Fetal Gender and Several Cytokines Are Associated with the Number of Fetal Cells in Maternal Blood – An Observational Study

Schlütter, Jacob Mørup; Kirkegaard, Ida; Petersen, Olav Bjørn; Larsen, Nanna; Christensen, B.; Hougaard, David M.; Kølvraa, Steen; Uldbjerg, Niels

doi:10.1371/journal.pone.0106934

Cited by 18 publications

(24 citation statements)

References 29 publications

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“…1, 2, 3). However, cytokine levels, HLA sharing, and fetal gender may be of importance [12,16]. Differences in placenta sizes have been previously studied but do not seem to be a factor at early gestational ages [12].…”

Section: Discussionmentioning

confidence: 99%

“…However, cytokine levels, HLA sharing, and fetal gender may be of importance [12,16]. Differences in placenta sizes have been previously studied but do not seem to be a factor at early gestational ages [12]. Furthermore, a decreased clearance of fetal cells in the maternal lungs during sleep might contribute to the overnight increase in the number of pEVTs, but such a mechanism does not likely explain the increased number of pEVTs after physical activity [17].…”

Section: Discussionmentioning

confidence: 99%

“…A prior study has suggested that when using the method by Hatt et al [15], approximately 12% of pregnant women have no pEVTs when only one sample is taken [12,15]. This is a problem when using single-cell diagnostics as at least one fetal cell is needed in all pregnant women for NIPD.…”

Section: Discussionmentioning

confidence: 99%

“…Our method isolated on average only 3 pEVTs per 30 ml blood [12], although it has been estimated that 2-6 fetal cells are circulating in 1 ml of maternal blood [2,13,14]. Furthermore, in 12% of cases, we were not able to isolate any pEVTs in maternal blood samples of 30 ml [12].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, in 12% of cases, we were not able to isolate any pEVTs in maternal blood samples of 30 ml [12]. Thus, it is essential to increase the number of pEVTs in maternal blood.…”

Section: Introductionmentioning

confidence: 99%

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The Number of Endovascular Trophoblasts in Maternal Blood Increases Overnight and after Physical Activity: An Experimental Study

et al. 2015

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Introduction: Fetal cells in maternal blood may be used for noninvasive prenatal diagnostics, although their low number is a challenge. This study's objectives were to evaluate whether physical activity, transabdominal and transvaginal ultrasound scans of the uterus, as well as overnight or day-to-day variation affect the number of isolated fetal cells, more specifically the presumed endovascular trophoblast (pEVT). Material and Methods: In each of 3 different experiments, 10 normal singleton pregnant women (gestational age 10⁺⁴-14⁺⁴ weeks) participated. The number of pEVTs was assessed in 30-36 ml blood using specific markers for enrichment and identification. Results: The number of pEVTs increased overnight (p = 0.001) from a median of 1.5 to 3.5 and even further to a median of 6.0 after 30 min of physical activity (p = 0.04) but was not affected by transabdominal and transvaginal ultrasound scans. Repeated sampling showed that the interindividual variation of pEVTs was higher than the intraindividual variation (p < 0.001). However, even in pregnant women with a consistently low number of pEVTs, isolation of the pEVTs for prenatal diagnoses was possible in all cases by doing 2 separate blood samplings a few days apart. Discussion: The number of pEVTs identified in maternal blood can be increased by presampling conditions or repeated sampling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Furthermore, in 12% of cases, we were not able to isolate any pEVTs in maternal blood samples of 30 ml [12]. Thus, it is essential to increase the number of pEVTs in maternal blood.…”

Section: Introductionmentioning

confidence: 99%

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The Number of Endovascular Trophoblasts in Maternal Blood Increases Overnight and after Physical Activity: An Experimental Study

et al. 2015

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Self‐Propelled Catalytically Powered Dual‐Engine Magnetic Nanobots for Rapid and Highly Efficient Capture of Circulating Fetal Trophoblasts

Wavhale

Dhobale

Patil

et al. 2022

Adv Materials Inter

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Here, chemically powered and magnetically guided janus magneto‐fluorescent dual‐engine nanobots (MFDEN) that harvest their energy from the reactions with two different fuels are reported. The Mg‐Fe3O4 Janus nanobots prepared by depositing Fe3O4 hemispherical layer on Mg nanoparticles are propelled efficiently by the thrust of oxygen bubble generated from the reactions of Fe3O4 in H2O2 media, and by hydrogen bubble produced at the partial Mg opening in aqueous media. High speeds and long lifetimes are achieved in complex biological media with H2O2 or with NaHCO3, respectively. For the first time, this study demonstrates the utility of nanobots for efficient isolation of trophoblastic cells from blood. Considering the extreme rarity of these cells in blood, efficient technique that enriches sufficient cells rapidly and with specificity is desired. The nanobots exhibit excellent capture efficiency of almost 100%, both in serum and whole blood for trophoblastic Be‐Wo cells. Furthermore, the high capture efficiency is achieved in 5 min. Feasibility of obtaining an isolated cell based diagnosis from whole blood is demonstrated. Although determining the exact sensitivity and specificity will require more data, this study supports the potential of the multiple fuel‐powered nanorobots for clinical translation of circulating fetal cell based non‐invasive prenatal testing.

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Isolation of Circulating Fetal Trophoblasts Using Inertial Microfluidics for Noninvasive Prenatal Testing

Winter

Hardy

Rezaei

et al. 2018

Adv Materials Technologies

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While noninvasive prenatal testing based on cell‐free fetal DNA has recently revolutionized the field of aneuploidy screening in pregnancy, it remains limited to aneuploidy and microdeletion screening, and is unable to reliably detect single gene disorders. A number of recent studies have demonstrated the potential of circulating trophoblastic cells in providing cell‐based noninvasive diagnosis with sequencing or array‐based assays. However, considering the extreme rarity of these cells in blood, efficient, high‐throughput, and clinically applicable enrichment technologies are yet to be developed. This study demonstrates for the first time the utility of inertial microfluidics for efficient isolation of trophoblastic cells from maternal peripheral blood. Under optimal operating conditions, high‐recovery yields (79%) are obtained using a trophoblastic cell‐line, which is subsequently confirmed with analysis of maternal blood. Feasibility of obtaining a diagnosis from cells isolated from a maternal sample is demonstrated in a case of confirmed fetal trisomy 21 in which six fetal cells are found in a 7 mL blood sample using fluorescence in situ hybridization. Finally, it is demonstrated that trophoblastic cells isolated using inertial microfluidics could be picked and subjected to a clinically validated sequencing assay, paving the way for further validation of this technology and larger clinical studies.

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Fetal Gender and Several Cytokines Are Associated with the Number of Fetal Cells in Maternal Blood – An Observational Study

Cited by 18 publications

References 29 publications

The Number of Endovascular Trophoblasts in Maternal Blood Increases Overnight and after Physical Activity: An Experimental Study

The Number of Endovascular Trophoblasts in Maternal Blood Increases Overnight and after Physical Activity: An Experimental Study

Self‐Propelled Catalytically Powered Dual‐Engine Magnetic Nanobots for Rapid and Highly Efficient Capture of Circulating Fetal Trophoblasts

Isolation of Circulating Fetal Trophoblasts Using Inertial Microfluidics for Noninvasive Prenatal Testing

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