Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia

Levine, Richard J.; Qian, Cong; LeShane, Erik S.; Yu, Kai; England, Lucinda J.; Schisterman, Enrique F.; Wataganara, Tuangsit; Romero, Roberto; Bianchi, Diana W.

doi:10.1016/j.ajog.2003.12.019

Cited by 233 publications

(189 citation statements)

References 25 publications

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“…This evidence, along with the established pro-inflammatory effects of cffDNA, underpins the theory that cffDNA may represent a common trigger to parturition in mammals (Phillippe 2014). Furthermore, elevated cffDNA in the maternal circulation has been observed in pathological pregnancies (Levine et al 2004, Alberry et al 2009, Girard et al 2014 in association with placental dysfunction and inflammation. For these reasons and others, cffDNA is increasingly used for diagnostic purposes to decrease the use of invasive amniocentesis.…”

Section: Cell-free Dnamentioning

confidence: 82%

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Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

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: 82%

“…cffDNA is elevated in pregnancies complicated by preeclampsia (Levine et al 2004, Lazar et al 2009, Vlkova et al 2015 and its levels correlate with the degree of impairment in placental perfusion (Sifakis et al 2009). For these reasons, it is broadly investigated as a biomarker of PE (Martin et al 2014).…”

Section: Cffdnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

View full text Add to dashboard Cite

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“…3,4 The resulting reduced uteroplacental blood flow produces placental ischemia and hypoxia. 5,6 The latter is associated with a maternal circulation containing reduced levels of angiogenic factors [7][8][9] and elevated levels of anti-angiogenic factors, 9 -11 placental debris, 12,13 reactive oxygen species, 14 -16 and proinflammatory cytokines. 16 -26 Altered levels of these circulating factors promote endothelial cell activation and vascular damage leading to proteinuria and hypertension, the primary symptoms of the maternal syndrome of preeclampsia.…”

mentioning

confidence: 99%

Preeclampsia-Related Inflammatory Cytokines Regulate Interleukin-6 Expression in Human Decidual Cells

Lockwood

Yen

Başar

et al. 2008

The American Journal of Pathology

144

100

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Preeclampsia, a common pregnancy disorder associated with an increase in systemic inflammation, is the leading cause of maternal and fetal morbidity and mortality throughout the world. It is associated with shallow extravillous trophoblast invasion of the decidua, leading to uteroplacental blood flow that is inadequate for the developing fetal-placental unit. In preeclamptic women, interleukin-6 (IL-6) levels in plasma, but not placenta, are elevated, prompting evaluation of the decidua as a potential source of this excess, circulating IL-6. The current study found significantly higher immunohistochemical staining for IL-6 in decidual cells from preeclamptic versus preterm, gestational age-matched control placentas. Proinflammatory cytokines associated with the genesis of preeclampsia (i.e., tumor necrosis factor-␣ and interleukin-1␤) enhanced IL-6 mRNA levels and increased secreted IL-6 levels in first trimester leukocytefree decidual cell incubations, as measured by real time quantitative RT-PCR , ELISA , and Western blotting. Therefore , decidual cell-derived IL-6 may contribute to excess circulating IL-6 levels that can promote both endothelial cell dysfunction (and subsequent vascular dysfunction) and the pathogenesis of preeclampsia whereas locally elevated IL-6 levels may contribute to an excess of decidual macrophages implicated in shallow extravillous trophoblast invasion of the decidua. Maternal-fetal interactions create a mild systemic inflammatory state exemplified by activation of both vascular endothelium and leukocytes that is most apparent in the third trimester of uncomplicated human pregnancies.

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“…Varios grupos 35,36 han mostrado elevados niveles de ffDNA previo al inicio de la pre-eclampsia. Levine y cols.…”

Section: Niveles De Adn Libre De Origen Fetal (Ffdna)unclassified

“…Levine y cols. 35 en un grupo de 120 mujeres que desarrollaron pre-eclampsia, mostraron que los niveles de ffDNA aumentaron ~4 veces en comparación con las mujeres control, a partir de las 17 semanas de gestación. Adicionalmente, mostraron que este aumento es bifásico, con una elevación inicial entre las 17 y 28 semanas; y otra, 3 semanas antes del inicio de los síntomas clínicos.…”

Section: Niveles De Adn Libre De Origen Fetal (Ffdna)unclassified

Purinas y ácido úrico en pre-eclampsia: interacciones fisiopatológicas y proyecciones en investigación

et al. 2013

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Uric acid and purine plasma levels as plausible markers for placental dysfunction in pre-eclampsia E l ácido úrico, producto final del metabolismo de las purinas, es utilizado como marcador de daño renal y factor de riesgo de morbilidad materna y neonatal en embarazos con pre-eclampsia 1-3 . Así, las mujeres hipertensas e hiperuricémicas tienen mayor riesgo de parto pretermino, retardo de crecimiento intrauterino (RCIU) y pre-eclampsia de origen temprano (< 34 semanas), que aquellas mujeres con embarazos normales o mujeres pre-eclámpticas sin hiperuricemia 3,4 . Conjuntamente, una serie de estudios 5-7 sugieren que los embarazos con preeclampsia cursan con altos niveles de purinas (i.e., ATP, ADP, AMP, adenosina). Las causas o efectos de este aumento en el metabolismo de las purinas hasta ácido úrico no se conocen; sin embargo, dado que pre-eclampsia (principalmente de origen temprano) se asocia a un aumento en la liberación de restos celulares hacia la circulación materna, es posible que estos constituyan el principal sustrato para el metabolismo de las purinas, y finalmente formación de ácido úrico 8 . Por ello, el aumento de ácido úrico y purinas en embarazos con pre-eclampsia no sólo obedecería a la alteración de la función renal, sino que sería un marcador de disfunción placentaria. El objetivo de este trabajo es contribuir en el análisis del rol de las purinas y el ácido úrico en la fisiopatología de pre-eclampsia y con ello replantear su potencial rol predictivo en pre-eclampsia y enfermedades cardiovasculares. Es necesario indicar que este es un análisis de la literatura disponible en el cual nos permitimos especular sobre estas posibles conexiones.

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Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia

Cited by 233 publications

References 25 publications

Sterile inflammation and pregnancy complications: a review

Sterile inflammation and pregnancy complications: a review

Preeclampsia-Related Inflammatory Cytokines Regulate Interleukin-6 Expression in Human Decidual Cells

Purinas y ácido úrico en pre-eclampsia: interacciones fisiopatológicas y proyecciones en investigación

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