Circulating trophoblast numbers as a potential marker for pregnancy complications

Abstract

Objective To explore the potential of circulating trophoblasts (TBs) as a non‐invasive tool to assess placental health and predict obstetric complications. Methods We retrospectively reviewed maternal characteristics and pregnancy outcomes of 369 women who enrolled in our original cell‐based NIPT (cbNIPT) study. The number of circulating TBs recovered from the maternal blood samples was recorded and expressed as fetal cell concentration (FCC). We evaluated if FCC can be used to predict pregnancy outcomes such as hypertensive disorders of pregnancy (HDP), fetal growth restriction, placental abruption, preterm labor, and pregnancy loss. Results Receiver operating characteristic (ROC) analysis was performed to find the best cut off value to classify FCC into a low and high FCC group, and this cut‐off point was calculated as 11.1 cells per 100 ml of blood. The adjusted odds ratio (aOR) for the composite morbidity was significantly increased for the high FCC group at an aOR of 1.6. Conclusion Circulating TB have the potential of predicting obstetrical complications such as HDP. Future studies, with larger sample sizes, should focus on the study of these cells as a biomarker for placental health and a possible screening or diagnostic tool for fetal genetic conditions.

Cell-based Noninvasive Prenatal Testing (cbNIPT)—A Review on the Current Developments and Future Prospects

“…36 In a recent retrospective analysis of cbNIPT samples in our institution, we found that higher numbers of recovered TB were associated with hypertensive disorders of pregnancy. 30 These results are promising and open the way for other studies to investigate the potential of cbNIPT as a screening tool for medical conditions related to placental health. 30…”

“…30 These results are promising and open the way for other studies to investigate the potential of cbNIPT as a screening tool for medical conditions related to placental health. 30…”

“…7 While the TB yield is lower with a higher maternal BMI, similar to the reduction in fetal fraction, cells have been collected at a very high BMI, which may be an advantage over cffDNA that should be further explored. 7,29,30 The number of circulating TB is also influenced by certain pregnancy complications such as hypertensive disorders, which may be associated with abnormal spiral artery remodeling and poor placental health, abnormal placentation, and the presence of certain fetal aneuploidies, with a tendency for a higher number of cells in pregnancies with trisomy 21. The aforementioned observations and the possibility of maternal exercise before sample collection, increasing the cell yield, require further verification in larger studies.…”

“…The aforementioned observations and the possibility of maternal exercise before sample collection, increasing the cell yield, require further verification in larger studies. 7,30,31 It has not yet been established what the minimum number of cells is that should be analyzed to obtain an accurate diagnosis. Correct diagnoses have been made from just a single cell in some studies, but it is likely that a high-confidence result will require at least 3 to 5 cells.…”

Whole-Chromosome Karyotyping of Fetal Nucleated Red Blood Cells Using the Ion Proton Sequencing Platform

“…Moreover, NIPS false-positive and false-negative test results have been highlighted by the US FDA in a recent safety communication [ 29 ]. There have been several recent studies demonstrating successful cell-based NIPD using trophoblasts from maternal blood [ 30 , 31 , 32 , 33 ] or from the cervix [ 34 , 35 , 36 ], which are present in the circulation at higher numbers, are easier to isolate, and are free of maternal DNA contamination; however, these studies do not totally avoid CPM [ 30 , 31 ]. Our results serve to highlight the advantage of FNRBCs over trophoblasts, namely, that FNRBCs represent the true fetal genotype, originating from the yolk sac and then from fetal liver at later gestations [ 37 ], and can be found within first-trimester placental villi, where they undergo terminal maturation processes [ 38 ], whereas trophoblasts are derived from the placenta.…”