Presence Of Fetal Cells Research Articles

Fetal microchimeric cells influence maternal lung health following term and preterm births

Fetal microchimerism, the presence of fetal cells in maternal tissues, has garnered interest for its potential role in maternal physiology. In this study, we aimed to explore the impact of fetal microchimeric cells on maternal lung health following term and preterm delivery, particularly in the context of infection-induced preterm birth and subsequent allergic challenges. We characterized the immune cells in maternal lungs using a transgenic mouse model (mT+ Ve, Td Tomato) and high dimensional mass cytometry (CyTOF) techniques. We evaluated their influence on lung function and inflammation. Our findings revealed distinct differences in the immune cell composition of maternal lungs between term and preterm deliveries. Mice delivered preterm significantly increased in fetal-specific cells, such as activated macrophages and Tbet + Ve memory B-cells, compared to term-delivered mice. Conversely, term deliveries showed elevated levels of CD4 cells. Furthermore, preterm-delivered dams demonstrated heightened airway hyperresponsiveness, pro-inflammatory cytokine expression, cellular infiltration, and lung mucous production compared to term-delivered dams. Co-culture experiments demonstrated that microchimeric cells from preterm births stimulated the production of inflammatory cytokines IL-6 and TNF-α in lung epithelial cells. These findings shed light on the complex immune dynamics postpartum and their role in lung complications after preterm birth. Understanding these mechanisms could provide insights for targeted interventions to improve maternal lung health in at-risk populations.

Testing of the filter function of a prototype device to eliminate fetal surrogate markers and bacterial load for autotransfusion in postpartum haemorrhage in low-resource settings

26 www.thelancet.com/lancetgh Published Online April 8, 2016 University of Illinois, Chicago, IL, USA (B Collofello BS, N Robinson MD, V Dobiesz MD, P Kutz CCP, A Koch MA, A Harrington PhD, H Esmailbeigi PhD, S Geller PhD) Correspondence to: Brandon Collofello, 1940 W Taylor M/C 584, Center for Global Health, Chicago, IL 60612, USA bcollo2@uic.edu Testing of the fi lter function of a prototype device to eliminate fetal surrogate markers and bacterial load for autotransfusion in postpartum haemorrhage in low-resource settings Brandon Collofello, Nuriya Robinson, Valerie Dobiesz, Pam Kutz, Abby Koch, Amanda Harrington, Hananeh Esmailbeigi, Stacie Geller Abstract Background Postpartum haemorrhage is a leading cause of death in low-income and middle-income countries, but it is also largely preventable. As a potential solution for restoring blood volume in women with life-threatening haemorrhage in low-resource settings, a vaginal blood collection drape with adaptations for autotransfusion has been created. In this study, we aimed to assess the fi ltration function of the autotransfusion system prototype and to determine the degree to which the fi lter removes surrogate markers for amniotic fl uid, fetal cells, and inhibin A, as well as to quantify the reduction of bacterial contaminants in postpartum blood after vaginal delivery.Background Postpartum haemorrhage is a leading cause of death in low-income and middle-income countries, but it is also largely preventable. As a potential solution for restoring blood volume in women with life-threatening haemorrhage in low-resource settings, a vaginal blood collection drape with adaptations for autotransfusion has been created. In this study, we aimed to assess the fi ltration function of the autotransfusion system prototype and to determine the degree to which the fi lter removes surrogate markers for amniotic fl uid, fetal cells, and inhibin A, as well as to quantify the reduction of bacterial contaminants in postpartum blood after vaginal delivery. Methods We collected postpartum blood from four women who had normal spontaneous vaginal delivery of a term pregnancy using an adapted obstetrical blood collection drape. Immediately after the delivery, the research drape was placed under the buttocks of the participant and postpartum blood was collected. The blood entered a sterile system and was fi ltered through a Pall LeukoGuard BC2 Cardioplegia fi lter via a negative pressure pump. We tested prefi ltration and post-fi ltration samples for the presence of fetal cells, inhibin A, and surrogate markers for amniotic fl uid contamination. Cultures of prefi ltered and post-fi ltered blood underwent qualitative analysis, to identify specifi c bacterial species present, and quantitative analysis. Findings We identifi ed Escherichia coli, Bacteroides fragilis, Klebsiella pneumoniae, Enterococcus faecalis, Corynebacterium jeikeium, Lactobacillus spp, and Staphylococcus spp in prefi ltration blood samples. In samples from three of the four participants, bacterial load decreased after fi ltration. However, complete elimination of a bacterial species did not occur in two participants’ post-fi lter cultures. Fetal cells were present in one prefi ltration sample and decreased but remained present after fi ltration. Reduction in α-fetoprotein and inhibin A varied between the four participants’ post-fi ltration samples. Interpretation The fi lter tested in the autotransfusion system prototype did not signifi cantly reduce the surrogate markers tested nor eliminate bacteria in the four samples, although selective removal of Staphylococcus spp might have occurred. The system remains a promising solution to improve health outcomes of women who give birth in low-resource settings but improved fi lter function does need to be addressed. Future studies will test a leucocyte depletion fi lter, previously shown to successfully remove bacterial contaminants, as well as alter device fl ow rates for optimum fi lter function. Funding UIC Chancellor’s Innovation Fund: Spring 2014 Proof-of-Concept Award (V Dobiesz), UIC College of Medicine Craig Fellowship (B Collofello). Copyright © Collofello et al. Open Access article distributed under the terms of CC BY. Declaration of interests We declare no competing interests.

Fetal microchimerism and maternal health: a review and evolutionary analysis of cooperation and conflict beyond the womb.

The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g. enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional, and psychological health.Also watch the Video .

Maternal-fetal cellular trafficking: clinical implications and consequences.

Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells between mother and fetus during pregnancy. This results in the presence of fetal cells in the maternal circulation, known as fetal microchimerism, and maternal cells in the fetal circulation, known as maternal microchimerism. The biologic role of this transplacental cellular trafficking during pregnancy is not known, although it has been implicated in development of the fetal immune system, tolerance mechanisms during pregnancy, tissue repair in autoimmune disease and cancer, and immune surveillance. Clinical utility of MFCT has been identified in prenatal testing for aneuploidies and prediction of pregnancy complications. Additionally, this transplacental passage of cells has been implicated in the delicate balance between immunologic priming and tolerance, which can influence the occurrence of autoimmune disease and transplantation outcomes. Ongoing studies are evaluating the utility of microchimerism in predicting the risk of graft rejection in transplantation. In this review, we will discuss the clinical implications of MFCT in pregnancy, fetal surgery, autoimmune disease, transplantation, and cancer.

Clinical implications of maternal-fetal cellular trafficking

Maternal-fetal cellular trafficking (MFCT) is the bidirectional passage of cells that results in the presence of fetal cells in the mother and maternal cells in the fetus. This naturally occurring biological phenomenon has been implicated in the pathogenesis of autoimmune diseases in both mothers and children. However, MFCT may also have beneficial consequences in establishing and maintaining maternal-fetal tolerance and may have long-term consequences for transplantation tolerance. There is also evidence that trafficking is altered during pregnancy complications and fetal intervention. An improved understanding of cellular trafficking during pregnancy will lead to progress in multiple fields including autoimmunity, transplantation, and fetal surgery.

Fetal Nucleic Acids in Maternal Circulation: A Genetic Resource for Noninvasive Prenatal Diagnosis

Invasive prenatal diagnosis (PND) holds a multitude of psychological considerations for women, their partners, family and community as a whole. Earlier, the non-invasive screening methods for certain disorders were serum analytes or ultrasound with low sensitivity and high false positivity. The discovery of fetal DNA in maternal plasma has opened up an approach for noninvasive PND (NIPD). Presence of fetal cells and cell-free fetal DNA (cffDNA) in the blood of pregnant women has been accepted universally and constant efforts are being made to enrich fetal DNA from maternal blood/plasma. Real-time quantitative polymerase chain reaction (qrt-PCR) has enabled fetal DNA to serve as a marker for chromosomal abnormalities, for example, trisomy 21, preterm labor, and preeclampsia. In India, PND is provided in few centers since invasive methods require trained gynecologists, this limits investigation and therefore NIPD with cffDNA from mother's blood will revolutionize fetal medicine. The present paper deals with the latest developments in procurement of cffDNA, the probable source and enrichment of fetal DNA in maternal plasma, and the current status of its detection methodologies, applications, and its potential to be used as a powerful diagnostic tool.

Fetal cells in the adult female following pregnancy: an under-appreciated source of progenitor cells

Fetal cells in the adult female following pregnancy: an under-appreciated source of progenitor cells

Progress toward Noninvasive Prenatal Diagnosis

For decades, noninvasive analysis of the fetal genotype has been the holy grail of the field of prenatal diagnosis. Noninvasive prenatal diagnosis (NIPD)2 would use a sample source other than amniocentesis or chorionic villus sampling. The focus has been primarily on the use of maternal blood samples, with less attention given to the possibility of recovering fetal cells from maternal cervical samples (as would be collected for cervical cancer screening). The initial efforts focused on the presence of fetal cells in the maternal circulation, and evidence indicated as early as 1979 that fetal cells could be recovered via fluorescence-activated cell sorting. The elegant strategy of using antibodies to paternal HLA antigens to identify fetal cells was demonstrated. Attempts to recover fetal cells focused for a time on fetal nucleated red blood cells via analysis with fluorescence in situ hybridization and the PCR, but the disappointing results led to skepticism that NIPD would ever become a reality. By 1996 there were reports of tumor DNA detected in the plasma of cancer patients, and Lo et al. first reported in 1997 the presence of fetal DNA in maternal plasma. The use of fetal DNA in the plasma has important advantages over the use of fetal cells in that fetal DNA can be obtained consistently in virtually 100% of pregnancies, whereas fetal cells are recovered much less consistently. In recent years, the use of fetal DNA in maternal plasma to detect fetal sex has become a well-established clinical test [see references in Lo et al. (1) for background on this test and other details]. In fact, determining whether any genotype present in the father but not the mother has been transmitted to the fetus is relatively straightforward. This approach has been used to determine whether a fetus is Rh negative or positive …

Noninvasive Prenatal Diagnosis: Past, Present, and Future

The presence of fetal cells in the maternal circulation was first noted by Georg Schmorl when he documented the presence of multinucleated syncytial giant cells of placental origin in the lung tissue of women who had died from complications of eclampsia. In the intervening century, advances in cellular and molecular biology further elucidated both the physiology and pathophysiology of communication within the fetomaternal unit. This concept is at the foundation of the rapidly expanding field of noninvasive prenatal diagnosis. However, the clinical utility of this phenomenon had been limited until the presence of cell-free fetal DNA circulating in the maternal plasma was reported in 1997 and fetal messenger RNA was demonstrated to circulate in the maternal plasma in 2000. These circulating nucleic acids are found free-floating in the maternal plasma, unencumbered by a surrounding fetal cell. The analysis of these 3 fetal markers (fetal cells, cell-free fetal DNA, and fetal messenger RNA) for diagnostic and screening purposes is now being developed. The scope of noninvasive prenatal diagnosis is not limited to only the diagnosis of fetal genetic traits and aneuploidies. Recently, researchers have focused their investigations on the role of cell-free fetal DNA and fetal messenger RNA in preeclampsia, intrauterine growth restriction, and preterm labor. These biomarkers, the result of inherent placental dysfunction or the byproducts of placental trophoblastic apoptosis, may allow for improvements in the diagnosis and management of high-risk pregnancies.

Abstracts

Fetal cells enter the maternal circulation during all human and murine pregnancy. The presence of fetal microchimeric cells has been demonstrated in lesional skin of pregnant women affected with polymorphic eruptions of pregnancy. We aimed at determining in a mouse model the role of maternal inflammation in attracting microchimeric cells. Wild type female mice were mated to transgenic males for various reporter genes or wild type male controls. We used males transgenic for the luciferase gene under the control of an ubiquitous (CMV)(C-Luc) or the VEGFR2 (V-Luc) promoter. Alternatively we used males transgenic for the EGFP under the control of the beta-actin promoter. Female pregnant mice were sensitized on day 10 of pregnancy with 2% Oxazolone. On day 16 we revealed a contact hypersensitivity reaction (CHR) by painting the right ear with oxazolone while the left ear received only the vehicle. The presence of fetal cells was then monitored using one of the following: in vivo imaging to detect luciferase expressing fetal cell real time quantitative amplification of the egfp transgene or Y chromosome in situ hybridization to detect male microchimeric cells. On femalemice bearing V-Luc fetuses, a fetal signal could be detected only on the right ear that was significantly higher when compared to controls (3362 versus 1507 photons/s/cm2, p=0.02). Wealso detected fetal cells by real time quantitative PCR in the right as well as the left ear at similar frequencies. Finally, we demonstrated the presence of fetal cells in maternal inflamed ears. Fetal cells were either among the inflammatory cells or were part of the vascular wall. We demonstrate that maternal inflamed skin can recruit fetal microchimeric cells. The fetal cells adopt an endothelial phenotype in the inflamed maternal skin. Fetal cells may therefore participate in maternal angiogenesis and inflammation.

Detection of fetal cells from transcervical mucus plug before first‐trimester termination of pregnancy by cytokeratin‐7 immunohistochemistry

The presence of fetal cells in the endocervical mucus of pregnant women was first reported in 1971. The uterine cavity is patent during the first trimester prior to fusion of amnion and chorion. Fetal cells from degenerating chorion frondosum are theoretically shed into the uterine cavity between seven and 13 weeks' gestation and are trapped in the transcervical mucus; they can be identified by immunohistochemistry. Ninety-nine transcervical mucosal plugs from pregnant women of between 7 and 13 weeks before abortion were collected, fixed, embedded, sectioned and stained with monoclonal antibody of cytokeratin-7 (CK-7) by immunohistochemistry. The identification of trophoblasts on each slide was defined according to positive staining and histologically chorionic villous similarity under microscopic examination, using the following five categories: none (1), less than five single positive-stained cells per-section (2), more than five single positive-stained cells per-section (3), clumps of positive-stained cells (4), and histological-like intact or fragmented chorionic villi (5). From amongst 71 samples that qualified for analysis, individual slides were evaluated and categorized into three groups, with the following results: 32 (45.1%) fell into group 1 (category 1) denoting a negative result, 10 (14.1%) fell into group 2 (category 2) indicating a possible positive result and 29 (40.8%) fell into group 3 (any combination of categories 3-5) representing a positive result. Fetal cells, identified by CK-7, can be found in more than 59.2% of the transcervical mucus in early pregnancy by use of a minimally invasive sampling method. Prenatal diagnosis of single-gene or chromosome disorders may be possible in the pregnant transcervical mucus by use of modern molecular methods and they deserve further study.

Fetal Microchimerism in the Maternal Mouse Brain: A Novel Population of Fetal Progenitor or Stem Cells Able to Cross the Blood–Brain Barrier?

We investigated whether fetal cells can enter the maternal brain during pregnancy. Female wild-type C57BL/6 mice were crossed with transgenic Green Mice ubiquitously expressing enhanced green fluorescent protein (EGFP). Green Mouse fetal cells were found in the maternal brain. Quantitative real-time polymerase chain reaction (PCR) of genomic DNA for the EGFP gene showed that more fetal cells were present in the maternal brain 4 weeks postpartum than on the day of parturition. After an excitotoxic lesion to the brain, more fetal cells were detected in the injured region. The presence of fetal cells in the maternal brain was also confirmed by quantitative real-time PCR for the sex-determining region of the Y chromosome. Four weeks postpartum, EGFP-positive Green Mouse fetal cells in the maternal brain were found to adopt locations, morphologies, and expression of immunocytochemical markers indicative of perivascular macrophage-, neuron-, astrocyte-, and oligodendrocyte-like cell types. Expression of morphological and immunocytochemical characteristics of neuron- and astrocyte-like cell types was confirmed on identification of fetal cells in maternal brain by Y chromosome fluorescence in situ hybridization. Although further studies are required to determine whether such engraftment of the maternal brain has any physiological or pathophysiological functional significance, fetomaternal microchimerism provides a novel model for the experimental investigation of the properties of fetal progenitor or stem cells in the brain without prior in vitro manipulation. Characterization of the properties of these cells that allow them to cross both the placental and blood-brain barriers and to target injured brain may improve selection procedures for isolation of progenitor or stem cells for brain repair by intravenous infusion.

Thyroid Fetal Male Microchimerisms in Mothers with Thyroid Disorders: Presence of Y-Chromosomal Immunofluorescence in Thyroid-Infiltrating Lymphocytes Is More Prevalent in Hashimoto’s Thyroiditis and Graves’ Disease Than in Follicular Adenomas

The presence of fetal cells in a maternal compartment is defined as fetal-maternal microchimerism, which has been detected in thyroids of mothers suffering from autoimmunity. We analyzed the immunohistology of paraffin-embedded thyroid specimen taken at surgery from 49 women with Hashimoto's thyroiditis (n = 25), Graves' disease (n = 15), or nodular or diffuse follicular adenomas (n = 9), whose childbirth history was positive for sons. By fluorescence in situ hybridization we screened for X-chromosome- and Y-chromosome-specific staining and compared the finding with human leukocyte antigen (HLA) DQ types of the mothers and, where available, their offspring. In 23 thyroids we found Y-chromosome-specific staining, which was more frequent in thyroid autoimmune disease (60% Hashimoto's thyroiditis and 40% Graves' disease) than in follicular adenomas (22.2%). There was no significant difference for HLA DQ alleles among women whose thyroids showed Y-chromosome staining and those without. However, a subgroup of all investigated microchimerism-positive mother-child pairs and women with Hashimoto's thyroiditis and Graves' disease more often had the susceptibility alleles HLA DQA1*0501-DQB1*0201 or DQB1*0301. In conclusion, fetal microchimerism is observed in thyroids of mothers with sons, and this is found more frequently in thyroid autoimmune diseases.

Fetal nucleated erythrocytes in maternal circulation do not display a classic membrane-associated apoptotic characteristic (phosphatidylserine exposure) despite being positive by terminal dUTP nuclear end labeling.

The presence of fetal cells, especially fetal nucleated red blood cells (NRBCs), in the blood of pregnant women is now a widely demonstrated phenomenon and is being considered as the basis for a novel noninvasive means for prenatal diagnosis. However, at present little is known about the fate of fetal cells once they enter the maternal circulation. Fetal cells could be removed from the maternal circulation by the maternal immune system or by the induction of apoptosis by other means (1)(2)(3). These proposals are supported by reports indicating the presence of terminal dUTP nuclear end labeling (TUNEL)-positive fetal NRBCs in the maternal circulation, a feature that may be attributable to the increased oxygen concentration in the maternal circulation (4), as well as by the description of apoptotic fetal cells or their remnants in the maternal plasma. Elimination of fetal cells by apoptosis from the maternal periphery may not be as widespread as suggested, or it may not affect all fetal cell types equally. Fetal leukocytes or hemopoietic progenitor cells may persist in the maternal circulation for years to decades after delivery (5)(6), and fetal cells with stem cell-like characteristics may even contribute to the regeneration of maternal tissue (7). Furthermore, microchimerism of the order seen in pregnancy frequently also occurs in solid organ transplant recipients and has, in these instances, been suggested to promote tolerance toward the graft (8). By analogy, it is therefore conceivable that the passage of fetal cells into the maternal periphery may promote tolerance against the semiallogeneic fetus. A caveat of previous studies on the status of fetal NRBCs in the maternal periphery is that they studied only nuclear events (TUNEL positivity) as indicators of the apoptotic status of trafficking fetal cells. Sekizawa et al. (2) reported that >40% the …

Clinical Review 160: Postpartum autoimmune thyroid disease: the potential role of fetal microchimerism.

Fetal microchimerism is defined as the presence of fetal cells in maternal tissues established during pregnancy. Immune suppression of maternal immunity during pregnancy by the placenta may play an important role in allowing the establishment of such fetal microchimerism. However, peripheral blood fetal microchimerism that persists in the postpartum period is considered a natural event and implies the induction of tolerance during pregnancy. Identification of fetal cells that persist preferentially in maternal tissues subject to autoimmunity, such as skin and thyroid, has also suggested the possible immune modulation of the autoimmune response at the target tissue by fetal cells. Accumulating evidence suggests that fetal immune cells may be reactive to maternal antigens and, therefore, have the capacity to trigger graft vs. host reactions. This would provide a mechanism for the initiation and/or exacerbation of autoimmune disease. The course and severity of autoimmune thyroid disease have long been known to be profoundly influenced by pregnancy, with disease suppression prepartum and exacerbation postpartum. However, the precise mechanisms involved have not been fully understood. Here we have reviewed recent information on the possible role of fetal microchimerism in autoimmune thyroid disease, focusing on the immunological consequences of intrathyroidal fetal cells and their contribution to postpartum exacerbations.

Prenatal diagnosis of genetic abnormalities using fetal CD34+ stem cells in maternal circulation and evidence they do not affect diagnosis in later pregnancies.

In the present study, we report a new method for enrichment and analysis of fetal CD34+ stem cells after culture in order to determine whether it is feasible for noninvasive prenatal diagnosis. We also determined whether fetal CD34+ stem cells persist in maternal blood after delivery and assessed whether they have an impact on noninvasive prenatal diagnosis of genetic abnormalities. Peripheral blood samples were obtained from 35 pregnant women, 13 non-pregnant women who had given birth to male offsprings, 12 women who had never been pregnant, and eight pregnant women with male fetuses. CD34+ stem cells were enriched and either cultured for prenatal diagnosis or analyzed with fluorescence in situ hybridization (FISH)/polymerase chain reaction (PCR) to determine peristance in maternal blood. Fetal/maternal cells can be isolated and grown "in vitro" to provide enough cells for a more accurate fetal sex or aneuploid prediction than is provided by unenriched and uncultured CD34+ stem cells. The presence of fetal cells in maternal blood samples from mothers who had given birth to male offspring was found in 3 of 13 blood samples. PCR was positive for Y chromosome in one woman who had never been pregnant. Analysis of cultured CD34+ stem cells from mothers with Y PCR positivity did not detect any male cells in any samples. Even if PCR positivity is due to persistence of fetal stem cells from previous pregnancies, it does not seem to affect this new system of enrichment, culture, and FISH analysis of CD34+ fetal stem cells.

PRENATAL DIAGNOSIS USING FETAL CELLS AND FREE FETAL DNA IN MATERNAL BLOOD

The presence of fetal cells and free fetal DNA in maternal blood offers an exciting opportunity for the development of safe noninvasive forms of prenatal diagnosis. Research in this field has, however, also indicated that their levels in the maternal circulation are increased in certain pregnancy-related disorders, such as preeclampsia. Their closer examination may shed new light on the underlying etiology of this enigmatic disorder.

Disturbed Feto-Maternal Cell Traffic in Preeclampsia

In Brief Objective To investigate whether the transfer of fetal blood cells to the maternal circulation is perturbed in pregnancies affected by preeclampsia. Methods Fetal erythroblasts were isolated from eight women with clinically diagnosed preeclampsia (blood pressure values of at least 140/90 mmHg and associated proteinuria) and an equal number of matched corresponding controls. All patients in both groups were pregnant with male singleton fetuses. The presence of fetal cells was evaluated histologically and by fluorescence in situ hybridization for X and Y chromosomes. Results The number of fetal cells was higher in preeclamptic patients than in controls, with respect to both nucleated red blood cells (median per 200 cells 38 versus 7; P < .001) and the proportion of these cells that were of fetal origin (median per 2000 cells 9 versus 2; P = .001). Conclusion These results suggest that the trafficking of fetal cells into the maternal periphery is disturbed in patients with preeclampsia. Because it is unlikely that such an altered flow of cells is restricted to the erythroblasts examined in this study, these findings also may lead to interesting new concepts regarding the development of preeclampsia and possibly the associated syndrome of hemolysis, elevated liver enzymes, and low platelets. Fetal erythroblast numbers are elevated in the peripheral blood of preeclamptic patients in comparison with normal.

Disturbed Feto-Maternal Cell Traffic in Preeclampsia

Objective: To investigate whether the transfer of fetal blood cells to the maternal circulation is perturbed in pregnancies affected by preeclampsia. Methods: Fetal erythroblasts were isolated from eight women with clinically diagnosed preeclampsia (blood pressure values of at least 140/90 mmHg and associated proteinuria) and an equal number of matched corresponding controls. All patients in both groups were pregnant with male singleton fetuses. The presence of fetal cells was evaluated histologically and by fluorescence in situ hybridization for X and Y chromosomes. Results: The number of fetal cells was higher in preeclamptic patients than in controls, with respect to both nucleated red blood cells (median per 200 cells 38 versus 7; P < .001) and the proportion of these cells that were of fetal origin (median per 2000 cells 9 versus 2; P = .001). Conclusion: These results suggest that the trafficking of fetal cells into the maternal periphery is disturbed in patients with preeclampsia. Because it is unlikely that such an altered flow of cells is restricted to the erythroblasts examined in this study, these findings also may lead to interesting new concepts regarding the development of preeclampsia and possibly the associated syndrome of hemolysis, elevated liver enzymes, and low platelets.

Progress in the genetic analysis of fetal cells circulating in maternal blood

The presence of fetal cells in maternal blood has been demonstrated by many investigators who continue to refine methods to permit their isolation, identification and genetic analysis. The sensitivity and specificity of this technique for noninvasive aneuploidy detection is currently being addressed in a multicenter clinical trial. Significant advances have also occurred in fetal single-cell and single-gene analysis.