T cells from complex cell samples. This procedure, here termed single bead-enhanced cytofluorimetry (SBEC), was equally capable of enumerating eosinophils as well as subcellular fragments of apoptotic cells, moieties with very different optical and fluorescent characteristics. Relative to other proprietary products, SBEC is simple, inexpensive and requires no special software, suggesting that the method is suitable for the routine quantitation of most cells and other particles by flow cytometry.

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“…Nevertheless, only one out of eight treated children is a CAH-affected girl. Even with early foetal sex typing, using PCR amplification of cell-free foetal DNA in maternal blood, performed during the first trimester (13)(14)(15), the ethical dilemma remains that healthy foetuses (seven out of eight versus three out of eight) will be treated for a short period of time for the sake of benefit of others.…”

Section: Introductionmentioning

confidence: 99%

Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia: does dexamethasone cause behavioural problems?

Hirvikoski

Nordenström

Lindholm³

et al. 2008

European Journal of Endocrinology

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Objectives: To investigate the long-term effects of prenatal treatment of congenital adrenal hyperplasia (CAH) with emphasis on behavioural problems and temperament. Design: A population-based long-term follow-up study of Swedish children at risk for virilising CAH, who had received treatment prenatally with dexamethasone (DEX). The questionnaire-based follow-up was performed when the children had reached school age. Methods: Standardised parent-completed questionnaires were used to evaluate adaptive functioning, behavioural/emotional problems and psychopathology, social anxiety and temperament in DEXexposed school-aged children (nZ26) and matched controls (nZ35). In addition, the association between parental questionnaires and children's self-ratings was investigated. Results: There were no statistically significant differences between DEX-exposed children and controls in measures of psychopathology, behavioural problems and adaptive functioning. In a questionnaire on temperamental traits, DEX-exposed children were described by their parents as being more sociable than controls (PZ0.042). The correlation analysis showed only modest parent-child agreement on social anxiety, i.e. the increased social anxiety in children's self-ratings was not confirmed by their parents. Conclusions: DEX-treated children showed good overall adjustment. The parent-child agreement with respect to social anxiety was modest, highlighting the importance of multiple information sources and assessment methods. The clinical significance of the observed difference in sociability cannot be determined within the frameworks of this study. Additional studies of larger cohorts are essential to make more decisive conclusions on the safety of the treatment. Until then, it is important that parents are thoroughly informed about the benefits and potential risks and uncertainties of this controversial treatment.

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Cell-free fetal DNA in maternal blood: kinetics, source and structure

Cited by 147 publications

References 97 publications

Sterile inflammation and pregnancy complications: a review

Sterile inflammation and pregnancy complications: a review

A general method for bead-enhanced quantitation by flow cytometry

Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia: does dexamethasone cause behavioural problems?

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